Michael Jung, PhD
The goal of the research performed in Dr. Michael Jung's synthetic medicinal chemistry laboratory is to discovery new drugs for the treatment of human diseases. To do this, they collaborate with bioscientists of all stripes trying to design new analogues of active molecules that have the right properties to become drug candidates. They thus carry out structure-activity relationship studies aimed at increasing the beneficial biological activity while ensuring that the final molecules are ÒdruglikeÓÑ namely, that they are likely to have good pharmacokinetic (PK) properties and are unlikely to have any non-specific toxicity. At present, they have many collaborative programs in medicinal chemistry, including:
- the preparation and testing of novel small molecule androgen receptor degraders which degrade both the full length AR and the major AR splice variant, ArV7, for the treatment of prostate cancer;
- the preparation of analogues of metformin that show great promise as antitumor agents;
- the preparation and testing of new estrogen receptor degraders as potential anti-breast cancer agents;
- the preparation of small molecules which cause robust hair growth;
- the development of inhibitors of deoxycytidine kinase for the treatment of leukemia;
- the synthesis of small molecules, e.g., esters of alpha-ketoglutarate, which extend the life span of animals via a novel mechanism;
- the preparation of small molecules which differentiate stem cells into osteoblasts for bone growth;
- the design and preparation of small molecule inhibitors of the growth of many enveloped viruses and also specifically for enteroviruses;
- the design and preparation of small molecule inhibitors of protein tyrosine phosphatase-sigma as agents to increase stem cell production;
- the design and synthesis of novel small molecule radiomitigators;
- the development of small Òread-throughÓ molecules which allow the production of full-length dystrophin for the treatment of muscular dystrophy;
- the preparation and testing of small molecule which upregulate the production of Sirt1 for the treatment of Alzheimer's disease;
- the preparation of molecules that bind to the Sortase-A binding pocket as potential antibacterial agents.
- the design and synthesis of novel antitumor agents for the treatment of glioblastoma;
- the design of small molecular inhibitors of mTOR signaling via DEPTOR and RAPTOR;
- the design of small molecule inhibitors of WNT signaling as antitumor agents;
- the design of novel HDAC inhibitors for use as a treatment for inflammatory bowel disease; and
- the design and synthesis of novel broad spectrum antiviral agents.
Nathanson DA, Armijo AL, Tom M, Li Z, Dimitrova E, Austin WR, Nomme J, Campbell DO, Ta L, Le TM, Lee JT, Darvish R, Gordin A, Wei L, Liao HI, Wilks M, Martin C, Sadeghi S, Murphy JM, Boulos N, Phelps ME, Faull KF, Herschman HR, Jung ME, Czernin J, Lavie A, Radu CG. Co-targeting of convergent nucleotide biosynthetic pathways for leukemia eradication. J Exp Med. 2014 Mar 10;211(3):473-86. doi: 10.1084/jem.20131738. Epub 2014 Feb 24.
Nomme J, Li Z, Gipson RM, Wang J, Armijo AL, Le T, Poddar S, Smith T, Santarsiero BD, Nguyen HA, Czernin J, Alexandrova AN, Jung ME, Radu CG, Lavie A. Structure-guided development of deoxycytidine kinase inhibitors with nanomolar affinity and improved metabolic stability. J Med Chem. 2014 Nov 26;57(22):9480-94. doi: 10.1021/jm501124j. Epub 2014 Nov 7.
Clegg NJ, Wongvipat J, Joseph JD, Tran C, Ouk S, Dilhas A, Chen Y, Grillot K, Bischoff ED, Cai L, Aparicio A, Dorow S, Arora V, Shao G, Qian J, Zhao H, Yang G, Cao C, Sensintaffar J, Wasielewska T, Herbert MR, Bonnefous C, Darimont B, Scher HI, Smith-Jones P, Klang M, Smith ND, De Stanchina E, Wu N, Ouerfelli O, Rix PJ, Heyman RA, Jung ME, Sawyers CL, Hager JH. ARN-509: a novel antiandrogen for prostate cancer treatment. Cancer Res. 2012 Mar 15;72(6):1494-503. doi: 10.1158/0008-5472.CAN-11-3948. Epub 2012 Jan 20.
Jung ME, Ouk S, Yoo D, Sawyers CL, Chen C, Tran C, Wongvipat J. Structure-activity relationship for thiohydantoin androgen receptor antagonists for castration-resistant prostate cancer (CRPC). J Med Chem. 2010 Apr 8;53(7):2779-96. doi: 10.1021/jm901488g.
Tran C, Ouk S, Clegg NJ, Chen Y, Watson PA, Arora V, Wongvipat J, Smith-Jones PM, Yoo D, Kwon A, Wasielewska T, Welsbie D, Chen CD, Higano CS, Beer TM, Hung DT, Scher HI, Jung ME, Sawyers CL. Development of a second-generation antiandrogen for treatment of advanced prostate cancer. Science. 2009 May 8;324(5928):787-90. doi: 10.1126/science.1168175. Epub 2009 Apr 9.