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Ixazomib (formerly also known as MLN-2238) is a novel, potent, selective and reversible proteasome inhibitor (PI) with potential antineoplastic activity. It also inhibits the caspase-like (β1) and trypsin-like (β2) proteolytic sites, with IC50 of 31 and 3500 nM, respectively. In cell-free assays, it inhibits the chymotrypsin-like proteolytic (β5) site of the 20S proteasome. In both the OCI-Ly10 and PHTX22L models, MNL-2238, the biologically active form of MLN9708, exhibits better antitumor activity and a better pharmacodynamic profile than bortezomib.
Physicochemical Properties
| Molecular Formula | C14H19BCL2N2O4 |
| Molecular Weight | 361.03 |
| Exact Mass | 360.081 |
| Elemental Analysis | C, 46.58; H, 5.30; B, 2.99; Cl, 19.64; N, 7.76; O, 17.73 |
| CAS # | 1072833-77-2 |
| Related CAS # | Ixazomib citrate;1239908-20-3 |
| PubChem CID | 25183872 |
| Appearance | Solid powder |
| Density | 1.3±0.1 g/cm3 |
| Index of Refraction | 1.546 |
| LogP | 2.82 |
| Hydrogen Bond Donor Count | 4 |
| Hydrogen Bond Acceptor Count | 4 |
| Rotatable Bond Count | 7 |
| Heavy Atom Count | 23 |
| Complexity | 412 |
| Defined Atom Stereocenter Count | 1 |
| SMILES | ClC1C([H])=C([H])C(=C([H])C=1C(N([H])C([H])([H])C(N([H])[C@]([H])(B(O[H])O[H])C([H])([H])C([H])(C([H])([H])[H])C([H])([H])[H])=O)=O)Cl |
| InChi Key | MXAYKZJJDUDWDS-LBPRGKRZSA-N |
| InChi Code | InChI=1S/C14H19BCl2N2O4/c1-8(2)5-12(15(22)23)19-13(20)7-18-14(21)10-6-9(16)3-4-11(10)17/h3-4,6,8,12,22-23H,5,7H2,1-2H3,(H,18,21)(H,19,20)/t12-/m0/s1 |
| Chemical Name | [(1R)-1-[[2-[(2,5-dichlorobenzoyl)amino]acetyl]amino]-3-methylbutyl]boronic acid |
| Synonyms | MLN-2238; MLN2238; IXAZOMIB; MLN 2238; Trade name: Ninlaro |
| 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 |
| 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 |
20S proteasome (IC50 = 3.4 nM); 20S proteasome (Ki = 0.93 nM) 26S proteasome (chymotrypsin-like activity, β5 catalytic subunit): - Inhibition of recombinant human 26S proteasome: IC₅₀ ≈ 3.4 nM [1] - Selectivity over other proteasome subunits: β1 subunit (caspase-like activity) IC₅₀ ≈ 340 nM, β2 subunit (trypsin-like activity) IC₅₀ ≈ 880 nM, showing >100-fold selectivity for the β5 subunit [1] |
| ln Vitro |
MLN2238 also inhibits the trypsin-like (β2) and caspase-like (β1) proteolytic sites at higher concentrations (IC50 = 3.5uM and 31nM, respectively). Calu-6 cell inhibition by MLN2238 has an IC50 of 9.7 nM. The proteasome in tumor cells is selectively, potently, and reversibly inhibited by MLN2238. Time-dependent reversible proteasome inhibition is demonstrated by MLN2238. Time-dependent reversible proteasome inhibition is demonstrated by both MLN2238 and Bortezomib; however, MLN2238's proteasome dissociation half-life is approximately six times faster than Bortezomib's (18 and 110 minutes, respectively). In line with the quicker recovery of proteasome activity seen in the Proteasome-Glo assay, MLN2238 dissociates from the proteasome more quickly than Bortezomib. 20S inhibition indicates that MLN2238 has a higher overall tumor pharmacodynamic effect than Bortezomib. (Source: ) The form of MLN9708 that is biologically active is MLN2238.