Drug Information

Drug (ID: DG01668) and It's Reported Resistant Information

• Name: AUY922
• Synonyms: Luminespib; NVP-AUY922; 747412-49-3; AUY922; VER-52296; AUY-922; 5-(2,4-dihydroxy-5-isopropylphenyl)-N-ethyl-4-(4-(morpholinomethyl)phenyl)isoxazole-3-carboxamide; AUY922 (NVP-AUY922); Luminespib (NVP-AUY922); UNII-C6V1DAR5EB; Luminespib (AUY-922 ); VER 52296; NVP-AUY 922; C6V1DAR5EB; Luminespib (AUY-922, NVP-AUY922); 5-[2,4-DIHYDROXY-5-ISOPROPYLPHENYL]-N-ETHYL-4-[4-(4-MORPHOLINYLMETHYL)PHENYL]-3-ISOXAZOLECARBOXAMIDE; CHEMBL3900791; CHEBI:83656; 5-(2,4-dihydroxy-5-isopropyl-phenyl)-4-(4-morpholin-4-ylmethyl-phenyl)-isoxazole-3-carboxylic acid ethylamide; 5-[2,4-Dihydroxy-5-(1-methylethyl)phenyl]-N-ethyl-4-[4-(4-morpholinylmethyl)phenyl]-3-isoxazolecarboxamide; 5-[2,4-Dihydroxy-5-(1-Methylethyl)phenyl]-N-Ethyl-4-[4-(Morpholin-4-Ylmethyl)phenyl]isoxazole-3-Carboxamide; Luminespib [USAN:INN]; NVR-AUY 922; Isoxazole, 40f; 2GJ; VER-52296/NVP-AUY922; Luminespib (USAN/INN); Luminespib; NVP-AUY922; NVP-AUY922-NX; MLS006011081; NVP-AUY-922; SCHEMBL892205; CHEMBL252164; GTPL9261; SCHEMBL2682235; AUY922,NVP-AUY922; LUMINESPIB(NVP-AUY922); NVP-AUY922, LUMINESPIB; BDBM20926; CHEBI:91422; EX-A611; QCR-179; BCPP000145; HMS3295K23; HMS3654C15; AOB87330; AUY922 - NVP-AUY922; BCP01827; BDBM50274536; MFCD14635361; NSC755762; s1069; ZINC14974931; AKOS015966502; AKOS026750297; ZINC100015656; ZINC109565971; BCP9001007; CCG-264804; CS-0136; NSC-755762; SB16640; NCGC00247878-01; NCGC00387853-03; 5-(2,4-dihydroxy-5-propan-2-ylphenyl)-N-ethyl-4-[4-(morpholin-4-ylmethyl)phenyl]-1,2-oxazole-3-carboxamide; AC-33144; AS-17014; HY-10215; SMR004702869; A9562; FT-0700359; SW219319-1; X7556; CAS:747412-49-3;NVP-AUY922; D10646; 412D493; J-516600; BRD-K41859756-001-01-9; Q10859697; Q27082304; Q27163272; AUY922; VER-52296; AUY 922; VER 52296; AUY-922; VER-52296; 5-(2,4-dihydroxy-5-isopropylphenyl)-N-ethyl-4-[4-(morpholin-4-ylmethyl)phenyl]-1,2-oxazole-3-carboxamide; 5-[2,4-dihydroxy-5-(propan-2-yl)phenyl]-N-ethyl-4-[4-(morpholin-4-ylmethyl)phenyl]-1,2-oxazole-3-carboxamide; AUY-922; ; ; NVP-AUY922; ; ; VER-52296; ; ; (5Z)-N-Ethyl-5-(4-hydroxy-6-oxo-3-propan-2-ylcyclohexa-2,4-dien-1-ylidene)-4-[4-(morpholin-4-ylmethyl)phenyl]-2H-1,2-oxazole-3-carboxamide; N-ethyl-5-(4-hydroxy-6-oxo-3-propan-2-yl-1-cyclohexa-2,4-dienylidene)-4-[4-(4-morpholinylmethyl)phenyl]-2H-isoxazole-3-carboxamide
• Indication:
  In total 1 Indication(s)
  Bacterial infection [ICD-11: 1A00-1C4Z]; Phase 2; [1]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
  Lung cancer [ICD-11: 2C25]; [2]
  Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (1 diseases)
  Hematologic cancer [ICD-11: MG24]; [1]
• Target: Bacterial 70S ribosomal RNA (Bact 70S rRNA); NOUNIPROTAC; [2]
• Formula: 7
• IsoSMILES: CCNC(=O)C1=NOC(=C1C2=CC=C(C=C2)CN3CCOCC3)C4=CC(=C(C=C4O)O)C(C)C
• InChI: InChI=1S/C26H31N3O5/c1-4-27-26(32)24-23(18-7-5-17(6-8-18)15-29-9-11-33-12-10-29)25(34-28-24)20-13-19(16(2)3)21(30)14-22(20)31/h5-8,13-14,16,30-31H,4,9-12,15H2,1-3H3,(H,27,32)
• InChIKey: NDAZATDQFDPQBD-UHFFFAOYSA-N
• PubChem CID: 135539077
• ChEBI ID: CHEBI:83656
• TTD Drug ID: D0Q8NJ
• INTEDE ID: DR00742
• DrugBank ID: DB11881

