Target Binding Site Detail
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T80276 | Target Info | |||
| Target Name | PI3-kinase alpha (PIK3CA) | ||||
| Synonyms | p110alpha; Serine/threonine protein kinase PIK3CA; PtdIns3kinase subunit p110alpha; PtdIns3kinase subunit alpha; PtdIns-3-kinase subunit p110-alpha; PtdIns-3-kinase subunit alpha; Phosphoinositide3kinase catalytic alpha polypeptide; Phosphoinositide-3-kinase catalytic alpha polypeptide; Phosphatidylinositol 4,5bisphosphate 3kinase catalytic subunit alpha isoform; Phosphatidylinositol 4,5bisphosphate 3kinase 110 kDa catalytic subunit alpha; Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform; Phosphatidylinositol 4,5-bisphosphate 3-kinase 110 kDa catalytic subunit alpha; PI3kinase subunit alpha; PI3Kalpha; PI3K-alpha; PI3-kinase subunit alpha | ||||
| Target Type | Successful Target | ||||
| Gene Name | PIK3CA | ||||
| Biochemical Class | Kinase | ||||
| UniProt ID | |||||
| Ligand General Information | Top | ||||
|---|---|---|---|---|---|
| Ligand Name | N,N-Dimethyl-4-[(6r)-6-Methyl-5-(1h-Pyrrolo[2,3-B]pyridin-4-Yl)-4,5,6,7-Tetrahydropyrazolo[1,5-A]pyrazin-3-Yl]benzenesulfonamide | Ligand Info | |||
| Canonical SMILES | CC1CN2C(=C(C=N2)C3=CC=C(C=C3)S(=O)(=O)N(C)C)CN1C4=C5C=CNC5=NC=C4 | ||||
| InChI | 1S/C22H24N6O2S/c1-15-13-28-21(14-27(15)20-9-11-24-22-18(20)8-10-23-22)19(12-25-28)16-4-6-17(7-5-16)31(29,30)26(2)3/h4-12,15H,13-14H2,1-3H3,(H,23,24)/t15-/m1/s1 | ||||
| InChIKey | UGAYOLUDSWRLMK-OAHLLOKOSA-N | ||||
| PubChem Compound ID | 86306050 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 4WAF Crystal Structure of a novel tetrahydropyrazolo[1,5-a]pyrazine in an engineered PI3K alpha | ||||||
| Method | X-ray diffraction | Resolution | 2.39 Å | Mutation | Yes | [1] |
| PDB Sequence |
PPRPSSGELW
11 GIHLMPPRIL21 VECLLPNGMI31 VTLECLREAT41 LITIKHELFK51 EARKYPLHQL 61 LQDESSYIFV71 SVTQEAEREE81 FFDETRRLCD91 LRLFQPFLKV101 IEPVGNREEK 111 ILNREIGFAI121 GMPVCEFDMV131 KDPEVQDFRR141 NILNVCKEAV151 DLRDLNSPHS 161 RAMYVYPPNV171 ESSPELPKHI181 YNKLDKGQII191 VVIWVIVSPN201 NDKQKYTLKI 211 NHDCVPEQVI221 AEAIRKKTRL234 SSEQLKLCVL244 EYQGKYILKV254 CGCDEYFLEK 264 YPLSQYKYIR274 SCIMLGRMPN284 LMLMAKESLY294 SQLPMDCFTM304 PSYSRRISST 324 KSLWVINSAL334 RIKILCATYV344 NVNIRDIDKI354 YVRTGIYHGG364 EPLCDNVNTQ 374 RVPCSNPRWN384 EWLNYDIYIP394 DLPRAARLCL404 SICSVKGRKG414 AKEEHCPLAW 424 GNINLFDYTD434 TLVSGKMALN444 LWPVPHGLED454 LLNPIGVTGS464 NPNKETPCLE 474 LEFDWFSSVV484 KFPDMSVIEE494 HANWSVREND527 KEQLKAISTR537 DPLSEITEQE 547 KDFLWSHRHY557 CVTIPEILPK567 LLLSVKWNSR577 DEVAQMYCLV587 KDWPPIKPEQ 597 AMELLDCNYP607 DPMVRGFAVR617 CLEKYLTDDK627 LSQYLIQLVQ637 VLKYEQYLDN 647 LLVRFLLKKA657 LTNQRIGHFF667 FWHLKSEMHN677 KTVSQRFGLL687 LESYCRACGM 697 YLKHLNRQVE707 AMEKLINLTD717 