Yali He

Director of Medicinal Chemistry Center

Ph.D.

Medicinal chemistry and early clinical drug discovery of small molecules

(+86) 010 81912652 yalihe(at)cibr.ac.cn

https://medchem.cibr.ac.cn/

Education Experience

Ph. D. in Medicinal Chemistry, the University of Tennessee Health Science Center (UTHSC), Memphis, Tennessee, USA.

M. Sc. in Medicinal Chemistry, Peking Union Medical College / Chinese Academy of Medical Sciences, Beijing, China.

B. Sc. Pharmacy, Inner Mongolia Medical University, Huhhot, China

Professional Experience

2022-Present Director of Medicinal Chemistry Center, Chinese Institute for Brain Research, Beijing (CIBR), China

2015-2022 Medicinal Chemist / Dr. Duane D. Miller’s Associate, the University of Tennessee Health Science Center (UTHSC), USA

2004-2014 Senior Scientist, GTx Inc. (merged with Oncterenal Therapeutics), USA

2000-2004 Senior Scientist, Patheon by Thermo Fisher Scientific, USA

Research Description

Research in the center is interdisciplinary and built around the key themes of medicinal chemistry and drug discovery. Our research utilizes modern medicinal chemistry and organic chemistry techniques to rationally design and synthesize novel compounds for a range of CNS targets which are associated with conditions such as Alzheimer’s and Parkinson’s disease, dementia, as well as glioblastoma multiforme (GBM).

Medicinal chemistry center is to provide

(1) medicinal chemistry and early clinical drug discovery for small molecules;

(2) structure-activity relationships (SAR) of anti-tumor drug and CNS bioactive molecules;

(3) rationale CNS drug and anti-tumor drug design and evaluation;

(4) preclinical and early clinical drug discovery process, from target identification, hit and lead optimization, to candidate selection, preclinical development and Phase I clinical studies planning;

(5) modern concepts in drug discovery, including property- and structure-based drug design, fragment-based drug discovery, ligand-based analogs design, in silico methods and ADME-T principles.

Publications

1. Novel structural-related analogs of PFI-3 (SRAPs) that target the BRG1 catalytic subunit of the SWI/SNF complex increase the activity of temozolomide in glioblastoma cells, Yali He, Chuanhe Yang, Yinan Wang, Joshua R. Sacher, Michelle M. Sims, Lawrence M. Pfeffer, Duane D. Miller. Bioorg. Med. Chem., 2022, 53, 116533.

2. Targeting the bromodomain of BRG-1/BRM subunit of the SWI/SNF complex increases the anticancer activity of temozolomide in glioblastoma, Chuanhe Yang, Yinan Wang, Michelle M. Sims, Yali He, Duane D. Miller, and Lawrence M. Pfeffer. Pharmaceuticals, 2021, 14(9), 904.

3. Exploration and biological evaluation of basic heteromonocyclic propanamide derivatives as SARDs for the treatment of enzalutamide-resistant prostate cancer, Yali He, Dong-Jin Hwang, Suriyan Ponnusamy, Thirumagal Thiyagarajan, Michael L. Mohler, Ramesh Narayanan, Duane D. Miller. J. Med. Chem., 2021, 64(15), 11045-11062.

4. An Overview of Next-Generation Androgen Receptor-Targeted Therapeutics in Development for the Treatment of Prostate Cancer. Michael Mohler, Arunima Sikdar, Suriyan Ponnusamy, Dong-Jin Hwang, Yali He, Duane D. Miller, Ramesh Narayanan. Int. J. Mol. Sci., 2021, 22(4), 2124.

5. Pyrazol-1-yl-Propanamides as SARD and Pan-Antagonists for the Treatment of Enzalutamide-Resistant Prostate Cancer. Yali He, Dong-Jin Hwang, Suriyan Ponnusamy, Thirumagal Thiyagarajan, Michael L. Mohler, Ramesh Narayanan, Duane D. Miller. J. Med. Chem., 2020, 63(21), 12642-12665.Clinical Cancer Research, 2019, 25(22), 6764-6780.

7. A New Generation of Selective Androgen Receptor Degraders: Our Initial Design, Synthesis, and Biological Evaluation of New Compounds with Enzalutamide-Resistant Prostate Cancer Activity. Dong-Jin Hwang, Yali He, Suriyan Ponnusamy, Michael L. Mohler, Thirumagal Thiyagarajan, Iain J. McEwan, Ramesh Narayanan, Duane D. Miller. J. Med. Chem., 2019, 62(2), 491-511.

