5UBR

CRYSTAL STRUCTURE OF PI3K ALPHA IN COMPLEX WITH A 7-(3-(PIPERAZIN-1-YL)PHENYL)PYRROLO[2,1-F][1,2,4] TRIAZIN-4-AMINE DERIVIATINE

Summary for 5UBR

• Entry DOI: 10.2210/pdb5ubr/pdb
• Related: 5ubt
• Descriptor: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform, 1-[4-(3-{4-amino-5-[1-(oxan-4-yl)-1H-pyrazol-5-yl]pyrrolo[2,1-f][1,2,4]triazin-7-yl}phenyl)piperazin-1-yl]ethan-1-one (3 entities in total)
• Functional Keywords: lipid kinase, inhibitor, pi3k alpha, transferase-transferase inhibitor complex, transferase-transferase regulator complex, transferase/transferase regulator
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 110283.45

Authors

Sack, J.S. (deposition date: 2016-12-21, release date: 2017-02-08, Last modification date: 2024-03-06)

Primary citation

Qin, L.Y.,Ruan, Z.,Cherney, R.J.,Dhar, T.G.,Neels, J.,Weigelt, C.A.,Sack, J.S.,Srivastava, A.S.,Cornelius, L.A.,Tino, J.A.,Stefanski, K.,Gu, X.,Xie, J.,Susulic, V.,Yang, X.,Yarde-Chinn, M.,Skala, S.,Bosnius, R.,Goldstein, C.,Davies, P.,Ruepp, S.,Salter-Cid, L.,Bhide, R.S.,Poss, M.A.
Discovery of 7-(3-(piperazin-1-yl)phenyl)pyrrolo[2,1-f][1,2,4]triazin-4-amine derivatives as highly potent and selective PI3K delta inhibitors.
Bioorg. Med. Chem. Lett., 27:855-861, 2017

PubMed Abstract: As demonstrated in preclinical animal models, the disruption of PI3Kδ expression or its activity leads to a decrease in inflammatory and immune responses. Therefore, inhibition of PI3Kδ may provide an alternative treatment for autoimmune diseases, such as RA, SLE, and respiratory ailments. Herein, we disclose the identification of 7-(3-(piperazin-1-yl)phenyl)pyrrolo[2,1-f][1,2,4]triazin-4-amine derivatives as highly potent, selective and orally bioavailable PI3Kδ inhibitors. The lead compound demonstrated efficacy in an in vivo mouse KLH model.

PubMed: 28108251
DOI: 10.1016/j.bmcl.2017.01.016

Experimental method

X-RAY DIFFRACTION (2.4 Å)