Drug Information

Drug (ID: DG01494) and It's Reported Resistant Information

• Name: Tanespimycin
• Synonyms: Tanespimycin; 75747-14-7; 17-AAG; 17-(Allylamino)-17-demethoxygeldanamycin; 17-(Allylamino)geldanamycin; 17AAG; NSC-330507; 17-Allylaminogeldanamycin; KOS-953; Cp 127374; NSC 330507; 17-Demethoxy-17-allylamino geldanamycin; UNII-4GY0AVT3L4; CHEBI:64153; 17-AAG (Tanespimycin); BMS-722782; 4GY0AVT3L4; MFCD04973892; NCGC00163424-01; 17-N-allylamino-17-demethoxygeldanamycin; 17-demethoxy-17-(2-propenylamino)geldanamycin; [(4E,6Z,8S,9S,10E,12S,13R,14S,16R)-13-hydroxy-8,14-dimethoxy-4,10,12,16-tetramethyl-3,20,22-trioxo-19-(prop-2-enylamino)-2-azabicyclo[16.3.1]docosa-1(21),4,6,10,18-pentaen-9-yl] carbamate; Geldanamycin, 17-demethoxy-17-(2-propenylamino)-; NSC330507; (4E,6Z,8S,9S,10E,12S,13R,14S,16R)-13-hydroxy-8,14-dimethoxy-4,10,12,16-tetramethyl-3,20,22-trioxo-19-(prop-2-en-1-ylamino)-2-azabicyclo[16.3.1]docosa-1(21),4,6,10,18-pentaen-9-yl carbamate; [(3S,5S,6R,7S,8E,10R,11S,12E,14E)-6-Hydroxy-5,11-dimethoxy-3,7,9,15-tetramethyl-16,20,22-trioxo-21-(prop-2-enylamino)-17-azabicyclo[16.3.1]docosa-8,12,14,18,21-pentaen-10-yl] carbamate; Tanespimycin [USAN:INN]; KOS 953; tanespimycina; tanespimycine; tanespimycinum; CCRIS 9401; 17-Demethoxy-17-allylaminogeldanamycin; C31H43N3O8; Tanespimycin (USAN); Tanespimycin (17-AAG); Geldanamycin, 17-(Allylamino)-17-demethoxy-; DSSTox_CID_26352; DSSTox_RID_81555; DSSTox_GSID_46352; BSPBio_001434; SCHEMBL2604976; DTXSID5046352; SCHEMBL13037468; SCHEMBL16226295; CHEBI:94756; CNF-101; CNF1010; HMS1361H16; HMS1791H16; HMS1989H16; HMS3402H16; (4E,6Z,8S,9S,10E,12S,13R,14S,16R)-19-(allylamino)-13-hydroxy-8,14-dimethoxy-4,10,12,16-tetramethyl-3,20,22-trioxo-2-azabicyclo[16.3.1]docosa-1(21),4,6,10,18-pentaen-9-yl carbamate; CNF-1010; EX-A4668; NSC-330507D; Tox21_112054; BDBM50008057; s1141; AKOS024456643; ZINC100014666; BCP9000064; CCG-208039; CS-0161; DB05134; NSC-704057; IDI1_033904; NCGC00163424-02; NCGC00163424-04; NCGC00163424-05; NCGC00163424-06; NCGC00163424-07; Allylamino-17-demethoxygeldanamycin, 17-; HY-10211; Geldanamycin, des-O-methyl-17-allylamino-; CAS-75747-14-7; CP-127374; Geldanamycin, 17-allylamino-17-demethoxy-; X7553; D06650; 747A147; Geldanamycin,17-demethoxy-17-(2-propenylamino)-; J-504153; BRD-K81473043-001-03-9; BRD-K81473043-001-08-8; 17-(Allylamino)-17-demethoxygeldanamycin, >=98% (HPLC), solid; (4E,6Z,8S,9S,10E,12S,13R,14S,16R)-13-Hydroxy-8,14-dimethoxy-4,10,12,16- tetramethyl-3,20,22-trioxo-19-(prop-2-enylamino)-2-azabicyclo(16.3.1)docosa- 1(21),4,6,10,18-penten-9-yl carbamate; [(3R,5S,6R,7S,8E,10S,11S,12Z,14E)-21-(allylamino)-6-hydroxy-5,11-dimethoxy-3,7,9,15-tetramethyl-16,20,22-trioxo-17-azabicyclo[16.3.1]docosa-1(21),8,12,14,18-pentaen-10-yl] carbamate; 17-AAG; ; ; 17-(Allylamino)-17-demethoxy-geldanamycin; ; ; [(3R,5S,6R,7S,8E,10S,11S,12Z,14E)-6-Hydroxy-5,11-dimethoxy-3,7,9,15-tetramethyl-16,20,22-trioxo-21-(prop-2-enylamino)-17-azabicyclo[16.3.1]docosa-1(21),8,12,14,18-pentaen-10-yl] carbamate
• Indication:
  In total 2 Indication(s)
  Multi-drug resistant tuberculosis [ICD-11: MG50-MG52]; Phase 2; [1]
  Mycobacterium infection [ICD-11: 1B10-1B21]; Phase 2; [1]
• Target: Bacterial Cell membrane (Bact CM); NOUNIPROTAC; [2]
• Formula: 7
• IsoSMILES: C[C@H]1C[C@@H]([C@@H]([C@H](/C=C(/[C@@H]([C@H](/C=C\\C=C(\\C(=O)NC2=CC(=O)C(=C(C1)C2=O)NCC=C)/C)OC)OC(=O)N)\\C)C)O)OC
• InChI: InChI=1S/C31H43N3O8/c1-8-12-33-26-21-13-17(2)14-25(41-7)27(36)19(4)15-20(5)29(42-31(32)39)24(40-6)11-9-10-18(3)30(38)34-22(28(21)37)16-23(26)35/h8-11,15-17,19,24-25,27,29,33,36H,1,12-14H2,2-7H3,(H2,32,39)(H,34,38)/b11-9-,18-10+,20-15+/t17-,19+,24+,25+,27-,29+/m1/s1
• InChIKey: AYUNIORJHRXIBJ-TXHRRWQRSA-N
• PubChem CID: 6505803
• ChEBI ID: CHEBI:64153
• TTD Drug ID: D0S3NU
• DrugBank ID: DB05134

