| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg | |||
| 100mg | |||
| 250mg | |||
| Other Sizes |
Purity: ≥98%
| Targets |
BTK (IC50 = 2.8 nM); TEC (IC50 = 13 nM); BLK (IC50 = 20 nM); BMX (IC50 = 24 nM); TrkA (IC50 = 30 nM)
BMS-935177 targets Bruton's tyrosine kinase (BTK), a key enzyme in B-cell receptor signaling. By reversibly inhibiting BTK, it blocks B-cell receptor signaling, thereby suppressing B-cell activation and inflammatory responses. BTK is a member of the Tec family of non-receptor tyrosine kinases and is critical for B-cell development and function. |
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| ln Vitro |
BMS-935177 exhibits selectivity over the SRC family of kinases by more than 50 times, including 110% selectivity over SRC. The remaining kinases, TRKA, HER4, TRKB, and RET, were inhibited with a potency less than 150 nM (50-fold selectivity). When peripheral B cells are stimulated with anti-IgM and anti-IgG, it suppresses CD69 surface expression and calcium flux in human Ramos B cells (IC50 = 27 nM). But when B cells are stimulated via the CD40 receptor using CD40 ligand, BMS-935177 has no effect on the expression of CD69 on their surface. With an IC50 value of 14 nM, BMS-935177 effectively inhibited TNFα production against IgG-containing immune complex-driven low affinity activating Fcγ receptor (FcγRIIa and FcγRIII) end points in peripheral blood mononuclear cells (PBMCs)[1].
In vitro, BMS-935177 inhibits BTK with an enzymatic IC50 of 2.8-3 nM. It shows good kinase selectivity, being more potent against BTK than other Tec family kinases including TEC, BMX, ITK, and TXK (5- to 67-fold selective). Detailed cellular activity data are not provided in the available references. |
| ln Vivo |
For BMS-935177, plasma protein binding is high across all species, with less than 1% free for humans. In spite of its low aqueous solubility, it has good oral bioavailability in all preclinical species, from both suspension and solution dosing. BMS-935177 has an oral bioavailability of 84% to 100% when given as a solution dose in rat, mouse, dog, and cynomolgus monkey studies. Single intravenous (IV) infusion studies show low clearance. The half-lives of BMS-935177 in mice and rats administered intravenously at a dose of 2 mg/kg are 4 and 5.1 hours, respectively[1].
In vivo activity data for BMS-935177 are not detailed in the available references. As an orally bioavailable BTK inhibitor, it would be expected to demonstrate efficacy in preclinical models of B-cell-driven diseases, including autoimmune disorders and B-cell malignancies, by suppressing B-cell activation and proliferation. |
| Enzyme Assay |
BMS-935177 is tested at 11 different concentrations after being dissolved at 10 mM in DMSO. BMS-935177, 1 nM of human recombinant BTK, 1.5 μM of fluoresceinated peptide, 20 μM (Km app) of ATP, and 20 mM HEPES, pH 7.4, 10 mM MgCl2, 0.015% Brij 35 surfactant, and 4 mM DTT in 1.6% DMSO) are added to V-bottom 384-well plates, with a final volume of 30 μL of assay buffer. 45 μL of 35 mM EDTA is added to each sample to stop the reaction after it has been incubated for 60 minutes at room temperature. By electrophoretic separation of the fluorescent substrate and phosphorylated product (excitation, 488 nm; emission, 530 nm), the reaction mixture is examined.
BTK kinase inhibitory activity is determined using cell-free kinase assays with recombinant BTK enzyme, a peptide substrate, and ATP. Phosphorylation of the substrate is measured, and IC50 values are calculated from dose-response curves. Selectivity is assessed by profiling against a panel of kinases including other Tec family kinases. |
| Cell Assay |
Cell-based assays for BMS-935177 would typically use B-cell lines or primary B cells treated with varying concentrations of the compound. BTK autophosphorylation and downstream signaling (e.g., PLCγ2, ERK) would be assessed by Western blot. B-cell proliferation and activation markers would be measured to evaluate functional inhibition.
