Drug Information

Drug (ID: DG01591) and It's Reported Resistant Information

• Name: Taselisib
• Synonyms: Taselisib; GDC-0032; 1282512-48-4; GDC 0032; 2-(4-(2-(1-isopropyl-3-methyl-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-9-yl)-1H-pyrazol-1-yl)-2-methylpropanamide; GDC0032; Taselisib (GDC0032); UNII-L08J2O299M; RG7604; RG-7604; CHEMBL2387080; L08J2O299M; RG 7604; Taselisib [INN]; 2-Methyl-2-(4-{2-[3-Methyl-1-(Propan-2-Yl)-1h-1,2,4-Triazol-5-Yl]-5,6-Dihydroimidazo[1,2-D][1,4]benzoxazepin-9-Yl}-1h-Pyrazol-1-Yl)propanamide; Taselisib [USAN:INN]; TaselisibGDC-0032; Taselisib (USAN/INN); Taselisib (GDC-0032); GTPL7794; SCHEMBL1485247; DTXSID00155842; SYN1202; HMS3674G19; AMY39941; BCP09253; EX-A1581; BDBM50434806; MFCD26142641; NSC777425; NSC800985; s7103; ZINC68267049; AKOS026750303; CCG-269338; CS-1817; DB12108; GDC-0032, Taselisib; RG-7604; NSC-777425; NSC-800985; SB16576; NCGC00387039-02; 2-methyl-2-[4-[2-(5-methyl-2-propan-2-yl-1,2,4-triazol-3-yl)-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepin-9-yl]pyrazol-1-yl]propanamide; AC-32794; AS-10662; BG166285; HY-13898; QC-11626; D11774; J-690119; Q27088940; 1H-Pyrazole-1-acetamide, 4-[5,6-dihydro-2-[3-methyl-1-(1-methylethyl)-1H-1,2,4-triazol-5-yl]imidazo[1,2-d][1,4]benzoxazepin-9-yl]-alpha,alpha-dimethyl-; 2-(4-(2-(1-isopropyl-3-methyl-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-9-yl)-1H-pyrazol-1-yl)-2-methylpropanamide(GDC-0032); 3-({[(3R,5R)-3-Butyl-3-ethyl-7-methoxy-1,1-dioxido-5-phenyl-2,3,4,5-tetrahydro-1,4-benzothiazepin-8-yl]methyl}amino)pentanedioic aci d; 4-[5,6-Dihydro-2-[3-methyl-1-(1-methylethyl)-1H-1,2,4-triazol-5-yl]imidazo[1,2-d][1,4]benzoxazepin-9-yl]-; A,; A-dimethyl-1H-pyrazole-1-acetamide
• Indication:
  In total 1 Indication(s)
  Solid tumour/cancer [ICD-11: 2A00-2F9Z]; Phase 3; [1]
• Target: Serine/threonine-protein kinase ATR (FRP1); ATR_HUMAN; [1]
• Formula: 5
• IsoSMILES: CC1=NN(C(=N1)C2=CN3CCOC4=C(C3=N2)C=CC(=C4)C5=CN(N=C5)C(C)(C)C(=O)N)C(C)C
• InChI: InChI=1S/C24H28N8O2/c1-14(2)32-22(27-15(3)29-32)19-13-30-8-9-34-20-10-16(6-7-18(20)21(30)28-19)17-11-26-31(12-17)24(4,5)23(25)33/h6-7,10-14H,8-9H2,1-5H3,(H2,25,33)
• InChIKey: BEUQXVWXFDOSAQ-UHFFFAOYSA-N
• PubChem CID: 51001932
• TTD Drug ID: D0G0BJ
• DrugBank ID: DB12108

Type(s) of Resistant Mechanism of This Drug

  ADTT: Aberration of the Drug's Therapeutic Target

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Their Corresponding Diseases

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

Lung cancer [ICD-11: 2C25]