8. Novel Selective Agents for the Degradation of Androgen Receptor Variants to Treat Castration-Resistant Prostate Cancer. Suriyan Ponnusamy, Christopher C. Coss, Thirumagal Thiyagarajan, Kate Watts, Dong-Jin Hwang, Yali He, Luke A. Selth, Iain J. McEwan, Carles B. Duke, Jayaprakash Pagadala, Geetika Singh, Robert W. Wake, Christopher Ladbetter, Wayne D. Tilley, Tudor Moldoveanu, James T. Dalton, Duane D Miller, and Ramesh Narayanan. Cancer Research, 77(22), November 15, 2017, 6282-6298.

9. Discovery and preclinical characterization of Novel Small molecule TRK and ROS1 Tyrosine Kinase Inhibitors for the Treatment of Cancer and Inflammation. Ramesh Narayanan, Muralimohan Yepuru, Christopher C. Coss, Zhongzhi Wu, Matthew N. Bauler, Christina M. Barrett, Michael L. Mohler, Yun Wang, Juhyun Kim, Linda M. Snyder, Yali He, Nelson Levy, Duane D. Miller, James T. Dalton. PLOS ONE, 2013; 8(12): 1-14.

10. Role and pharmacologic significance of cytochrome P-450 2D6 in oxidative metabolism of toremifene and tamoxifen. Juhyun Kim, Christopher C. Coss, Christina M. Barrett, Michael L. Mohler, Casey E. Bohl, Chien-Ming Li, Yali He, Karen A. Veverka, and James T. Dalton. International Journal of Cancer, 2013; 132(6): 1475-1485.

11. Effects of Nonsteroidal Selective Androgen Receptor Modulators on Female Sexual Behavior. Amanda Jones, Dong Jin Hwang, Charles B. Duke, Yali He, Anjaiah Siddam, Duane D. Miller, James T. Dalton. Journal of Pharmacology and Experimental Therapeutics (JPET), 2010; 334: 439-448.

12. Estrogen Receptor Beta Selective Nonsteroidal Estrogens: Seeking Tissue Specificity: Michael L Mohler, Ramesh Narayanan, Christopher C. Coss, Kejiang Hu, Yali He, Zhongzhi Wu, Seoung-Soo Hong, Dong Jin Hwang, Duane D Miller, and James T. Dalton. Expert Opin. Ther. Patents, 2010; 20(4): 507-534.

13. Perspective Article: Nonsteroidal Selective Androgen Receptor Modulators (SARMs): Dissociating the Anabolic and Androgenic Activities of the Androgen Receptor for Therapeutic Benefit: Michael L Mohler, Casey E. Bohl, Amanda Jones, Christopher C. Coss, Ramesh Narayanan, Yali He, Dong Jin Hwang, James T. Dalton, and Duane D Miller. J. Med. Chem., 2009; 52(12): 3597-3617.

14. Recent and Emerging Anti-Diabetes Targets. Michael L Mohler, Yali He, Zhongzhi Wu, Dong Jin Hwang, and Duane D Miller. Medicinal Research Reviews, 2009; 29(1): 125-195.

15. Nonsteroidal tissue-selective androgen receptor modulators. Mohler, Michael L.; Bohl, Casey E.; Narayanan, Ramesh; He, Yali; Hwang, Dong Jin; Dalton, James T.; Miller, Duane D. Methods and Principles in Medicinal Chemistry. 2008, 39 (Nuclear Receptors as Drug Targets), 249-304.

16. Hydroxysteroid Dehydrogenase (17β-HSD3, 17β-HSD5, and 3α-HSD3) Inhibitors: Extragonadal Regulation of Intracellular Sex Steroid Hormone Levels: Michael L Mohler, Ramesh Narayanan, Yali He, Duane D Miller and James T. Dalton. Recent Patents on Endocrine, Metabolic & Immune Drug Discovery, 2007; 1: 103-118.

17. Non-steroidal glucocorticoid receptor antagonists: the race to replace RU-486 for anti-glucocorticoid therapy: Michael L Mohler, Yali He, Zhongzhi Wu, Seoung-Soo Hong & Duane D Miller. Expert Opin. Ther. Patents, 2007; 17(1): 59-81.

18. Dissociated non-steroidal glucocorticoids: tuning out untoward effects: Michael L Mohler, Yali He, Zhongzhi Wu, Seoung-Soo Hong & Duane D Miller. Expert Opin. Ther. Patents, 2007; 17(1): 37-58.

