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GSK3179106

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Chemical Structure| 1627856-64-7 同义名 : RET KInase inhibitor 1;​RET Kinase Inhibitor 1
CAS号 : 1627856-64-7
货号 : A723612
分子式 : C22H21F4N3O4
纯度 : 99%+
分子量 : 467.413
MDL号 : MFCD30747847
存储条件：

粉末 Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 105 mg/mL(224.64 mM)，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
描述 Rearranged during transfection (RET) kinase is a neuronal growth factor receptor tyrosine kinase that is activated upon binding to one of four neurotrophic factors. RET activity is critical for the development of the ENS (enteric nervous system), the kidney, and spermatogenesis. Inhibition of RET in the ENS represents a novel therapeutic strategy for the normalization of neuronal function and the symptoms of IBS (irritable bowel syndrome) patients. GSK3179106 is a potent, selective, and gut-restricted pyridone hinge binder small molecule RET kinase inhibitor with an IC50 of 0.3 nM and is efficacious in vivo. It presents IC50s of 0.4 and 11 nM in the biochemical assay and cellular assay, respectively. GSK3179106 competely binds to the kinobeads with pKdapp of 7.9 or Kd of 0.02 μM. GSK3179106 dosed orally at 10 mg/kg (n = 7) for 3.5 days BID reduced the visceromotor response to colorectal distension in comparison to rats given an acetic acid enema and dosed with vehicle. GSK3179106 was further progressed to rodent safety studies and found to have a favorable safety profile to support clinical testing[1].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.14mL

0.43mL

0.21mL

10.70mL

2.14mL

1.07mL

21.39mL

4.28mL

2.14mL
参考文献

[1]Schenck Eidam H, Russell J, Raha K, et al. Discovery of a First-in-Class Gut-Restricted RET Kinase Inhibitor as a Clinical Candidate for the Treatment of IBS. ACS Med Chem Lett. 2018;9(7):623-628.