Drug Information

Drug (ID: DG01669) and It's Reported Resistant Information

• Name: Ganetespib
• Synonyms: Ganetespib; 888216-25-9; Ganetespib (STA-9090); STA-9090; STA9090; STA 9090; UNII-2E8412Y946; 5-[2,4-Dihydroxy-5-(1-methylethyl)phenyl]-2,4-dihydro-4-(1-methyl-1H-indol-5-yl)-3H-1,2,4-triazol-3-one; 2E8412Y946; 3-(2,4-dihydroxy-5-propan-2-ylphenyl)-4-(1-methylindol-5-yl)-1H-1,2,4-triazol-5-one; (5Z)-5-(4-hydroxy-6-oxo-3-propan-2-ylcyclohexa-2,4-dien-1-ylidene)-4-(1-methylindol-5-yl)-1,2,4-triazolidin-3-one; 4-(5-hydroxy-4-(1-methyl-1H-indol-5-yl)-4H-1,2,4-triazol-3-yl)-6-isopropylbenzene-1,3-diol; 5-[2,4-dihydroxy-5-(1-methylethyl)phenyl]-4-(1-methyl-1H-indol-5-yl)-2,4-dihydro-3H- 1,2,4-triazol-3-one; 5-[2,4-Dihydroxy-5-(Propan-2-Yl)phenyl]-4-(1-Methyl-1h-Indol-5-Yl)-2,4-Dihydro-3h-1,2,4-Triazol-3-One; Ganetespib [USAN:INN]; Genetespib; 5-(2,4-Dihydroxy-5-(1-methylethyl)phenyl)-4-(1-methyl-1H-indol-5-yl)-2,4-dihydro-3H- 1,2,4-triazol-3-one; Ganetespib (USAN); Ganetespib,STA-9090; Ganetespib (STA9090); Ganetespib(STA-9090); Ganetespib - STA-9090; SCHEMBL419750; CHEMBL2103879; EX-A250; QCR-148; CHEBI:177770; HMS3654K12; HMS3673E09; AMY16782; AOB87158; BCP22669; 2422AH; BDBM50439621; MFCD22420818; NSC765435; NSC777169; s1159; ZINC43130413; AKOS026750420; AKOS032947228; ZINC109565954; ZINC109565957; CCG-268213; CS-0697; DB12047; NSC-765435; NSC-777169; SB16526; 3-(2,4-dihydroxy-5-isopropyl-phenyl)-4-(1-methyl-indol-5-yl)-5-hydroxy-[1,2,4]triazole; NCGC00346678-01; NCGC00346678-04; AC-32480; AS-35117; HY-15205; BCP0726000115; A4385; FT-0700397; SW220253-1; D10126; STA-9090; STA9090; STA 9090; Q27254612; 3-(2,4-dihydroxy-5-isopropyl-phenyl)-4-(N-methyl-indol-5-yl)-5-hydroxy-[1,2,4]triazole; 2,4-Dihydro-5-[2,4-dihydroxy-5-isopropylphenyl]-4-(1-methyl-1H-indol-5-yl)-3H-1,2,4-triazol-3-one; 3-(2,4-Dihydroxy-5-isopropylphenyl)-4-(1-methyl-1H-indol-5-yl)-1H-1,2,4-triazol-5(4H)-one; 3-[2,4-Dihydroxy-5-(propan-2-yl)phenyl]-4-(1-methyl-1H-indol-5-yl)-4,5-dihydro-1H-1,2,4-triazol-5-one; 3H-1,2,4-Triazol-3-one, 5-(2,4-dihydroxy-5-(1-methylethyl)phenyl)-2,4-dihydro-4-(1- methyl-1H-indol-5-yl)-
• Indication:
  In total 2 Indication(s)
  Multiple myeloma [ICD-11: 2A83]; Phase 3; [1]
  Solid tumour/cancer [ICD-11: 2A00-2F9Z]; Phase 3; [1]
• Target: Heat shock protein 90 alpha (HSP90A); HS90A_HUMAN; [2]
• Formula: 3
• IsoSMILES: CC(C)C1=C(C=C(C(=C1)C2=NNC(=O)N2C3=CC4=C(C=C3)N(C=C4)C)O)O
• InChI: InChI=1S/C20H20N4O3/c1-11(2)14-9-15(18(26)10-17(14)25)19-21-22-20(27)24(19)13-4-5-16-12(8-13)6-7-23(16)3/h4-11,25-26H,1-3H3,(H,22,27)
• InChIKey: RVAQIUULWULRNW-UHFFFAOYSA-N
• PubChem CID: 135564985
• TTD Drug ID: D05BYA
• DrugBank ID: DB12047

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

Solid tumour/cancer [ICD-11: 2A00-2F9Z]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [3]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Complex-indel; p.G776_776delinsVC (c.2326_2328delinsGTATGT)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Sanger cDNA sequencing assay
• Experiment for Drug Resistance: CCK-8 assay

