生物活性
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.
化学数据
| 分子量 | 425.46 |
| 分子式 | C20H19D3N8O3 |
| CAS号 | 1609392-27-9 |
| 纯度 | >99.5% |
| 溶解性（25°C） | DMSO ≥ 30 mg/mL |
| 储存和运输条件 | 固体粉末： -20°C 冷藏长期储存
常温运输及临时存放 |
实验操作 来自于公开的文献，仅供相同实验参考（如实验材料、目的不同，请参考其他文献）
| 细胞实验 |
|---|
| 细胞系 | CD3+ T-cells, CD161+ CD3+ T-cells, TF-1 cells, mononuclear cells, platelets |
| 方法 | 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. |
| 浓度 | 0-10 μM |
| 处理时间 | - |
| 动物实验 |
|---|
| 动物模型 | 6–8 weeks old C57BL/6 female mice |
| 配制 | - |
| 剂量 | 7.5 mg/kg, 15 mg/kg, and 30 mg/kg |
| 给药处理 | oral gavage |
不同实验动物依据体表面积的等效剂量转换表（数据来源于FDA指南）
| 小鼠 | 大鼠 | 兔 | 豚鼠 | 仓鼠 | 狗 |
| 重量 (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
| 体表面积 (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
| Km系数 | 3 | 6 | 12 | 8 | 5 | 20 |
| 动物 A (mg/kg) = 动物 B (mg/kg) × | 动物 B的Km系数 |
| 动物 A的Km系数 |
例如，依据体表面积折算法，将化合物用于小鼠的剂量20 mg/kg 换算成大鼠的剂量，需要将20 mg/kg 乘以小鼠的Km系数（3），再除以大鼠的Km系数（6），得到化合物用于大鼠的等效剂量为10 mg/kg。
储备液配制
以下数据基于产品分子量，对于特殊产品，请参照COA中的储备液配制条件和说明进行操作。
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 2.3504 mL | 11.752 mL | 23.504 mL |
| 5 mM | 0.4701 mL | 2.3504 mL | 4.7008 mL |
| 10 mM | 0.235 mL | 1.1752 mL | 2.3504 mL |
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