Oncogene Fusion Protein

Oncogene Fusion Protein

A small individual group of tyrosine kinase inhibitors is specifically targeting oncogenic fusion proteins. The expression of these proteins is caused by a reciprocal translocation between chromosomes, 9 and 22 in case of the BCR-ABL fusion protein. About 95% of the patients suffering from chronic myelogenous leukaemia show expression of this particular protein, yet it is also found in two other acute forms of leukaemia. Our product line includes both the very first drug registered on the market inhibiting this specific tyrosine kinase (Axon 1394: STI 571 or Imatinib (Novartis)), as well as well-known follow-up inhibitors, being more potent and/or more active against the emerging Gleevec/Glivec resistant BCR-ABL clones that originate from point mutations inside the kinase domain of the Bcr-Abl protein and disrupt the binding site of Imatinib on the tyrosine kinase (e.g. Axon 1392 and Axon 1396 (Dasatinib and Nilotinib resp.)

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More About Oncogene Fusion Protein

A small individual group of tyrosine kinase inhibitors is specifically targeting oncogenic fusion proteins. The expression of these proteins is caused by a reciprocal translocation between chromosomes, 9 and 22 in case of the BCR-ABL fusion protein. About 95% of the patients suffering from chronic myelogenous leukaemia show expression of this particular protein, yet it is also found in two other acute forms of leukaemia[1],[2]. Our product line includes both the very first drug registered on the market inhibiting this specific tyrosine kinase (Axon 1394: STI 571 or Imatinib (Novartis)), as well as well-known follow-up inhibitors, being more potent and/or more active against the emerging Gleevec/Glivec resistant BCR-ABL clones that originate from point mutations inside the kinase domain of the Bcr-Abl protein and disrupt the binding site of Imatinib on the tyrosine kinase (e.g. Axon 1392 and Axon 1396 (Dasatinib and Nilotinib resp.)[3]

[1] The molecular genetics ofPhiladelphia chromosome-positive leukemias. Kurzrock, R., Gutterman, J. Talpaz, M. N. Engl. J. Med. 1988, 319, 990-998.
[2] Dasatinib in imatinib-resistantPhiladelphia chromosome-positive leukemias. Talpaz M, Shah NP, Kantarjian H, et al. N. Engl. J. Med. 2006, 354 2531–2541.
[3] BCR-ABL tyrosine kinase inhibitors in the treatment ofPhiladelphia chromosome positive chronic myeloid leukemia: a review. An, X.; Tiwari, A.; Sun, Y.; Ding, P.; Ashby Jr, C.; Chen, Z. Leukemia research 2010, 34, 1255–1268.

 

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