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

Colorectal cancer [ICD-11: 2B91]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Cellular tumor antigen p53 (TP53) [3]

• Molecule Alteration: Missense mutation; p.R248Q (c.743G>A)
• Sensitive Disease: Colorectal cancer [ICD-11: 2B91.1]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: JAKT2/STAT3 signaling pathway; Inhibition; hsa04030
• In Vitro Model: HT29 Cells; Colon; Homo sapiens (Human); CVCL_A8EZ
• In Vitro Model: SW480 cells; Colon; Homo sapiens (Human); CVCL_0546
• In Vitro Model: H1299 cells; Lung; Homo sapiens (Human); CVCL_0060
• In Vitro Model: SW1116 cells; Colon; Homo sapiens (Human); CVCL_0544
• In Vitro Model: LS1034 cells; Colon; Homo sapiens (Human); CVCL_1382
• In Vitro Model: SW48 cells; Colon; Homo sapiens (Human); CVCL_1724
• In Vitro Model: Colo320 cells; Colon; Homo sapiens (Human); CVCL_1989
• In Vitro Model: SW837 cells; Colon; Homo sapiens (Human); CVCL_1729
• In Vitro Model: DLD-1 cells; Colon; Homo sapiens (Human); CVCL_0248
• In Vitro Model: SW1463 cells; Rectum; Homo sapiens (Human); CVCL_1718
• In Vivo Model: C57BL/6 mouse model; Mus musculus
• Experiment for Molecule Alteration: BCA protein assay; SDS-PAGE assay
• Experiment for Drug Resistance: Scratch assay; Transwell migration assay; Fluorescent in situ hybridization assay
• Mechanism Description: The most common p53 mutant R248Q (mutp53) enhances Stat3 activation by binding to Stat3 and displacing SHP2 in colorectal cancer cells. Reduction of mutp53 genetically or by using the HSP90 inhibitor 17AAG reduces Stat3 signaling and the growth of mutp53-driven tumors.

Lung cancer [ICD-11: 2C25]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: ALK tyrosine kinase receptor (ALK) [2]

• Molecule Alteration: IF-insertion; p.T1151_L1152 (c.3453_3454)
• Sensitive Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: H3122 cells; Lung; Homo sapiens (Human); CVCL_5160
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: The if-insertion p.T1151_L1152 (c.3453_3454) in gene ALK cause the sensitivity of Tanespimycin by unusual activation of pro-survival pathway.

Key Molecule: ALK tyrosine kinase receptor (ALK) [2]

• Molecule Alteration: Missense mutation; p.G1202R (c.3604G>A)
• Sensitive Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: H3122 cells; Lung; Homo sapiens (Human); CVCL_5160
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: The missense mutation p.G1202R (c.3604G>A) in gene ALK cause the sensitivity of Tanespimycin by unusual activation of pro-survival pathway

Melanoma [ICD-11: 2C30]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: GTPase Nras (NRAS) [4]

• Molecule Alteration: Missense mutation; p.G13D (c.38G>A)
• Sensitive Disease: Melanoma [ICD-11: 2C30.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Human melanoma tissue; N.A.
• Mechanism Description: The missense mutation p.G13D (c.38G>A) in gene NRAS cause the sensitivity of Tanespimycin by unusual activation of pro-survival pathway

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]

• Molecule Alteration: Missense mutation; p.L194F (c.580C>T)
• Sensitive Disease: Breast adenocarcinoma [ICD-11: 2C60.1]
• 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 blotting 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: Mechanisms of acquired crizotinib resistance in ALK-rearranged lung Cancers. Sci Transl Med. 2012 Feb 8;4(120):120ra17. doi: 10.1126/scitranslmed.3003316. Epub 2012 Jan 25.
• Ref 3: Therapeutic Ablation of Gain-of-Function Mutant p53 in Colorectal Cancer Inhibits Stat3-Mediated Tumor Growth and InvasionCancer Cell. 2018 Aug 13;34(2):298-314.e7. doi: 10.1016/j.ccell.2018.07.004.
• Ref 4: BRAF and NRAS mutations in melanoma: potential relationships to clinical response to HSP90 inhibitorsMol Cancer Ther. 2008 Apr;7(4):737-9. doi: 10.1158/1535-7163.MCT-08-0145. Epub 2008 Mar 28.