Bcr-abl Inhibitor IV; Imatinib

Biochem/physiol Actions

Reversible: yes

Primary TargetAbl

Secondary TargetPDGFR, c-kit

Cell permeable: yes

General description

A cell-permeable, orally bioavailable 2-phenylaminopyrimidine derived compound that competitively binds to ATP-binding site of Abl and stabilizes the inactive conformation, and acts as a highly potent and reversible inhibitor of Abl (IC₅₀ = 38, 25 and 25 nM for v-Abl, Bcr-Abl, and c-Abl, respectively). Also shown to block the activity of PDGFR and c-kit (IC₅₀ = 50 and 100 nM). Exhibits high selectivity over IR, IGF-1R, EGFR, c-Src, JAK-2, PKA, PKC isozymes, CKI, and CKII (IC₅₀ >100 µM). Preferentially blocks the proliferation of leukemic immature cobblestone-forming area cells and Bcr-abl transfected cell lines, M07/p210 and Ba/F3/p185 (~1 -10 µM), and suppresses tumor growth in mice (50 mg/kg, i.p.). Induces apoptosis in Bcr-abl positive cells via intrinsic mitochondrial pathway by down-regulating Bcl-X, promoting cytochrome c release, and activating caspase-9. Does not affect the levels of Bcl-2. Also reported to induce a caspase-independent, necrosis-like programmed cell death mediated by the serine protease activity of Omi/HtrA2.

Legal Information

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Other Notes

Lin, Y.L., et al. 2013. Proc. Natl. acad. Sci. USA110, 1664.Okada, M., et al. 2004. Blood103, 2299.Capdeville, R., et al. 2002. Nat. Rev. Drug. Res.1, 493.Oetzel, C., et al. 2000. Clin Cancer Res.6, 1958.Schindler, T., et al. 2000. Science289, 1938.Buchdunger, E., et al. 2000. J. Pharmacol. Exp. Ther.295, 139.Carroll. M., et al. 1997. Blood90, 4947.r>Zimmermann, J., et al. 1997. Bioorg. Med. Chem. Lett.7, 187.Druker, B.J., et al. 1996. Nat. Med.2, 561.

Packaging

Packaged under inert gas

50 mg in Glass bottle

Reconstitution

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.

Warning

Toxicity: Standard Handling (A)