Key Molecule: Cellular tumor antigen p53 (TP53) [1]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.R248Q (c.743G>A)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SkBR3 cells; Breast; Homo sapiens (Human); CVCL_0033
• In Vitro Model: H1975 cells; Lung; Homo sapiens (Human); CVCL_1511
• In Vitro Model: T47D cells; Breast; Homo sapiens (Human); CVCL_0553
• In Vitro Model: ES2 cells; Ovary; Homo sapiens (Human); CVCL_AX39
• In Vitro Model: DU145 cells; Prostate; Homo sapiens (Human); CVCL_0105
• In Vitro Model: MDA-MB-231 cells; Breast; Homo sapiens (Human); CVCL_0062
• In Vitro Model: MDA-46 cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: HOC7 cells; Ascites; Homo sapiens (Human); CVCL_5455
• In Vitro Model: EFO21 cells; Ascites; Homo sapiens (Human); CVCL_0029
• In Vitro Model: COV434 cells; N.A.; Homo sapiens (Human); CVCL_2010
• In Vitro Model: COLO704 cells; Ascites; Homo sapiens (Human); CVCL_1994
• In Vitro Model: HOC7 cells; Ascites; Homo sapiens (Human); CVCL_5455
• In Vivo Model: Athymic (nu/nu) male xenograft mouse model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis; Quantitative PCR analysis
• Experiment for Drug Resistance: CellTiter-blue cell viability assay

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [3]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Duplication; p.Y772_A775 (c.2314_2325)/p.A775_G776insYVMA + p.C805S
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Sanger cDNA sequencing assay
• Experiment for Drug Resistance: CCK-8 assay

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [3]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Duplication; p.Y772_A775 (c.2314_2325)/p.A775_G776insYVMA + p.C805S
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Sanger cDNA sequencing assay
• Experiment for Drug Resistance: CCK-8 assay

Melanoma [ICD-11: 2C30]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [2]

• Sensitive Disease: Melanoma [ICD-11: 2C30.0]
• Molecule Alteration: Missense mutation; p.V600E (c.1799T>A)
• Wild Type Structure: Method: X-ray diffraction; Resolution: 2.55 Å; PDB: 4E26
• Mutant Type Structure: Method: X-ray diffraction; Resolution: 3.20 Å; PDB: 4G9R

RMSD: 1.53; TM score: 0.95765; Amino acid change: V600E

• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: WST-1 cell proliferation assay

Breast cancer [ICD-11: 2C60]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Cellular tumor antigen p53 (TP53) [1]

• Sensitive Disease: Breast adenocarcinoma [ICD-11: 2C60.1]
• Molecule Alteration: Missense mutation; p.R175H (c.524G>A)
• Wild Type Structure: Method: X-ray diffraction; Resolution: 2.37 Å; PDB: 6VR1
• Mutant Type Structure: Method: X-ray diffraction; Resolution: 2.38 Å; PDB: 6VR5

RMSD: 0.18; TM score: 0.89418; Amino acid change: R175H

• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SkBR3 cells; Breast; Homo sapiens (Human); CVCL_0033
• In Vitro Model: H1975 cells; Lung; Homo sapiens (Human); CVCL_1511
• In Vitro Model: T47D cells; Breast; Homo sapiens (Human); CVCL_0553
• In Vitro Model: ES2 cells; Ovary; Homo sapiens (Human); CVCL_AX39
• In Vitro Model: DU145 cells; Prostate; Homo sapiens (Human); CVCL_0105
• In Vitro Model: MDA-MB-231 cells; Breast; Homo sapiens (Human); CVCL_0062
• In Vitro Model: MDA-46 cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: HOC7 cells; Ascites; Homo sapiens (Human); CVCL_5455
• In Vitro Model: EFO21 cells; Ascites; Homo sapiens (Human); CVCL_0029
• In Vitro Model: COV434 cells; N.A.; Homo sapiens (Human); CVCL_2010
• In Vitro Model: COLO704 cells; Ascites; Homo sapiens (Human); CVCL_1994
• In Vitro Model: HOC7 cells; Ascites; Homo sapiens (Human); CVCL_5455
• In Vivo Model: Athymic (nu/nu) male xenograft mouse model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis; Quantitative PCR analysis
• Experiment for Drug Resistance: CellTiter-blue cell viability assay

Key Molecule: Cellular tumor antigen p53 (TP53) [1]

• Sensitive Disease: Breast adenocarcinoma [ICD-11: 2C60.1]
• Molecule Alteration: Missense mutation; p.R280K (c.839G>A)
• Wild Type Structure: Method: X-ray diffraction; Resolution: 2.05 Å; PDB: 2OCJ
• Mutant Type Structure: Method: X-ray diffraction; Resolution: 2.00 Å; PDB: 6FF9