19. Design, Synthesis, and Biological Characterization of Metabolically Stable Selective Androgen Receptor Modulators: Craig A. Marhefka, Wenqing Gao, Kiwon Chung, Juhyun Kim, Yali He, Donghua Yin, Casey Bohl, James T. Dalton, and Duane D. Miller. J. Med. Chem., 2004; 47(4): 993-998.

20. Key Structural Features of Nonsteroidal Ligands for Binding and Activation of the Androgen Receptor. Donghua Yin, Yali He, Minoli A. Perera, Seoung Soo Hong, Craig Marhefka, Nina Stourman, Leonid Kirkovsky, Duane D. Miller, and James T. Dalton. Molecular Pharmacology, 2003; 63 (1): 211-223.

21. Pharmacology, Pharmacokinetics, and Metabolism of Acetothiolutamide, A Novel Nonsteroidal Agonist for the Androgen Receptor. Donghua Yin, Huiping Xu, Yali He, Leonid Kirkovsky, Duane D. Miller, and James T. Dalton. Journal of Pharmacology and Experimental Therapeutics (JPET), 2003; 304(3): 1323-1333.

22. Pharmacodynamics of Selective Androgen Receptor Modulators (SARMs). Donghua Yin, Wenqing Gao, Jeff Kearbey, Huiping Xu, Kiwon Chung, Yali He, Craig Marhefka, Karen A. Veverka, Duane D. Miller and James T. Dalton. Journal of Pharmacology and Experimental Therapeutics (JPET), 2003; 304(3): 1334-1340.

23. Novel nonsteroidal ligands with high binding affinity and functional activity for the androgen receptor. Yali He, Donghua Yin, Minoli Perera, Leonid Kirkovsky, Nina Stourman, Wei Li, James T. Dalton, and Duane D. Miller. Eur. J. Med. Chem., 2002; 37(8): 619-634.

24. Synthesis and human b-adrenoceptor activity of 1-(3,5-diiodo-4- methoxybenzyl)-1,2,3,4-tetrahydroisoquinoline-6-ol derivatives in vivo. Yali He, Victor I. Nikulin, Sandeep S. Vansal, Dennis R. Feller, and Duane D. Miller. J. Med. Chem., 2000; 43(4): 591-598.

Full List Available upon request.

BOOKS/CHAPTERS

1. Nuclear Receptors as Drug Targets (Methods and Principles in Medicinal Chemistry). Eckhard Ottow, Hilmar Weinmann, both of Schering Pharma, Germany; Editors, 480 pages, 2008, ISBN 978-3-527-31872-8, Wiley-VCH

US PATENTS

1. Selective Androgen Receptor Degrader (SARD) Ligands and Methods of use thereof. Ramesh Narayanan; Duane D. Miller; Thamarai Ponnusamy; Dong-Jin Hwang; Yali He. US 11,273,147 B2, March 15, 2022.

2. Selective Androgen Receptor Degrader (SARD) Ligands and Methods of use thereof. Ramesh Narayanan; Duane D. Miller; Thamarai Ponnusamy; Dong-Jin Hwang; Yali He. US 10,865,184 B2, December 20, 2020.

3. Selective Androgen Receptor Degrader (SARD) Ligands and Methods of use thereof. Ramesh Narayanan; Duane D. Miller; Thamarai Ponnusamy; Dong-Jin Hwang; Yali He. US 10,806,720 B2, October 20, 2020.

4. Selective Androgen Receptor Degrader (SARD) Ligands and Methods of use thereof. Ramesh Narayanan; Duane D. Miller; Thamarai Ponnusamy; Dong-Jin Hwang; Yali He. US 10,806,719 B2, October 20, 2020.

5. Selective Androgen Receptor Degrader (SARD) Ligands and Methods of use thereof. Ramesh Narayanan; Duane D. Miller; Thamarai Ponnusamy; Dong-Jin Hwang; Yali He. US 10,654,809 B2, May 19, 2020.

6. Selective Androgen Receptor Degrader (SARD) Ligands and Methods of use thereof. Ramesh Narayanan; Duane D. Miller; Thamarai Ponnusamy; Dong-Jin Hwang; Yali He; Jayaprakash Pagadala; Charles B. Duke; Christopher C. Coss; James T. Dalton. US 10,441,570 B2, October 15, 2019.

