Download MendeleyRapid Elaboration of Fragments into Leads by X-ray Crystallographic Screening of Parallel Chemical Libraries (REFiLX).
Bentley, M.R., Ilyichova, O.V., Wang, G., Williams, M.L., Sharma, G., Alwan, W.S., Whitehouse, R.L., Mohanty, B., Scammells, P.J., Heras, B., Martin, J.L., Totsika, M., Capuano, B., Doak, B.C., Scanlon, M.J.(2020) J Med Chem 63: 6863-6875
- PubMed: 32529824
- DOI: https://doi.org/10.1021/acs.jmedchem.0c00111
- Primary Citation of Related Structures:
5QKC, 5QKD, 5QKE, 5QKF, 5QKG, 5QKH, 5QKI, 5QKJ, 5QKK, 5QKL, 5QKM, 5QKN, 5QKO, 5QKP, 5QKQ, 5QKR, 5QKS, 5QKT, 5QKU, 5QKV, 5QKW, 5QKX, 5QKY, 5QKZ, 5QL0, 5QL1, 5QL2, 5QL3, 5QL4, 5QL5, 5QL6, 5QL7, 5QL8, 5QL9, 5QLA, 5QLB, 5QLC, 5QLD, 5QLE, 5QLF, 5QLG, 5QLH, 5QLI, 5QLJ, 5QLK, 5QLL, 5QLM, 5QLN, 5QLO, 5QLP - PubMed Abstract:
A bottleneck in fragment-based lead development is the lack of systematic approaches to elaborate the initial fragment hits, which usually bind with low affinity to their target. Herein, we describe an analysis using X-ray crystallography of a diverse library of compounds prepared using microscale parallel synthesis. This approach yielded an 8-fold increase in affinity and detailed structural information for the resulting complex, providing an efficient and broadly applicable approach to early fragment development.
- Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC 3052, Australia.
Organizational Affiliation:
