Deucravacitinib free base · Synonyms: BMS-986165

BMS-986165 is a highly selective, orally bioavailable allosteric TYK2 inhibitor.

For research use only. Not for human or veterinary use.

Target JAK Interleukin Related

Research area Inflammation/Immunology

Purity >99% Stock Inquire

Data Sheet SDS COA

Deucravacitinib structure

CAS No.: 1609392-27-9

Download structure (.mol)

Pack sizes & pricing

Size	Price	SKU	Stock
1 g	USD 285.00	BP-01903-1g	In stock	Get quote
5 g	USD 785.00	BP-01903-5g	In stock	Get quote
10 g	USD 1,285.00	BP-01903-10g	In stock	Get quote
25 g	Inquire	BP-01903-25g	Inquire	Inquire
50 g	Inquire	BP-01903-50g	Inquire	Inquire

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Description

BMS-986165 is a highly selective, orally bioavailable allosteric TYK2 inhibitor for the treatment of autoimmune diseases. BMS-986165 inhibits IL-12/23 and type I IFN pathways.

Biological activity

In Vitro Deucravacitinib potently inhibits TYK2-dependent IFNα-induced STAT5 phosphorylation in human CD3+ T cells, with an IC50 of 2 nM. Deucravacitinib potently inhibits TYK2-dependent IL-23-induced STAT3 phosphorylation in human CD161+ CD3+ T cells, with an IC50 of 9 nM. Deucravacitinib potently inhibits TYK2-dependent IFNα-induced STAT5 phosphorylation in human whole blood with an IC50 of 13 nM, while exhibiting high functional selectivity for signaling pathways dependent on JAK2, JAK1 and JAK3. Biological Activity Description IC50 & Target In Vitro Parmacokinetics In Vivo Clinical Trial Application Chemical Information Publications (36) Solvent & Solubility In Vitro In Vivo Purity & Documentation References Classifications Bioz Biological Activity Description Deucravacitinib (BMS-986165) is an orally active allosteric inhibitor of tyrosine kinase 2 (TYK2), with an IC50 of 0.2 nM and a Ki of 0.02 nM against the JH2 domain of TYK2, and it exhibits selectivity over other JAK subtypes and most of the kinome. Deucravacitinib blocks IL-23, IL-12, p-STAT1/3 and Type I IFN signaling, and inhibits Th17/Th1-mediated psoriasis inflammation. Deucravacitinib can be used in research related to moderate-to-severe plaque psoriasis, inflammatory bowel disease and systemic lupus erythematosus[1][2]. IC50 & Target[2] Tyk2 0.2 nM (IC50) JAK1 1 nM (IC50) IL-23 IL-12 STAT1 STAT3 All JAK Isoforms : JAK1 JAK2 JAK3 Tyk2 JAK All STAT Isoforms : STAT3 STAT5 STAT6 STAT1 All Interleukin Related Isoforms : IL-1 IL-2 IL-3 IL-4 IL-5 IL-6 IL-8 IL-10 IL-12 IL-13 IL-15 IL-17 IL-23 IL-7 IL-33 IL-22 IL-18 In Vitro Deucravacitinib potently inhibits TYK2-dependent IFNα-induced STAT5 phosphorylation in human CD3+ T cells, with an IC50 of 2 nM[2]. Deucravacitinib potently inhibits TYK2-dependent IL-23-induced STAT3 phosphorylation in human CD161+ CD3+ T cells, with an IC50 of 9 nM[2]. Deucravacitinib potently inhibits TYK2-dependent IFNα-induced STAT5 phosphorylation in human whole blood with an IC50 of 13 nM, while exhibiting high functional selectivity for signaling pathways dependent on JAK2, JAK1 and JAK3[2]. MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Parmacokinetics Species Dose Route Cmax AUC Bioavailability CL Vss T1/2 MRT Mice[2] 1 mg/kg i.v. / / / 13.2 mL/min/kg 2.9 L/kg 4.2 h 3.6 h Mice[2] 10 mg/kg p.o. 7.5 μM 36.4 μM·h 122 % / / / / Dog[2] 2 mg/kg i.v. / / / 6.8 mL/min/kg 2.3 L/kg 4.6 h 5.5 h Dog[2] 10 mg/kg p.o. 6.9 μM 73.6 μM·h 128 % / / / / Monkey[2] 2 mg/kg i.v. / / / 4.8 mL/min/kg 2 L/kg 5.3 h 7 h Monkey[2] 10 mg/kg p.o. 5.9 μM 75.7 μM·h 87 % / / / / In Vivo Deucravacitinib (7.5-30 mg/kg; p.o.; twice daily; for 9 consecutive days) exhibits dose-dependent efficacy in a mouse IL-23-driven psoriasis model. Deucravacitinib (50 mg/kg; p.o.; twice daily) almost completely inhibits body weight loss and significantly reduces histological damage in a mouse model of anti-CD40-induced colitis. Deucravacitinib (30 mg/kg; p.o.; once daily; for 3 consecutive months) is well tolerated in a mouse lupus model and exerts significant efficacy in preventing nephritis.

Identifiers

SMILES: O=C(C1=NN=C(NC(C2CC2)=O)C=C1NC3=CC=CC(C4=NN(C)C=N4)=C3OC)NC([2H])([2H])[2H]
InChIKey: BZZKEPGENYLQSC-FIBGUPNXSA-N

Specifications

MW (average): 425.4590
Formula: C₂₀H₂₂N₈O₃
CAS No.: 1609392-27-9
Physical state: Solid
Color: Off-white to light yellow
Shipping: 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: Powder -20℃ 2 years; In solvent -20℃ 1 month;

Solubility

Soluble in DMSO

Documents

References

[1]. Wrobleski ST, et al. Highly Selective Inhibition of Tyrosine Kinase 2 (TYK2) for the Treatment of Autoimmune Diseases: Discovery of the Allosteric Inhibitor BMS-986165. J Med Chem. 2019 Jul 18.

[2]. Catlett I, et al. SAT0226 A first-in-human, study of BMS-986165, a selective, potent, allosteric small molecule inhibitor of tyrosine kinase 2. Annals of the Rheumatic Diseases 2017;76:859.

Same target

Search JAK

Same research area

Search Inflammation/Immunology