GSK3179106

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

GSK3179106 (GSK-3179106, GSK 3179106) 是一种有效、选择性、一流的肠道限制性 RET 激酶抑制剂，在生化测定和细胞测定中的 IC50 分别为 0.4 和 11 nM。

GSK3179106 (GSK-3179106, GSK 3179106) is a potent, selective, first-in-class and gut-restricted RET kinase inhibitor with IC50 of 0.4 and 11 nM in the biochemical assay and cellular assay respectively, 273-fold selectivity over KDR; possesses good kinase selectivity, only 26 out of a set of >300 recombinant kinases were found to be inhibited at 1 uM; GSK3179106 dosed orally at 10 mg/kg 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 has been developed for the treatment of IBS in a clinical setting.Irritable Bowel Syndrome,Phase 1 Clinical(In Vitro):GSK3179106 (10 nM-100 μM; 8 days for TT cells, 3 days for SK-N-AS and A549 cells) inhibits the proliferation of the RET-dependent TT cell line with a mean IC50 value of 25.5 nM however has no effect on the proliferation of the RET-independent SK-NAS and A549 cell lines (mean IC50>10 μM and IC30>17 μM, respectively).GSK3179106 inhibits RET phosphorylation in SK-N-AS cells and TT cells with mean IC50s of 4.6 nM and 11.1 nM, respectively.(In Vivo):GSK3179106 (3 or 10 mg/kg; orally; for 3.5 days BID) reduces the visceromotor response (VMR) in comparison to rats given an acetic acid enema and dosed with vehicle.

GSK3179106 (10 nM-100 μM; 8 days for TT cells, 3 days for SK-N-AS and A549 cells) inhibits the proliferation of the RET-dependent TT cell line with a mean IC50 value of 25.5 nM however has no effect on the proliferation of the RET-independent SK-NAS and A549 cell lines (mean IC50>10 μM and IC30>17 μM, respectively).GSK3179106 inhibits RET phosphorylation in SK-N-AS cells and TT cells with mean IC50s of 4.6 nM and 11.1 nM, respectively. Cell Viability Assay Cell Line:TT, SK-N-AS and A549 cells Concentration:10 nM-100 μM Incubation Time:8 days for TT cells, 3 days for SK-N-AS and A549 cells Result:Inhibited the proliferation of TT cell line with a mean IC50 value of 25.5 nM however had no effect on the proliferation of the SK-NAS and A549 cell lines (mean IC50>10 μM and IC30>17 μM, respectively).

GSK3179106 (3 or 10 mg/kg; orally; for 3.5 days BID) reduces the visceromotor response (VMR) in comparison to rats given an acetic acid enema and dosed with vehicle. Animal Model:Seventy male Sprague Dawley rats (225-250 g, ~7-8 weeks old); Fifty male Fischer 344 rats (225-250 g, ~10-12 weeks old); Sprague Dawley female rats Dosage:3 and 10 mg/kg Administration:Oral gavage ; administered BID at 8:00 and 16:00 for 3.5 days Result:Reduced the visceral motor response.Led to a 34-43% inhibition in VMR to colorectal distension (CRD) at 10 mg/kg.

GSK 3179106 | GSK-3179106

Tyrosine Kinase

c-RET

c-RET

Other Indications

Irritable Bowel Syndrome

1627856-64-7

467.421

C22H21F4N3O4

>98% (HPLC)

DMSO : ≥ 100 mg/mL 213.94 mM

O=C(NC1=NOC(C(C)(C)C(F)(F)F)=C1)CC2=CC=C(C(C(OCC)=C3)=CNC3=O)C=C2F

2-[4-(4-Ethoxy-6-oxo-1,6-dihydropyridin-3-yl)-2-fluorophenyl]-N-[5-(1,1,1-trifluoro-2-methylpropan-2-yl)isoxazol-3-yl]acetamide

(-20℃)

With Ice Pack

≥ 2 years