Imatinib

Imatinib (STI571) is an orally bioavailable tyrosine kinases inhibitor that selectively inhibits BCR/ABL, v-Abl, PDGFR and c-kit kinase activity. Imatinib (STI571) works by binding close to the ATP binding site, locking it in a closed or self-inhibited conformation, therefore inhibiting the enzyme activity of the protein semicompetitively^[1][2][3][4]. Imatinib also is an inhibitor of SARS-CoV and MERS-CoV^[5]. IC50 & Target:BCR/ABL, v-Abl, PDGFR, c-kit^[1][2][4] In Vitro:Imatinib (STI571) inhibits c-Kit autophosphorylation, activation of MAPK, and activation of Akt without altering total protein levels of c-kit, MAPK, or Akt. The concentration that produces 50% inhibition for these effects is approximately 100 nM^[1].
Imatinib (STI571) is very effective (in vitro IC₅₀ of 25 nM) against the chronic myeloid leukemia-causing kinase Bcr-Abl. Imatinib also efficiently inhibits Kit (in vitro IC₅₀, 410 nM) and PDGFR (in vitro IC₅₀, 380 nM)^[2].
Imatinib (STI571) is a multi-target inhibitor of v-Abl, c-Kit and inhibits Bcr/Abl, v-Abl, Tel/Abl, the native PDGFβ receptor, and c-Kit, but it does not inhibit Src family kinases, c-Fms, Flt3, the EGFR or multiple other tyrosine kinases. Imatinib inhibits tyrosine phosphorylation and cell growth of Ba/F3 cells expressing Bcr/Abl, Tel/Abl, Tel/PDGFβR, and Tel/Arg with an IC₅₀ of approximately 0.5 μM in each case, but it has no effect on untransformed Ba/F3 cells growing in IL-3 or on Ba/F3 cells transformed by Tel/JAK2^[4].
The IC₅₀s of Imatinib(STI571) is a multi-target inhibitor of v-Abl, c-Kit and on BON-1 and H727 cells after exposure for 48 h are 32.4 and 32.8 μM, respectively^[6]. In Vivo:In the phosphorothioate antisense oligodeoxynucleotides (PS-ASODN) group, tumor growth is inhibited by 59.437%, which is markedly higher than in the Imatinib (STI571) is a multi-target inhibitor of v-Abl, c-Kit and group (11.071%) and liposome negative control group (2.759%). Telomerase activity is significantly lower (P<0.01) in the PS-ASODN group (0.689±0.158) compare with the Imatinib group (1.838±0.241), liposome negative control group (2.013±0.273), and saline group (2.004±0.163)^[7].
Imatinib (25 mg/kg/day, p.o.) suppresses the growth of endometriotic tissue and reduces the number of ovarian follicles in a rat model. Imatinib effectively treats experimental endometriosis by its inhibitor effects on angiogenesis and cell proliferation^[8].