Last update 01 Nov 2024

PGAM1

Last update 01 Nov 2024

Basic Info

Synonyms

BPG-dependent PGAM 1, PGAM-B, PGAM1

+ [3]

Introduction

Catalyzes the interconversion of 2-phosphoglycerate and 3-phosphoglyceratea crucial step in glycolysis, by using 2,3-bisphosphoglycerate (PubMed:23653202). Also catalyzes the interconversion of (2R)-2,3-bisphosphoglycerate and (2R)-3-phospho-glyceroyl phosphate (PubMed:23653202).

Drugs associated with PGAM1

HK-B99

Target

PGAM1

Mechanism

PGAM1 inhibitors

Active Org.

Fudan University [+1]

Originator Org.

China Pharmaceutical University

Active Indication

Non-Small Cell Lung Cancer

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

CN118185914

Patent Mining

Target

PGAM1

Mechanism-

Active Org.

Tongji Hospital Tongji Medical College of HUST

Originator Org.

Tongji Hospital Tongji Medical College of HUST

Active Indication

Cardiovascular Diseases

Inactive Indication-

Drug Highest PhaseDiscovery

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

KH-3 (Allist Pharmaceutical)

Target

PGAM1

Mechanism

PGAM1 inhibitors

Active Org.-

Originator Org.

Fudan University

Active Indication-

Inactive Indication

Pancreatic Cancer

Drug Highest PhaseDiscontinued

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with PGAM1

100 Translational Medicine associated with PGAM1

0 Patents (Medical) associated with PGAM1

384

Literatures (Medical) associated with PGAM1

01 Oct 2024·Cancer Biotherapy and Radiopharmaceuticals

Circ-PGAM1 Enhances Matrine Resistance of Non-Small Cell Lung Cancer via the miR-326/CXCR5 Axis

Article

Author: Dong, Caijun ; Yang, Liangwei ; Zhao, Guofang

Background: Circular RNAs (circ-RNAs) have been demonstrated to influence initiation, drug resistance, and metastasis of tumors. However, the effects of circular-phosphoglycerate mutase 1 (circ-PGAM1) on matrine resistance in nonsmall cell lung cancer (NSCLC) remain unknown. Materials and Methods: The reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to determine gene expression. The terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and cell colony formation assays were used to evaluate NSCLC apoptosis and cell proliferation after indicated treatments, respectively. Results: circ-PGAM1 was upregulated in human NSCLC cell lines (H1299 and A549) compared with the human normal lung epithelial (BEAS-2B) cells. circ-PGAM1 overexpression reversed the matrine treatment-induced inhibition on proliferation of NSCLC cells (A549 and H1299) and rescued the matrine treatment-stimulated apoptosis of these cells. miR-326 was demonstrated to interact with circ-PGAM1. circ-PGAM1 knockdown enhanced the antitumor effect of matrine on NSCLC cell proliferation and apoptosis, which was reversed by miR-326 inhibition. The authors also identified CXCR5 as a key downstream target of miR-326 in A549 cells. Conclusions: circ-PGAM1 enhances matrine resistance of NSCLC cells through the miR-326/CXCR5 axis. The authors' findings provide new insights into NSCLC-targeted therapy.

02 Sep 2024·Journal of Leukocyte Biology

PGAM1 suppression remodels the tumor microenvironment in triple-negative breast cancer and synergizes with anti–PD-1 immunotherapy

Article

Author: Zhang, Dong ; Ren, Xiubao ; Wang, Wenying ; Sun, Qian ; Yu, Wenwen ; Ma, Shiya ; Wang, Min

AbstractTriple-negative breast cancer is a high-risk form of breast cancer with a high metastatic potential and lack of effective therapies. Immunotherapy has shown encouraging clinical benefits, and its efficacy in triple-negative breast cancer is affected by immunocyte infiltration in the tumor microenvironment. PGAM1 is a key enzyme involved in cancer metabolism; however, its role in the tumor microenvironment remains unclear. In this study, we aimed to investigate the role of PGAM1 in triple-negative breast cancer and determine the potential of PGAM1 inhibition in combination with anti–PD-1 immunotherapy. Our results showed that PGAM1 is highly expressed in triple-negative breast cancer and is associated with poor prognosis. In vivo experiments demonstrated that PGAM1 inhibition synergizes with anti–PD-1 immunotherapy, significantly remodeling the tumor microenvironment and leading to an increase in antitumor immunocytes, such as CD8+ T cells and M1 macrophages, and a reduction in immunosuppressive cell infiltration, including myeloid-derived suppressor cells, M2 macrophages, and regulatory T cells. Functional and animal experiments showed that this synergistic mechanism inhibited tumor growth in vitro and in vivo. We identified PGAM1 as a novel target that exhibits an antitumor effect via the regulation of immunocyte infiltration. Our results show that PGAM1 can synergize with anti–PD-1 immunotherapy, providing a novel treatment strategy for triple-negative breast cancer.

01 Sep 2024·Free Radical Biology and Medicine

G protein pathway suppressor 2 suppresses aerobic glycolysis through RACK1-mediated HIF-1α degradation in breast cancer

Article

Author: Zhang, Liang ; Zhan, Xiangrong ; Liu, Xuewen ; Gu, Manxiang ; Yang, Dan ; Jin, Xin ; Sheng, Songran ; Yu, Qingqing ; Ou, Hongling ; Peng, Wenkang ; Liu, Ying ; Si, Yuan

Aerobic glycolysis has been recognized as a hallmark of human cancer. G protein pathway suppressor 2 (GPS2) is a negative regulator of the G protein-MAPK pathway and a core subunit of the NCoR/SMRT transcriptional co-repressor complex. However, how its biological properties intersect with cellular metabolism in breast cancer (BC) development remains poorly elucidated. Here, we report that GPS2 is low expressed in BC tissues and negatively correlated with poor prognosis. Both in vitro and in vivo studies demonstrate that GPS2 suppresses malignant progression of BC. Moreover, GPS2 suppresses aerobic glycolysis in BC cells. Mechanistically, GPS2 destabilizes HIF-1α to reduce the transcription of its downstream glycolytic regulators (PGK1, PGAM1, ENO1, PKM2, LDHA, PDK1, PDK2, and PDK4), and then suppresses cellular aerobic glycolysis. Notably, receptor for activated C kinase 1 (RACK1) is identified as a key ubiquitin ligase for GPS2 to promote HIF-1α degradation. GPS2 stabilizes the binding of HIF-1α to RACK1 by directly binding to RACK1, resulting in polyubiquitination and instability of HIF-1α. Amino acid residues 70-92 aa of the GPS2 N-terminus bind RACK1. A 23-amino-acid-long GPS2-derived peptide was developed based on this N-terminal region, which promotes the interaction of RACK1 with HIF-1α, downregulates HIF-1α expression and significantly suppresses BC tumorigenesis in vitro and in vivo. In conclusion, our findings indicate that GPS2 decreases the stability of HIF-1α, which in turn suppresses aerobic glycolysis and tumorigenesis in BC, suggesting that targeting HIF-1α degradation and treating with peptides may be a promising approach to treat BC.

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PGAM1

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