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.H1047X (c.3139_3141)
• Sensitive Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: PI3K signaling pathway; Inhibition; hsa04151
• In Vitro Model: KPL-4 cells; Breast; Homo sapiens (Human); CVCL_5310
• In Vivo Model: SCID beige mouse PDX model; Mus musculus

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.H1047R (c.3140A>G)
• Sensitive Disease: Breast adenocarcinoma [ICD-11: 2C60.1]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: PI3K signaling pathway; Inhibition; hsa04151
• In Vitro Model: KPL-4 cells; Breast; Homo sapiens (Human); CVCL_5310
• In Vivo Model: SCID beige mouse PDX model; Mus musculus

Head and neck cancer [ICD-11: 2D42]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: PI3-kinase alpha (PIK3CA) [2]

• Molecule Alteration: Missense mutation; p.H1047R (c.3140A>G)
• Sensitive Disease: Head and neck squamous cell carcinoma [ICD-11: 2D42.1]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: FaDu cells; Pharynx; Homo sapiens (Human); CVCL_1218
• In Vitro Model: SCC25 cells; Oral; Homo sapiens (Human); CVCL_1682
• In Vitro Model: SCC4 cells; Tongue; Homo sapiens (Human); CVCL_1684
• In Vitro Model: SCC9 cells; Tongue; Homo sapiens (Human); CVCL_1685
• In Vitro Model: SCC15 cells; Tongue; Homo sapiens (Human); CVCL_1681
• In Vitro Model: UPCI-SCC-90 cells; Tongue; Homo sapiens (Human); CVCL_1899
• In Vitro Model: UPCI-SCC-154 cells; Tongue; Homo sapiens (Human); CVCL_2230
• In Vitro Model: UM-SCC-47 cells; Tongue; Homo sapiens (Human); CVCL_7759
• In Vitro Model: UM-SCC-104 cells; Cervical lymph node; Homo sapiens (Human); CVCL_7712
• In Vitro Model: UD-SCC-2 cells; Neck; Homo sapiens (Human); CVCL_E325
• In Vitro Model: SNU46 cells; Larynx; Homo sapiens (Human); CVCL_5063
• In Vitro Model: SNU cells; Stomach; Homo sapiens (Human); CVCL_0099
• In Vitro Model: HSC-4 cells; Cervical lymph node; Homo sapiens (Human); CVCL_1289
• In Vitro Model: HSC-3 cells; Cervical lymph node; Homo sapiens (Human); CVCL_1288
• In Vitro Model: HSC-2 cells; Cervical lymph node; Homo sapiens (Human); CVCL_1287
• In Vitro Model: Detroit 562 cells; Pleural effusion; Homo sapiens (Human); CVCL_1171
• In Vitro Model: Cal-33 cells; Tongue; Homo sapiens (Human); CVCL_1108
• In Vitro Model: BICR-31 cells; Tongue; Homo sapiens (Human); CVCL_2312
• In Vitro Model: BICR-22 cells; Lymph node; Homo sapiens (Human); CVCL_2310
• In Vitro Model: BICR-18 cells; Lymph Node; Homo sapiens (Human); CVCL_2309
• In Vitro Model: BICR-16 cells; Tongue; Homo sapiens (Human); CVCL_2308
• In Vitro Model: 93-VU-147T cells; Oral cavity; Homo sapiens (Human); CVCL_L895
• In Vivo Model: Nu/Nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Crystal violet staining assay

References

• Ref 1: Phase I Dose-Escalation Study of Taselisib, an Oral PI3K Inhibitor, in Patients with Advanced Solid TumorsCancer Discov. 2017 Jul;7(7):704-715. doi: 10.1158/2159-8290.CD-16-1080. Epub 2017 Mar 22.
• Ref 2: Taselisib (GDC-0032), a Potent Beta-Sparing Small Molecule Inhibitor of PI3K, Radiosensitizes Head and Neck Squamous Carcinomas Containing Activating PIK3CA AlterationsClin Cancer Res. 2016 Apr 15;22(8):2009-19. doi: 10.1158/1078-0432.CCR-15-2245. Epub 2015 Nov 20.