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| Animal Protocol |
Rats: In the PK studies, male Sprague-Dawley rats weighing 255-298 g are employed. Rats are given T99.5% 10 mM citrate buffer, pH 4, 0.02% DOSS, Methocel A4M, and BMS-935177 by oral gavage (1, 5, and 20 mg/kg) in order to examine the oral bioavailability of the drug following crystalline microsuspension doses. Following oral dosage, serial blood samples are taken at 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, and 24 hours later. After centrifugation at 4 °C (1500-2000g), plasma samples are kept at -20 °C until analysis.
Mice: BMS-935177 (10 and 30 mg/kg) is tested in a mouse anti-collagen antibody-induced arthritis (CAIA) inflammation model to compare its effectiveness with vehicle and dexamethasone (Dex). Four different combinations of monoclonal antimouse type II collagen antibodies—one milligram of each—are injected intraperitoneally (ip) into mice. The vehicle (EtOH:TPGS:PEG300, 5:5:90), BMS-935177 (10 or 30 mg/kg), or dexamethasone (dex, 1 mg/kg) is immediately started as a daily oral dose. The mice receive an intraperitoneal injection of 1.25 mg/kg lipopolysaccharide (LPS) after three days. The mice are then observed three times a week to observe the progression and intensity of paw inflammation. In vivo animal studies for BMS-935177 would be conducted in mouse models of autoimmune diseases or B-cell malignancies. The compound would be administered orally, and efficacy endpoints would include disease severity scores, B-cell numbers and activation status, and survival. Detailed protocols are not provided in the available references. |
| ADME/Pharmacokinetics |
BMS-935177 has the molecular formula C₃₁H₂₆N₄O₃ and a molecular weight of 502.56. It is orally bioavailable. It is soluble in DMSO (100 mg/mL) and ethanol (100 mg/mL) but insoluble in water. Detailed pharmacokinetic parameters such as half-life and bioavailability are not disclosed.
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| Toxicity/Toxicokinetics |
No specific toxicity data are available in the provided references. As a BTK inhibitor, potential toxicities may include immunodeficiency, bleeding risk, and gastrointestinal effects, which are class effects of BTK inhibitors. The compound's selectivity profile may contribute to a favorable safety margin.
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| References | |
| Additional Infomation |
BMS-935177 is a research compound that has been studied as a potent and selective BTK inhibitor. Its reversible binding mechanism and good kinase selectivity make it a valuable tool for studying BTK-mediated signaling in B-cell biology and for exploring therapeutic applications in B-cell-driven diseases.
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| Molecular Formula |
C31H26N4O3
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| Molecular Weight |
502.56
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| Exact Mass |
502.2
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| Elemental Analysis |
C, 74.09; H, 5.21; N, 11.15; O, 9.55
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| CAS # |
1231889-53-4
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| Related CAS # |
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| PubChem CID |
70647728
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
805.4±75.0 °C at 760 mmHg
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| Flash Point |
440.9±37.1 °C
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| Vapour Pressure |
0.0±3.0 mmHg at 25°C
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| Index of Refraction |
1.707
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| LogP |
3.98
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
38
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| Complexity |
951
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| Defined Atom Stereocenter Count |
0
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| SMILES |
OC(C)(C)C1C=CC2=C(C=1)NC1C(C(N)=O)=CC=C(C3C=CC=C(C=3C)N3C=NC4C=CC=CC=4C3=O)C2=1
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| InChi Key |
TVJRDCQUZMGBAB-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C31H26N4O3/c1-17-19(8-6-10-26(17)35-16-33-24-9-5-4-7-22(24)30(35)37)20-13-14-23(29(32)36)28-27(20)21-12-11-18(31(2,3)38)15-25(21)34-28/h4-16,34,38H,1-3H3,(H2,32,36)
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| Chemical Name |
7-(2-hydroxypropan-2-yl)-4-[2-methyl-3-(4-oxoquinazolin-3-yl)phenyl]-9H-carbazole-1-carboxamide
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 3.75 mg/mL (7.46 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 37.5 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: 3.75 mg/mL (7.46 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 37.5 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9898 mL | 9.9491 mL | 19.8981 mL | |
| 5 mM | 0.3980 mL | 1.9898 mL | 3.9796 mL | |
| 10 mM | 0.1990 mL | 0.9949 mL | 1.9898 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.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
J Med Chem.2016 Sep 8;59(17):7915-35. |
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