7. Selective Androgen Receptor Degrader (SARD) Ligands and Methods of use thereof. Ramesh Narayanan; Duane D. Miller; Thamarai Ponnusamy; Dong-Jin Hwang; Yali He. US 10,314,797 B2, July 11, 2019.

8. Selective Androgen Receptor Degrader (SARD) Ligands and Methods of use thereof. Ramesh Narayanan; Duane D. Miller; Thamarai Ponnusamy; Dong-Jin Hwang; Jayaprakash Pagadala; Charles B. Duke; Christopher C. Coss; James T. Dalton; Yali He. US 10,035,763 B2, July 31, 2018.

9. Selective Androgen Receptor Degrader (SARD) Ligands and Methods of use thereof. Ramesh Narayanan; Duane D. Miller; Thamarai Ponnusamy; Dong-Jin Hwang; Jayaprakash Pagadala; Charles B. Duke; Christopher C. Coss; James T. Dalton; Yali He. US 10,017,471 B2, July 15, 2018.

10. Selective Androgen Receptor Degrader (SARD) ligands and methods of use thereof. Ramesh Narayanan; Duane D. Miller; Thamarai Ponnusamy; Dong-Jin Hwang; Jayaprakash Pagadala; Charles B. Duke; Christopher C. Coss; James T. Dalton; Yali He. US 9,814,698 B2, November 14, 2017.

11. Treating Androgen Decline in Aging Male (ADAM)-Associated Conditions with SARMS. James T. Dalton; Duane D. Miller; Donghua Yin; Yali He. US 9,493,403 B2, November 15, 2016.

12. Estrogen Receptor Ligands and Methods of Use Thereof. Dalton; James T., Herring; Christina, Miller; Duane D., Hong; Seoung-Soo, He; Yali, Mohler; Michael, L., Narayanan; Ramesh, Wu; Zhongzhi. US 9,409,856 B2, August 9, 2016.

13. Nuclear Receptor Binding Agents. James T Dalton, Christina Barrett, Duane D. Miller, Seoung-Soo Hong, Yali He, Michael, L Mohler, Ramesh Narayanan, Zhongzhi Wu. US 8,637,706 B2, January 28, 2014.

14. Treating Androgen Decline in Aging Male (ADAM)-Associated Conditions with SARMS. James T. Dalton; Duane D. Miller; Donghua Yin; Yali He. US 8,445,534 B2, May 21, 2013.

15. Nuclear Receptor Binding Agents. James T Dalton, Christina Barrett, Yali He, Seoung-Soo Hong, Duane D. Miller, Michael, L Mohler, Ramesh Narayanan, Zhongzhi Wu. US 8,158,828 B2, April 17, 2012.

16. Selective Androgen Receptor Modulators and Methods of Use Thereof. James T. Dalton; Duane D. Miller; Yali He; Donghua Yin. US 7,919,647 B2, April 5, 2011.

17. Synthesis of Selective Androgen Receptor Modulators. James T. Dalton; Duane D. Miller; Yali He; Donghua Yin. US 7,759,520 B2, July 20, 2010.

18. Selective Androgen Receptor Modulators. James T. Dalton; Duane D. Miller; Yali He; Donghua Yin. US 7,518,013 B2, April 14, 2009.

19. Selective Androgen Receptor Modulators. James T. Dalton; Duane D. Miller; Yali He; Donghua Yin. US 7,205,437 B2, April 17, 2007.

20. Selective Androgen Receptor Modulators and Methods of Use Thereof. James T. Dalton; Duane D. Miller; Yali He; Donghua Yin. US 6,998,500 B2, February 14, 2006.

21. Synthesis of Selective Androgen Receptor Modulators. James T. Dalton; Duane D. Miller; Yali He; Donghua Yin. US 6,995,284 B2, February 7, 2006.

22. Formulations Comprising Selective Androgen Receptor Modulators. Mitchell S. Steiner; Karen A. Veverka; James T. Dalton; Duane D. Miller; Yali He; Donghua Yin. US 6,838,484 B2, January 4, 2005.

23. Selective Androgen Receptor Modulators and Methods of Use Thereof. James T. Dalton; Duane D. Miller; Donghua Yin; Yali He. US 6,569,896 B2, May 27, 2003.

24. Selective Androgen Receptor Modulators and Methods of Use Thereof. James T. Dalton; Duane D. Miller; Donghua Yin; Yali He. US 6,492,554 B2, December 10, 2002.

Full List Available upon request.