Title Avapritinib-based SAR studies unveil a binding pocket in KIT and PDGFRA. Journal, issue, pages Nat Commun , Vol. 15, Page 63-63, Year 2024Publish date Jul 11, 2023 (structure data deposition date) AuthorsTeuber, A. / Schulz, T. / Fletcher, B.S. / Gontla, R. / Muhlenberg, T. / Zischinsky, M.L. / Niggenaber, J. / Weisner, J. / Kleinbolting, S.B. / Lategahn, J. ...Teuber, A. / Schulz, T. / Fletcher, B.S. / Gontla, R. / Muhlenberg, T. / Zischinsky, M.L. / Niggenaber, J. / Weisner, J. / Kleinbolting, S.B. / Lategahn, J. / Sievers, S. / Muller, M.P. / Bauer, S. / Rauh, D. External links Nat Commun / PubMed:38167404Methods X-ray diffraction Resolution 1.5 - 2.6 Å Structure data PDB-8pq9 : Structure viewer c-KIT kinase domain in complex with avapritinib Method : X-RAY DIFFRACTION / Resolution : 1.7 Å
PDB-8pqa : Structure viewer c-KIT kinase domain in complex with avapritinib derivative 4 Method : X-RAY DIFFRACTION / Resolution : 1.65 Å
PDB-8pqb : Structure viewer c-KIT kinase domain in complex with avapritinib derivative 8 Method : X-RAY DIFFRACTION / Resolution : 1.87 Å
PDB-8pqc : Structure viewer c-KIT kinase domain in complex with avapritinib derivative 9 Method : X-RAY DIFFRACTION / Resolution : 1.77 Å
PDB-8pqd : Structure viewer c-KIT kinase domain in complex with avapritinib derivative 10 Method : X-RAY DIFFRACTION / Resolution : 1.5 Å
PDB-8pqe : Structure viewer c-KIT kinase domain in complex with avapritinib derivative 11 Method : X-RAY DIFFRACTION / Resolution : 2.0 Å
PDB-8pqf : Structure viewer c-KIT kinase domain in complex with avapritinib derivative 12 Method : X-RAY DIFFRACTION / Resolution : 1.9 Å
PDB-8pqg : Structure viewer c-KIT T670I mutated kinase domain in complex with avapritinibMethod : X-RAY DIFFRACTION / Resolution : 2.4 Å
PDB-8pqh : Structure viewer PDGFRA T674I mutant kinase domain in complex with avapritinibMethod : X-RAY DIFFRACTION / Resolution : 2.5 Å
PDB-8pqi : Structure viewer PDGFRA T674I mutant kinase domain in complex with avapritinib derivative 9 Method : X-RAY DIFFRACTION / Resolution : 2.6 Å
PDB-8pqj : Structure viewer PDGFRA wild-type kinase domainMethod : X-RAY DIFFRACTION / Resolution : 1.82 Å
PDB-8pqk : Structure viewerAPO crystal structure of PDGFRA-T674I kinase domainMethod : X-RAY DIFFRACTION / Resolution : 2.0 Å
Chemicals ChemComp-9JI : Structure viewer (1~{S})-1-(4-fluorophenyl)-1-[2-[4-[6-(1-methylpyrazol-4-yl)pyrrolo[2,1-f][1,2,4]triazin-4-yl]piperazin-1-yl]pyrimidin-5-yl]ethanamine
ChemComp-98A : Structure viewer 6-(1-methylpyrazol-4-yl)-4-(4-pyrimidin-2-ylpiperazin-1-yl)pyrrolo[2,1-f][1,2,4]triazine
ChemComp-9XO : Structure viewer (1~{S})-1-(4-fluorophenyl)-~{N},~{N}-dimethyl-1-[2-[4-[6-(1-methylpyrazol-4-yl)pyrrolo[2,1-f][1,2,4]triazin-4-yl]piperazin-1-yl]pyrimidin-5-yl]ethanamine
ChemComp-9OO : Structure viewer (1~{S})-~{N}-ethyl-1-(4-fluorophenyl)-1-[2-[4-[6-(1-methylpyrazol-4-yl)pyrrolo[2,1-f][1,2,4]triazin-4-yl]piperazin-1-yl]pyrimidin-5-yl]ethanamine
ChemComp-9VV : Structure viewer ~{N}-[(1~{S})-1-(4-fluorophenyl)-1-[2-[4-[6-(1-methylpyrazol-4-yl)pyrrolo[2,1-f][1,2,4]triazin-4-yl]piperazin-1-yl]pyrimidin-5-yl]ethyl]ethanamide
ChemComp-EDO : Structure viewer 1,2-ETHANEDIOL / Ethylene glycol
ChemComp-9WU : Structure viewer ~{N}-[(1~{S})-1-(4-fluorophenyl)-1-[2-[4-[6-(1-methylpyrazol-4-yl)pyrrolo[2,1-f][1,2,4]triazin-4-yl]piperazin-1-yl]pyrimidin-5-yl]ethyl]prop-2-enamide
ChemComp-9KI : Structure viewer methyl ~{N}-[(1~{S})-1-(4-fluorophenyl)-1-[2-[4-[6-(1-methylpyrazol-4-yl)pyrrolo[2,1-f][1,2,4]triazin-4-yl]piperazin-1-yl]pyrimidin-5-yl]ethyl]carbamate
ChemComp-PEG : Structure viewer DI(HYDROXYETHYL)ETHER / Diethylene glycol
Source homo sapiens (human) Keywords TRANSFERASE / c-KIT protein kinase / avapritinib / inhibitor / tyrosine kinase / transmembrane receptor / stem cell factor / SCF / stem cell factor receptor / GIST / gastrointestinal stromal tumors / P10721 / c-KIT / protein kinase / gatekeeper mutant / gatekeeper mutation / PDGFRA protein kinase / platelet-derived growth factor receptor alpha / PDGF / platelet-derived growth factor / P16234 / PDGFRA / platelet-derived growth factor receptor / cancer