Drug Information

Drug (ID: DG01557) and It's Reported Resistant Information

• Name: WYE-125132
• Synonyms: 1144068-46-1; WYE-125132; WYE125132; WYE-132; N-[4-[1-(1,4-Dioxaspiro[4.5]dec-8-yl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-N'-methylurea; WYE 125132; CHEMBL601661; WYE-125132 (WYE-132); 1-(4-(4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-1-(1,4-dioxaspiro[4.5]decan-8-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl)phenyl)-3-methylurea; 1-[4-(1-{1,4-dioxaspiro[4.5]decan-8-yl}-4-{8-oxa-3-azabicyclo[3.2.1]octan-3-yl}pyrazolo[3,4-d]pyrimidin-6-yl)phenyl]-3-methylurea; N-[4-[1-(1,4-Dioxaspiro[4.5]dec-8-yl)-4-(8-oxa-3-azabicyclo[3.2.1]-oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-N'-methylurea; 1-[4-[1-(1,4-dioxaspiro[4.5]decan-8-yl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-methylurea; SCHEMBL54355; MLS006011010; WYE132; CHEBI:91364; DTXSID70649521; HMS3265K19; HMS3265K20; HMS3265L19; HMS3265L20; HMS3656J09; AOB87378; BCP02227; EX-A2183; BDBM50306633; s2661; AKOS025405223; CCG-269851; CS-0066; SB19261; NCGC00346635-01; NCGC00346635-10; AC-31521; HY-10044; SMR004702808; Urea, N-[4-[1-(1,4-dioxaspiro[4.5]dec-8-yl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]; WYE-132; WYE-125132; SW219487-1; WYE-125132 - WYE-132; A25638; J-003090; J-523341; BRD-A45498368-001-02-2; Q27163233; 1-[4-[1-(1,4-dioxaspiro[4.5]decan-8-yl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-6-pyrazolo[3,4-d]pyrimidinyl]phenyl]-3-methylurea; N-[1-(1.4-dioxaspiro[4.5]dec-8-yl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3.4-d]pyrimidin-6-yl]phenyl]-N-methyl-urea; N-{4-[1-(1,4-Dioxaspiro[4.5]decan-8-yl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}-N'-methylurea
• Indication:
  In total 1 Indication(s)
  Solid tumour/cancer [ICD-11: 2A00-2F9Z]; Phase 2; [1]
• Target: PI3-kinase gamma (PIK3CG); PK3CG_HUMAN; [1]
• Formula: 4
• IsoSMILES: CNC(=O)NC1=CC=C(C=C1)C2=NC3=C(C=NN3C4CCC5(CC4)OCCO5)C(=N2)N6CC7CCC(C6)O7
• InChI: InChI=1S/C27H33N7O4/c1-28-26(35)30-18-4-2-17(3-5-18)23-31-24(33-15-20-6-7-21(16-33)38-20)22-14-29-34(25(22)32-23)19-8-10-27(11-9-19)36-12-13-37-27/h2-5,14,19-21H,6-13,15-16H2,1H3,(H2,28,30,35)
• InChIKey: QLHHRYZMBGPBJG-UHFFFAOYSA-N
• PubChem CID: 25260757

Type(s) of Resistant Mechanism of This Drug

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-02: Benign/in-situ/malignant neoplasm

Breast cancer [ICD-11: 2C60]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: PI3-kinase alpha (PIK3CA) [1]

• Molecule Alteration: Missense mutation; p.E545K (c.1633G>A)
• Sensitive Disease: Breast adenocarcinoma [ICD-11: 2C60.1]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: H1975 cells; Lung; Homo sapiens (Human); CVCL_1511
• In Vitro Model: LNCaP cells; Prostate; Homo sapiens (Human); CVCL_0395
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: MDA-MB-231 cells; Breast; Homo sapiens (Human); CVCL_0062
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vitro Model: Hela cells; Cervix uteri; Homo sapiens (Human); CVCL_0030
• In Vitro Model: H460 cells; Lung; Homo sapiens (Human); CVCL_0459
• In Vitro Model: MG63 cells; Bone marrow; Homo sapiens (Human); CVCL_0426
• In Vitro Model: MDA-MB-468 cells; Breast; Homo sapiens (Human); CVCL_0419
• In Vitro Model: H157 cells; Lung; Homo sapiens (Human); CVCL_2458
• In Vitro Model: BT549 cells; Breast; Homo sapiens (Human); CVCL_1092
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• In Vitro Model: 786-O cells; Kidney; Homo sapiens (Human); CVCL_1051
• In Vitro Model: U87MG cells; Brain; Homo sapiens (Human); CVCL_GP63
• In Vitro Model: A498 cells; Kidney; Homo sapiens (Human); CVCL_1056
• In Vitro Model: MDA-MB-361 cells; Breast; Homo sapiens (Human); CVCL_0620
• In Vitro Model: Rat1 cells; Whole embryo; Rattus norvegicus (Rat); CVCL_0492
• Experiment for Molecule Alteration: Western blotting analysis
• Mechanism Description: The missense mutation p.E545K (c.1633G>A) in gene PIK3CA cause the sensitivity of WYE-125132 by unusual activation of pro-survival pathway

References

• Ref 1: Beyond rapalog therapy: preclinical pharmacology and antitumor activity of WYE-125132, an ATP-competitive and specific inhibitor of mTORC1 and mTORC2Cancer Res. 2010 Jan 15;70(2):621-31. doi: 10.1158/0008-5472.CAN-09-2340. Epub 2010 Jan 12.