Structure-based identification of bioactive phytochemicals targeting kallikrein-related peptidase 2 for prostate cancer therapy DOI Creative Commons

Deeba Shamim Jairajpuri,

Afzal Hussain, Mohamed F. Alajmi

et al.

Frontiers in Chemistry, Journal Year: 2025, Volume and Issue: 13

Published: March 26, 2025

Kallikrein-related peptidase 2 (KLK2) is a serine protease exhibiting antiangiogenic properties through proteolytic activity. KLK2 overexpressed in prostate cancer and plays pivotal role progression, establishing it as potential therapeutic target. Despite the promising results of small molecule inhibitors targeting treatment, there are still many challenges development application these inhibitors. As consequence, very few have advanced to clinical trials because issues with specificity selectivity. Moreover, precise mechanisms underlying KLK2’s interactions remain inadequately understood. This study used structure-based virtual screening phytochemical library found three compounds, Phaseolin, Withaphysalin D, Nicandrenone, These compounds exhibited high binding affinities (−8.9 −8.8 kcal/mol), favorable pharmacokinetic profiles, stable catalytic residues (including His65) docking studies. Their was further validated MM-PBSA free energy calculations, which confirmed energetically KLK2. The findings suggest that phytochemicals be exploited novel improved efficacy. While experimental validation enzymatic inhibition antitumor efficacy required, this provides structural mechanistic foundation for advancing candidates into preclinical testing. also highlight use libraries dynamics-driven developing targeted therapies cancer.

Language: Английский

Current Landscape and Prospects of CAR-T Cell Therapy in Prostate Cancer: A Clinical Trial Review DOI Creative Commons

Jiasheng Zhou

Theoretical and Natural Science, Journal Year: 2025, Volume and Issue: 68(1), P. 215 - 220

Published: Jan. 13, 2025

This review talks about the causes and dangers of prostate cancer. The widespread cancer shortcomings traditional therapies are discovered, principles, significance, prospects CAR-T therapy were discussed. Through discussing significance progress clinical trials. paper relevant targets for such as PSMA, PSCA, reviews purpose, process results currently approved hopes to find focus current in trials contributes development more efficient

Language: Английский

Citations

0
Structure-based identification of bioactive phytochemicals targeting kallikrein-related peptidase 2 for prostate cancer therapy DOI Creative Commons

Deeba Shamim Jairajpuri,

Afzal Hussain, Mohamed F. Alajmi

et al.

Frontiers in Chemistry, Journal Year: 2025, Volume and Issue: 13

Published: March 26, 2025

Kallikrein-related peptidase 2 (KLK2) is a serine protease exhibiting antiangiogenic properties through proteolytic activity. KLK2 overexpressed in prostate cancer and plays pivotal role progression, establishing it as potential therapeutic target. Despite the promising results of small molecule inhibitors targeting treatment, there are still many challenges development application these inhibitors. As consequence, very few have advanced to clinical trials because issues with specificity selectivity. Moreover, precise mechanisms underlying KLK2’s interactions remain inadequately understood. This study used structure-based virtual screening phytochemical library found three compounds, Phaseolin, Withaphysalin D, Nicandrenone, These compounds exhibited high binding affinities (−8.9 −8.8 kcal/mol), favorable pharmacokinetic profiles, stable catalytic residues (including His65) docking studies. Their was further validated MM-PBSA free energy calculations, which confirmed energetically KLK2. The findings suggest that phytochemicals be exploited novel improved efficacy. While experimental validation enzymatic inhibition antitumor efficacy required, this provides structural mechanistic foundation for advancing candidates into preclinical testing. also highlight use libraries dynamics-driven developing targeted therapies cancer.

Language: Английский

Citations

0