Post by De Gruyter Brill Life Sciences

KLK7 is a serine protease associated with skin disorders and tumorigenesis, making it a promising therapeutic target. A new study details the development and optimisation of #KLK7 inhibitors, progressing from substrate-based compounds to a more selective non-peptide series, guided by insights from crystal structures. 🧪 Crucially, these inhibitors block KLK7-mediated functions without inducing cytotoxicity in murine ovarian #Cancer cells. By introducing a species-adapted mutation, the research establishes a robust preclinical mouse model for evaluating human KLK7 inhibitors. 🧬 This work represents a significant advance in targeted cancer research. Read the full #OpenAccess article entitled “Development of kallikrein-related peptidase 7 (KLK7) inhibitors and their use in a species-adapted model for ovarian cancer”, by Torsten Steinmetzer, Laury Sofia Mesa Rangel, Sadaf Janghorban, Sajad Sabzi, Charlotte Boller, Alexander Maiwald, Heike Lang-Henkel, Sophia Bielesch, Julia Milisterfer, Giulia Magno, Prof. Dr. med. Holger Bronger, Dalila Darmoul, Viktor Magdolen & Tobias Dreyer, published in Biological Chemistry here: https://lnkd.in/e47KYMQf 📷 Modelled binding mode of inhibitor 44 (shown with carbons in yellow) in complex with KLK7 taken from the crystal structure of KLK7 in complex with inhibitor 6 (PDB: 5FAH). (A) The modeled complex is superimposed with the crystal structure of the structurally related inhibitor 6 (carbons in cyan). The residues of the catalytic triad are given with orange carbon atoms and additional KLK7 residues involved in polar contacts to the inhibitor are provided with carbons in green. KLK7 is shown with a transparent surface in light gray, a bound water molecule is shown as red sphere. (B) Polar contacts of the modelled inhibitor 44/KLK7 complex and the distance between the chlorine and the centroid of Tyr228 are shown as black lines with distances given in Å. Philipps University of Marburg - GERMANY Universidad Nacional de Colombia Technical University of Munich INSERM Sorbonne Université GBM - Gesellschaft für Biochemie und Molekularbiologie e.V.