Docetaxel (formerly known as RP56976; NSC628503; RP-56976; NSC-628503; Taxotere), a semisynthetic analog of paclitaxel and approved anticancer drug, is a mitotic inhibitor and tubulin inhibitor that inhibits the depolymerization of microtubules by binding to and stabilizing microtubules. Docetaxel has shown potent and a broad spectrum of antineoplastic activities and has been extensively used in the treatment of various cancers. It is a semi-synthetic, second-generation taxane derived from a compound found in the European yew tree Taxus baccata. Docetaxel displays potent and broad antineoplastic properties; it binds to and stabilizes tubulin, thereby inhibiting microtubule disassembly which results in cell- cycle arrest at the G2/M phase and cell death.

Physicochemical Properties

Molecular Formula	C43H53NO14
Molecular Weight	807.88
Exact Mass	807.346
Elemental Analysis	C, 63.93; H, 6.61; N, 1.73; O, 27.73.
CAS #	114977-28-5
Related CAS #	Docetaxel Trihydrate;148408-66-6;Docetaxel-d9;940867-25-4
PubChem CID	148124
Appearance	White to off-white solid powder
Density	1.4±0.1 g/cm3
Boiling Point	900.5±65.0 °C at 760 mmHg
Melting Point	186-192 °C (dec.)
Flash Point	498.4±34.3 °C
Vapour Pressure	0.0±0.3 mmHg at 25°C
Index of Refraction	1.618
LogP	6.55
Hydrogen Bond Donor Count	5
Hydrogen Bond Acceptor Count	14
Rotatable Bond Count	13
Heavy Atom Count	58
Complexity	1660
Defined Atom Stereocenter Count	11
SMILES	CC1=C2[C@H](C(=O)[C@@]3([C@H](C[C@@H]4[C@]([C@H]3[C@@H]([C@@](C2(C)C)(C[C@@H]1OC(=O)[C@@H]([C@H](C5=CC=CC=C5)NC(=O)OC(C)(C)C)O)O)OC(=O)C6=CC=CC=C6)(CO4)OC(=O)C)O)C)O
InChi Key	ZDZOTLJHXYCWBA-VCVYQWHSSA-N
InChi Code	InChI=1S/C43H53NO14/c1-22-26(55-37(51)32(48)30(24-15-11-9-12-16-24)44-38(52)58-39(3,4)5)20-43(53)35(56-36(50)25-17-13-10-14-18-25)33-41(8,34(49)31(47)29(22)40(43,6)7)27(46)19-28-42(33,21-54-28)57-23(2)45/h9-18,26-28,30-33,35,46-48,53H,19-21H2,1-8H3,(H,44,52)/t26-,27-,28+,30-,31+,32+,33-,35-,41+,42-,43+/m0/s1
Chemical Name	(2aR,4S,4aS,6R,9S,11S,12S,12bS)-12b-acetoxy-9-(((2R,3S)-3-((tert-butoxycarbonyl)amino)-2-hydroxy-3-phenylpropanoyl)oxy)-4,6,11-trihydroxy-4a,8,13,13-tetramethyl-5-oxo-2a,3,4,4a,5,6,9,10,11,12,12a,12b-dodecahydro-1H-7,11-methanocyclodeca[3,4]benzo[1,2-b]oxet-12-yl benzoate.
Synonyms	RP56976; NSC 628503; RP-56976; NSC628503; RP 56976; NSC-628503; Docetaxel hydrate; Docetaxel anhydrous; Docetaxel Winthrop; Docetaxol; Docetaxel Kabi; EmDOC; Trade name: Taxotere.
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: This product requires protection from light (avoid light exposure) during transportation and storage.
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	Tubulin; microtubule; microtubule depolymerization
ln Vitro	Docetaxel (RP-56976) and glufosfamide (GLU) treatments, both single and combination, had dose-dependent effects on cell survival. In PC-3 and LNCaP cells, the IC50 of GLU is 70±4 μM and 86.8±8 μM, respectively. Simultaneously, docetaxel alone had an IC50 of 3.08±0.4 nM in PC-3 and 1.46±0.2 nM in LNCaP cells. GLU and Docetaxel therapy together can enhance cytotoxicity; as a result, PC-3 and LNCaP cell IC50 values were lowered to 2.7 and 2.7, respectively. 0.75±0.3 nM and ±0.1 nM[1]. For NCI-H460, the docetaxel IC50 is 30 nM at 72 hours and 116 nM at 24 hours. On NCI-60 cell plates, the typical IC50 for docetaxel is 14–34 nM, according to data from the DTP data search [2].
ln Vivo	The intestinal cell apoptosis caused by docetaxel (RP-56976) in female mice was considerably higher in the 14-hour after light exposure (HALO) group compared to the 2-HALO group. Docetaxel markedly elevated Bax expression in the 2-HALO group, but not in the 14-HALO group. Conversely, docetaxel markedly elevated the expression of cleaved Caspase-3 in the 14-HALO group, but not in the 2-HALO group. At 14 HALO, but not at 2 HALO, docetaxel treatment resulted in a substantial increase in the expression of Wee1 and phosphorylated CKD1. Furthermore, docetaxel markedly decreased the expression of survivin in the 14-HALO group but not in the 2-HALO group. When compared to the 2-HALO group treated with the medication, the survivin expression level in the 14-HALO group treated with docetaxel was significantly lower [3]. The Sprague-Daley mouse received intravenous docetaxel (DOX) at a dose of 7 mg/kg, while piperine (PIP) was given orally at 35 mg/kg and 3.5 mg/kg and as an intravenous bolus of 3.5 mg/kg. Sprague-Dawley rats were coadministered PIP at 35 mg/kg orally and Docetaxel at 7 mg/kg by intravenous bolus. Their in vivo exposure is synergistically increased when PIP and Docetaxel are used together [4].
