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]
• Drug Resistance Disease(s):
  Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (2 diseases)
  Acute leukaemias of ambiguous lineage [ICD-11: 2A61]; [2]
  Acute lymphocytic leukemia [ICD-11: 2B33]; [2]
  Disease(s) with Resistance Information Validated by in-vivo Model for This Drug (1 diseases)
  Esophageal cancer [ICD-11: 2B70]; [3]
• Target: Bacterial Cell membrane (Bact CM); NOUNIPROTAC; [4]
• 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

  ADTT: Aberration of the Drug's Therapeutic Target

  EADR: Epigenetic Alteration of DNA, RNA or Protein

  IDUE: Irregularity in Drug Uptake and Drug Efflux

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Their Corresponding Diseases

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

Myeloproliferative neoplasm [ICD-11: 2A22]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Tyrosine-protein kinase JAK2 (JAK3) [5]

• Sensitive Disease: Myeloproliferative neoplasm [ICD-11: 2A22.0]
• Molecule Alteration: Mutation; V617F+L902Q
• 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 sequencing assay
• Experiment for Drug Resistance: MTS-based assay
• Mechanism Description: These results indicate that these mutants are dependent on the HSP90 for their folding. To know that downregulation of JAK2 protein leads to the decrease of cell proliferation, we performed biochemical analysis on these mutant JAK2 cells and found that ruxolitinib-resistant variants are sensitive towards 17-AAG and treatment of the cells with 17-AAG leads to the downregulation of JAK2 protein and decrease of STAT5 activation. This study shows that HSP90 inhibitors are potent against ruxolitinib-resistant variants through the JAK2 degradation and provides the rationale for clinical evaluation of potent HSP90 inhibitors in genetic resistance driven by JAK2 inhibitors.

Key Molecule: Tyrosine-protein kinase JAK2 (JAK3) [5]

• Sensitive Disease: Myeloproliferative neoplasm [ICD-11: 2A22.0]
• Molecule Alteration: Mutation; V617F+L902Q+E1028K
• 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 sequencing assay
• Experiment for Drug Resistance: MTS-based assay
• Mechanism Description: These results indicate that these mutants are dependent on the HSP90 for their folding. To know that downregulation of JAK2 protein leads to the decrease of cell proliferation, we performed biochemical analysis on these mutant JAK2 cells and found that ruxolitinib-resistant variants are sensitive towards 17-AAG and treatment of the cells with 17-AAG leads to the downregulation of JAK2 protein and decrease of STAT5 activation. This study shows that HSP90 inhibitors are potent against ruxolitinib-resistant variants through the JAK2 degradation and provides the rationale for clinical evaluation of potent HSP90 inhibitors in genetic resistance driven by JAK2 inhibitors.

Key Molecule: Tyrosine-protein kinase JAK2 (JAK3) [5]

• Sensitive Disease: Myeloproliferative neoplasm [ICD-11: 2A22.0]
• Molecule Alteration: Mutation; V617F+L902Q+R938E
• 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 sequencing assay
• Experiment for Drug Resistance: MTS-based assay
• Mechanism Description: These results indicate that these mutants are dependent on the HSP90 for their folding. To know that downregulation of JAK2 protein leads to the decrease of cell proliferation, we performed biochemical analysis on these mutant JAK2 cells and found that ruxolitinib-resistant variants are sensitive towards 17-AAG and treatment of the cells with 17-AAG leads to the downregulation of JAK2 protein and decrease of STAT5 activation. This study shows that HSP90 inhibitors are potent against ruxolitinib-resistant variants through the JAK2 degradation and provides the rationale for clinical evaluation of potent HSP90 inhibitors in genetic resistance driven by JAK2 inhibitors.

