General Information
- Project ID
- OEP000515
- Project Name
- An allosteric PGAM1 inhibitor effectively suppresses pancreatic ductal adenocarcinoma
- Description
- Glycolytic enzyme phosphoglycerate mutase 1 (PGAM1) plays a critical role in cancer metabolism by coordinating glycolysis and biosynthesis. A well-validated PGAM1 inhibitor, however, has not been reported for treating pancreatic ductal adenocarcinoma (PDAC), which is one of the deadliest malignancies worldwide. By uncovering the elevated PGAM1 expressions were statistically related to worse prognosis of PDAC in a cohort of 50 patients, we developed a series of allosteric PGAM1 inhibitors by structureguided optimization. The compound KH3 significantly suppressed proliferation of various PDAC cells by down-regulating the levels of glycolysis and mitochondrial respiration in correlation with PGAM1 expression. Similar to PGAM1 depletion, KH3 dramatically hampered the canonic pathways highly involved in cancer metabolism and development. Additionally, we observed the shared expression profiles of several signature pathways at 12 h after treatment in multiple PDAC primary cells of which the matched patient-derived xenograft (PDX) models responded similarly to KH3 in the 2 wk treatment. The better responses to KH3 in PDXs were associated with higher expression of PGAM1 and longer/ stronger suppressions of cancer metabolic pathways. Taken together, our findings demonstrate a strategy of targeting cancer metabolism by PGAM1 inhibition in PDAC. Also, this work provided “proof of concept” for the potential application of metabolic treatment in clinical practice.
- Publications
-
An allosteric PGAM1 inhibitor effectively suppresses pancreatic ductal adenocarcinoma
Wen C, Huang K, Jiang L, et al. An allosteric PGAM1 inhibitor effectively suppresses pancreatic ductal adenocarcinoma. Proceedings of the National Academy of Sciences Oct 2019, 201914557.
(PMID: 31662475) (DOI: 10.1073/pnas.1914557116)
Project information
- Experiments
- 1
Experiment ID Experiment name Experiment type Create Date OEX001971 Pancreatic_proj_RNA-Seq Transcriptomic 2019-09-29 - Samples
- 39
Sample ID Sample Name Sample Subject Type Organism Tissue Create Date OES020757 pc15N1 Cell line Homo sapiens cell line 2019-09-29 OES020758 pc15N2 Cell line Homo sapiens cell line 2019-09-29 OES020759 pc15N3 Cell line Homo sapiens cell line 2019-09-29 OES020760 pc15P1 Cell line Homo sapiens cell line 2019-09-29 OES020761 pc15P2 Cell line Homo sapiens cell line 2019-09-29 OES020762 pc15P3 Cell line Homo sapiens cell line 2019-09-29 OES020763 pc37N1 Cell line Homo sapiens cell line 2019-09-29 OES020764 pc37N2 Cell line Homo sapiens cell line 2019-09-29 OES020765 pc37N3 Cell line Homo sapiens cell line 2019-09-29 OES020766 pc37P1 Cell line Homo sapiens cell line 2019-09-29 OES020767 pc37P2 Cell line Homo sapiens cell line 2019-09-29 OES020768 pc37P3 Cell line Homo sapiens cell line 2019-09-29 OES020769 pc49N1 Cell line Homo sapiens cell line 2019-09-29 OES020770 pc49N2 Cell line Homo sapiens cell line 2019-09-29 OES020771 pc49N3 Cell line Homo sapiens cell line 2019-09-29 OES020772 pc49P1 Cell line Homo sapiens cell line 2019-09-29 OES020773 pc49P3 Cell line Homo sapiens cell line 2019-09-29 OES020774 p1 Cell line Homo sapiens cell line 2019-09-29 OES020775 