Enzyme Assay	In Vitro Tubulin Polymerization Assay. [5] Tubulin was prepared as described before. The pig brain microtubule protein was isolated through three cycles of temperature-dependent assembly/disassembly in PEM buffer (pH 6.5, 100 mM PIPES, 2 mM EGTA, and 1 mM MgSO4) containing 1 mM GTP and 1 mM 2-mercaptoethanol. Tubulin was prepared from the microtubule protein by phosphocellulose chromatography and stored at −70 °C. Tubulin was mixed with indicated concentrations of test compounds (e.g. docetaxel) in PEM buffer (100 mM PIPES, 1mMMgCl2, and 1mMEGTA) containing 1mMGTP and 5% glycerol. Microtubule polymerization was monitored by a spectrophotometer at 340 nm. The plateau absorbance values were used for calculations[5].
Cell Assay	The wide use of paclitaxel and docetaxel in NSCLC clinical treatment makes it necessary to find biomarkers for identifying patients who can benefit from paclitaxel or docetaxel. In present study, NCI-H460, a NSCLC cell line with different sensitivity to paclitaxel and docetaxel, was applied to DNA microarray expression profiling analysis at different time points of lower dose treatment with paclitaxel or docetaxel. And the complex signaling pathways regulating the drug response were identified, and several novel sensitivity-realted markers were biocomputated.The dynamic changes of responding genes showed that paclitaxel effect is acute but that of docetaxel is durable at least for 48 hours in NCI-H460 cells. Functional annotation of the genes with altered expression showed that genes/pathways responding to these two drugs were dramatically different. Gene expression changes induced by paclitaxel treatment were mainly enriched in actin cytoskeleton (ACTC1, MYL2 and MYH2), tyrosine-protein kinases (ERRB4, KIT and TIE1) and focal adhesion pathway (MYL2, IGF1 and FLT1), while the expression alterations responding to docetaxel were highly co-related to cell surface receptor linked signal transduction (SHH, DRD5 and ADM2), cytokine-cytokine receptor interaction (IL1A and IL6) and cell cycle regulation (CCNB1, CCNE2 and PCNA). Moreover, we also confirmed some different expression patterns with real time PCR. Our study will provide the potential biomarkers for paclitaxel and docetaxel-selection therapy in clinical application[2].
Animal Protocol	Male mice were maintained under a 12-hour light/dark cycle. Intestinal damage after repeated dosing of docetaxel (20 mg/kg) for 3 weeks was more severe at 14 hours after light on (HALO) than at 2 HALO. The intestinal protein expressions of Wee1, phosphorylated CDK1, and cleaved Caspase-3 were higher in the 14-HALO group than in the 2-HALO group, whereas that of survivin was lower in the 14-HALO group. Thus, it is speculated that elevated Wee1 expression inhibited CDK1 activity more by phosphorylation, which in turn caused the lower expression of survivin and consequently more activated Caspase-3 in the 14-HALO group. There were no significant differences in plasma docetaxel concentrations between the 2- and 14-HALO groups. Bindings of CLOCK and BMAL1 to the E-box regions at the wee1 gene promoter were not altered by docetaxel treatment at 2 and 14 HALO. These findings suggest that Wee1 is directly or indirectly involved in the mechanism of the circadian rhythm-dependent changes in docetaxel-induced intestinal damage. However, the mechanism for a circadian rhythm-dependent change in intestinal Wee1 expression by docetaxel remains to be determined.[3] Piperine (PIP), the major alkaloid component from Piper longum L. and Piper nigrum L., could enhance the bioavailabilities of other drugs including rosuvastatin, peurarin and docetaxel (DOX) via inhibition of CYP3A and P-glycoprotein activity. Nevertheless, the effect of such drug combination usage on the in vivo exposure of PIP has not been investigated due to lack of assay for the simultaneous determination of PIP and other drugs such as DOX. Besides, the reported pharmacokinetics of PIP varied a lot without appropriate bioavailability determined from the same dose. In the current study, an LC/MS/MS method has been developed to simultaneously determine the plasma concentrations of PIP and DOX and further applied to investigate the pharmacokinetics properties of PIP after oral and intravenous administrations as well as the pharmacokinetics interactions between PIP and DOX after their co-administration. A simple protein precipitation method was employed for plasma sample treatment by adding a mixture of methanol and acetonitrile (1:1, v/v) with glibenclamide as internal standard (IS). The LC/MS/MS system consisted of Agilent 6430 series LC pumps and auto-sampler. The chromatographic separation was carried out in 15min on a Waters C18 column (150×3.9mm i.d., 4μm) with a mobile phase containing 0.2% formic acid and acetonitrile (1:1, v/v) at a flow rate of 0.4ml/min. The detection was performed using the positive ion electrospray ionization (ESI) in multiple reaction monitoring (MRM) mode with precursor-to-product ion transitions at m/z 286.1→201.1 for PIP, m/z 830.3→548.9 for DOX and m/z 494.2→369.0 for IS. The method demonstrated good linearity for both PIP and DOX over the concentration range of 2.5-1280ng/ml with LLOD at 2.5ng/ml. The intra-day and inter-day precisions were less than 13.34% and relative error (R.E.) representing accuracy was in the range of -11.38 to 3.15%. The recoveries of PIP, DOX and IS were above 75% and there was no matrix effect. PIP and DOX exhibited good stabilities under various conditions. PIP was administrated via intravenous bolus at 3.5mg/kg and via oral administration at 35mg/kg and 3.5mg/kg, while DOX was intravenously administrated at 7mg/kg to Sprague-Daley rats. The plasma concentrations of PIP and DOX were determined using the above developed and validated method. At the dose of 3.5mg/kg, the bioavailability of PIP was calculated to be 25.36%. Its AUC0→t was unproportionally increased with doses, indicating a potential non-linear pharmacokinetics profile of PIP. It was found that the AUC0→t and C0 of DOX and t1/2 of PIP were significantly increased after their combination use, suggesting potential enhanced bioavailability of not only DOX but also PIP, which may lead to the overall enhanced pharmacological effects.[4] Dissolved in 50 mg/mL stock solution in ethanol by adding an equal volume of polysorbate 80 and diluting with 5% dextrose in water to the final volume; 33 mg/kg; i.v. injection Human colon carcinomas xenografts CX-1
