Entry Database : PDB / ID : 7ukr Structure visualization Downloads & linksTitle Crystal Structure of SOS1 with MRTX0902, a Potent and Selective Inhibitor of the SOS1:KRAS Protein-Protein Interaction ComponentsSon of sevenless homolog 1 Details Keywords SIGNALING PROTEIN/INHIBITOR / SOS1 / KRAS / RAS / protein-protein interaction / SIGNALING PROTEIN / SIGNALING PROTEIN-INHIBITOR complexFunction / homology Function and homology informationFunction Domain/homology Component
midbrain morphogenesis / regulation of pro-B cell differentiation / vitellogenesis / pericardium morphogenesis / cardiac atrium morphogenesis / heart trabecula morphogenesis / regulation of T cell differentiation in thymus / GTPase complex / positive regulation of small GTPase mediated signal transduction / Interleukin-15 signaling ... midbrain morphogenesis / regulation of pro-B cell differentiation / vitellogenesis / pericardium morphogenesis / cardiac atrium morphogenesis / heart trabecula morphogenesis / regulation of T cell differentiation in thymus / GTPase complex / positive regulation of small GTPase mediated signal transduction / Interleukin-15 signaling / Activation of RAC1 / blood vessel morphogenesis / positive regulation of epidermal growth factor receptor signaling pathway / Regulation of KIT signaling / epidermal growth factor receptor binding / leukocyte migration / regulation of T cell proliferation / NRAGE signals death through JNK / roof of mouth development / eyelid development in camera-type eye / Fc-epsilon receptor signaling pathway / GRB2:SOS provides linkage to MAPK signaling for Integrins / B cell homeostasis / neurotrophin TRK receptor signaling pathway / SOS-mediated signalling / RET signaling / Activated NTRK3 signals through RAS / Activated NTRK2 signals through RAS / hair follicle development / SHC1 events in ERBB4 signaling / Signalling to RAS / fibroblast growth factor receptor signaling pathway / SHC-related events triggered by IGF1R / Activated NTRK2 signals through FRS2 and FRS3 / Role of LAT2/NTAL/LAB on calcium mobilization / Interleukin receptor SHC signaling / Signal attenuation / SHC-mediated cascade:FGFR3 / MET activates RAS signaling / Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants / Signaling by PDGFRA extracellular domain mutants / Schwann cell development / SHC-mediated cascade:FGFR2 / SHC-mediated cascade:FGFR4 / Signaling by FGFR4 in disease / SHC-mediated cascade:FGFR1 / Erythropoietin activates RAS / FRS-mediated FGFR3 signaling / Signaling by FLT3 ITD and TKD mutants / FRS-mediated FGFR2 signaling / FRS-mediated FGFR4 signaling / Signaling by FGFR3 in disease / Tie2 Signaling / FRS-mediated FGFR1 signaling / Signaling by FGFR2 in disease / GRB2 events in EGFR signaling / SHC1 events in EGFR signaling / RAC1 GTPase cycle / EGFR Transactivation by Gastrin / Signaling by FLT3 fusion proteins / FLT3 Signaling / Signaling by FGFR1 in disease / GRB2 events in ERBB2 signaling / myelination / NCAM signaling for neurite out-growth / SHC1 events in ERBB2 signaling / Downstream signal transduction / Constitutive Signaling by Overexpressed ERBB2 / FCERI mediated Ca+2 mobilization / Insulin receptor signalling cascade / GTPase activator activity / guanyl-nucleotide exchange factor activity / insulin-like growth factor receptor signaling pathway / Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants / molecular condensate scaffold activity / Antigen activates B Cell Receptor (BCR) leading to generation of second messengers / response to ischemia / FCERI mediated MAPK activation / Signaling by ERBB2 TMD/JMD mutants / axon guidance / B cell receptor signaling pathway / Constitutive Signaling by EGFRvIII / Signaling by ERBB2 ECD mutants / Signaling by ERBB2 KD Mutants / epidermal growth factor receptor