ABL

The ABL1 protooncogene encodes a cytoplasmic and nuclear protein tyrosine kinase (ABL1; EC 2.7.10.2) that has been implicated in processes of cell differentiation, cell division, cell adhesion, and stress response. It is a member of the src family of tyrosine kinases, and its DNA-binding activity is regulated by CDC2-mediated phosphorylation. Moreover, the activity of c-Abl protein is negatively regulated by its SH3 domain, and deletion of the SH3 domain turns ABL1 into an oncogene. This translocation results in the head-to-tail fusion of the BCR and ABL1 genes, leading to a fusion gene present in many cases of chronic myelogenous leukemia[1]. 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[2],[3]. Our product line includes both the very first drug registered on the market inhibiting this specific tyrosine kinase (Axon 1394: STI 571-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.)[4]


[1] D.S. Goodsell. The molecular perspective: c-Abl tyrosine kinase. Oncologist. 2005, 10, 758-759.
[2] The molecular genetics ofPhiladelphia chromosome-positive leukemias. Kurzrock, R., Gutterman, J. Talpaz, M. N. Engl. J. Med. 1988, 319, 990-998.
[3] Dasatinib in imatinib-resistantPhiladelphia chromosome-positive leukemias. Talpaz M, Shah NP, Kantarjian H, et al. N. Engl. J. Med. 2006, 354 2531–2541.
[4]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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Axon ID Name Description From price
1456 AZD 0530 difumarate Inhibitor of SRC and ABL tyrosine kinases €105.00
1892 NM-PP1, 1- Potent tyrosine kinase inhibitor (TKI) of multiple targets (Src, Fyn, Abl, CDK, Trk) €95.00

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