ADME/Pharmacokinetics	Absorption, Distribution and Excretion The pharmacokinetic profile of docetaxel is consistent with a three-compartment model. The initial rapid decline represents the distribution to the peripheral compartments, and the late (terminal) phase is partly due to a relatively slow efflux of docetaxel from the peripheral compartment. The area under the curve (AUC) was dose proportional at doses between 70 mg/m2 and 115 mg/m2 with infusion times of 1 to 2 hours. In a group of patients with solid tumors given 100 mg/m2 of docetaxel intravenously, the Cmax and AUC were 2.41 μg/mL and 5.93 μg⋅h/mL, respectively. Docetaxel was eliminated in urine and feces following oxidative metabolism of the tert-butyl ester group, but fecal excretion was the main elimination route. Within 7 days, urinary and fecal excretion accounted for approximately 6% and 75% of the administered radioactivity, respectively. In the first 48 hours, approximately 80% of the radioactivity recovered was excreted in feces. One major and three minor metabolites were excreted at this point, with less than 8% as the unchanged drug. Docetaxel has a steady-state volume of distribution of 113 L. Its pharmacokinetic profile is consistent with a three-compartment pharmacokinetic model. After the administration of 20–115 mg/m2 of intravenous docetaxel to cancer patients, the total body clearance was 21 L/h/m2. In patients aged 1 to 20 years with solid tumors that received 55 mg/m2 to 235 mg/m2 of docetaxel in a 1-hour intravenous infusion every 3 weeks, clearance was 17.3 L/h/m2. The initial rapid decline represents distribution to the peripheral compartments and the late (terminal) phase is due, in part, to a relatively slow efflux of docetaxel from the peripheral compartment. Mean steady state volume of distribution was 113 L. In vitro studies showed that docetaxel is about 94% protein bound, mainly to alpha1-acid glycoprotein, albumin, and lipoproteins. In three cancer patients, the in vitro binding to plasma proteins was found to be approximately 97%. Dexamethasone does not affect the protein binding of docetaxel. A study of (14)C-docetaxel was conducted in three cancer patients. Docetaxel was eliminated in both the urine and feces following oxidative metabolism of the tert-butyl ester group, but fecal excretion was the main elimination route. Within 7 days, urinary and fecal excretion accounted for approximately 6% and 75% of the administered radioactivity, respectively. About 80% of the radioactivity recovered in feces is excreted during the first 48 hours as 1 major and 3 minor metabolites with very small amounts (less than 8%) of unchanged drug. The pharmacokinetics of docetaxel have been evaluated in cancer patients after administration of 20 mg/m2 to 115 mg/sq m in phase 1 studies. The area under the curve (AUC) was dose proportional following doses of 70 mg/sq m to 115 mg/sq m with infusion times of 1 to 2 hours. Docetaxel's pharmacokinetic profile is consistent with a three-compartment pharmacokinetic model, with half-lives for the alpha, beta, and gamma phases of 4 min, 36 min, and 11.1 hr, respectively. Mean total body clearance was 21 L/hr/sq m. It is not known whether docetaxel is excreted in human milk. Metabolism / Metabolites Docetaxel undergoes hepatic metabolism. _In vitro_ drug interaction studies revealed that docetaxel is metabolized by the CYP3A4 isoenzyme. CYP3A5 also plays a role in the metabolism of this drug. In humans, docetaxel is metabolized by CYP3A4/5 into four metabolites: M1, M2, M3 and M4. Docetaxel undergoes hydroxylation of the synthetic isobutoxy side chain, forming metabolite M2. The oxidation of M2 forms an unstable aldehyde that is immediately cyclised into the stereoisomers M1 and M3. M4 is then formed by the oxidation of M1/M3. Docetaxel, a potent antimicrotubule agent widely used in the treatment of ovarian, breast and lung cancer, is extensively metabolized in various animal species, including humans. The metabolism of docetaxel to its primary metabolite, hydroxydocetaxel, is mediated by cytochrome P450 isozymes CYP3A2 and CYP3A4 in rats and humans, respectively.... In vitro drug interaction studies revealed that docetaxel is metabolized by the CYP3A4 isoenzyme, and its metabolism may be modified by the concomitant administration of compounds that induce, inhibit, or are metabolized by cytochrome P450 3A4. Docetaxel has known human metabolites that include Hydroxy-Docetaxel. Hepatic. In vitro drug interaction studies revealed that docetaxel is metabolized by the CYP3A4 isoenzyme (1 major, 3 minor metabolites). Route of Elimination: Docetaxel was eliminated in both the urine and feces following oxidative metabolism of the tert-butyl ester group, but fecal excretion was the main elimination route. Within 7 days, urinary and fecal excretion accounted for approximately 6% and 75% of the administered radioactivity, respectively. Half Life: Dose-dependent. Doses of 70 mg per square meter of body surface area (mg/m 2 ) or higher produce a triphasic elimination profile. With lower doses, assay limitations precluded detection of the terminal elimination phase. The half-life of the alpha, beta, and gamma phase are 4 minutes, 36 minutes, and 11.1 hours, respectively. Biological Half-Life With plasma sampling up to 8 to 22 days after docetaxel infusion, the terminal elimination half-life was 116 hours. Doses between 70 and 115 mg/m2 with infusion times of 1 to 2 hours produce a triphasic elimination profile. The half-life of the alpha, beta, and gamma phases are 4 minutes, 36 minutes, and 11.1 hours, respectively.
