Entry Database : PDB / ID : 8exo Structure visualization Downloads & linksTitle Crystal structure of PI3K-alpha in complex with compound 19 ComponentsPhosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform Details Keywords CELL CYCLE / PI3K / drug / inhibitor / cancer / oncologyFunction / homology Function and homology informationFunction Domain/homology Component
response to muscle inactivity / negative regulation of actin filament depolymerization / response to L-leucine / regulation of actin filament organization / response to butyrate / IRS-mediated signalling / cellular response to hydrostatic pressure / autosome genomic imprinting / PI3K events in ERBB4 signaling / Activated NTRK2 signals through PI3K ... response to muscle inactivity / negative regulation of actin filament depolymerization / response to L-leucine / regulation of actin filament organization / response to butyrate / IRS-mediated signalling / cellular response to hydrostatic pressure / autosome genomic imprinting / PI3K events in ERBB4 signaling / Activated NTRK2 signals through PI3K / positive regulation of protein localization to membrane / Activated NTRK3 signals through PI3K / negative regulation of fibroblast apoptotic process / phosphatidylinositol 3-kinase complex, class IB / vasculature development / Signaling by cytosolic FGFR1 fusion mutants / regulation of cellular respiration / cardiac muscle cell contraction / phosphatidylinositol 3-kinase complex, class IA / anoikis / phosphatidylinositol 3-kinase complex / Nephrin family interactions / Signaling by LTK in cancer / PI3K events in ERBB2 signaling / relaxation of cardiac muscle / Costimulation by the CD28 family / Signaling by LTK / 1-phosphatidylinositol-4-phosphate 3-kinase activity / 1-phosphatidylinositol-4,5-bisphosphate 3-kinase activity / MET activates PI3K/AKT signaling / PI3K/AKT activation / phosphatidylinositol-4,5-bisphosphate 3-kinase / vascular endothelial growth factor signaling pathway / phosphatidylinositol 3-kinase / phosphatidylinositol-3-phosphate biosynthetic process / negative regulation of macroautophagy / 1-phosphatidylinositol-3-kinase activity / Signaling by ALK / GAB1 signalosome / PI-3K cascade:FGFR3 / Erythropoietin activates Phosphoinositide-3-kinase (PI3K) / PI-3K cascade:FGFR2 / protein kinase activator activity / response to dexamethasone / PI-3K cascade:FGFR4 / PI-3K cascade:FGFR1 / CD28 dependent PI3K/Akt signaling / Synthesis of PIPs at the plasma membrane / phosphatidylinositol-mediated signaling / phosphatidylinositol phosphate biosynthetic process / negative regulation of anoikis / intercalated disc / RET signaling / Interleukin-3, Interleukin-5 and GM-CSF signaling / insulin receptor substrate binding / regulation of multicellular organism growth / PI3K Cascade / endothelial cell migration / positive regulation of TOR signaling / RAC2 GTPase cycle / Role of phospholipids in phagocytosis / Role of LAT2/NTAL/LAB on calcium mobilization / Interleukin receptor SHC signaling / adipose tissue development / Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants / Signaling by PDGFRA extracellular domain mutants / phagocytosis / positive regulation of lamellipodium assembly / Signaling by FGFR4 in disease / cardiac muscle contraction / energy homeostasis / Signaling by FLT3 ITD and TKD mutants / Signaling by FGFR3 in disease / Tie2 Signaling / GPVI-mediated activation cascade / Signaling by FGFR2 in disease / T cell costimulation / response to muscle stretch / Signaling by FLT3 fusion proteins / RAC1 GTPase cycle / FLT3 Signaling / Signaling by FGFR1 in disease / phosphatidylinositol 3-kinase/protein kinase B signal transduction / phosphorylation / Downstream signal transduction / positive regulation of smooth muscle cell proliferation / insulin-like growth factor receptor signaling pathway / Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants / liver development / Constitutive Signaling by EGFRvIII / response to activity / Signaling by ERBB2 ECD mutants / Signaling by ERBB2 KD Mutants / epidermal growth factor receptor signaling pathway / Regulation of signaling by CBL / cellular response to glucose stimulus / regulation of