Type(s) of Resistant Mechanism of This Drug

  EADR: Epigenetic Alteration of DNA, RNA or Protein

  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

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Epidermal growth factor receptor (EGFR) [3]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: IF-insertion; p.A763_Y764insFQEA (c.2290_2291insTTCAAGAGGCAT)
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: EGFR signaling pathway; Inhibition; hsa01521
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Promega assay
• Mechanism Description: EGFR exon 20 insertion mutants associate with the heat shock protein 90 (Hsp90) chaperone system. The non-geldanamycin Hsp90 inhibitor luminespib (formerly AUY922) degrades EGFR exon 20 mutations, downstream targets and induces apoptosis.

Key Molecule: Epidermal growth factor receptor (EGFR) [3]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: IF-insertion; p.Y764_V765insHH (c.2292_2293insCATCAT)
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: EGFR signaling pathway; Inhibition; hsa01521
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Promega assay
• Mechanism Description: EGFR exon 20 insertion mutants associate with the heat shock protein 90 (Hsp90) chaperone system. The non-geldanamycin Hsp90 inhibitor luminespib (formerly AUY922) degrades EGFR exon 20 mutations, downstream targets and induces apoptosis.

Key Molecule: Epidermal growth factor receptor (EGFR) [3]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Duplication; p.S768_D770 (c.2302_2310)
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: EGFR signaling pathway; Inhibition; hsa01521
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Promega assay
• Mechanism Description: EGFR exon 20 insertion mutants associate with the heat shock protein 90 (Hsp90) chaperone system. The non-geldanamycin Hsp90 inhibitor luminespib (formerly AUY922) degrades EGFR exon 20 mutations, downstream targets and induces apoptosis.

Key Molecule: Epidermal growth factor receptor (EGFR) [3]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: IF-insertion; p.P772_H773insGNP (c.2316_2317insGGTAACCCT)
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: EGFR signaling pathway; Inhibition; hsa01521
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Promega assay
• Mechanism Description: EGFR exon 20 insertion mutants associate with the heat shock protein 90 (Hsp90) chaperone system. The non-geldanamycin Hsp90 inhibitor luminespib (formerly AUY922) degrades EGFR exon 20 mutations, downstream targets and induces apoptosis.

Key Molecule: Epidermal growth factor receptor (EGFR) [3]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Duplication; p.H773 (c.2317_2319)
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: EGFR signaling pathway; Inhibition; hsa01521
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Promega assay
• Mechanism Description: EGFR exon 20 insertion mutants associate with the heat shock protein 90 (Hsp90) chaperone system. The non-geldanamycin Hsp90 inhibitor luminespib (formerly AUY922) degrades EGFR exon 20 mutations, downstream targets and induces apoptosis.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [4]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Duplication; p.Y772_A775 (c.2314_2325)
• 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) [4]

• 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: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [4]

• 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

Hematologic cancer [ICD-11: 2B3Z]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Tyrosine-protein kinase JAK2 (JAK3) [1]

• Resistant Disease: Hematologic Cancer [ICD-11: MG24.Y]
• Molecule Alteration: Missense mutation; p.R867Q (c.2600G>A)
• 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

Lung cancer [ICD-11: 2C25]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

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

• Resistant Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Molecule Alteration: Missense mutation; p.C1156Y (c.3467G>A)
• Wild Type Structure: Method: X-ray diffraction; Resolution: 1.75 Å; PDB: 3AOX
• Mutant Type Structure: Method: X-ray diffraction; Resolution: 1.60 Å; PDB: 5A9U

RMSD: 0.78; TM score: 0.9838; Amino acid change: C1156Y

• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Biochemical and Structural StudiesCo-crystallization analysis
• Experiment for Drug Resistance: CellTiter-Glo assay

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Epidermal growth factor receptor (EGFR) [3]

• Sensitive Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Molecule Alteration: IF-insertion; p.A763_Y764insFQEA (c.2290_2291insTTCAAGAGGCAT)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: PC9 cells; Lung; Homo sapiens (Human); CVCL_B260
• In Vitro Model: NCI-H1975 cells; Lung; Homo sapiens (Human); CVCL_1511
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: NCI-H3255 cells; Lung; Homo sapiens (Human); CVCL_6831
• In Vitro Model: BID007 cells; Pleural effusion; Homo sapiens (Human); CVCL_W890
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CellTiter Glo assay; IC50 assay

