Deucravacitinib (BMS-986165) is a highly selective, orally bioavailable allosteric TYK2 inhibitor for the treatment of autoimmune diseases, which selectively binds to TYK2 pseudokinase (JH2) domain with IC50 of 1.0 nM and Ki value of 0.02 nM. Deucravacitinib (BMS-986165) inhibited IL-23, IL-12, and Type I interferon-driven cellular signaling and transcriptional responses (IC50 range 2-14 nM).
Deucravacitinib (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. Deucravacitinib (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.
Cell Experiment | |
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Cell lines | CD3+ T-cells, CD161+ CD3+ T-cells, TF-1 cells, mononuclear cells, platelets |
Preparation method | Deucravacitinib (BMS-986165) is evaluated in both binding and human cellular assays to determine selectivity within the JAK family and across the kinome. Mean values are determined from at least three separate experiments unless otherwise noted. Measuring STAT5 phosphorylation in CD3+ T-cells as end point. Measuring STAT3 phosphorylation in CD161+ CD3+ T-cells. Measuring STAT5A phosphorylation in TF-1 cells (n = 2). Measuring STAT6 phosphorylation in mononuclear cells (n = 2). Measuring STAT5 phosphorylation in platelets. Measuring STAT3 phosphorylation in CD3+ T-cells. |
Concentrations | 0-10 μM |
Incubation time | - |
Animal Experiment | |
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Animal models | 6−8 weeks old C57BL/6 female mice |
Formulation | - |
Dosages | 7.5 mg/kg, 15 mg/kg, and 30 mg/kg |
Administration | oral gavage |
Molecular Weight | 425.46 |
Formula | C20H19D3N8O3 |
CAS Number | 1609392-27-9 |
Solubility (25°C) | DMSO ≥ 30 mg/mL |
Storage | -20°C |
Species | Mouse | Rat | Rabbit | Guinea pig | Hamster | Dog |
Weight (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
Body Surface Area (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
Km factor | 3 | 6 | 12 | 8 | 5 | 20 |
Animal A (mg/kg) = Animal B (mg/kg) multiplied by | Animal B Km |
Animal A Km |
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
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