Imatinib mode of action (LQ)
|A||Competetive inhibitor of bcr abl gene product|
|B||P glycoprotein inhibitor|
|C||P glycoprotein stimulator|
|D||Competitively antagonizes the ATP binding site|
Imatinib has inhibitory activity against ABL and its derivatives V-ABL, BCR-ABL and EVT 6-ABL. Inhibit the proliferation of myeloid cell lines that express BCR-ABL fusion proteins. Eg: associated with CML. Also inhibit proliferation of cells dependent on KIT/PDGFR for proliferation.
These include mutant KIT associated with GIT tumours. ETV 6 PDGFR fusion associated with chronic myelomonocythic leukemia, FIP1 F1- PDGFR A associated with hypereosinophilic Syndrome.
b. Chronic Myelomonocytic leukemia
c. Hyper Eosinophilic syndrome
e. Myelo fibrosis
f. Prostatic carcinoma
a. Delayed: Myalgias, bone marrow suppression, edema, abnormal LFTs
b. Cells resistant to imatinib mesilate showed an overexpression of P-gp. it was reported that imatinib mesilate does not cross the blood-brain-barrier, that imatinib mesilate is a substrate of Pgp, and that this efflux transporter is an important determinant of the distribution of imatinib mesilate to the central nervous system
c. This support the notion that imatinib mesilate is a substrate of Pgp. Imatinib's mechanism has action has got nothing to do with P-glycoprotein.
Note: Other TK inhibitors:
Geftinib, Erlotinib - both block intracellular component of EGFR, used in Ca-Iung.