1. Protein Tyrosine Kinase/RTK
  2. Btk

BMS-935177 

Cat. No.: HY-101793 Purity: 99.05%
Handling Instructions

BMS-935177 is a potent and selective reversible inhibitor of Bruton’s tyrosine kinase (Btk) with an IC50 of 3 nM.

For research use only. We do not sell to patients.

BMS-935177 Chemical Structure

BMS-935177 Chemical Structure

CAS No. : 1231889-53-4

Size Price Stock Quantity
10 mM * 1 mL in DMSO USD 243 In-stock
Estimated Time of Arrival: December 31
2 mg USD 110 In-stock
Estimated Time of Arrival: December 31
5 mg USD 220 In-stock
Estimated Time of Arrival: December 31
10 mg USD 350 In-stock
Estimated Time of Arrival: December 31
25 mg USD 720 In-stock
Estimated Time of Arrival: December 31
50 mg USD 1250 In-stock
Estimated Time of Arrival: December 31
100 mg USD 2100 In-stock
Estimated Time of Arrival: December 31
200 mg   Get quote  
500 mg   Get quote  

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Customer Review

  • Biological Activity

  • Protocol

  • Technical Information

  • Purity & Documentation

  • References

Description

BMS-935177 is a potent and selective reversible inhibitor of Bruton’s tyrosine kinase (Btk) with an IC50 of 3 nM.

IC50 & Target

IC50: 3 nM (BTK)[1]

In Vitro

In B cells stimulated through the BCR, BMS-935177 selectively inhibits several different readouts. BMS-935177 inhibits calcium flux in human Ramos B cells (IC50=27 nM) and inhibits CD69 surface expression in peripheral B cells stimulated with antiIgM and anti-IgG. However, BMS-935177 has no effect on CD69 surface expression in B cells stimulated through the CD40 receptor with CD40 ligand. Against IgG-containing immune complexdriven low affinity activating Fcγ receptor (FcγRIIa and FcγRIII) end points in peripheral blood mononuclear cells (PBMCs), BMS-935177 effectively inhibits TNFα production with an IC50 value of 14 nM. BMS-935177 shows mean IC50 values of 550±100 (n=11) and 2060±240 nM (n=3) in human and mouse whole blood, respectively[1].

In Vivo

When dosed orally once daily at 5, 20, and 45 mg/kg to mice, BMS-935177 inhibits anti-KLH antibodies of the IgG isotype at day 14, with statistically significant reductions at all doses. In satellite mice from this study dosed with 6 at 5 mg/kg, the plasma concentration is maintained above the mouse whole blood BCR-stimulated CD69 IC50 value of 2 μM for only approximately 5 h. At once daily oral doses of 10, 20, and 30 mg/kg beginning on the day of primary immunization, BMS-935177 provides a clear dose-dependent reduction in both the severity and incidence of clinically evident disease in this rodent model of RA. At 10 mg/kg of BMS-935177, disease severity is reduced about 40% compared to vehicle treatment, and the percentage of animals showing any signs of disease is reduced by a third[1].

Solvent & Solubility
In Vitro: 

DMSO : ≥ 130 mg/mL (258.68 mM)

*"≥" means soluble, but saturation unknown.

Preparing
Stock Solutions
Concentration Solvent Mass 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
*Please refer to the solubility information to select the appropriate solvent.
References
Kinase Assay
[1]

BMS-935177 is dissolved at 10 mM in DMSO and evaluated at 11 concentrations . To V-bottom 384- well plates are added BMS-935177, human recombinant BTK (1 nM), fluoresceinated peptide (1.5 μM), ATP (20 μM (Km app)), and assay buffer (20 mM HEPES, pH 7.4, 10 mM MgCl2, 0.015% Brij 35 surfactant, and 4 mM DTT in 1.6% DMSO), with a final volume of 30 μL. After incubation at room temperature for 60 min, the reaction is terminated by adding 45 μL of 35 mM EDTA to each sample. The reaction mixture is analyzed on the by electrophoretic separation of the fluorescent substrate and phosphorylated product (excitation, 488 nm; emission, 530 nm)[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[1]

Rats[1]

Male Sprague−Dawley rats (255-298 g) are used in the PK studies. To investigate the oral bioavailability of BMS-935177 after crystalline microsuspension doses, rats receive BMS-935177 by oral gavage (1, 5, and 20 mg/kg), T99.5% 10 mM citrate buffer, pH 4, 0.02% DOSS, Methocel A4M. Serial blood samples are obtained after oral dosing at 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, and 24 h postdose. Plasma samples, obtained by centrifugation at 4 °C (1500-2000g), are stored at −20 °C until analysis[1].

Mice[1]

Efficacy of BMS-935177 (10 and 30 mg/kg) vs vehicle and dexamethasone (Dex) is studied in a mouse anti-collagen antibody-induced arthritis (CAIA) inflammation model. Mice are injected intraperitoneally (ip) with a mixture of four monoclonal antimouse type II collagen antibodies (1 mg of each). Daily oral dosing is immediately started with vehicle (EtOH:TPGS:PEG300, 5:5:90), BMS-935177 (10 or 30 mg/kg), or dexamethasone (dex, 1 mg/kg). Three days later, the mice are injected ip with 1.25 mg/kg LPS. Thereafter, mice are monitored 3×/ week for the development and severity of paw inflammation[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References
Molecular Weight

502.56

Formula

C₃₁H₂₆N₄O₃

CAS No.

1231889-53-4

SMILES

O=C(C1=CC=C(C2=CC=CC(N3C=NC4=C(C=CC=C4)C3=O)=C2C)C5=C1NC6=C5C=CC(C(C)(O)C)=C6)N

Storage
Powder -20°C 3 years
  4°C 2 years
In solvent -80°C 6 months
  -20°C 1 month
Shipping

Room temperature in continental US; may vary elsewhere

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Product Name:
BMS-935177
Cat. No.:
HY-101793
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BMS-935177

Cat. No.: HY-101793