Cho, Hanna published the artcileIdentification of Novel Resorcinol Amide Derivatives as Potent and Specific Pyruvate Dehydrogenase Kinase (PDHK) Inhibitors, Application of 1-Methylurea, the main research area is neoplasm antitumor resorcinol amide pyruvate dehydrogenase kinase combination chemotherapy; satraplatin.
Pyruvate dehydrogenase kinases (PDHKs) promote abnormal respiration in cancer cells. Studies with novel resorcinol amide derivatives based on VER-246608 (6) led to the identification of 19n(I) and 19t(II) containing 5-membered heteroaromatic ring as unique structural features. These substances possess single-digit nanomolar activities against PDHKs. II exhibits higher potencies against PDHK1/2/4 than does 6 and inhibits only PDHKs among 366 kinases. Moreover, 19g, 19l and 19s were found to be isotype-selective PDHK inhibitors. Mol. dynamics simulations provide a better understanding how the heteroaromatic rings affect the activities of I and II on PDHK1/2/3/4. Moreover, I possesses a much higher antiproliferative activity against cancer cells than does 6. We demonstrated that the results of PDH assays better correlate with cellular activities than do those of PDHK kinase assays. Furthermore, I induces apoptosis of cancer cells via mitochondrial dysfunction, suppresses tumorigenesis and displays a synergistic effect on satraplatin suppression of cancer cell proliferation.
Journal of Medicinal Chemistry published new progress about Antitumor agents. 598-50-5 belongs to class isoquinoline, name is 1-Methylurea, and the molecular formula is C2H6N2O, Application of 1-Methylurea.
Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem