Anti-CDK2 (full length) polyclonal antibody

A characteristic feature of leukemia cells is a blockade of differentiation in cellular maturation. All-trans-retinoic acid (ATRA) has been successfully applied for the treatment of M3-type AML (APL, 10 %), but it fails to demonstrate a significant efficacy on the remaining patients with non-APL AML (90 %). Therefore, the research for strategies to extend the efficacy of ATRA-based therapy to non-APL AML is a key avenue of investigation. Here, we evaluate the synergetic effect of CDK2 inhibition and ATRA in AML both in vitro and in vivo. We have determined that both the CDK2 depletion and pharmacological inhibitor of CDK2 significantly sensitize three subtypes of AML cells (including two non-APL cells) to ATRA-induced cell differentiation. RNA-sequence results indicate that transcription activation of differentiation and maturation pathways plays an important role in this synergetic effect. Furthermore, the down-regulation of CDK2 sensitized AML cells to ATRA-induced engraftment prevention of leukemia cells in NOD-SCID mice and promotes the primary AML blasts differentiation when combined with ATRA. Thus, our work not only provides relevant experimental evidence for further validating CDK2 as a target for differentiation therapy, but also uncovers the future clinical application of CDK2 inhibitors in ATRA-based differentiation therapeutics for AML.

A new series of chromene-triazole-coumarin triads (T1 to T6) have been synthesized through the employment of a solvent-free mechanochemical multicomponent reaction, followed by a copper catalyzed (3+2) azide-alkyne cycloaddition (click chemistry). The molecules were investigated for their fluorescence and CDK induced anticancer properties. Half of the molecules (T1, T4, and T5) showed fluorescence in the solution state through ICT based electronic transitions, whereas the other half (T2, T3, and T6) showed solid-state fluorescence through aggregation induction. Computational studies on binding affinity revealed that all the molecules are generally selective towards CDK2 and CDK4. The in vitro biological activity studies showed that the molecules T2 and T5 exhibit potential as fluorescent inhibitors of CDK2/CDK4 induced tumors. T2 and T5 showed an IC50 of 7.5 mu g mL(-1) and 4 mu g mL(-1) respectively against the human cervical cancer cell line (HeLa).