William J. Moore, Ph.D.

  • Center for Cancer Research
  • National Cancer Institute
Chemical Biology Laboratory


Dr. Moore is a drug hunter and medicinal chemist with experience from the pharmaceutical industry and most recently at Leidos Biomedical Research where he was supporting the NCI Experimental Therapeutics Program (NExT). He leads projects within the CCR Medicinal Chemistry Accelerator (MCA), a new resource for CCR investigators interested in developing small molecule inhibitors towards anticancer drug candidates. The MCA aims to promote the translation of basic science discoveries by CCR investigators into advanced small molecule hits and leads that can be accelerated towards anticancer drug candidates. These efforts require resources that are beyond the scope of individual CCR sections, and are accomplished through collaborative interactions with investigators, the MCA, and contract research organizations (CROs).

Dr. Moore works collaboratively with principal investigators to enable CCR PI projects by leveraging in-house resources and CROs to apply iterative design and synthesis of hit compounds to improve potency and establish structure-activity/property relationships (SAR/SPR). Coupled with data from the intramural labs, resources to support structural biology (where applicable), physicochemical, selectivity and liability assays are applied to profile compounds in hit-to-lead optimization. Advanced compounds are optimized for pharmacokinetic, pharmacodynamic, toxicity and formulation characteristics as well as in vivo efficacy. Throughout this process, Dr. Moore also works closely with representatives from NCI’s Technology Transfer Center to facilitate the patenting process.

Areas of Expertise

1) medicinal chemistry 2) drug discovery 3) synthetic organic chemistry 4) parallel synthesis 5) structure based drug design 6) CRO management


Selected Key Publications

Structure-Based Discovery of Potent WD Repeat Domain 5 Inhibitors that Demonstrate Efficacy and Safety in Preclinical Animal Models

Kevin B. Teuscher, Somenath Chowdhury, Kenneth M. Meyers, Jianhua Tian, Jiqing Sai, Mayme Van Meveren, Taylor M. South, John L. Sensintaffar, Tyson A. Rietz, Soumita Goswami, Jing Wang, Brian C. Grieb, Shelly L. Lorey, Gregory C. Howard, Qi Liu, William J. Moore, Gordon M. Stott, William P. Tansey, Taekyu Lee, and Stephen W. Fesik
PNAS. 2022. [ Journal Article ]

Discovery of Potent Orally Bioavailable WD Repeat Domain 5 (WDR5) Inhibitors Using a Pharmacophore-Based Optimization

Kevin B. Teuscher, Kenneth M. Meyers, Qiangqiang Wei, Jonathan J. Mills, Jianhua Tian, Joseph Alvarado, Jiqing Sai, Mayme Van Meveren, Taylor M. South, Tyson A. Rietz, Bin Zhao, William J. Moore, Gordon M. Stott, William P. Tansey, Taekyu Lee, and Stephen W. Fesik*
J Med Chem. 65(8): 6287-6312, 2022.
Full-Text Article
[ Journal Article ]

Discovery and Optimization of 2 H-1λ 2-Pyridin-2-one Inhibitors of Mutant Isocitrate Dehydrogenase 1 for the Treatment of Cancer

Jason M Rohde, Surendra Karavadhi, Rajan Pragani, Li Liu, Yuhong Fang, Weihe Zhang, Andrew McIver, Hongchao Zheng, Qingyang Liu, Mindy I Davis, Daniel J Urban, Tobie D Lee, Dorian M Cheff, Melinda Hollingshead, Mark J Henderson, Natalia J Martinez, Kyle R Brimacombe, Adam Yasgar, Wei Zhao, Carleen Klumpp-Thomas, Sam Michael, Joseph Covey, William J Moore, Gordon M Stott, Zhuyin Li, Anton Simeonov, Ajit Jadhav, Stephen Frye, Matthew D Hall, Min Shen, Xiaodong Wang, Samarjit Patnaik, Matthew B Boxer
J Med Chem. 64(8): 4913-4946, 2013.
Full-Text Article
[ Journal Article ]

Pyrazole-Based Lactate Dehydrogenase Inhibitors with Optimized Cell Activity and Pharmacokinetic Properties

Ganesha Rai, Daniel J Urban, Bryan T Mott, Xin Hu, Shyh-Ming Yang, Gloria A Benavides, Michelle S Johnson, Giuseppe L Squadrito, Kyle R Brimacombe, Tobie D Lee, Dorian M Cheff, Hu Zhu, Mark J Henderson, Katherine Pohida, Gary A Sulikowski, David M Dranow, Md Kabir, Pranav Shah, Elias Padilha, Dingyin Tao, Yuhong Fang, Plamen P Christov, Kwangho Kim, Somnath Jana, Pavan Muttil, Tamara Anderson, Nitesh K Kunda, Helen J Hathaway, Donna F Kusewitt, Nobu Oshima, Murali Cherukuri, Douglas R Davies, Jeffrey P Norenberg, Larry A Sklar, William J Moore, Chi V Dang, Gordon M Stott, Leonard Neckers, Andrew J Flint, Victor M Darley-Usmar, Anton Simeonov, Alex G Waterson, Ajit Jadhav, Matthew D Hall, David J Maloney
J Med Chem. 63(19): 10984-11011, 2020.
Full-Text Article
[ Journal Article ]

Discovery of Potent Myeloid Cell Leukemia-1 (Mcl-1) Inhibitors That Demonstrate in Vivo Activity in Mouse Xenograft Models of Human Cancer

Taekyu Lee, Plamen P Christov, Subrata Shaw, James C Tarr, Bin Zhao, Nagarathanam Veerasamy, Kyu Ok Jeon, Jonathan J Mills, Zhiguo Bian, John L Sensintaffar, Allison L Arnold, Stuart A Fogarty, Evan Perry, Haley E Ramsey, Rebecca S Cook, Melinda Hollingshead, Myrtle Davis Millin, Kyung-Min Lee, Brian Koss, Amit Budhraja, Joseph T Opferman, Kwangho Kim, Carlos L Arteaga, William J Moore, Edward T Olejniczak, Michael R Savona, Stephen W Fesik
J Med Chem. 62(8): 3971-3988, 2019.
Full-Text Article
[ Journal Article ]