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]

• Molecule Alteration: IF-insertion; p.A763_Y764insFQEA (c.2290_2291insTTCAAGAGGCAT)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• 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 blotting 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]

• Molecule Alteration: IF-insertion; p.Y764_V765insHH (c.2292_2293insCATCAT)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• 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 blotting 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]

• Molecule Alteration: Duplication; p.S768_D770 (c.2302_2310)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• 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 blotting 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]

• Molecule Alteration: IF-insertion; p.P772_H773insGNP (c.2316_2317insGGTAACCCT)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• 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 blotting 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]

• Molecule Alteration: Duplication; p.H773 (c.2317_2319)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• 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 blotting 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]

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

• Molecule Alteration: Complex-indel; p.G776_776delinsVC (c.2326_2328delinsGTATGT)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• 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]

• Molecule Alteration: Duplication; p.Y772_A775 (c.2314_2325)/p.A775_G776insYVMA + p.C805S
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• 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]

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

• Molecule Alteration: Missense mutation; p.C1156Y (c.3467G>A)
• Resistant Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• 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]

• Molecule Alteration: IF-insertion; p.A763_Y764insFQEA (c.2290_2291insTTCAAGAGGCAT)
• Sensitive Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• 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 blotting analysis
• Experiment for Drug Resistance: CellTiter Glo assay; IC50 assay

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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.