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Nelfinavir (also known as AG-1341), is the mesylate salt of nelfinavir, an HIV-1 protease inhibitor with unique, strong, and orally bioavailable antiviral effects. It is used to treat HIV infection as an antiviral agent.
Physicochemical Properties
| Molecular Formula | C33H49N3O7S2 |
| Molecular Weight | 663.8881 |
| Exact Mass | 663.301 |
| Elemental Analysis | C, 59.70; H, 7.44; N, 6.33; O, 16.87; S, 9.66 |
| CAS # | 159989-65-8 |
| Related CAS # | Nelfinavir;159989-64-7 |
| PubChem CID | 64142 |
| Appearance | White to yellow solid powder |
| Boiling Point | 786.8ºC at 760 mmHg |
| Melting Point | 131-135ºC |
| Flash Point | 429.7ºC |
| LogP | 6.052 |
| Hydrogen Bond Donor Count | 5 |
| Hydrogen Bond Acceptor Count | 9 |
| Rotatable Bond Count | 10 |
| Heavy Atom Count | 45 |
| Complexity | 922 |
| Defined Atom Stereocenter Count | 5 |
| SMILES | S(C1C([H])=C([H])C([H])=C([H])C=1[H])C([H])([H])[C@@]([H])([C@@]([H])(C([H])([H])N1[C@]([H])(C(N([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H])=O)C([H])([H])[C@]2([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[C@]2([H])C1([H])[H])O[H])N([H])C(C1C([H])=C([H])C([H])=C(C=1C([H])([H])[H])O[H])=O.S(C([H])([H])[H])(=O)(=O)O[H] |
| InChi Key | NQHXCOAXSHGTIA-SKXNDZRYSA-N |
| InChi Code | InChI=1S/C32H45N3O4S.CH4O3S/c1-21-25(15-10-16-28(21)36)30(38)33-26(20-40-24-13-6-5-7-14-24)29(37)19-35-18-23-12-9-8-11-22(23)17-27(35)31(39)34-32(2,3)4;1-5(2,3)4/h5-7,10,13-16,22-23,26-27,29,36-37H,8-9,11-12,17-20H2,1-4H3,(H,33,38)(H,34,39);1H3,(H,2,3,4)/t22-,23+,26-,27-,29+;/m0./s1 |
| Chemical Name | (3S,4aS,8aS)-N-tert-butyl-2-[(2R,3R)-2-hydroxy-3-[(3-hydroxy-2-methylbenzoyl)amino]-4-phenylsulfanylbutyl]-3,4,4a,5,6,7,8,8a-octahydro-1H-isoquinoline-3-carboxamide;methanesulfonic acid |
| Synonyms | Nelfinavir mesylate hydrate; AG-1343; AG1343; AG 1343; Nelfinavir; Viracept |
| 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: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| 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 |
HIV-1 Suppression of insulin signaling pathway components: Insulin Receptor-β (IR-β), Insulin Receptor Substrate-1 (IRS-1), Phosphatidylinositol 3-kinase (PI3K/p85α), Akt (Protein Kinase B), and Endothelial Nitric Oxide Synthase (eNOS). |
| ln Vitro |
Nelfinavir (AG1341) Mesylate (1-10 μM; 48 hours) suppresses the growth of several myeloma cells[4]. Nelfinavir Mesylate suppresses the activity of 26S chymotrypsin-like proteasomes, hinders myeloma cell line proliferation, and induces apoptosis in newly generated plasma cells[4]. Nelfinavir Mesylate (1-10 μM; 17 hours) cell lines undergo apoptosis when exposed to nelfinavir mesylate[4]. Nelfinavir Mesylate (5 μM; 0-24 hours) decreases the phosphorylation of AKT[4]. Nelfinavir Mesylate causes caspase-3 to cleave, phosphorylates AKT, STAT-3, and ERK1/2, and triggers the unfolded protein response system's pro-apoptotic pathway[4]. Nelfinavir has an IC50 of 35.93 μM, making it another SARS-CoV 3CLpro inhibitor[5]. Chronic exposure (72 hours) of Human Aortic Endothelial Cells (HAECs) to Nelfinavir at physiological concentrations (0.25 - 2 μg/mL) significantly decreased both basal (2.5-fold) and insulin-induced nitric oxide (NO) production (4- to 5-fold), as measured by fluorimetric assays using DAF-FM DA and DAF-2 DA dyes. Nelfinavir (1 and 2 μg/mL) suppressed insulin-induced phosphorylation of Akt at Ser473 and eNOS at Ser1177 in a dose-dependent manner, as determined by Western blot analysis. Nelfinavir (1 and 2 μg/mL) suppressed insulin-induced tyrosine phosphorylation of upstream insulin signaling components: IR-β, IRS-1, and the PI3K/p85α subunit, as shown by immunoprecipitation followed by immunoblotting with anti-phosphotyrosine antibody. The suppressive effects of Nelfinavir on insulin-induced Akt/eNOS phosphorylation and NO production were ameliorated by co-treatment with the thiazolidinedione insulin sensitizer Troglitazone (TRO, 250 nM). Chronic Nelfinavir exposure (2 μg/mL) also suppressed insulin-induced eNOS gene (mRNA) expression, which was partially restored by TRO co-treatment. [1] |
