Drug Information

Drug (ID: DG01517) and It's Reported Resistant Information

• Name: Tivantinib
• Synonyms: Tivantinib; 905854-02-6; ARQ 197; ARQ-197; ARQ197; (3R,4R)-3-(5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-4-(1H-indol-3-yl)pyrrolidine-2,5-dione; UNII-PJ4H73IL17; Tivantinib (ARQ 197); PJ4H73IL17; 1000873-98-2; (3R,4R)-3-(5,6-Dihydro-4H-pyrrolo(3,2,1-ij)quinolin-1-yl)-4-(1H-indol-3-yl)pyrrolidine-2,5-dione; 905853-99-8; rel-(3R,4R)-3-(5,6-Dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-4-(1H-indol-3-yl)-2,5-pyrrolidinedione; Tivantinib [USAN:INN]; Tivantinib; ARQ197; ARQ 197 (Tivantinib); Tivantinib (ARQ-197); SCHEMBL44944; Tivantinib (JAN/USAN/INN); GTPL7948; CHEMBL2103882; CHEBI:91398; DTXSID60920316; QCR-102; ARQ-197,Tivantinib, ARQ197; ARQ197; ARQ-197;Tivantinib; BCPP000042; AOB87130; BCP02529; EX-A2169; CAS:905854-02-6;Tivantinib; BDBM50146168; NSC758242; NSC800951; s2753; AKOS022182739; ZINC100016063; CCG-268285; DB12200; NSC-758242; NSC-800951; (-)-trans-3-(5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-4-(1H-indol-3-yl)pyrrolidine-2,5-dione; AC-25009; AS-16991; HY-50686; J3.496.311H; C77073; D10173; E82820; A857990; J-501255; BRD-K33379087-001-01-8; Q17123902; (+/-)-trans-3-(5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-4(1H-indol-3-yl)pyrrolidine-2,5-dione; (+/-)-trans-3-(5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-4-(1H-indol-3-yl) pyrrolidine-2,5-dione; (+/-)-trans-3-(5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-4-(1H-indol-3-yl)pyrrolidine-2,5-dione; (_)-trans-3-(5,6-dihydro-4h-pyrrolo[3,2,1-ij]quinolin-1-yl)-4(1h-indol-3-yl)pyrrolidine-2,5-dione; (3R,4R)-3-(1-azatricyclo[6.3.1.04,12]dodeca-2,4,6,8(12)-tetraen-3-yl)-4-(1H-indol-3-yl)pyrrolidine-2,5-dione; (3R,4R)-3-(2,3-dihydro-1H-pyrrolo[3,2,1-ij]quinolin-6-yl)-4-(1H-indol-3-yl)pyrrolidine-2,5-dione; (3R,4R)-3-(5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-4-(1H-indol-3-yl)-pyrrolidine-2,5-dione; (3R,4R)-3-(5,6-Dihydro-4H-pyrrolo[3,2,1-ij]quinoline-1-yl)-4-(1H-indole-3-yl)pyrrolidine-2,5-dione; 2,5-Pyrrolidinedione, 3-(5,6-dihydro-4H-pyrrolo(3,2,1-ij)quinolin-1-yl)-4-(1H-indol-3-yl)-, (3R,4R)-; 2,5-Pyrrolidinedione,3-(5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-4-(1H-indol-3-yl)-,(3R,4R)-rel-; 3-(5,6-Dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-5-hydroxy-4-(1H-indol-3-yl)-3,4-dihydro-2H-pyrrol-2-one; TIV; trans 3-(5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-4-(1H-indol-3-yl)-pyrrolidine-2,5-dione
• Indication:
  In total 1 Indication(s)
  Breast cancer [ICD-11: 2C60]; Phase 3; [1]
• Drug Resistance Disease(s):
  Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (2 diseases)
  Breast cancer [ICD-11: 2C60]; [2]
  Solid tumour/cancer [ICD-11: 2A00-2F9Z]; [1]
• Target: Erbb2 tyrosine kinase receptor (HER2); ERBB2_HUMAN; [1]
• Formula: 2
• IsoSMILES: C1CC2=C3C(=CC=C2)C(=CN3C1)[C@H]4[C@@H](C(=O)NC4=O)C5=CNC6=CC=CC=C65
• InChI: InChI=1S/C23H19N3O2/c27-22-19(16-11-24-18-9-2-1-7-14(16)18)20(23(28)25-22)17-12-26-10-4-6-13-5-3-8-15(17)21(13)26/h1-3,5,7-9,11-12,19-20,24H,4,6,10H2,(H,25,27,28)/t19-,20-/m0/s1
• InChIKey: UCEQXRCJXIVODC-PMACEKPBSA-N
• PubChem CID: 11494412
• ChEBI ID: CHEBI:91398
• TTD Drug ID: D0BM7M
• DrugBank ID: DB12200

Type(s) of Resistant Mechanism of This Drug

  ADTT: Aberration of the Drug's Therapeutic Target

  EADR: Epigenetic Alteration of DNA, RNA or Protein

Drug Resistance Data Categorized by Their Corresponding Diseases

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

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

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Hepatocyte growth factor receptor (MET) [1]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.D1010Y (c.3028G>T)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: WEHI-3 cells; Peripheral blood; Mus musculus (Mouse); CVCL_3622
• In Vitro Model: Hs746T cells; Skeletal muscle; Homo sapiens (Human); CVCL_0333
• In Vitro Model: Gp2-293 cells; Fetal kidney; Homo sapiens (Human); CVCL_WI48
• Experiment for Molecule Alteration: Direct sequencing assay
• Experiment for Drug Resistance: CCK-8 assay

Key Molecule: Hepatocyte growth factor receptor (MET) [1]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.Y1003F (c.3008A>T)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: WEHI-3 cells; Peripheral blood; Mus musculus (Mouse); CVCL_3622
• In Vitro Model: Hs746T cells; Skeletal muscle; Homo sapiens (Human); CVCL_0333
• In Vitro Model: Gp2-293 cells; Fetal kidney; Homo sapiens (Human); CVCL_WI48
• Experiment for Molecule Alteration: Direct sequencing assay
• Experiment for Drug Resistance: CCK-8 assay

Breast cancer [ICD-11: 2C60]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-miR-637 [2]

• Resistant Disease: Breast cancer [ICD-11: 2C60.2]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: BT-20 cells; Mammary gland; Homo sapiens (Human); CVCL_0178
• In Vitro Model: BT-474 cells; Breast; Homo sapiens (Human); CVCL_0179
• In Vitro Model: BT-549 cells; Breast; Homo sapiens (Human); CVCL_1092
• In Vitro Model: CAMA-1 cells; Breast; Homo sapiens (Human); CVCL_1115
• In Vitro Model: HCC1143 cells; Breast; Homo sapiens (Human); CVCL_1245
• In Vitro Model: HCC1806 cells; Breast; Homo sapiens (Human); CVCL_1258
• In Vitro Model: HCC1937 cells; Breast; Homo sapiens (Human); CVCL_0290
• In Vitro Model: HCC1954 cells; Breast; Homo sapiens (Human); CVCL_1259
• In Vitro Model: HCC38 cells; Breast; Homo sapiens (Human); CVCL_1267
• In Vitro Model: HCC70 cells; Breast; Homo sapiens (Human); CVCL_1270
• In Vitro Model: Hs578T cells; Breast; Homo sapiens (Human); CVCL_0332
• In Vitro Model: MCF-7 cells; Breast; Homo sapiens (Human); CVCL_0031
• In Vitro Model: MDA-MB-231 cells; Breast; Homo sapiens (Human); CVCL_0062
• In Vitro Model: MDA-MB-361 cells; Breast; Homo sapiens (Human); CVCL_0620
• In Vitro Model: MDA-MB-436 cells; Breast; Homo sapiens (Human); CVCL_0623
• In Vitro Model: MDA-MB-468 cells; Breast; Homo sapiens (Human); CVCL_0419
• In Vitro Model: SK-BR-3 cells; Pleural effusion; Homo sapiens (Human); CVCL_0033
• In Vitro Model: T47D cells; Breast; Homo sapiens (Human); CVCL_0553
• In Vitro Model: EVSA-T cells; Ascites; Homo sapiens (Human); CVCL_1207
• In Vitro Model: Sk-BR-7 cells; Breast; Homo sapiens (Human); CVCL_5218
• In Vitro Model: SUM159PT cells; Breast; Homo sapiens (Human); CVCL_5423/CVCL_5590
• In Vitro Model: SUM44PE cells; Breast; Homo sapiens (Human); CVCL_3424
• In Vitro Model: SUM52PE cells; Breast; Homo sapiens (Human); CVCL_3425
• Experiment for Molecule Alteration: Microarray analyses
• Mechanism Description: This gene is up-regulated in tipifarnib-resistance cells

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-miR-18a-5p [2]

• Sensitive Disease: Breast cancer [ICD-11: 2C60.2]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: BT-20 cells; Mammary gland; Homo sapiens (Human); CVCL_0178
• In Vitro Model: BT-474 cells; Breast; Homo sapiens (Human); CVCL_0179
• In Vitro Model: BT-549 cells; Breast; Homo sapiens (Human); CVCL_1092
• In Vitro Model: CAMA-1 cells; Breast; Homo sapiens (Human); CVCL_1115
• In Vitro Model: HCC1143 cells; Breast; Homo sapiens (Human); CVCL_1245
• In Vitro Model: HCC1806 cells; Breast; Homo sapiens (Human); CVCL_1258
• In Vitro Model: HCC1937 cells; Breast; Homo sapiens (Human); CVCL_0290
• In Vitro Model: HCC1954 cells; Breast; Homo sapiens (Human); CVCL_1259
• In Vitro Model: HCC38 cells; Breast; Homo sapiens (Human); CVCL_1267
• In Vitro Model: HCC70 cells; Breast; Homo sapiens (Human); CVCL_1270
• In Vitro Model: Hs578T cells; Breast; Homo sapiens (Human); CVCL_0332
• In Vitro Model: MCF-7 cells; Breast; Homo sapiens (Human); CVCL_0031
• In Vitro Model: MDA-MB-231 cells; Breast; Homo sapiens (Human); CVCL_0062
• In Vitro Model: MDA-MB-361 cells; Breast; Homo sapiens (Human); CVCL_0620
• In Vitro Model: MDA-MB-436 cells; Breast; Homo sapiens (Human); CVCL_0623
• In Vitro Model: MDA-MB-468 cells; Breast; Homo sapiens (Human); CVCL_0419
• In Vitro Model: SK-BR-3 cells; Pleural effusion; Homo sapiens (Human); CVCL_0033
• In Vitro Model: T47D cells; Breast; Homo sapiens (Human); CVCL_0553
• In Vitro Model: EVSA-T cells; Ascites; Homo sapiens (Human); CVCL_1207
• In Vitro Model: Sk-BR-7 cells; Breast; Homo sapiens (Human); CVCL_5218
• In Vitro Model: SUM159PT cells; Breast; Homo sapiens (Human); CVCL_5423/CVCL_5590
• In Vitro Model: SUM44PE cells; Breast; Homo sapiens (Human); CVCL_3424
• In Vitro Model: SUM52PE cells; Breast; Homo sapiens (Human); CVCL_3425
• Experiment for Molecule Alteration: Microarray analyses
• Mechanism Description: This gene is up-regulated in tivantinib-sensitive cells

Key Molecule: hsa-let-7d-5p [2]

• Sensitive Disease: Breast cancer [ICD-11: 2C60.2]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: BT-20 cells; Mammary gland; Homo sapiens (Human); CVCL_0178
• In Vitro Model: BT-474 cells; Breast; Homo sapiens (Human); CVCL_0179
• In Vitro Model: BT-549 cells; Breast; Homo sapiens (Human); CVCL_1092
• In Vitro Model: CAMA-1 cells; Breast; Homo sapiens (Human); CVCL_1115
• In Vitro Model: HCC1143 cells; Breast; Homo sapiens (Human); CVCL_1245
• In Vitro Model: HCC1806 cells; Breast; Homo sapiens (Human); CVCL_1258
• In Vitro Model: HCC1937 cells; Breast; Homo sapiens (Human); CVCL_0290
• In Vitro Model: HCC1954 cells; Breast; Homo sapiens (Human); CVCL_1259
• In Vitro Model: HCC38 cells; Breast; Homo sapiens (Human); CVCL_1267
• In Vitro Model: HCC70 cells; Breast; Homo sapiens (Human); CVCL_1270
• In Vitro Model: Hs578T cells; Breast; Homo sapiens (Human); CVCL_0332
• In Vitro Model: MCF-7 cells; Breast; Homo sapiens (Human); CVCL_0031
• In Vitro Model: MDA-MB-231 cells; Breast; Homo sapiens (Human); CVCL_0062
• In Vitro Model: MDA-MB-361 cells; Breast; Homo sapiens (Human); CVCL_0620
• In Vitro Model: MDA-MB-436 cells; Breast; Homo sapiens (Human); CVCL_0623
• In Vitro Model: MDA-MB-468 cells; Breast; Homo sapiens (Human); CVCL_0419
• In Vitro Model: SK-BR-3 cells; Pleural effusion; Homo sapiens (Human); CVCL_0033
• In Vitro Model: T47D cells; Breast; Homo sapiens (Human); CVCL_0553
• In Vitro Model: EVSA-T cells; Ascites; Homo sapiens (Human); CVCL_1207
• In Vitro Model: Sk-BR-7 cells; Breast; Homo sapiens (Human); CVCL_5218
• In Vitro Model: SUM159PT cells; Breast; Homo sapiens (Human); CVCL_5423/CVCL_5590
• In Vitro Model: SUM44PE cells; Breast; Homo sapiens (Human); CVCL_3424
• In Vitro Model: SUM52PE cells; Breast; Homo sapiens (Human); CVCL_3425
• Experiment for Molecule Alteration: Microarray analyses
• Mechanism Description: This gene is up-regulated in tivantinib-sensitive cells

References

• Ref 1: Sensitivity and Resistance of MET Exon 14 Mutations in Lung Cancer to Eight MET Tyrosine Kinase Inhibitors In VitroJ Thorac Oncol. 2019 Oct;14(10):1753-1765. doi: 10.1016/j.jtho.2019.06.023. Epub 2019 Jul 3.
• Ref 2: Alterations in p53 predict response to preoperative high dose chemotherapy in patients with gastric cancerMol Pathol. 2003 Oct;56(5):286-92. doi: 10.1136/mp.56.5.286.