p2 Cell line Homo sapiens cell line 2019-09-29 OES020776 p3 Cell line Homo sapiens cell line 2019-09-29 OES020777 pj1 Cell line Homo sapiens cell line 2019-09-29 OES020778 pj2 Cell line Homo sapiens cell line 2019-09-29 OES020779 pj3 Cell line Homo sapiens cell line 2019-09-29 OES020780 panc1N1 Cell line Homo sapiens cell line 2019-09-29 OES020781 panc1N2 Cell line Homo sapiens cell line 2019-09-29 OES020782 panc1sh1 Cell line Homo sapiens cell line 2019-09-29 OES020783 panc1sh2 Cell line Homo sapiens cell line 2019-09-29 OES020784 m1 Cell line Homo sapiens cell line 2019-09-29 OES020785 m2 Cell line Homo sapiens cell line 2019-09-29 OES020786 m3 Cell line Homo sapiens cell line 2019-09-29 OES020787 mj1 Cell line Homo sapiens cell line 2019-09-29 OES020788 mj2 Cell line Homo sapiens cell line 2019-09-29 OES020789 mj3 Cell line Homo sapiens cell line 2019-09-29 OES020790 swN1 Cell line Homo sapiens cell line 2019-09-29 OES020791 swN2 Cell line Homo sapiens cell line 2019-09-29 OES020792 swN3 Cell line Homo sapiens cell line 2019-09-29 OES020793 swP1 Cell line Homo sapiens cell line 2019-09-29 OES020794 swP2 Cell line Homo sapiens cell line 2019-09-29 OES020795 swP3 Cell line Homo sapiens cell line 2019-09-29 - Runs
-
39
Run ID Run Name Experiment Sample Data Num Create Date OER034769 m1 OEX001971 OES020784 2 2019-09-29 OER034770 m2 OEX001971 OES020785 2 2019-09-29 OER034771 m3 OEX001971 OES020786 2 2019-09-29 OER034772 mj1 OEX001971 OES020787 2 2019-09-29 OER034773 mj2 OEX001971 OES020788 2 2019-09-29 OER034774 mj3 OEX001971 OES020789 2 2019-09-29 OER034775 p1 OEX001971 OES020774 2 2019-09-29 OER034776 p2 OEX001971 OES020775 2 2019-09-29 OER034777 p3 OEX001971 OES020776 2 2019-09-29 OER034778 pj1 OEX001971 OES020777 2 2019-09-29 OER034779 pj2 OEX001971 OES020778 2 2019-09-29 OER034780 pj3 OEX001971 OES020779 2 2019-09-29 OER034781 panc1N1 OEX001971 OES020780 2 2019-09-29 OER034782 panc1N2 OEX001971 OES020781 2 2019-09-29 OER034783 panc1sh1 OEX001971 OES020782 2 2019-09-29 OER034784 panc1sh2 OEX001971 OES020783 2 2019-09-29 OER034785 pc15N1 OEX001971 OES020757 2 2019-09-29 OER034786 pc15N2 OEX001971 OES020758 2 2019-09-29 OER034787 pc15N3 OEX001971 OES020759 2 2019-09-29 OER034788 pc15P1 OEX001971 OES020760 2 2019-09-29 OER034789 pc15P2 OEX001971 OES020761 2 2019-09-29 OER034790 pc15P3 OEX001971 OES020762 2 2019-09-29 OER034791 pc37N1 OEX001971 OES020763 2 2019-09-29 OER034792 pc37N2 OEX001971 OES020764 2 2019-09-29 OER034793 pc37N3 OEX001971 OES020765 2 2019-09-29 OER034794 pc37P1 OEX001971 OES020766 2 2019-09-29 OER034795 pc37P2 OEX001971 OES020767 2 2019-09-29 OER034796 pc37P3 OEX001971 OES020768 2 2019-09-29 OER034797 pc49N1 OEX001971 OES020769 2 2019-09-29 OER034798 pc49N2 OEX001971 OES020770 2 2019-09-29 OER034799 pc49N3 OEX001971 OES020771 2 2019-09-29 OER034800 pc49P1 OEX001971 OES020772 2 2019-09-29 OER034801 pc49P3 OEX001971 OES020773 2 2019-09-29 OER034802 swN1 OEX001971 OES020790 2 2019-09-29 OER034803 swN2 OEX001971 OES020791 2 2019-09-29 OER034804 swN3 OEX001971 OES020792 2 2019-09-29 OER034805 swP1 OEX001971 OES020793 2 2019-09-29 OER034806 swP2 OEX001971 OES020794 2 2019-09-29 OER034807 swP3 OEX001971 OES020795 2 2019-09-29
Author Information
- Create Date
- 2019-09-28
- Last Modified
- 2021-02-05
- Submission
- Jinyan Huang
- Ruijin Hospital