| ln Vivo |
Nelfinavir Mesylate (75 mg/kg; i.p.; 5 days a week for 21 days) inhibits the growth of multiple myeloma cells in NOD/SCID mice. In H157 NSCLC xenograft models, intraperitoneal (i.p.) administration of nelfinavir (50 or 100 mg/kg, 5 days/week) significantly inhibited tumor growth by 61% and 63% respectively at day 11. In A549 NSCLC xenograft models, i.p. administration of nelfinavir (50 mg/kg daily) inhibited tumor growth by 48% at day 19. Oral administration (gavage) of nelfinavir (100 mg/kg, 5 days/week) also significantly inhibited H157 tumor growth. Tumors from nelfinavir-treated mice showed increased apoptosis (TUNEL-positive cells), dilation of the ER, presence of autophagic vacuoles (electron microscopy), and increased levels of phospho-eIF2α, ATF3, and LC3-II by immunoblotting, confirming induction of ER stress, autophagy, and apoptosis in vivo. Akt phosphorylation (S473) in tumors was not modulated by nelfinavir treatment in vivo. |
| Enzyme Assay |
26S Proteasome Activity Assay: Multiple myeloma cells were lysed. For each cell line, 30 µg of protein were collected in a Tris buffer and incubated with nelfinavir, bortezomib, or MG132 for 2 hours at 37°C. Subsequently, 1 mM of the fluorogenic substrate was added. The chymotrypsin-like activity was measured using the Z-Leu-Leu-Val-Tyr-AMC substrate, and the trypsin-like activity was measured using the Bz-Val-Gly-Arg-AMC substrate. Enzymatic activities were measured using a fluorescence plate reader. All experiments were performed in triplicate. |
| Cell Assay |
Cell Culture and Chronic Drug Treatment: Primary Human Aortic Endothelial Cells (HAECs) were maintained in endothelial growth medium. For experiments, cells at 70-80% confluency were treated with Nelfinavir (0.25, 0.5, 1, 2 μg/mL) and/or Troglitazone (TRO, 250 nM) for a total of 72 hours, with drugs replenished every 24 hours. Following chronic treatment, cells were stimulated with insulin (100 ng/mL) for 10 or 15 minutes prior to analysis. Nitric Oxide (NO) Measurement - Fluorescence Microscopy: HAECs cultured on coverslips were loaded with the fluorescent dye DAF-2 DA (5 μM) for 10 minutes in the dark after drug treatments and insulin stimulation. Cells were then washed, fixed, and mounted. Fluorescence (indicative of NO) was visualized using a fluorescence microscope with excitation at 480 nm and emission at 505 nm. Nitric Oxide (NO) Measurement - Fluorimetry: HAECs cultured in black 96-well plates were loaded with DAF-FM DA (5 μM) after treatments. Following incubation, cells were washed and incubated with L-arginine (100 μM) for 15 minutes. Fluorescence was measured using a fluorimeter (excitation 485 nm, emission 525 nm). Values were normalized to total protein content. Western Blot Analysis: After treatments, HAECs were lysed. Protein samples (≈50 μg) were separated by SDS-PAGE, transferred to nitrocellulose membranes, and probed with specific primary antibodies against total and phosphorylated forms of Akt (Ser473), eNOS (Ser1177), IR-β, IRS-1, and PI3K/p85α, followed by HRP-conjugated secondary antibodies. Proteins were detected using chemiluminescence. Immunoprecipitation: For analyzing tyrosine phosphorylation of IR-β and IRS-1, cell lysates (500 μg) were incubated overnight with respective antibodies. Immunocomplexes were captured using Protein A agarose beads, eluted, and then subjected to Western blotting using an anti-phosphotyrosine antibody. Reverse Transcription Polymerase Chain Reaction (RT-PCR): Total RNA was extracted from treated HAECs using TRIzol reagent. cDNA was synthesized from 1 μg RNA. Semi-quantitative PCR was performed using specific primers for eNOS and GAPDH (housekeeping gene). PCR products were separated on agarose gels, stained, and band intensities were quantified. [1] |
| Animal Protocol |
