ArticleFrontiers in endocrinology2022
Small molecules to regulate the GH/IGF1 axis by inhibiting the growth hormone receptor synthesis.
Article in Frontiers in endocrinology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 14 citations in OpenAlex.
- Local growth hormone promotes benign prostatic hyperplasia.JCI insight · 2026Article
- Bioinformatics driven in gene targeting platform for gold anticancer strategy delivery.Materials today. Bio · 2025Article
- In Vivo Effects of a GHR Synthesis Inhibitor During Prolonged Treatment in Dogs.Pharmaceuticals (Basel, Switzerland) · 2024Article
- WIP1 is a novel specific target for growth hormone action.iScience · 2023Article
- A novel antifolate suppresses growth of FPGS-deficient cells and overcomes methotrexate resistance.Life science alliance · 2023Article
- Construction of a high-density genetic linkage map and QTL mapping of growth and cold tolerance traits in Takifugu fasciatus.BMC genomics · 2023Article
- Ghrelin regulating liver activity and its potential effects on liver fibrosis andFrontiers in cellular and infection microbiology · 2023Review
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Growth hormone (GH) and insulin-like growth factor-1 (IGF1) play an important role in mammalian development, cell proliferation and lifespan. Especially in cases of tumor growth there is an urgent need to control the GH/IGF1 axis. In this study we screened a 38,480-compound library, and in two consecutive rounds of analogues selection, we identified active lead compounds based on the following criteria: inhibition the GH receptor (GHR) activity and its downstream effectors Jak2 and STAT5, and inhibition of growth of breast and colon cancer cells. The most active small molecule (BM001) inhibited both the GH/IGF1 axis and cell proliferation with an IC50 of 10-30 nM of human cancer cells. BM001 depleted GHR in human lymphoblasts. In preclinical xenografted experiments, BM001 showed a strong decrease in tumor volume in mice transplanted with MDA-MB-231 breast cancer cells. Mechanistically, the drug acts on the synthesis of the GHR. Our findings open the possibility to inhibit the GH/IGF1 axis with a small molecule.
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