2. Academic Validation
  3. Automated Molecular Design in BRADSHAW, Applied to the Optimization of ERAP1 Inhibitors

Automated Molecular Design in BRADSHAW, Applied to the Optimization of ERAP1 Inhibitors

  • J Med Chem. 2026 Apr 23;69(8):8869-8896. doi: 10.1021/acs.jmedchem.5c03071.
Robert P Law 1,  Ian D Wall 1,  Richard Lonsdale 1,  Ross P Hryczanek 1,  Daniel Barker 1,  Tim N Barrett 1,  Rino A Bit 1,  John J Coward 1,  Matthew W Gray 1,  Darren V S Green 1,  Callum J Hall 1,  Ashley P Hancock 1,  Carl Haslam 1,  David J Hirst 1,  Heather F Hryczanek 1,  Jonathan P Hutchinson 1,  Semra Kitchen 1,  David Marcus 1,  Jared Marklew 1,  Joseph Mason 1,  Nicholas D Measom 1,  Margarete Neu 1,  Simon Peace 1,  Alex Phillipou 1,  Stephen D Pickett 1,  Peter Pogány 1,  James Rowedder 1,  Paul Rowland 1,  Paul Scott-Stevens 1,  Gail A L Seal 1,  Hester Sheehan 1,  Efstratios Stratikos 2,  Chloe Tayler 1,  Jonathan A Taylor 1,  Christopher P Tinworth 1,  Giovanni Vitulli 1
Affiliations

Affiliations

  • 1 GSK, Medicines Research Centre, Stevenage SG1 2NY, U.K.
  • 2 National Centre for Scientific Research "Demokritos", Attiki 15341, Greece.
PMID: 41973545 DOI: 10.1021/acs.jmedchem.5c03071
Abstract

Generative design and machine learning are increasingly prevalent in medicinal chemistry. To pilot the comprehensive use of automated molecular design on a project, the BRADSHAW platform was used to optimize a series of inhibitors of Endoplasmic Reticulum Aminopeptidase 1 (ERAP1), an emerging target in Cancer Immunotherapy and autoimmune diseases. Through four consecutive iterations applying in silico molecular generation, property prediction and filtering, we conducted a multiparameter optimization of potency, physicochemical properties and pharmacokinetics. Continuous refinement of Machine Learning (ML) models led to improved scoring accuracy and compound quality, culminating in identification of in vitro and in vivo tool molecules. We also discuss our reflections on the pilot and integration of automated design into medicinal chemistry projects, including observations of the human factors resulting from increased use of computational design, and recommendations for future projects.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-183267
    ERAP1抑制剂
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z