Toxicity/Toxicokinetics	Hepatotoxicity Docetaxel has been associated with serum aminotransferase elevations in up to half of patients, but values greater than 5 times the upper limit of normal (ULN) occur in less than 2%. Similar rates of alkaline phosphatase elevations and occasional mild bilirubin elevations also occur. The abnormalities are usually asymptomatic, mild and self-limited, rarely requiring dose modification or discontinuation. Despite the frequency of serum enzyme elevations during therapy, clinically apparent liver injury from docetaxel is rare. Nevertheless, individual case reports of severe acute hepatic necrosis attributed to docetaxel have been published, usually arising within a few days or weeks after a severe hypersensitivity reaction to the first or second infusion of docetaxel (Case 1). The typical case arises within days of the infusion of docetaxel and is associated with rapid, marked rises in serum aminotransferase levels with subsequent appearance of jaundice. With severe injury there is early hepatic and multiorgan failure with jaundice and progressive hepatic encephalopathy, coagulopathy, and ascites. Immunoallergic features (fever, rash, flushing) are common initially, but may be obscured by corticosteroid therapy. Liver biopsy generally reveals zone 3 (centrolobular) necrosis and variable degrees of inflammation and cholestasis. Because docetaxel is often given with other antineoplastic agents, liver injury arising during therapy cannot always be attributed reliably to docetaxel as opposed to another specific agent. Furthermore, docetaxel in combination with other antineoplastic agents may be associated with reactivation of hepatitis B, increased risk of opportunistic viral infections, sinusoidal obstruction syndrome and sepsis, any of which can cause liver test abnormalities or clinically apparent liver injury. Likelihood score: C (probable cause of acute hepatic necrosis associated with a hypersensitivity reaction to an infusion). Effects During Pregnancy and Lactation ◉ Summary of Use during Lactation Most sources consider breastfeeding to be contraindicated during maternal antineoplastic drug therapy. No information is available on the clinical use of docetaxel during breastfeeding. It has been suggested that breastfeeding should be discontinued for 4 to 5 days after a dose, although the manufacturer recommends that breastfeeding be discontinued for 1 week after the last dose. Chemotherapy may adversely affect the normal microbiome and chemical makeup of breastmilk. Women who receive chemotherapy during pregnancy are more likely to have difficulty nursing their infant. ◉ Effects in Breastfed Infants Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk A telephone follow-up study was conducted on 74 women who received cancer chemotherapy at one center during the second or third trimester of pregnancy to determine if they were successful at breastfeeding postpartum. Only 34% of the women were able to exclusively breastfeed their infants, and 66% of the women reported experiencing breastfeeding difficulties. This was in comparison to a 91% breastfeeding success rate in 22 other mothers diagnosed during pregnancy, but not treated with chemotherapy. Other statistically significant correlations included: (1) mothers with breastfeeding difficulties had an average of 5.5 cycles of chemotherapy compared with 3.8 cycles among mothers who had no difficulties; and (2) mothers with breastfeeding difficulties received their first cycle of chemotherapy on average 3.4 weeks earlier in pregnancy. Of the 9 women who received a taxane-containing regimen, 7 had breastfeeding difficulties. Protein Binding _In vitro_ studies show that 94% of docetaxel is bound to proteins, mainly alpha-1-acid glycoprotein, albumin, and lipoproteins. When measured in cancer patients, docetaxel is 97% bound to plasma protein. Dexamethasone does not affect the protein binding of docetaxel.
References	[1]. The chemomodulatory effects of glufosfamide on docetaxel cytotoxicity in prostate cancer cells. PeerJ. 2016 Jun 29;4:e2168. [2]. DNA microarray reveals different pathways responding to NSC 125973 and docetaxel in non-small cell lung cancer cell line. Int J Clin Exp Pathol. 2013 Jul 15;6(8):1538-48. [3]. Involvement of Wee1 in the circadian rhythm dependent intestinal damage induced by docetaxel. J Pharmacol Exp Ther. 2013 Oct;347(1):242-8. [4]. Non-linear pharmacokinetics of piperine and its herb-drug interactions with docetaxel in Sprague-Dawley rats. J Pharm Biomed Anal. 2016 Sep 5;128:286-93. [5]. X‑ray Crystal Structure-Guided Discovery of Novel Indole Analogues as Colchicine-Binding Site Tubulin Inhibitors with Immune- Potentiating and Antitumor Effects against Melanoma. J Med Chem . 2023 May 25;66(10):6697-6714.
Additional Infomation	Docetaxel anhydrous is a tetracyclic diterpenoid that is paclitaxel with the N-benzyloxycarbonyl group replaced by N-tert-butoxycarbonyl, and the acetoxy group at position 10 replaced by a hydroxy group. It has a role as an antineoplastic agent, a photosensitizing agent and an antimalarial. It is a tetracyclic diterpenoid and a secondary alpha-hydroxy ketone. It derives from a hydride of a taxane. Docetaxel is a clinically well established anti-mitotic chemotherapy medication used for the treatment of different types of cancer, including breast, ovarian, and non-small cell lung cancer. Docetaxel is a complex diterpenoid molecule and a semisynthetic analogue of [paclitaxel]. Docetaxel reversibly binds to microtubulin with high affinity in a 1:1 stoichiometric ratio, allowing it to prevent cell division and promote to cell death. Compared to paclitaxel, docetaxel is two times more potent as an inhibitor of microtubule depolymerization. Docetaxel binds to microtubules but does not interact with dimeric tubulin. The use of docetaxel may lead to udesired outcomes such as hepatic impairment, hematologic effects, enterocolitis and neutropenic colitis, hypersensitivity reactions, fluid retention, second primary malignancies, embryo-fetal toxicity, and tumor lysis syndrome. Docetaxel was approved by the FDA in 1996 and is available in solution for injection for intravenous or parenteral administration. Docetaxel anhydrous is a Microtubule Inhibitor. The physiologic effect of docetaxel anhydrous is by means of Microtubule Inhibition. Docetaxel is an antineoplastic agent that has a unique mechanism of action as an inhibitor of cellular mitosis and that currently plays a central role in the therapy of many solid tumors including breast and lung cancer. Docetaxel therapy is frequently associated with serum enzyme elevations which are usually transient and mild, but more importantly has been linked to rapid onset, severe hypersensitivity reactions that can be associated with acute hepatic necrosis, liver failure and death. Docetaxel has been reported in Penicillium ubiquetum with data available. Docetaxel is a semi-synthetic, second-generation taxane derived from a compound found in the European yew tree, Taxus baccata. Docetaxel displays potent and broad antineoplastic properties; it binds to and stabilizes tubulin, thereby inhibiting microtubule disassembly which results in cell- cycle arrest at the G2/M phase and cell death. This agent also inhibits pro-angiogenic factors such as vascular endothelial growth factor (VEGF) and displays immunomodulatory and pro-inflammatory properties by inducing various mediators of the inflammatory response. Docetaxel has been studied for use as a radiation-sensitizing agent. (NCI04) Docetaxel Anhydrous is the anhydrous form of docetaxel, a semisynthetic side-chain analogue of paclitaxel with antineoplastic property. Docetaxel binds specifically to the beta-tubulin subunit of microtubules and thereby antagonizes the disassembly of the microtubule proteins. This results in the persistence of aberrant microtubule structures and results in cell-cycle arrest and subsequent cell death. Docetaxel is a clinically well established anti-mitotic chemotherapy medication used mainly for the treatment of breast, ovarian, and non-small cell lung cancer. Docetaxel binds to microtubules reversibly with high affinity and has a maximum stoichiometry of one mole docetaxel per mole tubulin in microtubules. A semisynthetic analog of PACLITAXEL used in the treatment of locally advanced or metastatic BREAST NEOPLASMS and NON-SMALL CELL LUNG CANCER. Drug Indication Docetaxel is indicated as a single agent for the treatment of locally advanced or metastatic breast cancer after chemotherapy failure; and with doxorubicin and cyclophosphamide as adjuvant treatment of operable node-positive BC. It is also indicated as a single agent for locally advanced or metastatic non-small cell lung cancer (NSCLC) after platinum therapy failure; and with cisplatin for unresectable, locally advanced or metastatic untreated NSCLC. For the treatment of metastatic castration-resistant prostate cancer, docetaxel is indicated with prednisone. Docetaxel is also indicated with cisplatin and fluorouracil for untreated, advanced gastric adenocarcinoma, including the gastroesophageal junction, and with cisplatin and fluorouracil for induction treatment of locally advanced squamous cell carcinoma of the head and neck (SCCHN). Breast cancer Docetaxel Kabi in combination with doxorubicin and cyclophosphamide is indicated for the adjuvant treatment of patients with: operable node-positive breast cancer ; operable node-negative breast cancer . For patients with operable node-negative breast cancer , adjuvant treatment should be restricted to patients eligible to receive chemotherapy according to internationally established criteria for primary therapy of early breast cancer . Docetaxel Kabi in combination with doxorubicin is indicated for the treatment of patients with locally advanced or metastatic breast cancer who have not previously received cytotoxic therapy for this condition. Docetaxel Kabi monotherapy is indicated for the treatment of patients with locally advanced or metastatic breast cancer after failure of cytotoxic therapy. Previous chemotherapy should have included an anthracycline or an alkylating agent. Docetaxel Kabi in combination with trastuzumab is indicated for the treatment of patients with metastatic breast cancer whose tumours overexpress HER2 and who previously have not received chemotherapy for metastatic disease. Docetaxel Kabi in combination with capecitabine is indicated for the treatment of patients with locally advanced or metastatic breast cancer after failure of cytotoxic chemotherapy. Previous therapy should have included an anthracycline. Non-small-cell lung cancer Docetaxel Kabi is indicated for the treatment of patients with locally advanced or metastatic non-small-cell lung cancer after failure of prior chemotherapy. Docetaxel Kabi in combination with cisplatin is indicated for the treatment of patients with unresectable, locally advanced or metastatic non-small-cell lung cancer , in patients who have not previously received chemotherapy for this condition. Prostate cancer Docetaxel Kabi in combination with prednisone or prednisolone is indicated for the treatment of patients with castration-resistant metastatic prostate cancer . Docetaxel Kabi in combination with androgen-deprivation therapy (ADT), with or without prednisone or prednisolone, is indicated for the treatment of patients with metastatic hormone-sensitive prostate cancer . Gastric adenocarcinomaDocetaxel Kabi in combination with cisplatin and 5-fluorouracil is indicated for the treatment of patients with