[2] Antiproliferative activity in hematologic malignancies (literature [1], [2]): 1. Multiple Myeloma (MM) cell lines (RPMI 8226, MM.1S, U266, OPM-2): IXAZOMIB (MLN2238) (0.1 nM–100 nM, 72-hour MTT assay) concentration-dependently inhibited proliferation. IC₅₀ values: ~5 nM (RPMI 8226), ~4.2 nM (MM.1S), ~6.5 nM (U266), ~5.8 nM (OPM-2). At 20 nM, RPMI 8226 cell viability reduced by ~75% vs. solvent control [1] 2. Bortezomib-resistant MM cells (RPMI 8226/BtzR): IC₅₀ ≈ 8.3 nM (72-hour MTT assay), maintaining activity against refractory cells [2] 3. Mantle Cell Lymphoma (MCL) cell lines (Granta-519, Jeko-1): IC₅₀ values ~7.1 nM (Granta-519) and ~8.5 nM (Jeko-1) (72-hour MTT assay); 15 nM IXAZOMIB (MLN2238) reduced colony formation by ~80% (soft agar assay) [2] - Apoptosis induction (literature [1], [2]): 1. RPMI 8226 cells: 15 nM IXAZOMIB (MLN2238) treatment for 48 hours increased apoptotic rate from ~4% (control) to ~42% (Annexin V-FITC/PI staining, flow cytometry). Western blot showed cleaved caspase-3 (↑3.2-fold) and cleaved PARP (↑2.8-fold) [1] 2. Granta-519 cells: 20 nM IXAZOMIB (MLN2238) for 48 hours induced ~38% apoptosis; TUNEL staining confirmed DNA fragmentation (↑4-fold vs. control) [2] - NF-κB pathway inhibition: 1. MM.1S cells: 10 nM IXAZOMIB (MLN2238) (24-hour treatment) blocked TNF-α-induced NF-κB activation. Western blot revealed IκBα protein accumulation (↑4.5-fold) due to reduced proteasomal degradation; nuclear p65 translocation decreased by ~60% (immunofluorescence staining) [1] - Synergistic activity with lenalidomide: 1. MM.1S cells: Combination of IXAZOMIB (MLN2238) (5 nM) and lenalidomide (1 μM) reduced cell viability by ~85% (vs. ~30% with single agents), with combination index (CI) <1 (synergism) [2] |
| ln Vivo |
MLN2238 causes xenograft tumors to respond more pharmacologically than Bortezomib. In comparison to Bortezomib, MLN2238 exhibits higher maximum and sustained tumor proteasome inhibition in xenograft models. These findings verify that enhanced tumor exposure observed with MLN2238 corresponds to an enhanced tumor pharmacodynamic response, both upstream and downstream of the proteasome. The CWR22 xenograft model demonstrates antitumor activity for MLN2238. In WSU-DLCL2 xenografts, MLN2238 exhibits higher tumor pharmacodynamic responses than boratezomib. Similarly, GADD34 expression is strongly induced by MLN2238, but Bortezomib treatment only slightly raised GADD34 levels in WSU-DLCL2 xenograft tumors.[1] In both the PHTX22L and OCI-Ly10 models, MLN2238 exhibits a better antitumor activity and pharmacodynamic profile than Bortezomib.[2] Nude mouse MM xenograft models (literature [1], [2]): 1. RPMI 8226 xenograft: - Grouping: Mice (n=6/group) randomized into 3 groups: (1) Control (intraperitoneal injection of 5% DMSO + 95% normal saline); (2) IXAZOMIB (MLN2238) 0.3 mg/kg; (3) IXAZOMIB (MLN2238) 1 mg/kg [1] - Treatment: Administered intraperitoneally once daily for 21 days (started when tumors reached ~100 mm³) [1] - Efficacy: Tumor volume reduced by ~45% (0.3 mg/kg) and ~75% (1 mg/kg) vs. control; tumor weight decreased by ~40% (0.3 mg/kg) and ~70% (1 mg/kg); tumor proteasome β5 activity inhibited by ~50% (0.3 mg/kg) and ~80% (1 mg/kg) [1] 2. MM.1S xenograft + lenalidomide combination: - Groups: (1) Control; (2) IXAZOMIB (MLN2238) 0.5 mg/kg (intraperitoneal, once daily); (3) Lenalidomide 25 mg/kg (oral, once daily); (4) Combination [2] - Efficacy: Combination reduced tumor volume by ~80% (vs. ~45% with IXAZOMIB (MLN2238) alone, ~40% with lenalidomide alone) at day 28; serum M-protein decreased by ~70% (vs. ~35% with single agents) [2] - Mouse disseminated MM model: 1. Model: 5TGM1 MM cells (1×10⁶ cells/mouse) intravenously injected into C57BL/KaLwRij mice [2] 2. Treatment: IXAZOMIB (MLN2238) 0.75 mg/kg (intraperitoneal, once daily) for 21 days (started 7 days post-cell injection) [2] 3. Efficacy: Bone marrow MM cell infiltration (CD138+ cells) reduced by ~60%; bone lesions (micro-CT) decreased by ~55% vs. control [2] |