Key Molecule: Epidermal growth factor receptor (EGFR) [5]

• Sensitive Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Molecule Alteration: Duplication; p.A767_V769 (c.2299_2307)
• Experimental Note: Identified from the Human Clinical Data

Key Molecule: Epidermal growth factor receptor (EGFR) [5]

• Sensitive Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Molecule Alteration: Duplication; p.S768_D770 (c.2302_2310)
• Experimental Note: Identified from the Human Clinical Data

Key Molecule: Epidermal growth factor receptor (EGFR) [5]

• Sensitive Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Molecule Alteration: IF-insertion; p.A767_V769dupASV (c.2308_2309insCAAGCGTAG)
• Experimental Note: Identified from the Human Clinical Data

Key Molecule: Epidermal growth factor receptor (EGFR) [5]

• Sensitive Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Molecule Alteration: Duplication; p.D770_P772 (c.2308_2316)
• Experimental Note: Identified from the Human Clinical Data

Key Molecule: Epidermal growth factor receptor (EGFR) [5]

• Sensitive Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Molecule Alteration: IF-insertion; p.D770_N771insGV (c.2310_2311insGGTGTA)
• Experimental Note: Identified from the Human Clinical Data

Key Molecule: Epidermal growth factor receptor (EGFR) [5]

• Sensitive Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Molecule Alteration: IF-insertion; p.D770_N771insGF (c.2310_2311insGGTTTT)
• Experimental Note: Identified from the Human Clinical Data

Key Molecule: Epidermal growth factor receptor (EGFR) [5]

• Sensitive Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Molecule Alteration: IF-insertion; p.S768_D770dupSVD (c.2311_2312insGCGTAGACA)
• Experimental Note: Identified from the Human Clinical Data

Key Molecule: Epidermal growth factor receptor (EGFR) [5]

• Sensitive Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Molecule Alteration: Duplication; p.P772_H773 (c.2314_2319)
• Experimental Note: Identified from the Human Clinical Data

Key Molecule: Epidermal growth factor receptor (EGFR) [5]

• Sensitive Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Molecule Alteration: IF-insertion; p.P772_H773insYNP (c.2315_2316insTTATAACCC)
• Experimental Note: Identified from the Human Clinical Data

Key Molecule: Epidermal growth factor receptor (EGFR) [5]

• Sensitive Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Molecule Alteration: Duplication; p.H773 (c.2317_2319)
• Experimental Note: Identified from the Human Clinical Data

Key Molecule: Epidermal growth factor receptor (EGFR) [5]

• Sensitive Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Molecule Alteration: IF-insertion; p.H773_V774insAH (c.2320_2321insCACATG)
• Experimental Note: Identified from the Human Clinical Data

Key Molecule: Epidermal growth factor receptor (EGFR) [5]

• Sensitive Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Molecule Alteration: IF-insertion; p.A763_Y764insFQEA
• Experimental Note: Identified from the Human Clinical Data

Key Molecule: Epidermal growth factor receptor (EGFR) [5]

• Sensitive Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Molecule Alteration: IF-insertion; p.A767_V774ins
• Experimental Note: Identified from the Human Clinical Data

Key Molecule: Epidermal growth factor receptor (EGFR) [5]

• Sensitive Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Molecule Alteration: IF-insertion; p.V769_D770insASV
• Experimental Note: Identified from the Human Clinical Data

Key Molecule: Epidermal growth factor receptor (EGFR) [5]

• Sensitive Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Molecule Alteration: IF-insertion; p.A770_N771insNPY
• Experimental Note: Identified from the Human Clinical Data

Key Molecule: Epidermal growth factor receptor (EGFR) [5]

• Sensitive Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Molecule Alteration: IF-insertion; p.D770_N771insSVD
• Experimental Note: Identified from the Human Clinical Data

Kidney cancer [ICD-11: 2C90]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Vascular endothelial growth factor A (VEGFA) [6]

• Sensitive Disease: Clear cell renal cell carcinoma [ICD-11: 2C90.Y]
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: HIF-1alpha/VEGFA/VEGFR signalling pathway; Regulation; N.A.
• In Vitro Model: ACHN cells; Pleural effusion; Homo sapiens (Human); CVCL_1067
• Experiment for Molecule Alteration: Western blot assay
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Our study is the first to identify that AUY922 can enhance the sensitivity of ccRCC to sunitinib. AUY922 not only has an inhibitory effect on ccRCC cells, but also enhances the inhibitory effect of sunitinib on ccRCC cells. Additionally, our research is the first to explore the mechanism of AUY922 in ccRCC, demonstrating that it targets the HIF-1/VEGFA/VEGFR pathway by inhibiting HSP90B1.