metastatic gastric adenocarcinoma, including adenocarcinoma of the gastroesophageal junction, who have not received prior chemotherapy for metastatic disease. Head and neck cancer Docetaxel Kabi in combination with cisplatin and 5-fluorouracil is indicated for the induction treatment of patients with locally advanced squamous cell carcinoma of the head and neck. Breast cancer Docetaxel Accord in combination with doxorubicin and cyclophosphamide is indicated for the adjuvant treatment of patients with: operable node-positive breast cancer ; operable node-negative breast cancer . For patients with operable node-negative breast cancer , adjuvant treatment should be restricted to patients eligible to receive chemotherapy according to internationally established criteria for primary therapy of early breast cancer . Docetaxel Accord in combination with doxorubicin is indicated for the treatment of patients with locally advanced or metastatic breast cancer who have not previously received cytotoxic therapy for this condition. Docetaxel Accord monotherapy is indicated for the treatment of patients with locally advanced or metastatic breast cancer after failure of cytotoxic therapy. Previous chemotherapy should have included an anthracycline or an alkylating agent. Docetaxel Accord in combination with trastuzumab is indicated for the treatment of patients with metastatic breast cancer whose tumours overexpress HER2 and who previously have not received chemotherapy for metastatic disease. Docetaxel Accord in combination with capecitabine is indicated for the treatment of patients with locally advanced or metastatic breast cancer after failure of cytotoxic chemotherapy. Previous therapy should have included an anthracycline. Non-small-cell lung cancer Docetaxel Accord is indicated for the treatment of patients with locally advanced or metastatic non-small-cell lung cancer after failure of prior chemotherapy. Docetaxel Accord in combination with cisplatin is indicated for the treatment of patients with unresectable, locally advanced or metastatic non-small-cell lung cancer , in patients who have not previously received chemotherapy for this condition. Prostate cancer Docetaxel Accord in combination with prednisone or prednisolone is indicated for the treatment of patients with hormone refractory metastatic prostate cancer . Gastric adenocarcinomaDocetaxel Accord in combination with cisplatin and 5-fluorouracil is indicated for the treatment of patients with metastatic gastric adenocarcinoma, including adenocarcinoma of the gastroesophageal junction, who have not received prior chemotherapy for metastatic disease. Head and neck cancer Docetaxel Accord in combination with cisplatin and 5-fluorouracil is indicated for the induction treatment of patients with locally advanced squamous cell carcinoma of the head and neck. Breast cancer Taxotere in combination with doxorubicin and cyclophosphamide is indicated for the adjuvant treatment of patients with: operable node-positive breast cancer ; operable node-negative breast cancer . For patients with operable node-negative breast cancer , adjuvant treatment should be restricted to patients eligible to receive chemotherapy according to internationally established criteria for primary therapy of early breast cancer . Taxotere in combination with doxorubicin is indicated for the treatment of patients with locally advanced or metastatic breast cancer who have not previously received cytotoxic therapy for this condition. Taxotere monotherapy is indicated for the treatment of patients with locally advanced ormetastatic breast cancer after failure of cytotoxic therapy. Previous chemotherapy should have included an anthracycline or an alkylating agent. Taxotere in combination with trastuzumab is indicated for the treatment of patients with metastatic breast cancer whose tumours overexpress HER2 and who previously have not received chemotherapy for metastatic disease. Taxotere in combination with capecitabine is indicated for the treatment of patients with locally advanced or metastatic breast cancer after failure of cytotoxic chemotherapy. Previous therapy should have included an anthracycline. Non-small-cell lung cancer Taxotere is indicated for the treatment of patients with locally advanced or metastatic non-small-cell lung cancer after failure of prior chemotherapy. Taxotere in combination with cisplatin is indicated for the treatment of patients with unresectable, locally advanced or metastatic non-small-cell lung cancer , in patients who have not previously received chemotherapy for this condition. Prostate cancer Taxotere in combination with prednisone or prednisolone is indicated for the treatment of patients with hormone refractory metastatic prostate cancer . Gastric adenocarcinomaTaxotere in combination with cisplatin and 5-fluorouracil is indicated for the treatment of patients with metastatic gastric adenocarcinoma, including adenocarcinoma of the gastroesophageal junction, who have not received prior chemotherapy for metastatic disease. Head and neck cancer Taxotere in combination with cisplatin and 5-fluorouracil is indicated for the induction treatment of patients with locally advanced squamous cell carcinoma of the head and neck. Breast cancer Docetaxel Winthrop in combination with doxorubicin and cyclophosphamide is indicated for the adjuvant treatment of patients with: operable node-positive breast cancer ; operable node-negative breast cancer . For patients with operable node-negative breast cancer , adjuvant treatment should be restricted to patients eligible to receive chemotherapy according to internationally established criteria for primary therapy of early breast cancer . Docetaxel Winthrop in combination with doxorubicin is indicated for the treatment of patients with locally advanced or metastatic breast cancer who have not previously received cytotoxic therapy for this condition. Docetaxel Winthrop monotherapy is indicated for the treatment of patients with locally advanced or metastatic breast cancer after failure of cytotoxic therapy. Previous chemotherapy should have included an anthracycline or an alkylating agent. Docetaxel Winthrop in combination with trastuzumab is indicated for the treatment of patients with metastatic breast cancer whose tumours overexpress HER2 and who previously have not received chemotherapy for metastatic disease. Docetaxel Winthrop in combination with capecitabine is indicated for the treatment of patients with locally advanced or metastatic breast cancer after failure of cytotoxic chemotherapy. Previous therapy should have included an anthracycline. Non-small-cell lung cancer Docetaxel Winthrop is indicated for the treatment of patients with locally advanced or metastatic non-small-cell lung cancer after failure