Synonym
BMS-986165; BMS 986165; BMS986165; Deucravacitinib
IUPAC/Chemical Name
6-(cyclopropanecarboxamido)-4-((2-methoxy-3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-N-(methyl-d3)pyridazine-3-carboxamide
InChi Key
BZZKEPGENYLQSC-FIBGUPNXSA-N
InChi Code
InChI=1S/C20H22N8O3/c1-21-20(30)16-14(9-15(25-26-16)24-19(29)11-7-8-11)23-13-6-4-5-12(17(13)31-3)18-22-10-28(2)27-18/h4-6,9-11H,7-8H2,1-3H3,(H,21,30)(H2,23,24,25,29)/i1D3
SMILES Code
O=C(C1=NN=C(NC(C2CC2)=O)C=C1NC3=CC=CC(C4=NN(C)C=N4)=C3OC)NC([2H])([2H])[2H]
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>3 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
BMS-986165 was approximately 200-fold selective against JAK1/3-dependent signaling in IL-2-stimulated T cells and >3,000-fold selective over JAK2-dependent EPO-induced signaling in TF-1 cells. In human whole blood, BMS-986165 inhibited Tyk2-dependent IFNa-induced signaling with an IC50 of 13 nM. Addition of BMS-986165 to whole blood from lupus patients led to reduced expression of Type I IFN response genes, a response identical to that achieved with an anti-IFNAR Ab and superior to an anti-IFNa Ab. BMS-986165 treatment in NZB/W lupus-prone mice rapidly (24 hours) reduced the elevated expression of Type I interferon-dependent genes and dose-dependently protected from nephritis and other disease endpoints with chronic dosing, with efficacy correlating with inhibition of Type I interferon-dependent gene expression. Protection from nephritis at 10 mpk trended to be superior to a blocking anti-Type I IFN receptor antibody (anti-IFNAR). BMS-986165 was also highly efficacious in the anti-CD40-induced colitis model in SCID mice, providing protection against both weight loss (wasting) and histologically evident colitis, and was as effective as an anti-p40 antibody.
Biological target:
Deucravacitinib (BMS-986165) is a highly selective allosteric TYK2 inhibitor (IC50=1.0 nM) that inhibits IL-12/23 and type I IFN pathways and blocks receptor-mediated Tyk2 activation by stabilizing the regulatory JH2 domain.
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
30.0 |
70.50 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
425.47
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
TBD
1: Papp K, Gordon K, Thaçi D, Morita A, Gooderham M, Foley P, Girgis IG, Kundu S, Banerjee S. Phase 2 Trial of Selective Tyrosine Kinase 2 Inhibition in Psoriasis. N Engl J Med. 2018 Oct 4;379(14):1313-1321. doi: 10.1056/NEJMoa1806382. Epub 2018 Sep 11. PubMed PMID: 30205746.
2. Gillooly K, Zhang Y, Yang X, Zupa-Fernandez A, Cheng L, Strnad J, Cunningham M, Heimrich E, Zhou X, Chen J, Chaudhry C, Li S, McIntyre K, Carman J, Moslin R, Wrobleski S, Weinstein D, Burke J. BMS-986165 Is a Highly Potent and Selective Allosteric Inhibitor of Tyk2, Blocks IL-12, IL-23 and Type I Interferon Signaling and Provides for Robust Efficacy in Preclinical Models of Systemic Lupus Erythematosus and Inflammatory Bowel Disease [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/bms-986165-is-a-highly-potent-and-selective-allosteric-inhibitor-of-tyk2-blocks-il-12-il-23-and-type-i-interferon-signaling-and-provides-for-robust-efficacy-in-preclinical-models-of-systemic-lupus-e/. Accessed November 7, 2018.
