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| Type |
Poster Presentation |
| Area |
Medicinal Chemistry |
| Room No. |
Exhibition Hall 2 |
| Time |
4월 18일 (목요일) 11:00~12:30 |
| Code |
MEDI.P-383 |
| Subject |
Discovery and Development of Allosteric Inhibitors of Kidney Type Glutaminase with high PK Properties and good Solubility. |
| Authors |
Krishna babu Duggirala, Seonghyeon Sim1, Heeyeon Kang2, Yueun Hwang3, Ge Hyeong Lee4, Kwangho Lee5,*
University of Science & Technology, India
1Chemistry, Sogang University, Korea
2Ewha Womans University, Korea
3Chemistry, Kwangwoon University, Korea
4Center for Medicinal Chemistry, Korea Research Institute of Chemical Technology, Korea
5Korea Research Institute of Chemical Technology, Korea
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| Abstract |
Glutamine is the most abundant amino acid in the blood. Glutaminase catalyzes the hydrolysis of glutamine into glutamate and ammonia in mitochondria through glutaminolysis. Warburg effect explains glutaminolysis is the main energy source for the growth and viability of malignant tumors. Two isoforms of glutaminase exits in mammalian cells, i.e. kidney type glutaminase (GLS) and liver-type glutaminase (GLS2). GLS was found to be overexpressed in many glutamine dependent cancer cells. Therefore, GLS has become a key target for small molecule therapeutic intervention. Numerous competitive inhibitors (DON) and allosteric inhibitors (BEPTS and CB- 839) were developed. However to date, only CB-839 have entered clinical trials for the treatment of advanced solid tumors and hematological malignancies. Although, several potent inhibitors have been developed, the drug-like properties need to be optimized. Combination of inhibitors with efficient GLS inhibitors could be a potential strategy for patients harboring glutaminase dependent tumors. |
| E-mail |
krishna@krict.re.kr |
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123rd General Meeting of the KCS