AZ12799734 是一种选择性的、具有口服活性的TGFBR1激酶抑制剂，IC50为 47 nM。 AZ12799734 也是一种BMP和TGFβ抑制剂。
| 生物活性 | AZ12799734 is a selective, orally activeTGFBR1kinase inhibitor with anIC50of 47 nM. AZ12799734 is also a panBMPandTGFβinhibitor[1]. |
| IC50& Target | TGFBR1 47 nM (IC50) | ALK6 0.017 μM (Kd) | ALK5 0.74 μM (Kd) | ALK4 1 μM (Kd) | ACVR1 6.2 μM (Kd) | ALK1 7.1 μM (Kd) | BMPR1A 40 μM (Kd) | BMP |
|
体外研究
(In Vitro) | AZ12799734 inhibits ligand activated SMAD3/4 transcription[1].
AZ12799734 (10 nM; 24 h) inhibits phosphorylation of both SMAD1 and SMAD2[1].
AZ12799734 (500 nM; 36 h) inhibits TGFβ-induced migration in HaCaT epithelial cells[1].
Western Blot Analysis[1] | Cell Line: | HaCaT cells and NIH3T3 cells | | Concentration: | 10 nM | | Incubation Time: | 10 days (HaCaT) or 24 h (NIH3T3) | | Result: | Blocked TGFβ-mediated induction of SMAD2 phosphorylation. Inhibited phosphorylation of both SMAD1 and SMAD2. |
Cell Migration Assay[1] | Cell Line: | HaCaT epithelial cells | | Concentration: | 500 nM | | Incubation Time: | 36 h | | Result: | A dose-dependent decrease in TGFβ-induced migration was observed. |
|
体内研究
(In Vivo) | AZ12799734 (0-400 mg/kg/day; p.o.; 3-7 days) induces histopathologic heart valve lesions in rat[2].
AZ12799734 (50 mg/kg; p.o.; once) shows total and free pharmacokinetic (PK) levels in the nude mouse with time over in vitro IC50of 0.01885 μM[1].
| Animal Model: | Ten-week-old female HsdHan:WIST rats[2] | | Dosage: | 200 and 400 mg/kg/day | | Administration: | Oral, 3-7 days | | Result: | Hemorrhage into the heart valves was evident at low magnification and the normal architecture of the leaflet was replaced by hemorrhage.
Increased valvular interstitial cells in size and number and shows increased cytoplasm, an enlarged round to spindeloid nucleus, and frequently undergoing mitosis. |
| Animal Model: | Female BALB/c mice[1] | | Dosage: | 50 mg/kg | | Administration: | Oral administration (Pharmacokinetic Analysis) | | Result: | Showed total and free pharmacokinetic (PK) levels with time over in vitro IC50of 0.01885 μM. |
|
| 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. |
