The propensity for cancer cells to accumulate additional centrosomes relative to normal cells could be exploited for therapeutic benefit in oncology. Following literature reports that suggested TNKS1 (tankyrase 1) and PARP16 may be involved with spindle structure and function and may play a role in suppressing multi-polar spindle formation in cells with supernumerary centrosomes, we initiated a phenotypic...
The discovery of the activating mutation V617F in the JH2 domain of Jak2 and the modulation of oncogenic Stat3 by Jak2 inhibitors have spurred a great interest in the inhibition of the Jak2/Stat pathway in oncology. In this Letter, we communicate the discovery of novel inhibitors of the Jak2/Stat5 axis, the N-(1H-pyrazol-3-yl)pyrimidin-2-amino derivatives. The rationale, synthesis and biological evaluation...
Thiazol-2-yl amine was identified as an isosteric replacement for pyrazol-3-yl amine during our efforts to identify potent and selective JAK2 inhibitors. The rationale, synthesis and biological evaluation of several analogs is reported, along with the in vivo evaluation of the lead compounds.
A novel series of substituted 3-[3-(aminopropyl)-4,5,6,7-tetrahydro-1H-indol-2-ylmethylene]-1,3-dihydro-in dole-2-ones was discovered as potent inhibitors of the non-receptor tyrosine kinase Src and Yes. A structure-activity relationship was developed in order to optimize their potency and selectivity. Syntheses of these compounds are also described herein.
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