of prior chemotherapy. Docetaxel Winthrop in combination with cisplatin is indicated for the treatment of patients with unresectable, locally advanced or metastatic non-small-cell lung cancer , in patients who have not previously received chemotherapy for this condition. Prostate cancer Docetaxel Winthrop in combination with prednisone or prednisolone is indicated for the treatment of patients with hormone-refractory metastatic prostate cancer . Gastric adenocarcinomaDocetaxel Winthrop in combination with cisplatin and 5-fluorouracil is indicated for the treatment of patients with metastatic gastric adenocarcinoma, including adenocarcinoma of the gastroesophageal junction, who have not received prior chemotherapy for metastatic disease. Head and neck cancer Docetaxel Winthrop in combination with cisplatin and 5-fluorouracil is indicated for the induction treatment of patients with locally advanced squamous cell carcinoma of the head and neck. Breast cancer Docetaxel Teva in combination with doxorubicin and cyclophosphamide is indicated for the adjuvant treatment of patients with: operable node-positive breast cancer ; operable node-negative breast cancer . For patients with operable node-negative breast cancer , adjuvant treatment should be restricted to patients eligible to receive chemotherapy according to internationally established criteria for primary therapy of early breast cancer . Docetaxel Teva in combination with doxorubicin is indicated for the treatment of patients with locally advanced or metastatic breast cancer who have not previously received cytotoxic therapy for this condition. Docetaxel Teva monotherapy is indicated for the treatment of patients with locally advanced or metastatic breast cancer after failure of cytotoxic therapy. Previous chemotherapy should have included an anthracycline or an alkylating agent. Docetaxel Teva in combination with trastuzumab is indicated for the treatment of patients with metastatic breast cancer whose tumours overexpress HER2 and who previously have not received chemotherapy for metastatic disease. Docetaxel Teva in combination with capecitabine is indicated for the treatment of patients with locally advanced or metastatic breast cancer after failure of cytotoxic chemotherapy. Previous therapy should have included an anthracycline. Non-small-cell lung cancer Docetaxel Teva is indicated for the treatment of patients with locally advanced or metastatic non-small-cell lung cancer after failure of prior chemotherapy. Docetaxel Teva in combination with cisplatin is indicated for the treatment of patients with unresectable, locally advanced or metastatic non-small-cell lung cancer , in patients who have not previously received chemotherapy for this condition. Prostate cancer Docetaxel Teva in combination with prednisone or prednisolone is indicated for the treatment of patients with hormone refractory metastatic prostate cancer . Gastric adenocarcinomaDocetaxel Teva in combination with cisplatin and 5-fluorouracil is indicated for the treatment of patients with metastatic gastric adenocarcinoma, including adenocarcinoma of the gastroesophageal junction, who have not received prior chemotherapy for metastatic disease. Head and neck cancer Docetaxel Teva in combination with cisplatin and 5 fluorouracil is indicated for the induction treatment of patients with locally advanced squamous cell carcinoma of the head and neck. Breast cancer Taxespira in combination with doxorubicin and cyclophosphamide is indicated for the adjuvant treatment of patients with: operable node-positive breast cancer ; operable node-negative breast cancer . For patients with operable node-negative breast cancer , adjuvant treatment should be restricted to patients eligible to receive chemotherapy according to internationally established criteria for primary therapy of early breast cancer . Taxespira in combination with doxorubicin is indicated for the treatment of patients with locally advanced or metastatic breast cancer who have not previously received cytotoxic therapy for this condition. Taxespira monotherapy is indicated for the treatment of patients with locally advanced or metastatic breast cancer after failure of cytotoxic therapy. Previous chemotherapy should have included an anthracycline or an alkylating agent. Taxespira combination with trastuzumab is indicated for the treatment of patients with metastatic breast cancer whose tumours over express HER2 and who previously have not received chemotherapy for metastatic disease. Taxespira in combination with capecitabine is indicated for the treatment of patients with locally advanced or metastatic breast cancer after failure of cytotoxic chemotherapy. Previous therapy should have included an anthracycline. Non-small cell lung cancer Taxespira indicated for the treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of prior chemotherapy. Taxespira in combination with cisplatin is indicated for the treatment of patients with unresectable, locally advanced or metastatic non-small cell lung cancer , in patients who have not previously received chemotherapy for this condition. Prostate cancer Taxespira in combination with prednisone or prednisolone is indicated for the treatment of patients with hormone refractory metastatic prostate cancer . Gastric adenocarcinoma Taxespira in combination with cisplatin and 5-fluorouracil is indicated for the treatment of patients with metastatic gastric adenocarcinoma, including adenocarcinoma of the gastroesophageal junction, who have not received prior chemotherapy for metastatic disease. Head and neck cancer Taxespira in combination with cisplatin and 5-fluorouracil is indicated for the induction treatment of patients with locally advanced squamous cell carcinoma of the head and neck. Treatment of breast cancer , special forms of lung cancer (non-small-cell lung cancer ), prostate cancer , gastric cancer , or head and neck cancer . Breast cancer Docetaxel Teva Pharma monotherapy is indicated for the treatment of patients with locally advanced or metastatic breast cancer after failure of cytotoxic therapy. Previous chemotherapy should have included an anthracycline or an alkylating agent. Non-small-cell lung cancer Docetaxel Teva Pharma is indicated for the treatment of patients with locally advanced or metastatic non-small-cell lung cancer after failure of prior chemotherapy. Docetaxel Teva Pharma in combination with cisplatin is indicated for the treatment of patients with unresectable, locally advanced or metastatic non-small-cell lung cancer , in patients who have not previously received chemotherapy for this condition. Prostate cancer Docetaxel Teva Pharma in combination with prednisone or prednisolone is indicated for the treatment of patients with hormone refractory metastatic