Forskolin sensitizes human acute myeloid leukemia cells to H3K27me2/3 demethylases GSKJ4 inhibitor via protein kinase A was written by Illiano, Michela;Conte, Mariarosaria;Sapio, Luigi;Nebbioso, Angela;Spina, Annamaria;Altucci, Lucia;Naviglio, Silvio. And the article was included in Frontiers in Pharmacology in 2018.Synthetic Route of C24H27N5O2 The following contents are mentioned in the article:
Acute myeloid leukemia (AML) is an aggressive hematol. malignancy occurring very often in older adults, with poor prognosis depending on both rapid disease progression and drug resistance occurrence. GSKJ4 is a novel inhibitor of the histone demethylases JMJD3 and UTX. Here, we investigate the effects of forskolin on the sensitivity of human leukemia U937 cells to GSKJ4 through flow cytometry-based assays (cell-cycle progression and cell death), cell number counting, and immunoblotting experiments We provide evidence that forskolin markedly potentiates GSKJ4-induced antiproliferative effects by apoptotic cell death induction, accompanied by a dramatic BCL2 protein down-regulation as well as caspase 3 activation and PARP protein cleavage. Comparable effects are observed with the phosphodiesterase inhibitor IBMX and 8-Br-cAMP analogous, but not by using 8-pCPT-2-O-Me-cAMP Epac activator. Moreover, the forskolin-induced enhancement of sensitivity to GSKJ4 is counteracted by pre-treatment with Protein Kinase A (PKA) inhibitors. Altogether, our data strongly suggest that forskolin sensitizes U937 cells to GSKJ4 inhibitor via a cAMP/PKA-mediated mechanism. Our findings provide initial evidence of anticancer activity induced by forskolin/GSKJ4 combination in leukemia cells and underline the potential for use of forskolin and GSKJ4 in the development of innovative and effective therapeutic approaches for AML treatment. This study involved multiple reactions and reactants, such as Ethyl 3-((6-(4,5-dihydro-1H-benzo[d]azepin-3(2H)-yl)-2-(pyridin-2-yl)pyrimidin-4-yl)amino)propanoate (cas: 1373423-53-0Synthetic Route of C24H27N5O2).
Ethyl 3-((6-(4,5-dihydro-1H-benzo[d]azepin-3(2H)-yl)-2-(pyridin-2-yl)pyrimidin-4-yl)amino)propanoate (cas: 1373423-53-0) belongs to pyrimidine derivatives. The pyrimidine derivatives can easily interact with enzymes, genetic materials, and bio components within the cell. Drugs having the pyrimidine motif have manifested to exhibit gratifying biological activity like anticancer, antiviral, anti-inflammatory, antibacterial, and antihypertensive activities.Synthetic Route of C24H27N5O2
Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia