Journal
JOURNAL OF MEDICINAL CHEMISTRY
Volume 61, Issue 6, Pages 2533-2551Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.jmedchem.7b01884
Keywords
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Categories
Funding
- AbbVie [1097737]
- Bayer Pharma AG [1097737]
- Boehringer Ingelheim [1097737]
- Canada Foundation for Innovation [1097737]
- Eshelman Institute for Innovation [1097737]
- Genome Canada [1097737]
- Innovative Medicines Initiative (EU/EFPIA) [ULTRA-DD grant] [1097737, 115766]
- Janssen [1097737]
- Merck KGaA Darmstadt Germany [1097737]
- MSD [1097737]
- Novartis Pharma AG [1097737]
- Ontario Ministry of Economic Development and Innovation [1097737]
- Pfizer [1097737]
- Sao Paulo Research Foundation-FAPESP [1097737]
- Takeda [1097737]
- Wellcome [1097737, 106169/ZZ14/Z]
Ask authors/readers for more resources
Recent literature has both suggested and questioned MTH1 as a novel cancer target. BAY-707 was just published as a target validation small molecule probe for assessing the effects of pharmacological inhibition of MTH1 on tumor cell survival, both in vitro and in vivo.(1) In this report, we describe the medicinal chemistry program creating BAY-707, where fragment based methods were used to develop a series of highly potent and selective MTH1 inhibitors. Using structure-based drug design and rational medicinal chemistry approaches, the potency was increased over 10,000 times from the fragment starting point while maintaining high ligand efficiency and drug-like properties.
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