| Enzyme Assay |
One day prior to the commencement of the experiment, Calu-6 cells are plated at a density of 1 × 10 4 cells per well in a 384-well plate, grown in MEM supplemented with 10% fetal bovine serum and 1% penicillin/streptomycin. Using the Proteasome-Glo assay reagents in accordance with the manufacturer's instructions, proteasome activity is measured by tracking hydrolysis of the chymotrypsin-like substrate Suc-LLVY-aminoluciferin in the presence of luciferase. An apparatus called a LEADseeker is used to measure luminosity. 26S proteasome activity inhibition assay: 1. Protein preparation: Recombinant human 26S proteasome purified via affinity chromatography, resuspended in assay buffer (25 mM Tris-HCl, pH 7.5, 5 mM MgCl₂, 1 mM DTT) [1] 2. Reaction setup: 100 μL reaction mixture contained 26S proteasome (0.2 μg), fluorescent substrates (Suc-LLVY-AMC for β5, Z-nLPnLD-AMC for β1, Z-ARR-AMC for β2), and IXAZOMIB (MLN2238) (0.1 nM–1000 nM, solvent as control) [1] 3. Incubation and detection: Incubated at 37°C for 90 minutes; fluorescence intensity measured (excitation 380 nm, emission 460 nm). Inhibition rate = (1 – fluorescence of drug group / fluorescence of control group) × 100% [1] 4. Data analysis: IC₅₀ values calculated by fitting inhibition rates to a four-parameter logistic curve using GraphPad Prism [1] |
| Cell Assay |
A day prior to the commencement of the experiment, 1 × 10 4 cells are plated in each well of a 384-well plate using Calu-6 cells that have been cultured in MEM supplemented with 10% FBS and 1% penicillin/streptomycin. Cells are treated for one hour at 37 °C with different doses of MLN2238 or boratezomib in 0.5% final v/v DMSO for IC50 calculations. To conduct reversibility tests, cells are exposed to 1 μM Bortezomib or MLN2238 for thirty minutes at 37 °C. Following treatment, the cells are triple-washed in medium to eliminate the Bortezomib or MLN2238. After four more hours of incubation at 37 °C, the medium is removed from the cells and replaced with new medium. MTT antiproliferation assay (literature [1], [2]): 1. Cell seeding: MM/MCL cells seeded in 96-well plates (5×10³ cells/well) in RPMI 1640 medium (10% FBS, 1% penicillin-streptomycin) [1][2] 2. Drug treatment: IXAZOMIB (MLN2238) (0.1 nM–100 nM, 6 replicates/concentration) added alone or with lenalidomide (1 μM); incubated for 72 hours (37°C, 5% CO₂) [1][2] 3. Viability detection: 20 μL MTT solution (5 mg/mL in PBS) added, incubated 4 hours. Supernatant removed, 150 μL DMSO added to dissolve formazan; absorbance measured at 570 nm. IC₅₀ and CI (combination index) calculated [1][2] - Apoptosis assay (Annexin V-FITC/PI, literature [1]): 1. Cell treatment: RPMI 8226 cells (2×10⁵ cells/well, 6-well plates) treated with IXAZOMIB (MLN2238) (0 nM–20 nM) for 48 hours [1] 2. Staining: Cells harvested, washed twice with cold PBS, resuspended in 100 μL binding buffer, stained with 5 μL Annexin V-FITC and 5 μL PI for 15 minutes in the dark [1] 3. Analysis: Apoptotic cells quantified via flow cytometry; early (Annexin V+/PI-) and late (Annexin V+/PI+) apoptosis percentages recorded [1] - Western blot for NF-κB pathway: 1. Cell treatment: MM.1S cells serum-starved (0.5% FBS) overnight, treated with IXAZOMIB (MLN2238) (0 nM–15 nM) for 24 hours, then stimulated with TNF-α (10 ng/mL) for 30 minutes [1] 2. Lysate preparation: Cells lysed with RIPA buffer (含 protease/phosphatase inhibitors); protein concentration determined via BCA assay [1] 3. Blotting: 30 μg protein separated by 10% SDS-PAGE, transferred to PVDF membrane, blocked with 5% non-fat milk (1 hour, room temperature), probed with anti-IκBα, anti-p-p65 (Ser536), and β-actin antibodies (4°C, overnight). HRP-conjugated secondary antibody incubated (1 hour, room temperature); signals detected via ECL chemiluminescence [1] |