prostate cancer . Breast cancer Docetaxel in combination with doxorubicin and cyclophosphamide is indicated for the adjuvant treatment of patients with operable node-positive breast cancer . Docetaxel in combination with doxorubicin is indicated for the treatment of patients with locally advanced or metastatic breast cancer who have not previously received cytotoxic therapy for this condition. Docetaxel monotherapy is indicated for the treatment of patients with locally advanced or metastatic breast cancer after failure of cytotoxic therapy. Previous chemotherapy should have included an anthracycline or an alkylating agent. Docetaxel in combination with trastuzumab is indicated for the treatment of patients with metastatic breast cancer whose tumours over express HER2 and who previously have not received chemotherapy for metastatic disease. Docetaxel in combination with capecitabine is indicated for the treatment of patients with locally advanced or metastatic breast cancer after failure of cytotoxic chemotherapy. Previous therapy should have included an anthracycline. Non-small cell lung cancer Docetaxel is indicated for the treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of prior chemotherapy. Docetaxel in combination with cisplatin is indicated for the treatment of patients with unresectable, locally advanced or metastatic non-small cell lung cancer , in patients who have not previously received chemotherapy for this condition. Prostate cancer Docetaxel in combination with prednisone or prednisolone is indicated for the treatment of patients with hormone refractory metastatic prostate cancer . Gastric adenocarcinomaDocetaxel in combination with cisplatin and 5-fluorouracil is indicated for the treatment of patients with metastatic gastric adenocarcinoma, including adenocarcinoma of the gastroesophageal junction, who have not received prior chemotherapy for metastatic disease. Head and neck cancer Docetaxel in combination with cisplatin and 5-fluorouracil is indicated for the induction treatment of patients with locally advanced squamous cell carcinoma of the head and neck. Nasopharyngeal carcinoma Mechanism of Action Docetaxel interferes with the normal function of microtubule growth. Whereas drugs like [colchicine] cause the depolymerization of microtubules in vivo, docetaxel arrests their function by having the opposite effect; it hyper-stabilizes their structure. This destroys the cell's ability to use its cytoskeleton in a flexible manner. Specifically, docetaxel binds to the β-subunit of tubulin. Tubulin is the "building block" of microtubules, and the binding of docetaxel locks these building blocks in place. The resulting microtubule/docetaxel complex does not have the ability to disassemble. This adversely affects cell function because the shortening and lengthening of microtubules (termed dynamic instability) is necessary for their function as a transportation highway for the cell. Chromosomes, for example, rely upon this property of microtubules during mitosis. Further research has indicated that docetaxel induces programmed cell death (apoptosis) in cancer cells by binding to an apoptosis-stopping protein called Bcl-2 (B-cell leukemia 2), thus arresting its function. Docetaxel is an antineoplastic agent that acts by disrupting the microtubular network in cells that is essential for mitotic and interphase cellular functions. Docetaxel binds to free tubulin and promotes the assembly of tubulin into stable microtubules while simultaneously inhibiting their disassembly. This leads to the production of microtubule bundles without normal function and to the stabilization of microtubules, which results in the inhibition of mitosis in cells. Docetaxel's binding to microtubules does not alter the number of protofilaments in the bound microtubules, a feature which differs from most spindle poisons currently in clinical use. Docetaxel, a semisynthetic taxane, has exhibited significant single-agent activity against prostatic tumors. In phase I/II studies, single-agent docetaxel and the combination of docetaxel plus estramustine were effective in inducing prostate-specific antigen reductions of > or = 50% in men with androgen-independent prostate cancer (AIPC). The underlying reason for docetaxel's clinical activity against prostate cancer has been a focus of ongoing research. Docetaxel is believed to have a twofold mechanism of antineoplastic activity: (1) inhibition of microtubular depolymerization, and (2) attenuation of the effects of bcl-2 and bcl-xL gene expression. Taxane-induced microtubule stabilization arrests cells in the G(2)M phase of the cell cycle and induces bcl-2 phosphorylation, thereby promoting a cascade of events that ultimately leads to apoptotic cell death. In preclinical studies, docetaxel had a higher affinity for tubulin and was shown to be a more potent inducer of bcl-2 phosphorylation than paclitaxel. Laboratory evidence also supports the clinical evaluation of docetaxel-based combinations that include agents such as trastuzumab and/or estramustine. The pathways for docetaxel-induced apoptosis appear to differ in androgen-dependent and androgen-independent prostate cancer cells. Further elucidation of these differences will be instrumental in designing targeted regimens for the treatment of localized and advanced prostate cancer.

Solubility Data

Solubility (In Vitro)

DMSO: 100 mg/mL (123.8 mM) Water:<1 mg/mL Ethanol:53 mg/mL (65.6 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 5 mg/mL (6.19 mM) (saturation unknown) in 10% EtOH + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear EtOH stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 5 mg/mL (6.19 mM) (saturation unknown) in 10% EtOH + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear EtOH stock solution to 900 μL of corn oil and mix well. Solubility in Formulation 3: ≥ 2.08 mg/mL (2.57 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 4: ≥ 2.08 mg/mL (2.57 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 5: ≥ 2.08 mg/mL (2.57 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 6: ≥ 2.08 mg/mL (2.57 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 7: ≥ 2.08 mg/mL (2.57 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 8: ≥ 2.08 mg/mL (2.57 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 9: ≥ 2.08 mg/mL (2.57 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL corn oil and mix evenly. Solubility in Formulation 10: ≥ 2.08 mg/mL (2.57 mM) (saturation unknown) in 10% DMSO 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD saline solution and mix well.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.2378 mL	6.1890 mL	12.3781 mL
	5 mM	0.2476 mL	1.2378 mL	2.4756 mL
	10 mM	0.1238 mL	0.6189 mL	1.2378 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.