Takeuchi, Tomoki published the artcileDiscovery of Aryloxyphenyl-Heptapeptide Hybrids as Potent and Selective Matrix Metalloproteinase-2 Inhibitors for the Treatment of Idiopathic Pulmonary Fibrosis, Computed Properties of 71989-31-6, the publication is Journal of Medicinal Chemistry (2022), 65(12), 8493-8510, database is CAplus and MEDLINE.
Matrix metalloproteinase-2 (MMP2) is a zinc-dependent endopeptidase that plays important roles in the degradation of extracellular matrix proteins. MMP2 is considered to be an attractive target for the treatment of various diseases such as cancer, arthritis, and fibrosis. In this study, we have developed a novel class of MMP2-selective inhibitors by hybridizing the peptide that binds to a zinc ion and S2-S5 pockets with small mols. that bind to the S1′ pocket. Structural modifications based on X-ray crystallog. revealed that the introduction of 2,4-diaminobutanoic acid (Dab) at position 4 dramatically enhanced MMP2 selectivity by forming an electrostatic interaction with Glu130. After improving the metabolic and chem. stability, TP0556351 (9)(I) was identified. It exhibited potent MMP2 inhibitory activity (IC50 = 0.20 nM) and extremely high selectivity. It suppressed the accumulation of collagen in a bleomycin-induced idiopathic pulmonary fibrosis model in mice, demonstrating the efficacy of MMP2-selective inhibitors for fibrosis.
Journal of Medicinal Chemistry published new progress about 71989-31-6. 71989-31-6 belongs to catalysis-chemistry, auxiliary class Amino acide derivatives,pyrrolidine, name is Fmoc-Pro-OH, and the molecular formula is C38H74Cl2N2O4, Computed Properties of 71989-31-6.
Referemce:
https://courses.lumenlearning.com/boundless-chemistry/chapter/catalysis/,
Catalysis – Wikipedia