NOD/SCID mice (bearing U266-luc cells)[4] 75 mg/kg I.p.; 5 days a week for 21 days H157 Xenograft - Intraperitoneal Administration: Six-week-old male athymic nude mice were injected subcutaneously with H157 cells. When tumors were palpable, mice were divided into groups receiving i.p. injections of vehicle (4% DMSO, 5% polyethylene glycol, 5% Tween 80 in saline) or nelfinavir (50 or 100 mg/kg dissolved in vehicle) once daily on specified days (days 1-4, 7, 8, 10-12). Mice were weighed and tumors measured every other day. A549 Xenograft - Intraperitoneal Administration: Six-week-old male athymic nude mice were injected subcutaneously with A549 cells in Matrigel. When tumors reached ~200 mm³, mice received daily i.p. injections of vehicle or nelfinavir (50 mg/kg). Mice were weighed and tumors measured three times weekly. H157 Xenograft - Oral (Gavage) Administration: Eight-week-old female athymic nude mice bearing H157 xenografts received daily gavage (5 days/week) of vehicle or nelfinavir (100 mg/kg dissolved in 35% ethanol). Tumor volume was calculated using the formula (a b²) / 2. Pharmacokinetic Study in Mice: Six-week-old female athymic nude mice received a single i.p. injection of nelfinavir (50 or 100 mg/kg in vehicle). Blood was collected via cardiac puncture at various time points under anesthesia. Plasma was separated and stored at -80°C until analysis by HPLC. Tissue Analysis: Formalin-fixed, paraffin-embedded tumor sections were used for TUNEL staining according to kit instructions. For immunoblotting, frozen tumors were homogenized in lysis buffer. |
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion Distribution of nelfinavir into body tissues and fluids has not been fully characterized. The volume of distribution of nelfinavir following oral administration in animals is 27 L/kg, suggesting extensive tissue distribution. Studies in rats indicate that, at 4 hours after oral administration of radiolabeled nelfinavir, concentrations of the drug in liver, lymph nodes, pancreas, kidney, lungs, submaxillary glands, heart, and spleen exceed concurrent plasma concentrations. Nelfinavir has been detected in brain tissue in rats. Nelfinavir is greater than 98% bound to plasma proteins, mostly to albumin and alpha1-acid glycoprotein. It is present in the CSF at less than 1% of plasma concentrations, at least in part due to its extensive binding to plasma protein but perhaps also due to the P-glycoprotein at the blood-brain barrier. Nelfinavir and its metabolites are eliminated primarily in feces, with less than 2% of the drug being excreted in the urine. Moderate or severe liver disease may prolong the half-life and increase plasma concentrations of the parent drug while lowering plasma concentrations of M8 /(a major hydroxy-t-butylamide metabolite)/. Nelfinavir absorption is very sensitive to food effects; a moderate fat meal increases the AUC 2 to 3 fold, and higher concentrations are achieved with high fat meals. For more Absorption, Distribution and Excretion (Complete) data for NELFINAVIR MESYLATE (8 total), please visit the HSDB record page. Metabolism / Metabolites Nelfinavir undergoes oxidative metabolism in the liver primarily by CYP3A4, but also by CYP2C19 and CYP2D6. Its major hydroxy-t-butylamide metabolite (M8) has in vitro antiretroviral activity comparable to that of the parent drug but achieves plasma levels that are only 40% of nelfinavir levels. The M8 metabolite is generated primarily by CYP2C19. Biological Half-Life The plasma elimination half-life of nelfinavir in individuals 13 years of age and older is 3.5-5 hours. Following a single i.p. dose in mice, nelfinavir plasma concentrations peaked (Cmax) at 30 minutes: 23.21 μg/mL (~34.96 μmol/L) for 50 mg/kg and 54.33 μg/mL (~81.83 μmol/L) for 100 mg/kg. The drug was rapidly cleared, with levels dropping to 0.1 μg/mL (~0.15 μmol/L) and 3 μg/mL (~4.5 μmol/L) for the 50 and 100 mg/kg groups, respectively, at 4 hours post-injection. The area under the plasma concentration-time curve (AUC) was approximately 2.5-fold higher in the 100 mg/kg group (3445.53 minμg/mL) compared to the 50 mg/kg group (1398.26 minμg/mL). The study mentions that the Cmax of nelfinavir in HIV patients is approximately 7-9 μmol/L, exceeding the mean in vitro GI50 of 5.2 μmol/L. The human oral half-life is cited as 3-5 hours. |
| Toxicity/Toxicokinetics |