signaling pathway / multicellular organism growth / Signaling by SCF-KIT / cytokine-mediated signaling pathway / SH3 domain binding / Signaling by CSF1 (M-CSF) in myeloid cells / G alpha (12/13) signalling events / Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants / insulin receptor signaling pathway / DAP12 signaling / regulation of cell population proliferation / RAF/MAP kinase cascade / Potential therapeutics for SARS / Ras protein signal transduction / protein heterodimerization activity / neuronal cell body Similarity search - Function Ras guanine-nucleotide exchange factor, conserved site / Ras Guanine-nucleotide exchange factors domain signature. / RasGEF N-terminal motif / Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal motif / Ras-like guanine nucleotide exchange factor, N-terminal / Ras guanine-nucleotide exchange factors N-terminal domain profile. / Ras-like guanine nucleotide exchange factor / Ras guanine-nucleotide exchange factor, catalytic domain superfamily / Ras guanine nucleotide exchange factor domain superfamily / RasGEF domain ... Ras guanine-nucleotide exchange factor, conserved site / Ras Guanine-nucleotide exchange factors domain signature. / RasGEF N-terminal motif / Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal motif / Ras-like guanine nucleotide exchange factor, N-terminal / Ras guanine-nucleotide exchange factors N-terminal domain profile. / Ras-like guanine nucleotide exchange factor / Ras guanine-nucleotide exchange factor, catalytic domain superfamily / Ras guanine nucleotide exchange factor domain superfamily / RasGEF domain / Ras guanine-nucleotide exchange factors catalytic domain profile. / Guanine nucleotide exchange factor for Ras-like small GTPases / Ras guanine-nucleotide exchange factors catalytic domain / Dbl homology (DH) domain superfamily / RhoGEF domain / Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases / Dbl homology (DH) domain / Dbl homology (DH) domain profile. / PH domain / PH domain profile. / Pleckstrin homology domain. / Pleckstrin homology domain / Histone-fold / PH-like domain superfamily Similarity search - Domain/homologyBiological species Homo sapiens (human)Method X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution : 2.5 Å DetailsAuthors Gunn, R.J. / Lawson, J.D. / Ketcham, J.M. / Marx, M.A. Funding support 1items Details Hide detailsOrganization Grant number Country Not funded
CitationJournal : J.Med.Chem. / Year : 2022Title : Design and Discovery of MRTX0902, a Potent, Selective, Brain-Penetrant, and Orally Bioavailable Inhibitor of the SOS1:KRAS Protein-Protein Interaction.Authors: Ketcham, J.M. / Haling, J. / Khare, S. / Bowcut, V. / Briere, D.M. / Burns, A.C. / Gunn, R.J. / Ivetac, A. / Kuehler, J. / Kulyk, S. / Laguer, J. / Lawson, J.D. / Moya, K. / Nguyen, N. / ... Authors : Ketcham, J.M. / Haling, J. / Khare, S. / Bowcut, V. / Briere, D.M. / Burns, A.C. / Gunn, R.J. / Ivetac, A. / Kuehler, J. / Kulyk, S. / Laguer, J. / Lawson, J.D. / Moya, K. / Nguyen, N. / Rahbaek, L. / Saechao, B. / Smith, C.R. / Sudhakar, N. / Thomas, N.C. / Vegar, L. / Vanderpool, D. / Wang, X. / Yan, L. / Olson, P. / Christensen, J.G. / Marx, M.A. History Deposition Apr 1, 2022 Deposition site : RCSB / Processing site : RCSBRevision 1.0 Jul 27, 2022 Provider : repository / Type : Initial releaseRevision 1.1 Aug 10, 2022 Group : Database references / Category : citation / citation_authorItem : _citation.journal_abbrev / _citation.journal_id_ISSN ... _citation.journal_abbrev / _citation.journal_id_ISSN / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation_author.identifier_ORCID Revision 1.2 Oct 18, 2023 Group : Data collection / Refinement descriptionCategory : chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model
Show all Show less