PROTAC approaches against drug-resistant EGFRC797S/L858R/T790M mutants: biological evaluation and SAR studies (2020–2025)

Ankush Kumar, Vishakha Sharma, Pallvi Kumari, Rajwinder Kaur and Rohit Bhatia

RSC Med. Chem., 2026, 17, 1888
DOI: 10.1039/D5MD01113B

Beyond-Rule-of-Five Compounds Are Not Different: In Vitro–In Vivo Extrapolation of Female CD-1 Mouse Clearance Based on Merck Healthcare KGaA Compound Set

Christine K. Maurer, Zhizhou Fang, Heide M. Duevel, Stephanie Harlfinger and Carl Petersson

Pharmaceuticals, 2025, 18, 568
DOI: 10.3390/ph18040568

PBPK Modelling of PROTACs: Learnings from ARV-110 as a Case Example

Farzaneh Salem, Ali Tabatabaeian Nimavardi, Abhishek Srivastava, Katharina Krollik, Andreas Reichel, David Cebrian, Kunal S. Taskar, James W. T. Yates, Caroline Rynn and Heide Marika Duevel

AAPS J, 2026, 28
DOI: 10.1208/s12248-026-01231-0

Methods to Study the Molecular Mechanism and Drive the Design of Protein Degraders

Charlotte Crowe and Alessio Ciulli

Chem. Rev., 2026, 126, 5755
DOI: 10.1021/acs.chemrev.5c00800

Enhancing Solubility in VHL-Based PROTACs: Optimized USP7 Degraders for Improved Developability

Sophie Wittenburg, Maximilian R. Zuleeg, Kirsten Peter, Patricia Lemnitzer, Rabea Voget, Aleša Bricelj, Martina Gobec, Nele Dierlamm, Michael B. Braun, Thomas M. Geiger, Christopher Heim, Alicia Stakemeier, Karl G. Wagner, Radosław P. Nowak, Marcus D. Hartmann, Izidor Sosič, Michael Gütschow, Jan Krönke and Christian Steinebach

J. Med. Chem., 2025, 68, 15711
DOI: 10.1021/acs.jmedchem.5c00718

Natural Products Beyond Inhibition: A Mechanistic Framework Spanning Pockets, Interfaces, and Kinetic Barriers

Shuo Miao, Huadong Zhao, Aizhe Liu, Ning Xu, Xiangsheng Liu and Xie Wang

Molecules, 2026, 31, 1577
DOI: 10.3390/molecules31101577

Exploiting Pharmacokinetic/Pharmacodynamic Methods for Optimizing and Accelerating Drug Development of Innovative Anti‐Infectives

Katharina Rox

ChemMedChem, 2026, 21
DOI: 10.1002/cmdc.202500743

In vitro-in vivo extrapolation of intrinsic clearance based on data from human hepatocyte spheroids – a case study with the low-clearance drug xevinapant

Dominik Jacob, Ulrike Gradhand, Christine K. Maurer, Holger Scheible, Christian Stelz, Marlene Hagel, Jonny Nachtigall, Benedikt Lang, Lilian H.J. Richter, Frederic Massiere, Annick Menetrey and Felix Rohdich

Xenobiotica, 2025, 55, 729
DOI: 10.1080/00498254.2025.2587283

Conformational Dynamics in the Cell Membrane Interactions of Bispecific Targeted Degrader Therapeutics

Emma Inganäs, Hanna Lavén, Rémi Caraballo, Fredrik Klingegård, MyLan Eklund, Linda Andersson, Constanze Hilgendorf and Pär Matsson

J. Med. Chem., 2025, 68, 25881
DOI: 10.1021/acs.jmedchem.5c01499

Evaluation of the disconnect between hepatocyte and microsomal intrinsic clearance at intracellular and extracellular pH

Christine Katharina Maurer, Zhizhou Fang, Stephanie Harlfinger and Carl Petersson

Drug Metabolism and Disposition, 2026, 54, 100288
DOI: 10.1016/j.dmd.2026.100288

The In Vivo Effect of Amorphous Drug Nanoprecipitates on the Intestinal Absorption of the PROTACs ARV-110 (Bavdeglutamide) and ARV-471 (Vepdegestrant)

Janis Niessen, Mirko Koziolek, Anura Indulkar, Thomas Borchardt, Markus Sjöblom, Mikael Hedeland, Hans Lennernäs and David Dahlgren

Mol. Pharmaceutics, 2026, 23, 3445
DOI: 10.1021/acs.molpharmaceut.6c00207

Diastereomeric Branched-Ester dBET1 Analogs Exhibit Conformation-Dependent Differences in Passive Membrane Permeability

Mazin A. S. Abdelwahid, Eisuke Hayakawa, Keigo Hirai, Mayumi Ishii, Kayoko Kanamitsu, Saori Yasuda, Fumiaki Ohtake, Shinichi Sato, Shusuke Tomoshige and Minoru Ishikawa

J. Med. Chem., 2026, 69, 2900
DOI: 10.1021/acs.jmedchem.5c02791

Misconceptions among medicinal chemists regarding ADME and PK optimization

Yue Pan

Med Chem Res, 2026, 35, 668
DOI: 10.1007/s00044-026-03543-4

Environmentally sensitive fluorescent probes for the visualization of selective proteins: Recent progress and biomedical applications

Jinhui Hu, Lulu Jiang, Lanqing Li and Wen-Hua Chen

European Journal of Medicinal Chemistry, 2025, 300, 118158
DOI: 10.1016/j.ejmech.2025.118158

Rational Design of PROTAC Linkers Featuring Ferrocene as a Molecular Hinge to Enable Dynamic Conformational Changes

Alessandra Salerno, Lianne H. E. Wieske, Claudia J. Diehl and Alessio Ciulli

J. Am. Chem. Soc., 2025, 147, 13328
DOI: 10.1021/jacs.4c18354

Lessons learned in linking PROTACs from discovery to the clinic

Andy Pike, Esther C. Y. Lee, Iacovos N. Michaelides, Markus Schade, Ankit Sharma, James S. Scott and Abhishek Srivastava

Nat Rev Chem, 2025, 10, 117
DOI: 10.1038/s41570-025-00784-6

Advances in computational methods for PROTAC drug discovery

Massyel S. Martinez-Cortés, Carlos A. Velázquez-Martínez and José L. Medina-Franco

Drug Discovery Today, 2026, 31, 104627
DOI: 10.1016/j.drudis.2026.104627