Effects During Pregnancy and Lactation ◉ Summary of Use during Lactation Nelfinavir levels in milk are low and the drug is usually not detectable in the serum of breastfed infants. However, some evidence of nelfinavir-induced adverse reactions in breastfed infants exists. Nelfinavir is not a recommended agent during breastfeeding. Achieving and maintaining viral suppression with antiretroviral therapy decreases breastfeeding transmission risk to less than 1%, but not zero. Individuals with HIV who are on antiretroviral therapy with a sustained undetectable viral load and who choose to breastfeed should be supported in this decision. If a viral load is not suppressed, banked pasteurized donor milk or formula is recommended. ◉ Effects in Breastfed Infants A study compared the frequency of rash, hepatotoxicity, and hyperbilirubinemia among 464 breastfed infants whose mothers were taking either nelfinavir (n = 206) or nevirapine (n = 258) along with zidovudine and lamivudine for HIV infection during pregnancy and postpartum. Infants were examined during the first, second and sixth weeks postpartum. Moderate rash occurred in 7 (2.7%) of the infant exposed to nevirapine and one (0.5%) infant exposed to nelfinavir. Rash occurred at a median of 2 weeks postpartum. Four infants (1.9%) exposed to nelfinavir developed hepatotoxicity (3 moderate and 1 severe) and none exposed to nevirapine. Twenty-one infants (4.5%) developed high-risk hyperbilirubinemia, all prior to 48 hours of age, but there was no difference in exposure between the two drugs. ◉ Effects on Lactation and Breastmilk Gynecomastia has been reported among men receiving highly active antiretroviral therapy. Gynecomastia is unilateral initially, but progresses to bilateral in about half of cases. No alterations in serum prolactin were noted and spontaneous resolution usually occurred within one year, even with continuation of the regimen. Some case reports and in vitro studies have suggested that protease inhibitors might cause hyperprolactinemia and galactorrhea in some male patients, although this has been disputed. The relevance of these findings to nursing mothers is not known. The prolactin level in a mother with established lactation may not affect her ability to breastfeed. Interactions Exploiting protein homeostasis is a new therapeutic approach in cancer. Nelfinavir (NFV) is an HIV protease inhibitor that induces endoplasmic reticulum (ER) stress in cancer cells. Under conditions of ER stress, misfolded proteins are transported from the ER back to the cytosol for subsequent degradation by the ubiquitin-proteasome system. Bortezomib (BZ) is a proteasome inhibitor and interferes with degradation of misfolded proteins. Here, we show that NFV and BZ enhance proteotoxicity in non-small cell lung cancer (NSCLC) and multiple myeloma (MM) cells. The combination synergistically inhibited cell proliferation and induced cell death. Activating transcription factor (ATF)3 and CCAAT-enhancer binding protein homologous protein (CHOP), markers of ER stress, were rapidly increased, and their siRNA-mediated knockdown inhibited cell death. Knockdown of double-stranded RNA activated protein kinase-like ER kinase, a signal transducer in ER stress, significantly decreased apoptosis. Pretreatment with the protein synthesis inhibitor, cycloheximide, decreased levels of ubiquitinated proteins, ATF3, CHOP, and the overall total cell death, suggesting that inhibition of protein synthesis increases cell survival by relieving proteotoxic stress. The NFV/BZ combination inhibited the growth of NSCLC xenografts, which correlated with the induction of markers of ER stress and apoptosis. Collectively, these data show that NFV and BZ enhance proteotoxicity in NSCLC and MM cells, and suggest that this combination could tip the precarious balance of protein homeostasis in cancer cells for therapeutic gain. Competition for the cytochrome p450 enzyme CYP3A by nelfinavir may inhibit the metabolism of these medications /amiodarone, astemizole, cisapride, ergot derivatives, midazolam, quinidine, terfenadine, triazolam/ and create the potential for serious and/or life threatening cardiac arrhythmias or prolonged