/fep-benchmark

Benchmark set for relative free energy calculations.

MIT LicenseMIT

fep-benchmark

Benchmark set for relative free energy calculations.

Created by Christina Schindler and Daniel Kuhn, Merck KGaA, Darmstadt, Germany.

December 2018

DOI: 10.5281/zenodo.3360435

Manuscript

Schindler et al. "Large-Scale Assessment of Binding Free Energy Calculations in Active Drug Discovery Projects" (2020) JCIM. 10.1021/acs.jcim.0c00900

Previously presented at Alchemical Free Energy Workshop 2019 in Goettingen, Germany.

DOI: 10.5281/zenodo.3258925

References for datasets used in benchmark

CDK8

Schiemann, Kai, et al. "Discovery of potent and selective CDK8 inhibitors from an HSP90 pharmacophore." Bioorganic & medicinal chemistry letters 26.5 (2016): 1443-1451.

DOI: 10.1016/j.bmcl.2016.01.062

c-Met

Dorsch, Dieter, et al. "Identification and optimization of pyridazinones as potent and selective c-Met kinase inhibitors." Bioorganic & medicinal chemistry letters 25.7 (2015): 1597-1602.

DOI: 10.1016/j.bmcl.2015.02.002

Eg5

Schiemann, Kai, et al. "The discovery and optimization of hexahydro-2H-pyrano [3, 2-c] quinolines (HHPQs) as potent and selective inhibitors of the mitotic kinesin-5." Bioorganic & medicinal chemistry letters 20.5 (2010): 1491-1495.

DOI: 10.1016/j.bmcl.2010.01.110

Hif2a

Wallace, Eli M., et al. "A small-molecule antagonist of HIF2α is efficacious in preclinical models of renal cell carcinoma." Cancer research 76.18 (2016): 5491-5500.

DOI: 10.1158/0008-5472.CAN-16-0473

Dixon, Darryl David, et al. "Aryl ethers and uses thereof." U.S. Patent No. 9,908,845. 6 Mar. 2018.

URL: Google Patents

Hif2a JMC 2023

Buchstaller et al. "Discovery of Cycloalkyl[c]thiophenes as Novel Scaffolds for Hypoxia-Inducible Factor-2α Inhibitors" J. Med. Chem. (2023) 66, 13, 8666–8686.

DOI: 10.1021/acs.jmedchem.3c00332

PFKFB3

Boutard, Nicolas, et al. "Discovery and Structure–Activity Relationships of N-Aryl 6-Aminoquinoxalines as Potent PFKFB3 Kinase Inhibitors." ChemMedChem 14.1 (2019): 169-181.

DOI: 10.1002/cmdc.201800569

SHP2

Chen, Ying-Nan P., et al. "Allosteric inhibition of SHP2 phosphatase inhibits cancers driven by receptor tyrosine kinases." Nature 535.7610 (2016): 148.

DOI:10.1038/nature18621

Garcia Fortanet, Jorge, et al. "Allosteric inhibition of SHP2: identification of a potent, selective, and orally efficacious phosphatase inhibitor." Journal of medicinal chemistry 59.17 (2016): 7773-7782.

DOI: 10.1021/acs.jmedchem.6b00680

Chen, Christine Hiu-tung, et al. "1-pyridazin-/triazin-3-yl-piper (-azine)/idine/pyrolidine derivatives and compositions thereof for inhibiting the activity of shp2." U.S. Patent Application No. 15/110,498.

URL: Google Patents

SYK

Currie, Kevin S., et al. "Discovery of GS-9973, a selective and orally efficacious inhibitor of spleen tyrosine kinase." Journal of medicinal chemistry 57.9 (2014): 3856-3873.

DOI: 10.1021/jm500228a

TNKS2

Buchstaller, Hans-Peter, et al. "Discovery and Optimization of 2-Arylquinazolin-4-ones into a Potent and Selective Tankyrase Inhibitor Modulating Wnt Pathway Activity." Journal of medicinal chemistry 62.17 (2019): 7897-7909.

DOI: 10.1021/acs.jmedchem.9b00656