RMSD: 0.29; TM score: 0.99711; Amino acid change: R280K

• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SkBR3 cells; Breast; Homo sapiens (Human); CVCL_0033
• In Vitro Model: H1975 cells; Lung; Homo sapiens (Human); CVCL_1511
• In Vitro Model: T47D cells; Breast; Homo sapiens (Human); CVCL_0553
• In Vitro Model: ES2 cells; Ovary; Homo sapiens (Human); CVCL_AX39
• In Vitro Model: DU145 cells; Prostate; Homo sapiens (Human); CVCL_0105
• In Vitro Model: MDA-MB-231 cells; Breast; Homo sapiens (Human); CVCL_0062
• In Vitro Model: MDA-46 cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: HOC7 cells; Ascites; Homo sapiens (Human); CVCL_5455
• In Vitro Model: EFO21 cells; Ascites; Homo sapiens (Human); CVCL_0029
• In Vitro Model: COV434 cells; N.A.; Homo sapiens (Human); CVCL_2010
• In Vitro Model: COLO704 cells; Ascites; Homo sapiens (Human); CVCL_1994
• In Vitro Model: HOC7 cells; Ascites; Homo sapiens (Human); CVCL_5455
• In Vivo Model: Athymic (nu/nu) male xenograft mouse model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis; Quantitative PCR analysis
• Experiment for Drug Resistance: CellTiter-blue cell viability assay

Key Molecule: Cellular tumor antigen p53 (TP53) [1]

• Sensitive Disease: Breast adenocarcinoma [ICD-11: 2C60.1]
• Molecule Alteration: Missense mutation; p.L194F (c.580C>T)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SkBR3 cells; Breast; Homo sapiens (Human); CVCL_0033
• In Vitro Model: H1975 cells; Lung; Homo sapiens (Human); CVCL_1511
• In Vitro Model: T47D cells; Breast; Homo sapiens (Human); CVCL_0553
• In Vitro Model: ES2 cells; Ovary; Homo sapiens (Human); CVCL_AX39
• In Vitro Model: DU145 cells; Prostate; Homo sapiens (Human); CVCL_0105
• In Vitro Model: MDA-MB-231 cells; Breast; Homo sapiens (Human); CVCL_0062
• In Vitro Model: MDA-46 cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: HOC7 cells; Ascites; Homo sapiens (Human); CVCL_5455
• In Vitro Model: EFO21 cells; Ascites; Homo sapiens (Human); CVCL_0029
• In Vitro Model: COV434 cells; N.A.; Homo sapiens (Human); CVCL_2010
• In Vitro Model: COLO704 cells; Ascites; Homo sapiens (Human); CVCL_1994
• In Vitro Model: HOC7 cells; Ascites; Homo sapiens (Human); CVCL_5455
• In Vivo Model: Athymic (nu/nu) male xenograft mouse model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis; Quantitative PCR analysis
• Experiment for Drug Resistance: CellTiter-blue cell viability assay

Ovarian cancer [ICD-11: 2C73]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Cellular tumor antigen p53 (TP53) [1]

• Sensitive Disease: Ovarian cancer [ICD-11: 2C73.0]
• Molecule Alteration: Missense mutation; p.S241F (c.722C>T)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SkBR3 cells; Breast; Homo sapiens (Human); CVCL_0033
• In Vitro Model: H1975 cells; Lung; Homo sapiens (Human); CVCL_1511
• In Vitro Model: T47D cells; Breast; Homo sapiens (Human); CVCL_0553
• In Vitro Model: ES2 cells; Ovary; Homo sapiens (Human); CVCL_AX39
• In Vitro Model: DU145 cells; Prostate; Homo sapiens (Human); CVCL_0105
• In Vitro Model: MDA-MB-231 cells; Breast; Homo sapiens (Human); CVCL_0062
• In Vitro Model: MDA-46 cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: HOC7 cells; Ascites; Homo sapiens (Human); CVCL_5455
• In Vitro Model: EFO21 cells; Ascites; Homo sapiens (Human); CVCL_0029
• In Vitro Model: COV434 cells; N.A.; Homo sapiens (Human); CVCL_2010
• In Vitro Model: COLO704 cells; Ascites; Homo sapiens (Human); CVCL_1994
• In Vitro Model: HOC7 cells; Ascites; Homo sapiens (Human); CVCL_5455
• In Vivo Model: Athymic (nu/nu) male xenograft mouse model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis; Quantitative PCR analysis
• Experiment for Drug Resistance: CellTiter-blue cell viability assay

References

• Ref 1: Improving survival by exploiting tumour dependence on stabilized mutant p53 for treatmentNature. 2015 Jul 16;523(7560):352-6. doi: 10.1038/nature14430. Epub 2015 May 25.
• Ref 2: Overcoming acquired BRAF inhibitor resistance in melanoma via targeted inhibition of Hsp90 with ganetespibMol Cancer Ther. 2014 Feb;13(2):353-63. doi: 10.1158/1535-7163.MCT-13-0481. Epub 2014 Jan 7.
• Ref 3: Activity of a novel HER2 inhibitor, poziotinib, for HER2 exon 20 mutations in lung cancer and mechanism of acquired resistance: An in vitro studyLung Cancer. 2018 Dec;126:72-79. doi: 10.1016/j.lungcan.2018.10.019. Epub 2018 Oct 17.