sedation; concurrent use is not recommended. Concurrent use /with lamivudine/ causes a 10% increase in the AUC of lamivudine. Concurrent administration /of oral contraceptives such as: ethinyl estradiol or norethindrone/ with nelfinavir causes a decrease in the plasma concentrations of these medications; alternate or additional contraceptive measures should be used. For more Interactions (Complete) data for NELFINAVIR MESYLATE (10 total), please visit the HSDB record page. The study states that Nelfinavir (a first-generation HIV protease inhibitor) is associated with severe metabolic side effects, including lipodystrophy, dyslipidemia, insulin resistance, and an increased risk of cardiovascular problems such as atherosclerosis and coronary artery disease in HIV patients on HAART. The in vitro experiments used physiologically relevant concentrations of Nelfinavir (0.25-2 μg/mL), which are achievable in human plasma during therapy. [1] |
| References |
[1]. Nelfinavir suppresses signaling and nitric oxide production by human aortic endothelial cells: protective effects of thiazolidinediones. Ochsner J. 2013 Spring;13(1):76-90. [2]. Nelfinavir, A lead HIV protease inhibitor, is a broad-spectrum, anticancer agent that inducesendoplasmic reticulum stress, autophagy, and apoptosis in vitro and in vivo. Clin Cancer Res. 2007 Sep 1;13(17):5183-94. [3]. Nelfinavir mesylate (AG1343): a potent, orally bioavailable inhibitor of HIV-1 protease. J Med Chem. 1997 Nov 21;40(24):3979-85. [4]. The human immunodeficiency virus-1 protease inhibitor nelfinavir impairs proteasome activity and inhibits the proliferation of multiple myeloma cells in vitro and in vivo. Haematologica. 2012;97(7):1101‐1109. [5]. Bardoxolone and bardoxolone methyl, two Nrf2 activators in clinical trials, inhibit SARS-CoV-2 replication and its 3C-like protease. Signal Transduct Target Ther. 2021 May 29;6(1):212. |
| Additional Infomation |
Therapeutic Uses HIV Protease Inhibitors. HIV protease inhibitors are associated with HIV protease inhibitor-related lipodystrophy syndrome. Researchers hypothesized that liposarcomas would be similarly susceptible to the apoptotic effects of an HIV protease inhibitor, nelfinavir. We conducted a phase I trial of nelfinavir for liposarcomas. There was no limit to prior chemotherapy. The starting dose was 1,250 mg twice daily (Level 1). Doses were escalated in cohorts of three to a maximally evaluated dose of 4,250 mg (Level 5). One cycle was 28 days. Steady-state pharmacokinetics (PKs) for nelfinavir and its primary active metabolite, M8, were determined at Levels 4 (3,000 mg) and 5. Twenty subjects (13 males) were enrolled. Median (range) age was 64 years (37-81). One subject at Level 1 experienced reversible, grade 3 pancreatitis after 1 week and was replaced. No other dose-limiting toxicities were observed. Median (range) number of cycles was 3 (0.6-13.5). Overall best responses observed were 1 partial response, 1 minor response, 4 stable disease, and 13 progressive disease. Mean peak plasma levels and AUCs for nelfinavir were higher at Level 4 (7.3 mg/L; 60.9 mg/L X hr) than 5 (6.3 mg/L; 37.7 mg/L X hr). The mean ratio of M8: nelfinavir AUCs for both levels was approximately 1:3. PKs demonstrate auto-induction of nelfinavir clearance at the doses studied, although the mechanism remains unclear. Peak plasma concentrations were within range where anticancer activity was demonstrated in vitro. M8 metabolite is present at approximately 1/3 the level of nelfinavir and may also contribute to the anticancer activity observed. Nelfinavir is indicated in the treatment of HIV infection when antiretroviral therapy is warranted. /Included in US product labeling/ A phase I/II dose-ranging open-label 28-day monotherapy study of the safety, pharmacokinetics, and antiviral activity of nelfinavir mesylate (Viracept), an inhibitor of human immunodeficiency virus (HIV)-1 protease, was done in 65 HIV-1-infected subjects. After 28 days, 54 responding subjects entered an open-label extension that allowed for the addition of nucleoside inhibitors of reverse transcriptase and dose escalation to maintain