Key Molecule: Tyrosine-protein kinase JAK2 (JAK3) [5]

• Sensitive Disease: Myeloproliferative neoplasm [ICD-11: 2A22.0]
• Molecule Alteration: Mutation; V617F+L902Q+R947Q
• 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 sequencing assay
• Experiment for Drug Resistance: MTS-based assay
• Mechanism Description: These results indicate that these mutants are dependent on the HSP90 for their folding. To know that downregulation of JAK2 protein leads to the decrease of cell proliferation, we performed biochemical analysis on these mutant JAK2 cells and found that ruxolitinib-resistant variants are sensitive towards 17-AAG and treatment of the cells with 17-AAG leads to the downregulation of JAK2 protein and decrease of STAT5 activation. This study shows that HSP90 inhibitors are potent against ruxolitinib-resistant variants through the JAK2 degradation and provides the rationale for clinical evaluation of potent HSP90 inhibitors in genetic resistance driven by JAK2 inhibitors.

Key Molecule: Tyrosine-protein kinase JAK2 (JAK3) [5]

• Sensitive Disease: Myeloproliferative neoplasm [ICD-11: 2A22.0]
• Molecule Alteration: Mutation; V617F+L983F
• 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 sequencing assay
• Experiment for Drug Resistance: MTS-based assay
• Mechanism Description: These results indicate that these mutants are dependent on the HSP90 for their folding. To know that downregulation of JAK2 protein leads to the decrease of cell proliferation, we performed biochemical analysis on these mutant JAK2 cells and found that ruxolitinib-resistant variants are sensitive towards 17-AAG and treatment of the cells with 17-AAG leads to the downregulation of JAK2 protein and decrease of STAT5 activation. This study shows that HSP90 inhibitors are potent against ruxolitinib-resistant variants through the JAK2 degradation and provides the rationale for clinical evaluation of potent HSP90 inhibitors in genetic resistance driven by JAK2 inhibitors.

Key Molecule: Tyrosine-protein kinase JAK2 (JAK3) [5]

• Sensitive Disease: Myeloproliferative neoplasm [ICD-11: 2A22.0]
• Molecule Alteration: Mutation; V617F+L983F+Q959H
• 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 sequencing assay
• Experiment for Drug Resistance: MTS-based assay
• Mechanism Description: These results indicate that these mutants are dependent on the HSP90 for their folding. To know that downregulation of JAK2 protein leads to the decrease of cell proliferation, we performed biochemical analysis on these mutant JAK2 cells and found that ruxolitinib-resistant variants are sensitive towards 17-AAG and treatment of the cells with 17-AAG leads to the downregulation of JAK2 protein and decrease of STAT5 activation. This study shows that HSP90 inhibitors are potent against ruxolitinib-resistant variants through the JAK2 degradation and provides the rationale for clinical evaluation of potent HSP90 inhibitors in genetic resistance driven by JAK2 inhibitors.

Key Molecule: Tyrosine-protein kinase JAK2 (JAK3) [5]

• Sensitive Disease: Myeloproliferative neoplasm [ICD-11: 2A22.0]
• Molecule Alteration: Mutation; V617F+Y931C
• 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 sequencing assay
• Experiment for Drug Resistance: MTS-based assay
• Mechanism Description: These results indicate that these mutants are dependent on the HSP90 for their folding. To know that downregulation of JAK2 protein leads to the decrease of cell proliferation, we performed biochemical analysis on these mutant JAK2 cells and found that ruxolitinib-resistant variants are sensitive towards 17-AAG and treatment of the cells with 17-AAG leads to the downregulation of JAK2 protein and decrease of STAT5 activation. This study shows that HSP90 inhibitors are potent against ruxolitinib-resistant variants through the JAK2 degradation and provides the rationale for clinical evaluation of potent HSP90 inhibitors in genetic resistance driven by JAK2 inhibitors.

