1py5
From Proteopedia
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Crystal Structure of TGF-beta receptor I kinase with inhibitor
Contents |
Overview
We have expanded our previously reported series of pyrazole-based, inhibitors of the TGF-beta type I receptor kinase domain (TbetaR-I) to now, include new 5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole analogues. Limited, examination of the SAR of this new series in both enzyme and cell based in, vitro assays has revealed selectivity differences with respect to p38 MAP, kinase (p38 MAPK) depending on the nature of the 'warhead' group on the, dihydropyrrolopyrazole ring. As with our original pyrazole series, phenyl, substituents tended to show greater selectivity against p38 MAPK than, those comprised of the quinoline-4-yl moiety. We have also achieved, co-crystallization and X-ray analysis of compounds 3 and 15, two potent, examples of this new series, with the TbetaR-I receptor kinase domain.
Disease
Known diseases associated with this structure: Aortic aneurysm, familial thoracic 5 OMIM:[190181], Furlong syndrome OMIM:[190181], Loeys-Dietz syndrome OMIM:[190181]
About this Structure
1PY5 is a Single protein structure of sequence from Homo sapiens with SO4 and PY1 as ligands. Active as Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 Full crystallographic information is available from OCA.
Reference
Synthesis and activity of new aryl- and heteroaryl-substituted 5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole inhibitors of the transforming growth factor-beta type I receptor kinase domain., Sawyer JS, Beight DW, Britt KS, Anderson BD, Campbell RM, Goodson T Jr, Herron DK, Li HY, McMillen WT, Mort N, Parsons S, Smith EC, Wagner JR, Yan L, Zhang F, Yingling JM, Bioorg Med Chem Lett. 2004 Jul 5;14(13):3581-4. PMID:15177479
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