ILKQEKKDET727 QKVQMKFLVE737 QMRRPDFMDA 747 LQGFLSPLNP757 AHQLGNLRLE767 ECRIMSSAKR777 PLWLNWENPD787 IMSELLFQNN 797 EIMFKNGDDL807 RQDMLTLQII817 RIMENIWQNQ827 GLDLRMLPYG837 CLSIGDCVGL 847 IEVVRNSHTI857 MQIQCKGFNS874 HTLHQWLKDK884 NKGEIYDAAI894 DLFTRSCAGY 904 CVATFILGIG914 DRHNSNIMVK924 DDGQLVHIDF934 GHFLDHKKKK944 FGYKRERVPF 954 VLTQDFLIVI964 SKGAQECTKT974 REFERFQEMC984 YKAYLAIRQH994 ANLFINLFSM 1004 MLGSGMPELQ1014 SFDDIAYIRK1024 TLALDKTEQE1034 ALEYFMKQMN1044 DAHHGGWTTK 1054 MDWIFHT
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| PDB ID: 5UKJ The co-structure of N,N-dimethyl-4-[(6R)-6-methyl-5-(1H-pyrrolo[2,3- b]pyridin-4-yl)-4,5,6,7-tetrahydropyrazolo[1,5- a]pyrazin-3-yl]benzenesulfonamide and a rationally designed PI3K-alpha mutant that mimics ATR | ||||||
| Method | X-ray diffraction | Resolution | 2.80 Å | Mutation | Yes | [2] |
| PDB Sequence |
PPRPSSGELW
11 GIHLMPPRIL21 VECLLPNGMI31 VTLECLREAT41 LITIKHELFK51 EARKYPLHQL 61 LQDESSYIFV71 SVTQEAEREE81 FFDETRRLCD91 LRLFQPFLKV101 IEPVGNREEK 111 ILNREIGFAI121 GMPVCEFDMV131 KDPEVQDFRR141 NILNVCKEAV151 DLRDLNSPHS 161 RAMYVYPPNV171 ESSPELPKHI181 YNKLDKGQII191 VVIWVIVSPN201 NDKQKYTLKI 211 NHDCVPEQVI221 AEAIRKKEQL239 KLCVLEYQGK249 YILKVCGCDE259 YFLEKYPLSQ 269 YKYIRSCIML279 GRMPNLMLMA289 KESLYSQLPM299 DCFTMPSYSR309 RISTSTKSLW 328 VINSALRIKI338 LCATYVNVNI348 RDIDKIYVRT358 GIYHGGEPLC368 DNVNTQRVPC 378 SNPRWNEWLN388 YDIYIPDLPR398 AARLCLSICS408 VKGRKGAKEE418 HCPLAWGNIN 428 LFDYTDTLVS438 GKMALNLWPV448 PHGLEDLLNP458 IGVTGSNPNK468 ETPCLELEFD 478 WFSSVVKFPD488 MSVIEEHANW498 SVSRELREND527 KEQLKAISTR537 DPLSEITEQE 547 KDFLWSHRHY557 CVTIPEILPK567 LLLSVKWNSR577 DEVAQMYCLV587 KDWPPIKPEQ 597 AMELLDCNYP607 DPMVRGFAVR617 CLEKYLTDDK627 LSQYLIQLVQ637 VLKYEQYLDN 647 LLVRFLLKKA657 LTNQRIGHFF667 FWHLKSEMHN677 KTVSQRFGLL687 LESYCRACGM 697 YLKHLNRQVE707 AMEKLINLTD717 ILKQEKKDET727 QKVQMKFLVE737 QMRRPDFMDA 747 LQGFLSPLNP757 AHQLGNLRLE767 ECEIMSSAKR777 PLKLNWENPD787 IMSELLFQNN 797 IIMFKNGDDL807 RQDMLTLQII817 RIMENIWQNQ827 GLDLRMLPYG837 CLSIGDCVGL 847 IEWVRNSHTI857 MQIQCKQFNS874 HTLHQWLKDK884 NKGEIYDAAI894 DLFTRSCAGY 904 CVATFILGIG914 DRHNSNIMVK924 DDGQLVHIDF934 GHFLDHKKKK944 FGYKRERVPF 954 VLTQDFLIVI964 SKGAQECTKT974 REFERFQEMC984 YKAYLAIRQH994 ANLFINLFSM 1004 MLGSGMPELQ1014 SFDDIAYIRK1024 TLALDKTEQE1034 ALEYFMKQMN1044 DAHHGGWTT |
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Structure-Based Drug Design of Novel Potent and Selective Tetrahydropyrazolo[1,5-a]pyrazines as ATR Inhibitors. ACS Med Chem Lett. 2014 Nov 20;6(1):37-41. | ||||
| REF 2 | Rationally Designed PI3KAlpha Mutants to Mimic ATR and Their Use to Understand Binding Specificity of ATR Inhibitors. J Mol Biol. 2017 Jun 2;429(11):1684-1704. | ||||
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