TYK2-IN-12 (compound 30) 是一种口服有效的和选择性的TYK2(酪氨酸激酶 2) 抑制剂，Ki为 0.51 nM。TYK2-IN-12 分别抑制 IL-12 诱导的人和小鼠全血中IFNγ，IC50值分别为 2.7 和 7.0 μM。TYK2-IN-12 可用于银屑病研究。
| 生物活性 | TYK2-IN-12 (compound 30) is an orally active, potent and selectiveTYK2(tyrosine kinase 2) inhibitor, with aKiof 0.51 nM. TYK2-IN-12 inhibitsIL-12inducedIFNγ, withIC50values of 2.7 and 7.0 μM in human and mouse whole blood, respectively. TYK2-IN-12 can be used for psoriasis research[1]. |
| IC50& Target | Tyk2 0.51 nM (Ki) | JAK3 6.63 nM (Ki) | JAK2 21.93 nM (Ki) | JAK1 45.9 nM (Ki) |
|
体外研究
(In Vitro) | TYK2-IN-12 (compound 30) shows 90, 43, and 13-fold selectivity over JAK1, JAK2, and JAK3, respectively[1].
TYK2-IN-12 exhibits excellent selectivity over hERG (IC50 >30 μM) and over a panel of 10 cytochrome P450 enzymes (IC50s >30 μM against CYP450s 3A4, 3D6, 2C9, 2C8, 1A2, 2A6, 2B6, 2C19, 2E1, and 3A5)[1].
TYK2-IN-12 shows cell-based potency and selectivity in human PBMC by blockade of IL-12 induced phospho-STAT4, GM-CSF induced phospho-STAT5, and IL-2 induced phospho-STAT5, with IC50values of 0.10 μM, 4.1 μM and 0.25 μM, respectively[1].
|
体内研究
(In Vivo) | TYK2-IN-12 (compound 30) (0-100 mg/kg, PO, daily for 10 days) dose-dependently reduces immune responses[1].
TYK2-IN-12 (3 mg/kg (IV), 10 mg/kg (PO), once) shows moderate clearance and volumes of distribution, and exhibits moderate to good oral absorption[1].
Pharmacokinetic Parameters of TYK2-IN-12 in male C57Bl/6 mice and smale Sprague-Dawley rats[1].
| Species | Mouse | Rat | | PPB Fumax(h) | 0.061 | 0.10 | | CL (mL/min/kg) | 28 | 27 | | t1/2(h) | 1.8 | 1.6 | | Vd (L/kg) | 1.2 | 1.9 | | F (%) | >90 | 32 |
| Animal Model: | C57BL/6 mice (IL-23 induced inflammation model)[1] | | Dosage: | 0, 10, 30, and 100 mg/kg | | Administration: | PO, daily for 10 days | | Result: | Dose-dependently reduced immune responses, with up to 74 % inhibition of ear swelling and 96 % inhibition of tissue levels of IL-17A at 100 mg/kg, highlighting the crucial role of TYK2 in IL-23 induced IL-17 and tissue inflammation. Exhibited improved skin histology and a dose-dependent reduction of spleen weight. |
| Animal Model: | Male C57Bl/6 mice, male SD rats[1] | | Dosage: | 3 mg/kg (IV), 10 mg/kg (PO) | | Administration: | IV or PO, once (Pharmacokinetic Analysis) | | Result: | Showed moderate clearance and volumes of distribution of 1.2 L/Kg and 1.9 L/Kg, respectively in mouse and rat IV PK, and exhibited moderate to good oral absorption, with oral bioavailabilities of 32-100%. |
|
| 分子量 | |
| Formula | |
| CAS 号 | |
| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | Please store the product under the recommended conditions in the Certificate of Analysis. |
m.cnreagent.com