Structural analysis of human KDM5B guides histone demethylase inhibitor development was written by Johansson, Catrine;Velupillai, Srikannathasan;Tumber, Anthony;Szykowska, Aleksandra;Hookway, Edward S.;Nowak, Radoslaw P.;Strain-Damerell, Claire;Gileadi, Carina;Philpott, Martin;Burgess-Brown, Nicola;Wu, Na;Kopec, Jola;Nuzzi, Andrea;Steuber, Holger;Egner, Ursula;Badock, Volker;Munro, Shonagh;LaThangue, Nicholas B.;Westaway, Sue;Brown, Jack;Athanasou, Nick;Prinjha, Rab;Brennan, Paul E.;Oppermann, Udo. And the article was included in Nature Chemical Biology in 2016.Name: 3-((2-(Pyridin-2-yl)-6-(1,2,4,5-tetrahydro-3H-benzo[d]azepin-3-yl)pyrimidin-4-yl)amino)propanoic acid The following contents are mentioned in the article:
Members of the KDM5 (also known as JARID1) family are 2-oxoglutarate- and Fe2+-dependent oxygenases that act as histone H3K4 demethylases, thereby regulating cell proliferation and stem cell self-renewal and differentiation. Here, the authors report crystal structures of the catalytic core of the human KDM5B enzyme in complex with 3 inhibitor chemotypes. These scaffolds exploitet several aspects of the KDM5 active site, and their selectivity profiles reflected their hybrid features with respect to the KDM4 and KDM6 families. Whereas GSK-J1, a previously identified KDM6 inhibitor, showed 鈭?-fold less inhibitory activity toward KDM5B than toward KDM6 proteins, KDM5-C49 displayed 25-100-fold selectivity between KDM5B and KDM6B. The cell-permeable derivative KDM5-C70 had an antiproliferative effect in myeloma cells, leading to genome-wide elevation of H3K4me3 levels. The selective inhibitor GSK467 exploited unique binding modes, but it lacked cellular potency in the myeloma system. Taken together, these structural leads deliver multiple starting points for further rational and selective inhibitor design. This study involved multiple reactions and reactants, such as 3-((2-(Pyridin-2-yl)-6-(1,2,4,5-tetrahydro-3H-benzo[d]azepin-3-yl)pyrimidin-4-yl)amino)propanoic acid (cas: 1373422-53-7Name: 3-((2-(Pyridin-2-yl)-6-(1,2,4,5-tetrahydro-3H-benzo[d]azepin-3-yl)pyrimidin-4-yl)amino)propanoic acid).
3-((2-(Pyridin-2-yl)-6-(1,2,4,5-tetrahydro-3H-benzo[d]azepin-3-yl)pyrimidin-4-yl)amino)propanoic acid (cas: 1373422-53-7) belongs to pyrimidine derivatives. The pyrimidine derivatives can easily interact with enzymes, genetic materials, and bio components within the cell. For example, the neurotoxin tetrodotoxin is a pyrimidine derivative. It is found in a number of species including the Japanese puffer fish, the blue-ringed octopus, and the orange-bellied newt. Tetrodotoxin prevents the transmission of nerve signals and can result in paralysis and death.Name: 3-((2-(Pyridin-2-yl)-6-(1,2,4,5-tetrahydro-3H-benzo[d]azepin-3-yl)pyrimidin-4-yl)amino)propanoic acid
Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia