129888-60-4Relevant articles and documents
Compound used as RET kinase inhibitor and application thereof
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Paragraph 0253-0257, (2021/07/01)
The invention relates to a compound used as an RET kinase inhibitor and application thereof, wherein the compound has a structure as shown in a formula F, has good inhibition capability on RET kinase, and has good pharmacodynamic and pharmacokinetic performance and lower toxic and side effects.
SMARCA DEGRADERS AND USES THEREOF
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Paragraph 00835; 00836, (2020/12/30)
The present invention provides compounds, pharmaceutically acceptable compositions thereof, and methods of using the same for the modulation of one or more SWI/SNF-related matrix associated actin dependent regulator of chromatin subfamily A (SMARCA) and/or polybromo-1 (PB-1) protein via ubiqitination and/or degradation by compounds. The compounds are bifunctional molecules that link a cereblon-binding moiety to a ligand that binds SMARCA and/or PB1 proteins.
Discovery of (R)-5-((5-(1-methyl-1H-pyrazol-4-yl)-4-(methylamino)pyrimidin-2-yl)amino)-3-(piperidin-3-yloxy)picolinonitrile, a novel CHK1 inhibitor for hematologic malignancies
Tong, Lexian,Song, Pinrao,Jiang, Kailong,Xu, Lei,Jin, Tingting,Wang, Peipei,Hu, Xiaobei,Fang, Sui,Gao, Anhui,Zhou, Yubo,Liu, Tao,Li, Jia,Hu, Yongzhou
, p. 44 - 62 (2019/04/17)
Through virtual screening, we identified the lead compound MCL1020, which exhibited modest CHK1 inhibitory activity. Then a series of 5-(pyrimidin-2-ylamino)picolinonitrile derivatives as CHK1 inhibitors were discovered by further rational optimization. One promising molecule, (R)-17, whose potency was one of the best, had an IC50 of 0.4 nM with remarkable selectivity (>4300-fold CHK1 vs. CHK2). Compound (R)-17 effectively inhibited the growth of malignant hematopathy cell lines especially Z-138 (IC50: 0.013 μM) and displayed low affinity for hERG (IC50 > 40 μM). Moreover, (R)-17 significantly suppressed the tumor growth in Z-138 cell inoculated xenograft model (20 mg/kg I.V., TGI = 90.29%) as a single agent with body weight unaffected. Taken together, our data demonstrated compound (R)-17 could be a promising drug candidate for the treatment of hematologic malignancies.