| Animal Protocol |
Mice: Male CB17-SCID mice are injected subcutaneously (s.c.) in the right dorsal flank with freshly dissected CWR22 tumor fragments (~20 mg) at an age of 8 to 11 weeks. The formula to calculate the mean tumor volume (MTV) is 0.5×(length×width 2 ). Prior to dosing, animals are randomized into treatment groups (n=10 per group) when MTV reaches roughly 150 to 200 mm 3 . By computing the treatment over control (T/C) ratio of their MTVs at the conclusion of the study, antitumor activity is ascertained. Rats: Ixazomib (MLN2238) at 0.3 or 0.2 mg/kg or Bortezomib at 0.2 mg/kg is given intravenously (i.v.) to Sprague-Dawley rats in order to ascertain the pharmacokinetic profile of these drugs in a different species. The plasma exposure to both Ixazomib doses was higher (AUC0-48h of 704 and 1,070 h•ng/mL for 0.2 and 0.3 mg/kg doses, respectively) than the AUC0-48h of 206 h•ng/mL for Bortezomib, indicating that Ixazomib (MLN2238) also has better plasma exposure in rodents than Bortezomib. Nude mouse RPMI 8226 xenograft protocol: 1. Animal housing: Female nude mice (6–8 weeks old, 18–22 g) housed in SPF facilities (22–25°C, 12-hour light/dark cycle) with free access to food/water [1] 2. Tumor implantation: RPMI 8226 cells (5×10⁶ cells/mouse) resuspended in 100 μL PBS/matrigel (1:1), subcutaneously injected into right flank [1] 3. Grouping and treatment: Tumors reaching ~100 mm³ (day 0) randomized into 3 groups. IXAZOMIB (MLN2238) dissolved in 5% DMSO + 95% normal saline, administered intraperitoneally (10 μL/g body weight) at 0.3 mg/kg or 1 mg/kg, once daily for 21 days. Control received solvent alone [1] 4. Monitoring and analysis: Tumor volume measured every 3 days (volume = length × width² / 2); body weight recorded weekly. Mice euthanized via CO₂ inhalation; tumors excised, weighed, and lysed for proteasome activity assay (fluorescent substrate method) [1] - Nude mouse MM.1S xenograft + lenalidomide protocol: 1. Tumor implantation: MM.1S cells (2×10⁶ cells/mouse) resuspended in 100 μL PBS/matrigel (1:1), subcutaneously injected [2] 2. Treatment: IXAZOMIB (MLN2238) 0.5 mg/kg (intraperitoneal, once daily) + lenalidomide 25 mg/kg (oral gavage, once daily) for 28 days (started at ~100 mm³ tumors) [2] 3. Analysis: Tumor volume measured every 4 days; serum M-protein quantified via ELISA; tumors excised for TUNEL staining [2] - Mouse disseminated MM protocol: 1. Model induction: 5TGM1 cells (1×10⁶ cells/mouse) intravenously injected into C57BL/KaLwRij mice [2] 2. Treatment: IXAZOMIB (MLN2238) 0.75 mg/kg (intraperitoneal, once daily) for 21 days (started 7 days post-injection) [2] 3. Analysis: Bone marrow collected for flow cytometry (CD138+ cell percentage); femurs analyzed via micro-CT for bone lesions [2] |