Key Molecule: Endoplasmin (HSP90B1) [6]

• Sensitive Disease: Clear cell renal cell carcinoma [ICD-11: 2C90.Y]
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: HIF-1alpha/VEGFA/VEGFR signalling pathway; Regulation; N.A.
• In Vitro Model: ACHN cells; Pleural effusion; Homo sapiens (Human); CVCL_1067
• Experiment for Molecule Alteration: Western blot assay
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Our study is the first to identify that AUY922 can enhance the sensitivity of ccRCC to sunitinib. AUY922 not only has an inhibitory effect on ccRCC cells, but also enhances the inhibitory effect of sunitinib on ccRCC cells. Additionally, our research is the first to explore the mechanism of AUY922 in ccRCC, demonstrating that it targets the HIF-1/VEGFA/VEGFR pathway by inhibiting HSP90B1.

Key Molecule: VEGF-2 receptor (KDR) [6]

• Sensitive Disease: Clear cell renal cell carcinoma [ICD-11: 2C90.Y]
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: HIF-1alpha/VEGFA/VEGFR signalling pathway; Regulation; N.A.
• In Vitro Model: ACHN cells; Pleural effusion; Homo sapiens (Human); CVCL_1067
• Experiment for Molecule Alteration: Western blot assay
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Our study is the first to identify that AUY922 can enhance the sensitivity of ccRCC to sunitinib. AUY922 not only has an inhibitory effect on ccRCC cells, but also enhances the inhibitory effect of sunitinib on ccRCC cells. Additionally, our research is the first to explore the mechanism of AUY922 in ccRCC, demonstrating that it targets the HIF-1/VEGFA/VEGFR pathway by inhibiting HSP90B1.

Key Molecule: Vascular endothelial growth factor receptor 1 (FLT1) [6]

• Sensitive Disease: Clear cell renal cell carcinoma [ICD-11: 2C90.Y]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: HIF-1alpha/VEGFA/VEGFR signalling pathway; Regulation; N.A.
• In Vitro Model: ACHN cells; Pleural effusion; Homo sapiens (Human); CVCL_1067
• Experiment for Molecule Alteration: Western blot assay
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Our study is the first to identify that AUY922 can enhance the sensitivity of ccRCC to sunitinib. AUY922 not only has an inhibitory effect on ccRCC cells, but also enhances the inhibitory effect of sunitinib on ccRCC cells. Additionally, our research is the first to explore the mechanism of AUY922 in ccRCC, demonstrating that it targets the HIF-1/VEGFA/VEGFR pathway by inhibiting HSP90B1.

Key Molecule: Hypoxia-inducible factor 1-alpha (HIF1A) [6]

• Sensitive Disease: Clear cell renal cell carcinoma [ICD-11: 2C90.Y]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: HIF-1alpha/VEGFA/VEGFR signalling pathway; Regulation; N.A.
• In Vitro Model: ACHN cells; Pleural effusion; Homo sapiens (Human); CVCL_1067
• Experiment for Molecule Alteration: Western blot assay
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Our study is the first to identify that AUY922 can enhance the sensitivity of ccRCC to sunitinib. AUY922 not only has an inhibitory effect on ccRCC cells, but also enhances the inhibitory effect of sunitinib on ccRCC cells. Additionally, our research is the first to explore the mechanism of AUY922 in ccRCC, demonstrating that it targets the HIF-1/VEGFA/VEGFR pathway by inhibiting HSP90B1.

References

• Ref 1: Germ-line JAK2 mutations in the kinase domain are responsible for hereditary thrombocytosis and are resistant to JAK2 and HSP90 inhibitorsBlood. 2014 Feb 27;123(9):1372-83. doi: 10.1182/blood-2013-05-504555. Epub 2014 Jan 7.
• Ref 2: Resensitization to Crizotinib by the Lorlatinib ALK Resistance Mutation L1198FN Engl J Med. 2016 Jan 7;374(1):54-61. doi: 10.1056/NEJMoa1508887. Epub 2015 Dec 23.
• Ref 3: EGFR Exon 20 Insertion Mutations Display Sensitivity to Hsp90 Inhibition in Preclinical Models and Lung AdenocarcinomasClin Cancer Res. 2018 Dec 15;24(24):6548-6555. doi: 10.1158/1078-0432.CCR-18-1541. Epub 2018 Aug 28.
• Ref 4: 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.
• Ref 5: Activity of the Hsp90 inhibitor luminespib among non-small-cell lung cancers harboring EGFR exon 20 insertionsAnn Oncol. 2018 Oct 1;29(10):2092-2097. doi: 10.1093/annonc/mdy336.
• Ref 6: AUY922 improves sensitivity to sunitinib in clear cell renal cell carcinoma based on network pharmacology and in vitro experiments. Heliyon. 2024 Jul 18;10(14):e34834.