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imatinib

Sunday 26 September 2004

Gleevec ®, imatinib mesylate , STI-571

Definition: Imatinib mesylate (STI 571, Gleevec) is an inhibitor of the tyrosine kinases c-kit, PDGFR and the fusion protein BCR/ABL. Imatinib also blocks the stem cell factor SCF receptor or c-KIT loop.

Gleevec ® (Ima­tinib mesy­late) is iden­ti­fied via BCR-ABL and used to treat Chronic Myloid Leukemia, for which it increases life expectancy from 5% — 95% at 5 years.

Imatinib is a small-molecule ABL kinase inhibitor. It is a highly effective therapy for early-phase chronic myeloid leukaemia (CML), which has constitutively active ABL kinase activity owing to the expression of the BCR-ABL fusion protein.

Therapeutics

- significant response in patients with chronic myelogenous leukemia and gastrointestinal stromal tumor (GIST)

Videos

- Gleevec mechanism of Action

Reviews

- O’hare T, Corbin AS, Druker BJ. Targeted CML therapy: controlling drug resistance, seeking cure. Curr Opin Genet Dev. 2006 Feb;16(1):92-9. PMID: #16343892#

- Klein S, McCormick F, Levitzki A. Killing time for cancer cells. Nat Rev Cancer. 2005 Jul;5(7):573-80. PMID: #15965492#

- Mohty M, Blaise D, Olive D, Gaugler B. Imatinib: the narrow line between immune tolerance and activation. Trends Mol Med. 2005 Sep;11(9):397-402. PMID: #16087402#

- Hannah AL. Kinases as drug discovery targets in hematologic malignancies. Curr Mol Med. 2005 Nov;5(7):625-42. PMID: #16305489#

- Savage DG, Antman KH. Imatinib mesylate—a new oral targeted therapy. N Engl J Med. 2002 Feb 28;346(9):683-93. PMID: #11870247#

References

- Krause DS, Van Etten RA. Tyrosine kinases as targets for cancer therapy. N Engl J Med 2005;353:172-187.

- Apperley JF, Gardembas M, Melo JV, et al. Response to imatinib mesylate in patients with chronic myeloproliferative diseases with rearrangements of the platelet-derived growth factor receptor beta. N Engl J Med 2002;347:481-487.

- David M, Cross NC, Burgstaller S, et al. Durable responses to imatinib in patients with PDGFRB fusion gene-positive and BCR-ABL-negative chronic myeloproliferative disorders. Blood 2007;109:61-64.

- Lichter P, Ward DC. Is non-isotopic in situ hybridization finally coming of age? Nature 1990;345:93-94.

- Baccarani M, Cilloni D, Rondoni M, et al. The efficacy of imatinib mesylate in patients with FIP1L1-PDGFRalpha-positive hypereosinophilic syndrome: results of a multicenter prospective study. Haematologica 2007;92:1173-1179.

- Cools J, DeAngelo DJ, Gotlib J, et al. A tyrosine kinase created by fusion of the PDGFRA and FIP1L1 genes as a therapeutic target of imatinib in idiopathic hypereosinophilic syndrome. N Engl J Med 2003;348:1201-1214.

- Deininger M, Buchdunger E, Druker BJ. The development of imatinib as a therapeutic agent for chronic myeloid leukemia. Blood 2005;105:2640-2653. PMID: #15618470#

- Druker BJ, Guilhot F, O’Brien SG, et al. Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med 2006;355:2408-2417.

- Gorre ME, Mohammed M, Ellwood K, et al. Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification. Science 2001;293:876-880.

PDGFRA

- Apperley JF, Gardembas M, Melo JV, et al. Response to imatinib mesylate in patients with chronic myeloproliferative diseases with rearrangements of the platelet-derived growth factor receptor beta. N Engl J Med 2002;347:481-487.

- David M, Cross NC, Burgstaller S, et al. Durable responses to imatinib in patients with PDGFRB fusion gene-positive and BCR-ABL-negative chronic myeloproliferative disorders. Blood 2007;109:61-64.

- Baccarani M, Cilloni D, Rondoni M, et al. The efficacy of imatinib mesylate in patients with FIP1L1-PDGFRalpha-positive hypereosinophilic syndrome: results of a multicenter prospective study. Haematologica 2007;92:1173-1179.

- Cools J, DeAngelo DJ, Gotlib J, et al. A tyrosine kinase created by fusion of the PDGFRA and FIP1L1 genes as a therapeutic target of imatinib in idiopathic hypereosinophilic syndrome. N Engl J Med 2003;348:1201-1214.