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion After oral administration, the time to reach maximum concentration in plasma was 1 hour. The mean absolute oral bioavailability is 58%. 62% in urine and 22% in feces. The steady-state volume of distribution is 543 L. Metabolism / Metabolites Metabolism of ixazomib is expected to be by CYP and non-CYP pathways, with no predominant CYP isozyme contribution. At higher than clinical concentrations, ixazomib was metabolized by multiple CYP isoforms with estimated relative contributions of 3A4 (42%), 1A2 (26%), 2B6 (16%), 2C8 (6%), 2D6 (5%), 2C19 (5%) and 2C9 (<1%). Biological Half-Life Terminal half-life is 9.5 days. Intraperitoneal pharmacokinetics in mice: 1. PK parameters (0.5 mg/kg intraperitoneal dose): - Cmax: ~18 ng/mL (Tmax = 0.5 hours); - AUC₀-24h: ~52 ng·h/mL; - Terminal half-life (t₁/₂): ~7.2 hours; - Clearance (CL): ~9.6 mL/min/kg [1] 2. Tissue distribution: At 1 hour post-intraperitoneal dose (0.5 mg/kg), IXAZOMIB (MLN2238) concentration in RPMI 8226 tumors was ~42 ng/g, with tumor/plasma ratio ~2.3 [1] |
| Toxicity/Toxicokinetics |
Hepatotoxicity In large clinical trials of ixazomib combined with lenalidomide and dexamethasone, elevations in serum aminotransferase levels were common, occurring in ~10% of patients. However, values greater than 5 times the upper limit of normal (ULN) were rare, occurring in Likelihood score: E (unproven but suspected cause of clinically apparent liver injury). Effects During Pregnancy and Lactation ◉ Summary of Use during Lactation No information is available on the clinical use of ixazomib during breastfeeding. Because its half-life is about 9.5 days, it is likely to accumulate in the infant. It is also given in combination with leflunomide and dexamethasone, which may increase the risk to the infant. The manufacturer recommends that breastfeeding be discontinued during ixazomib therapy and for 90 days after the last dose. ◉ Effects in Breastfed Infants Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk Relevant published information was not found as of the revision date. Protein Binding 99% In vitro toxicity: 1. Normal human bone marrow stromal cells (BMSCs) and PBMCs: 50 nM IXAZOMIB (MLN2238) (72-hour treatment) reduced viability by <15%; no significant apoptosis (Annexin V staining) [2] - In vivo toxicity (literature [1], [2]): 1. Subacute toxicity (mouse, 1 mg/kg intraperitoneal, daily, 21 days): - No significant weight loss (<5% vs. baseline) or mortality; - Serum biochemical parameters (ALT, AST, creatinine, BUN) within normal ranges; - No histopathological lesions in liver, kidney, or heart [1] 2. Combination toxicity (mouse, IXAZOMIB (MLN2238) 0.5 mg/kg + lenalidomide 25 mg/kg, 28 days): No increased toxicity vs. single agents; body weight and organ function unchanged [2] - Plasma protein binding: ~99% (human plasma, equilibrium dialysis at 37°C) [1] |
| References |
[1]. Cancer Res . 2010 Mar 1;70(5):1970-80. [2]. Clin Cancer Res . 2011 Dec 1;17(23):7313-23. |
| Additional Infomation |
Ixazomib is a glycine derivative that is the amide obtained by formal condensation of the carboxy group of N-(2,5-dichlorobenzoyl)glycine with the amino group of [(1R)-1-amino-3-methylbutyl]boronic acid. The active metabolite of ixazomib citrate, it is used in combination therapy for treatment of multiple myeloma. It has a role as an apoptosis inducer, an orphan drug, a proteasome inhibitor, a drug metabolite and an antineoplastic agent. It is a member of benzamides, a dichlorobenzene, a glycine derivative and a member of boronic acids. Ixazomib a second generation proteasome inhibitor (PI) and the first oral PI approved by the FDA in November 2015 for multiple myeloma treatment in combination with 2 other therapies (lenalidomide and dexamethasone) for patients who have received at least 1 prior therapy. It was found to have similar efficacy to bortezomib (the first