Acute leukaemias of ambiguous lineage [ICD-11: 2A61]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Multidrug resistance protein 1 (ABCB1) [2]

• Resistant Disease: bcr-abl1/leukemia [ICD-11: 2A61]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: K562 cells; Blood; Homo sapiens (Human); CVCL_0004
• Experiment for Drug Resistance: Colony forming unit assay
• Mechanism Description: Chronic long-term exposure to the clinically advanced HSP90i PU-H71 (Zelavespib) led to copy number gain and mutation (p.S164F) of the HSP90AA1 gene, and HSP90 overexpression. In contrast, acquired resistance toward other tested HSP90i (Tanespimycin and Coumermycin A1) was attained by MDR1 efflux pump overexpression. Remarkably, combined CDK7 and HSP90 inhibition display synergistic activity against therapy-resistant BCR-ABL1+ patient leukemia cells via blocking pro-survival HSR and HSP90 overexpression, providing a novel strategy to avoid the emergence of resistance against treatment with HSP90i alone.

Acute lymphocytic leukemia [ICD-11: 2B33]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: ATP-dependent translocase ABCB1 (ABCB1) [2]

• Resistant Disease: Acute lymphoblastic leukemia [ICD-11: 2B33.3]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: K562 cells; Blood; Homo sapiens (Human); CVCL_0004
• In Vitro Model: kCL22 cells; Pleural effusion; Homo sapiens (Human); CVCL_2091
• In Vitro Model: Sup-B15 cells; Bone marrow; Homo sapiens (Human); CVCL_0103
• In Vivo Model: NSG mice model; Mus musculus
• Experiment for Molecule Alteration: Immunofluorescence staining assay; Western blot assay
• Experiment for Drug Resistance: Colony forming unit assay; Caspase 3/7 Glo assay
• Mechanism Description: Tanespimycin and Coumermycin A1 was attained by MDR1 efflux pump overexpression.

Esophageal cancer [ICD-11: 2B70]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Histone H1.4 (H1-4) [3]

• Resistant Disease: Oesophagus adenocarcinoma [ICD-11: 2B70.0]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vivo Model: Patient-derived esophageal cancer model; Homo sapiens
• Experiment for Molecule Alteration: Gene expression analysis
• Experiment for Drug Resistance: Drug sensitivity analysis
• Mechanism Description: The results of drug sensitivity of risk genes showed that the high expression of HIST1H1E made tumor cells resistant to trametinib, selumetinib, RDEA119, Docetaxel and 17-AAG. The high expression of UBE2C makes tumor cells resistant to masitinib. The low expression of ERO1B makes the EC more sensitive to FK866

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) [6]

• Sensitive Disease: Colorectal cancer [ICD-11: 2B91.1]
• Molecule Alteration: Missense mutation; p.R248Q (c.743G>A)
• 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) [4]

• Sensitive Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Molecule Alteration: IF-insertion; p.T1151_L1152 (c.3453_3454)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: H3122 cells; Lung; Homo sapiens (Human); CVCL_5160
• Experiment for Molecule Alteration: Western blot 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) [4]

• Sensitive Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Molecule Alteration: Missense mutation; p.G1202R (c.3604G>A)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: H3122 cells; Lung; Homo sapiens (Human); CVCL_5160
• Experiment for Molecule Alteration: Western blot 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) [7]

• Sensitive Disease: Melanoma [ICD-11: 2C30.0]
• Molecule Alteration: Missense mutation; p.G13D (c.38G>A)
• Wild Type Structure: Method: X-ray diffraction; Resolution: 1.01 Å; PDB: 6P0Z
• Mutant Type Structure: Method: X-ray diffraction; Resolution: 1.40 Å; PDB: 8BLR

RMSD: 1.48; TM score: 0.8385; Amino acid change: G13D

• 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]

• 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

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: Co-targeting HSP90 alpha and CDK7 overcomes resistance against HSP90 inhibitors in BCR-ABL1+ leukemia cells. Cell Death Dis. 2023 Dec 6;14(12):799.
• Ref 3: Establishment of prognostic risk model and drug sensitivity based on prognostic related genes of esophageal cancer. Sci Rep. 2022 May 14;12(1):8008.
• Ref 4: 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 5: Type II mode of JAK2 inhibition and destabilization are potential therapeutic approaches against the ruxolitinib resistance driven myeloproliferative neoplasms. Front Oncol. 2024 Jul 18;14:1430833.
• Ref 6: 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 7: 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.