Category: 475216-25-2

Deng, Hongfeng published the artcileDiscovery and Optimization of Potent, Selective, and in Vivo Efficacious 2-Aryl Benzimidazole BCATm Inhibitors, Recommanded Product: 4-Fluoro-N-methyl-3-nitrobenzamide, the publication is ACS Medicinal Chemistry Letters (2016), 7(4), 379-384, database is CAplus and MEDLINE.

To identify BCATm inhibitors suitable for in vivo study, Encoded Library Technol. (ELT) was used to affinity screen a 117 million member benzimidazole based DNA encoded library, which identified an inhibitor series with both biochem. and cellular activities. Subsequent SAR studies led to the discovery of a highly potent and selective compound I with much improved PK properties. X-ray structure revealed that I binds to the active site of BACTm in a unique mode via multiple H-bond and van der Waals interactions. After oral administration, I raised mouse blood levels of all three branched chain amino acids as a consequence of BCATm inhibition.

ACS Medicinal Chemistry Letters published new progress about 475216-25-2. 475216-25-2 belongs to amides-buliding-blocks, auxiliary class Fluoride,Nitro Compound,Amine,Benzene,Amide,Benzene Compounds, name is 4-Fluoro-N-methyl-3-nitrobenzamide, and the molecular formula is C8H7FN2O3, Recommanded Product: 4-Fluoro-N-methyl-3-nitrobenzamide.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Medina, Jesus R. published the artcileCell-Based Drug Discovery: Identification and Optimization of Small Molecules that Reduce c-MYC Protein Levels in Cells, Quality Control of 475216-25-2, the publication is Journal of Medicinal Chemistry (2021), 64(21), 16056-16087, database is CAplus and MEDLINE.

Elevated expression of the c-MYC oncogene is one of the most common abnormalities in human cancers. Unfortunately, efforts to identify pharmacol. inhibitors that directly target MYC have not yet yielded a drug-like mol. due to the lack of any known small mol. binding pocket in the protein, which could be exploited to disrupt MYC function. We have recently described a strategy to target MYC indirectly, where a screening effort designed to identify compounds that can rapidly decrease endogenous c-MYC protein levels in a MYC-amplified cell line led to the discovery of a compound series that phenocopies c-MYC knockdown by siRNA. Herein, we describe our medicinal chem. program that led to the discovery of potent, orally bioavailable c-MYC-reducing compounds The development of a min. pharmacophore model based on empirical structure activity relationship as well as the property-based approach used to modulate pharmacokinetics properties will be highlighted.

Journal of Medicinal Chemistry published new progress about 475216-25-2. 475216-25-2 belongs to amides-buliding-blocks, auxiliary class Fluoride,Nitro Compound,Amine,Benzene,Amide,Benzene Compounds, name is 4-Fluoro-N-methyl-3-nitrobenzamide, and the molecular formula is C8H7FN2O3, Quality Control of 475216-25-2.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Steffek, Micah published the artcileA multifaceted hit-finding approach reveals novel LC3 family ligands, Synthetic Route of 475216-25-2, the publication is Biochemistry, database is CAplus and MEDLINE.

Autophagy-related proteins (Atgs) drive the lysosome-mediated degradation pathway, autophagy, to enable the clearance of dysfunctional cellular components and maintain homeostasis. In humans, this process is driven by the mammalian Atg8 (mAtg8) family of proteins comprising the LC3 and GABARAP subfamilies. The mAtg8 proteins play essential roles in the formation and maturation of autophagosomes and the capture of specific cargo through binding to the conserved LC3-interacting region (LIR) sequence within target proteins. Modulation of interactions of mAtg8 with its target proteins via small-mol. ligands would enable further interrogation of their function. Here we describe unbiased fragment and DNA-encoded library (DEL) screening approaches for discovering LC3 small-mol. ligands. Both strategies resulted in compounds that bind to LC3, with the fragment hits favoring a conserved hydrophobic pocket in mATG8 proteins, as detailed by LC3A-fragment complex crystal structures. Our findings demonstrate that the malleable LIR-binding surface can be readily targeted by fragments; however, rational design of addnl. interactions to drive increased affinity proved challenging. DEL libraries, which combine small, fragment-like building blocks into larger scaffolds, yielded higher-affinity binders and revealed an unexpected potential for reversible, covalent ligands. Moreover, DEL hits identified possible vectors for synthesizing fluorescent probes or bivalent mols. for engineering autophagic degradation of specific targets.

Biochemistry published new progress about 475216-25-2. 475216-25-2 belongs to amides-buliding-blocks, auxiliary class Fluoride,Nitro Compound,Amine,Benzene,Amide,Benzene Compounds, name is 4-Fluoro-N-methyl-3-nitrobenzamide, and the molecular formula is C9H13NO2, Synthetic Route of 475216-25-2.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Wu, Zining published the artcileCell-Based Selection Expands the Utility of DNA-Encoded Small-Molecule Library Technology to Cell Surface Drug Targets: Identification of Novel Antagonists of the NK3 Tachykinin Receptor, Computed Properties of 475216-25-2, the publication is ACS Combinatorial Science (2015), 17(12), 722-731, database is CAplus and MEDLINE.

DNA-encoded small-mol. library technol. has recently emerged as a new paradigm for identifying ligands against drug targets. To date, this technol. has been used with soluble protein targets that are produced and used in a purified state. Here, we describe a cell-based method for identifying small-mol. ligands from DNA-encoded libraries against integral membrane protein targets. We use this method to identify novel, potent, and specific inhibitors of NK3, a member of the tachykinin family of G-protein coupled receptors (GPCRs). The method is simple and broadly applicable to other GPCRs and integral membrane proteins. We have extended the application of DNA-encoded library technol. to membrane-associated targets and demonstrate the feasibility of selecting DNA-tagged, small-mol. ligands from complex combinatorial libraries against targets in a heterogeneous milieu, such as the surface of a cell.

ACS Combinatorial Science published new progress about 475216-25-2. 475216-25-2 belongs to amides-buliding-blocks, auxiliary class Fluoride,Nitro Compound,Amine,Benzene,Amide,Benzene Compounds, name is 4-Fluoro-N-methyl-3-nitrobenzamide, and the molecular formula is C9H9ClN2, Computed Properties of 475216-25-2.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics