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Imatinib mesylate is a tyrosine kinase inhibitor specifically directed toward BCR/ABL, KIT, FMS (the receptor for Colony Stimulating Factor 1), ARG (ABL-related gene) and PDGFR alpha and beta. It is an effective systemic therapy in most cases of DFSP. Imatinib competes with the adenosine triphosphate (ATP) molecule, blocking the tyrosine kinase receptor’s ability for autophosporylation, which results in inhibition of the damaged pathway of signal transduction and restoration of proper intracellular signaling.
The activity of IRSp53 is enhanced by Cdc42 or Rac1 GTPases during filopodia formation [81, 82, 83]. Although this protein performs several functions and binds other actin regulators such as Mena (a Ena/VASP family protein ) and formin (e. g. mDia1 ), its role in F-actin binding and crosslinking is well established and has been attributed to its IMD domain [83, 85]. Additional molecules contribute to the cross linking of actin filaments and these include fimbrin as well as lesser known actin crosslinking proteins such as Arg (Abl-related gene.
The consensus, HxR/H/KxxS/T, 9, 28 is present in c-Abl (ABL1) and Arg (Abl-related gene, ABL2) from higher organisms ( Figure 5b) and in v-Abl, but is not conserved in worms or flies. Likewise, it is not conserved in the related Src family kinase c-Src. A consensus sequence logo compiled by Prosite 35 from 444 SH2 domain sequences shows that the phosphorylation site S or T is not conserved among general SH2 domains (.
Utilizarea primului inhibitor de tirozin-kinaza (imatinib) în LGC a produs un adevarat «boom» pentru ca a schimbat radical evolutia bolii! Imatinibul este o molecula 2-fenilaminopirimidinica mica care inhiba activitatea kinazica a tuturor proteinelor care contin ABL, ABL-related gene (ARG) sau receptorul factorului de crestere derivat din plachete, precum si receptorul KIT. Doza de 400 mg de imatinib este considerata în mod curent doza standard pentru a initia terapia la pacientii nou diagnosticati aflati în faza cronica.
Salah, E. , Ugochukwu, E. , Barr, A. J. , von Delft, F. , Knapp, S. , and Elkins, J. M. (2011). Crystal structures of ABL-related gene (ABL2) in complex with imatinib, tozasertib (VX-680), and a type I inhibitor of the triazole carbothioamide class. J Med Chem 54, 2359-2367.
Crystal structures of ABL-related gene.