durability. The drug was well-tolerated and demonstrated robust antiviral activity, with demonstrable superiority of the 750 mg and 1000 mg three times daily regimens. Thirty subjects who continued to receive therapy at 12 months attained a persistent 1.6 log10 reduction in HIV RNA, accompanied by a mean increase in CD4 cells of 180-200/cu mm. Studies of viral genotype and phenotype after virus rebound revealed that the initial active site mutation allowing for nelfinavir resistance is mediated by a unique amino acid substitution in the HIV-1 protease D30N, which does not confer in vitro phenotypic cross-resistance to the currently available protease inhibitors. For more Therapeutic Uses (Complete) data for NELFINAVIR MESYLATE (6 total), please visit the HSDB record page. Drug Warnings In adults, the most frequent adverse effect associated with nelfinavir therapy is mild to moderate diarrhea. Rash has been reported in 13% of adults receiving nelfinavir in the recommended dosage in phase II/III clinical studies. Allergic reaction, dermatitis, folliculitis, fungal dermatitis, maculopapular rash, pruritus, sweating, and urticaria have occurred in less than 2% of adults receiving nelfinavir in clinical studies. Hypersensitivity reactions, including bronchospasm, moderate to severe rash, fever, and edema, possibly related to nelfinavir have been reported during postmarketing surveillance. In phase II/III clinical studies, asthenia occurred in 1% of adults receiving the usual dosage of nelfinavir in conjunction with 2 nucleoside reverse transcriptase inhibitors. Anxiety, depression, dizziness, emotional lability, headache (including migraine headache), hyperkinesia, insomnia,malaise, paresthesia, seizures, sleep disorders, somnolence, and suicidal ideation have been reported in less than 2% of adults receiving nelfinavir in clinical studies. Substantial increases in serum concentrations of AST (SGOT) or ALT (SGPT) (increase from normal baseline values to 5.1-10 times the usual normal value or increase from baseline values of 1.25-2.5 times the normal value to more than 10 times the usual normal value) occurred in up to 3% of adults receiving nelfinavir in clinical studies. Hepatitis, increases in serum alkaline phosphate concentrations, increases in Gamma-glutamyltransferase (GGT, GGTP) concentrations, or abnormal liver function test results have been reported in less than 2% of adults receiving nelfinavir in clinical studies. For more Drug Warnings (Complete) data for NELFINAVIR MESYLATE (19 total), please visit the HSDB record page. Nelfinavir is an HIV-1 protease inhibitor used in highly active antiretroviral therapy (HAART). This study investigates one of its major side effects: the induction of endothelial dysfunction. The mechanism involves Nelfinavir suppressing the insulin-PI3K/Akt-eNOS signaling axis in endothelial cells, leading to reduced nitric oxide production, which is crucial for vascular homeostasis and vasodilation. The study proposes that co-treatment with insulin-sensitizing thiazolidinediones (exemplified by Troglitazone) may protect against Nelfinavir-induced endothelial dysfunction, suggesting a potential adjunct therapy strategy. [1] |
Solubility Data
| Solubility (In Vitro) |
DMSO: ~100 mg/mL (~150.6 mM) Ethanol: ~100 mg/mL (~150.6 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5 mg/mL (7.53 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 50.0 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 2: ≥ 5 mg/mL (7.53 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 50.0 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 3: ≥ 5 mg/mL (7.53 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 50.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 4: ≥ 2.5 mg/mL (3.77 mM) (saturation unknown) in 5% DMSO + 40% PEG300 + 5% Tween80 + 50% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 5: ≥ 2.5 mg/mL (3.77 mM) (saturation unknown) in 5% DMSO + 95% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.5063 mL | 7.5314 mL | 15.0627 mL | |
| 5 mM | 0.3013 mL | 1.5063 mL | 3.0125 mL | |
| 10 mM | 0.1506 mL | 0.7531 mL | 1.5063 mL |