| Description | TD-198946, a potent chondrogenic agent, is a thienoindazole derivative. |
| In vitro | 在细胞和跖骨器官培养中，TD-198946 显著促进软骨生成分化，而不促进肥大。在 ATDC5 细胞中，TD-198946 比胰岛素更强地诱导 Col2a1 启动子活性。在 C3H10T1/2 细胞、ATDC5 细胞和初级小鼠软骨细胞中，TD-198946 剂量依赖性地刺激软骨细胞标志物 Acan 和 Col2a1 的内源性表达（最大效应：1-10 μM）。 |
| In vivo | TD-198946通过直接注入关节空间可以预防和修复关节软骨的退化。TD-198946调控Runx1的表达，该表达在鼠类和人类的骨关节炎（OA）软骨中相比正常组织被下调。TD-198946可能通过作用于剩余的软骨细胞而非修复受损软骨来防止骨关节炎的进展。通过将人类间充质干细胞以及犬和鼠类的肋软骨细胞与TD-198946一同培养于温度响应性培养皿上，可以生成软骨细胞片。 |
| Animal experiments | For intra-articular injection, TD-198946 is dissolved at 100 nM in a solution of 45% 2-hydropropyl-b-cyclodextrin in saline.Mouse: Each of the prevention and repair models had two groups: (1) TD-198946-treated animals and (2) saline-treated animals. In all the mice tested the left knee joints underwent the operation and the right knee joints are sham-operated. Mice are re-anesthetized and given a 10 μL intra-articular injection of TD-198946 or saline immediately after surgery (prevention model) or 4 weeks following surgery (repair model) every 5 days for 8 or 4 weeks, respectively. |
| Synonyms | TD198946, TD 198946 |
| molecular weight | 482.55 |
| Molecular formula | C27H22N4O3S |
| CAS | 364762-86-7 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| Solubility | DMSO: 50 mg/mL (103.62 mM) |
| References | 1. Yano F, et al. A novel disease-modifying osteoarthritis drug candidate targeting Runx1. Ann Rheum Dis. 2013 May;72(5):748-53. 2. Yano F, et al. Cell-sheet technology combined with a thienoindazole derivative small compound TD-1198946 for cartilage regeneration. Biomaterials. 2013 Jul;34(22):5581-7. 3. Yano F, et al. Disease-modifying effects of TD-1198946 on progressed osteoarthritis in a mouse model. Ann Rheum Dis. 2014 Nov;73(11):2062-4. |