protein phosphorylation / Signaling by SCF-KIT / cellular response to insulin stimulus / platelet activation Similarity search - Function PI3Kalpha, catalytic domain / PI3-kinase family, p85-binding domain / PI3-kinase family, p85-binding domain / Phosphatidylinositol 3-kinase, adaptor-binding domain / Phosphatidylinositol 3-kinase adaptor-binding (PI3K ABD) domain profile. / PI3-kinase family, Ras-binding domain / Phosphatidylinositol 3-kinase Ras-binding (PI3K RBD) domain / PI3-kinase family, ras-binding domain / Phosphatidylinositol 3-kinase Ras-binding (PI3K RBD) domain profile. / Phosphoinositide 3-kinase C2 ... PI3Kalpha, catalytic domain / PI3-kinase family, p85-binding domain / PI3-kinase family, p85-binding domain / Phosphatidylinositol 3-kinase, adaptor-binding domain / Phosphatidylinositol 3-kinase adaptor-binding (PI3K ABD) domain profile. / PI3-kinase family, Ras-binding domain / Phosphatidylinositol 3-kinase Ras-binding (PI3K RBD) domain / PI3-kinase family, ras-binding domain / Phosphatidylinositol 3-kinase Ras-binding (PI3K RBD) domain profile. / Phosphoinositide 3-kinase C2 / Phosphoinositide 3-kinase, region postulated to contain C2 domain / C2 phosphatidylinositol 3-kinase-type domain / C2 phosphatidylinositol 3-kinase (PI3K)-type domain profile. / Phosphoinositide 3-kinase, accessory (PIK) domain superfamily / Phosphoinositide 3-kinase family, accessory domain (PIK domain) / Phosphoinositide 3-kinase family, accessory domain (PIK domain) / Phosphoinositide 3-kinase, accessory (PIK) domain / Phosphatidylinositol kinase / PIK helical domain profile. / Phosphatidylinositol 3- and 4-kinases signature 1. / Phosphatidylinositol 3/4-kinase, conserved site / Phosphatidylinositol 3- and 4-kinases signature 2. / Phosphatidylinositol 3-/4-kinase, catalytic domain superfamily / Phosphoinositide 3-kinase, catalytic domain / Phosphatidylinositol 3- and 4-kinase / Phosphatidylinositol 3- and 4-kinases catalytic domain profile. / Phosphatidylinositol 3-/4-kinase, catalytic domain / C2 domain superfamily / Armadillo-type fold / Ubiquitin-like domain superfamily / Protein kinase-like domain superfamily Similarity search - Domain/homologyBiological species Homo sapiens (human)Method X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution : 2.46 Å DetailsAuthors Kiefer, J.R. / Eigenbrot, C. / Staben, S.T. / Hanan, E.J. / Wallweber, H.J.A. / Ultsch, M. / Braun, M.G. / Friedman, L.S. / Purkey, H.E. Funding support 1items Details Hide detailsOrganization Grant number Country Not funded
CitationJournal : J.Med.Chem. / Year : 2022Title : Discovery of GDC-0077 (Inavolisib), a Highly Selective Inhibitor and Degrader of Mutant PI3K alpha.Authors: Hanan, E.J. / Braun, M.G. / Heald, R.A. / MacLeod, C. / Chan, C. / Clausen, S. / Edgar, K.A. / Eigenbrot, C. / Elliott, R. / Endres, N. / Friedman, L.S. / Gogol, E. / Gu, X.H. / Thibodeau, R. ... Authors : Hanan, E.J. / Braun, M.G. / Heald, R.A. / MacLeod, C. / Chan, C. / Clausen, S. / Edgar, K.A. / Eigenbrot, C. / Elliott, R. / Endres, N. / Friedman, L.S. / Gogol, E. / Gu, X.H. / Thibodeau, R.H. / Jackson, P.S. / Kiefer, J.R. / Knight, J.D. / Nannini, M. / Narukulla, R. / Pace, A. / Pang, J. / Purkey, H.E. / Salphati, L. / Sampath, D. / Schmidt, S. / Sideris, S. / Song, K. / Sujatha-Bhaskar, S. / Ultsch, M. / Wallweber, H. / Xin, J. / Yeap, S. / Young, A. / Zhong, Y. / Staben, S.T. History Deposition Oct 25, 2022 Deposition site : RCSB / Processing site : RCSBRevision 1.0 Nov 30, 2022 Provider : repository / Type : Initial releaseRevision 1.1 Dec 14, 2022 Group : Database references / Category : citation / citation_authorItem : _citation.journal_abbrev / _citation.pdbx_database_id_DOI ... _citation.journal_abbrev / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title Revision 1.2 Jan 4, 2023 Group : Database references / Category : citation / citation_authorItem : _citation.journal_volume / _citation.page_first ... _citation.journal_volume / _citation.page_first / _citation.page_last / _citation_author.identifier_ORCID Revision 1.3 May 22, 2024 Group : Data collection / Category : chem_comp_atom / chem_comp_bond
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