Category: 2351929-82-1

Guo, Yinping published the artcileStructure-Guided Discovery of a Potent and Selective Cell-Active Inhibitor of SETDB1 Tudor Domain, COA of Formula: C7H6ClN3O, the publication is Angewandte Chemie, International Edition (2021), 60(16), 8760-8765, database is CAplus and MEDLINE.

SET domain bifurcated protein 1 (SETDB1) is a histone lysine methyltransferase that promotes the silencing of some tumor suppressor genes and is overexpressed in many cancers. SETDB1 contains a unique tandem tudor domain (TTD) that recognizes histone H3 sequences containing both methylated and acetylated lysines. Beginning with the identification of a hit compound (Cpd1, I), we discovered the first potent and selective small mol. SETDB1-TTD inhibitor (R,R)-59 (II) through stepwise structure-guided optimization. (R,R)-59 showed a K_D value of 0.088±0.045μM in the ITC assay. The high potency of (R,R)-59 was well explained by the cocrystal structure of the (R,R)-59-TTD complex. (R,R)-59 is an endogenous binder competitive inhibitor. Evidence has also demonstrated its cellular target engagement. Interestingly, the enantiomer (S,S)-59 did not show activity in all the assays, highlighting the potential of (R,R)-59 as a tool compound in exploring the biol. functions of SETDB1-TTD.

Angewandte Chemie, International Edition published new progress about 2351929-82-1. 2351929-82-1 belongs to pyrimidines, auxiliary class Pyrroles, name is 2-Chloro-3-methyl-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one, and the molecular formula is C7H6ClN3O, COA of Formula: C7H6ClN3O.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/Pyrimidine,
Pyrimidine – Wikipedia

Huang, Luyi published the artcileDiscovery of Pyrrolo[3,2-d]pyrimidin-4-one Derivatives as a New Class of Potent and Cell-Active Inhibitors of P300/CBP-Associated Factor Bromodomain, Category: pyrimidines, the publication is Journal of Medicinal Chemistry (2019), 62(9), 4526-4542, database is CAplus and MEDLINE.

Herein, we report the discovery of a series of new P300/CBP-associated factor (PCAF) bromodomain (BRD) inhibitors, which were obtained through a hit discovery process and subsequent structure-based optimization and structure-activity relationship analyses toward a retrieved hit compound (12). Among these inhibitors, (R,R)-36n is the most potent one with an IC₅₀ of 7 nM in homogeneous time-resolved fluorescence assay and a K_D of 78 nM in isothermal titration calorimetry assay. This compound also exhibited activity against GCN5 and FALZ, but weak or no activity against other 29 BRD proteins and 422 kinases, indicating considerable selectivity. X-ray cocrystal structure anal. revealed the mol. interaction mode and the precise stereochem. required for bioactivity. Cellular activity, preliminary RNA-seq anal., and pharmacokinetic properties were also examined for this compound Collectively, this study provides a versatile tool mol. to explore mol. mechanisms of PCAF BRD regulation and also offers a new lead compound for drug discovery targeting PCAF.

Journal of Medicinal Chemistry published new progress about 2351929-82-1. 2351929-82-1 belongs to pyrimidines, auxiliary class Pyrroles, name is 2-Chloro-3-methyl-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one, and the molecular formula is C7H6ClN3O, Category: pyrimidines.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/Pyrimidine,
Pyrimidine – Wikipedia