Drug Information

Drug (ID: DG00082) and It's Reported Resistant Information

• Name: Tesevatinib
• Synonyms: Tesevatinib; XL647; XL-647; 781613-23-8; EXEL-7647; UNII-F6XM2TN5A1; KD-019; XL 647; F6XM2TN5A1; 651031-01-5; 7-[[(3aS,6aR)-2-methyl-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-5-yl]methoxy]-N-(3,4-dichloro-2-fluorophenyl)-6-methoxyquinazolin-4-amine; Tesevatinib [USAN:INN]; EXEL 7647; 874286-84-7; KD 019; 1000599-06-3; SCHEMBL721994; SCHEMBL721993; SCHEMBL721992; C24H25Cl2FN4O2; GTPL7944; CHEMBL3544983; EX-A172; QCR-153; MolPort-044-724-458; BCP23438; ZINC38912363; 2809AH; AKOS027255007
• Indication:
  In total 5 Indication(s)
  Brain cancer [ICD-11: 2A00]; Phase 2; [1]
  Cystic/dysplastic kidney disease [ICD-11: GB8Y]; Phase 2; [1]
  Lung cancer [ICD-11: 2C25]; Phase 2; [1]
  Metastatic meninges neoplasm [ICD-11: 2D51]; Phase 2; [1]
  Metastatic tumour [ICD-11: 2D50-2E2Z]; Phase 2; [1]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
  Lung cancer [ICD-11: 2C25]; [1]
• Target: Ephrin type-B receptor 4 (EPHB4); EPHB4_HUMAN; [1]
• Target: Tyrosine-protein kinase (PTK); NOUNIPROTAC; [1]
• Formula: C24H25Cl2FN4O2
• IsoSMILES: CN1C[C@H]2CC(C[C@H]2C1)COC3=C(C=C4C(=C3)N=CN=C4NC5=C(C(=C(C=C5)Cl)Cl)F)OC
• InChI: 1S/C24H25Cl2FN4O2/c1-31-9-14-5-13(6-15(14)10-31)11-33-21-8-19-16(7-20(21)32-2)24(29-12-28-19)30-18-4-3-17(25)22(26)23(18)27/h3-4,7-8,12-15H,5-6,9-11H2,1-2H3,(H,28,29,30)/t13 ,14-,15+
• InChIKey: HVXKQKFEHMGHSL-GOOCMWNKSA-N
• PubChem CID: 10458325
• TTD Drug ID: D06WRF
• DrugBank ID: DB11973

Type(s) of Resistant Mechanism of This Drug

  ADTT: Aberration of the Drug's Therapeutic Target

Drug Resistance Data Categorized by Their Corresponding Diseases

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

Lung cancer [ICD-11: 2C25]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Epidermal growth factor receptor (EGFR) [1]

• Molecule Alteration: Missense mutation; p.T790M
• Resistant Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: Direct sequencing assay
• Experiment for Drug Resistance: Computed tomography assay
• Mechanism Description: The most common mechanism of acquired resistance is caused by the development of the T790M mutation in exon 20 of EGFR in nearly 50% of patients, whereas 10% of the patients have amplification of the oncogene MET as a means of resistance.

References

• Ref 1: Phase II study of the multitargeted tyrosine kinase inhibitor XL647 in patients with non-small-cell lung cancer. J Thorac Oncol. 2012 May;7(5):856-65. doi: 10.1097/JTO.0b013e31824c943f.