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| Type |
Poster Presentation |
| Area |
Life Chemistry |
| Room No. |
Exhibition Hall 2 |
| Time |
4월 19일 (금요일) 11:00~12:30 |
| Code |
LIFE.P-371 |
| Subject |
Identification of Polyphyllin D as a Selective Inhibitor of SHP2 Against the Non Receptor PTPs |
| Authors |
Se Jeong Kwon, Sang Jeon Chung*
College of Pharmacy, SungKyunKwan University, Korea
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| Abstract |
SHP2 (encoded by the PTPN11) has an important role in signal transduction downstream of receptor tyrosine kinase. Activating mutation or overexpression of SHP2 have been reported in various types of human leukemia cancer such as Noonan syndrome, Acute Myeloid Leukemia (AML), Acute Lymphoid Leukemia (ALL). SHP2 promotes the activation of RAS. And is regulates cell survival and proliferation primarily through activation of ERK, AKT by regulating upstream of RAS. Recently, it is known as important mediator of immune checkpoint pathways. In brief, If SHP2 inhibitor apply to RAS-ERK associated disease that will be promise drug candidate for cancer.
However, the majority of SHP2 inhibitors suffer from poor selectivity as they also target various other protein tyrosine phosphatases (PTPs), presumably due to the highly conserved active site of PTPs. To search SHP2 inhibitors, we screened 658 phytochemicals to identify natural product SHP2 inhibitors with strong inhibitory activity, however only polyphyllin D showed inhibitory selectivity to SHP2 over other PTPs although their inhibitory activities are moderate (Ki = 64.2 µM). Furthermore, SHP2 inhibitor induce stronger cancer cell apoptosis in the signal associated with ERK, AKT and Bcl2. Together, these data demonstrate that efficacy of SHP2 inhibition is a valid therapeutic approach for the treatment of leukemia cancers.
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| E-mail |
sejung1110@naver.com |
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123rd General Meeting of the KCS