Drug name: BMS-214662 + Dasatinib


Related CSCTT Targets

FNTA [ref.1]P49354
FNTB [ref.1]P49356

BMS-214662

Cas.no PubChem ID
195987-41-8 448545
Known Target
Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alphaP49354
Protein farnesyltransferase subunit betaP49356
Structure
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Introduction
BMS-214662 is a Farnesyltransferase inhibitor, is also a nonsedating benzodiazepine derivative with potential antineoplastic activity. BMS-214662 inhibits the enzyme farnesyltransferase and the post-translational farnesylation of number of proteins involved in signal transduction, which may result in the inhibition of Ras function and apoptosis in susceptible tumor cells. This agent may reverse the malignant phenotype of H-Ras-transformed cells and has been shown to be active against tumor cells with and without Ras mutations.

Dasatinib, BMS-354825

Cas.no PubChem ID
302962-49-8 3062316
Known Target
Tyrosine-protein kinase ABL1P00519
Proto-oncogene tyrosine-protein kinase SrcP12931
Ephrin type-A receptor 2P29317
Tyrosine-protein kinase LckP06239
Tyrosine-protein kinase YesP07947
Mast/stem cell growth factor receptor KitP10721
Platelet-derived growth factor receptor betaP09619
Signal transducer and activator of transcription 5BP51692
Abelson tyrosine-protein kinase 2P42684
Tyrosine-protein kinase FynP06241
Structure
...
Introduction
Dasatinib, at nanomolar concentrations, inhibits the following kinases: BCR-ABL, SRC family (SRC, LCK, YES, FYN), c-KIT, EPHA2, and PDGFRβ. Based on modeling studies, dasatinib is predicted to bind to multiple conformations of the ABL kinase. In vitro, dasatinib was active in leukemic cell lines representing variants of imatinib mesylate sensitive and resistant disease. Dasatinib inhibited the growth of chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL) cell lines overexpressing BCR-ABL. Under the conditions of the assays, dasatinib was able to overcome imatinib resistance resulting from BCR-ABL kinase domain mutations, activation of alternate signaling pathways involving the SRC family kinases (LYN, HCK), and multi-drug resistance gene overexpression.

Reference

  • [1] BMS-214662 potently induces apoptosis of chronic myeloid leukemia stem and progenitor cells and synergizes with tyrosine kinase inhibitors. Copland, M., et al. (2008).Blood. 111(5):2843-53.
    18156496. [ 18156496 ]

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