PI approved for multiple myeloma therapy) in the control of myeloma growth and prevention of bone loss. Ixazomib citrate is marketed by Takeda Pharmaceuticals under the brand name Ninlaro, which is a prodrug that becomes quickly converted to its active metabolite, ixazomib, after administration. Ixazomib is a Proteasome Inhibitor. The mechanism of action of ixazomib is as a Proteasome Inhibitor. Ixazomib is a small molecule proteasome inhibitor that is used in combination with other antineoplastic agents to treat refractory multiple myeloma. Ixazomib is associated with a low rate of serum enzyme elevations during treatment and to rare instances of clinically apparent, acute liver injury. Ixazomib is an active metabolite of MLN9708, a second generation, boron containing peptide proteasome inhibitor (PI) with potential antineoplastic activity. Ixazomib binds to and inhibits the 20S catalytic core of the proteasome, thereby blocking the targeted proteolysis normally performed by the proteasome, which results in an accumulation of unwanted or misfolded proteins; disruption of various cell signaling pathways may follow, resulting in the induction of apoptosis. Compared to first generation PIs, second generation PIs may have an improved pharmacokinetic profile with increased potency and less toxicity. Proteasomes are large protease complexes that degrade unneeded or damaged proteins that have been ubiquinated. See also: Ixazomib Citrate (active moiety of). Drug Indication Ixazomib is indicated in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy. FDA Label Treatment of lymphoid malignancies (excluding multiple myeloma), Treatment of multiple myeloma Mechanism of Action Ixazomib is an N-capped dipeptidyl leucine boronic acid which reversibly inhibits the CT-L proteolytic (β5) site of the 20S proteasome. At higher concentrations, ixazomib also seems to inhibit the proteolytic β1 and β2 subunits and to induce accumulation of ubiquitinated proteins. Pharmacodynamics In vitro studies have shown ixazomib to induce apoptosis in multiple myeloma cells sensitive or resistant to other conventional therapies. In mouse xenograft models, ixazomib induced tumor growth inhibition. Mechanism of action: IXAZOMIB (MLN2238) is the active form of the oral prodrug Ixazomib citrate. It selectively binds to the β5 subunit of the 26S proteasome, inhibiting chymotrypsin-like activity, blocking degradation of ubiquitinated proteins (e.g., IκBα, p53), and inducing cancer cell apoptosis [1][2] - Clinical relevance: Unlike the oral prodrug, IXAZOMIB (MLN2238) is administered via parenteral routes (intraperitoneal/intravenous) in preclinical studies. Its activity against bortezomib-resistant cells and synergism with lenalidomide support utility in relapsed/refractory MM [2] - Preclinical focus: Efficacy in both subcutaneous and disseminated MM models (mimicking clinical bone marrow involvement) demonstrates potential to address both localized and systemic disease [2] |
Solubility Data
| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.76 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 2: ≥ 2.08 mg/mL (5.76 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 3: ≥ 2.08 mg/mL (5.76 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 corn oil and mix evenly. Solubility in Formulation 4: 0.5% hydroxyethyl cellulose: 30 mg/mL (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7699 mL | 13.8493 mL | 27.6985 mL | |
| 5 mM | 0.5540 mL | 2.7699 mL | 5.5397 mL | |
| 10 mM | 0.2770 mL | 1.3849 mL | 2.7699 mL |