A fragment-like approach to PYCR1 inhibition was written by Milne, Kirsty;Sun, Jianhui;Zaal, Esther A.;Mowat, Jenna;Celie, Patrick H. N.;Fish, Alexander;Berkers, Celia R.;Forlani, Giuseppe;Loayza-Puch, Fabricio;Jamieson, Craig;Agami, Reuven. And the article was included in Bioorganic & Medicinal Chemistry Letters in 2019.Reference of 61150-57-0 This article mentions the following:
Pyrroline-5-carboxylate reductase 1 (PYCR1) is the final enzyme involved in the biosynthesis of proline and has been found to be upregulated in various forms of cancer. Due to the role of proline in maintaining the redox balance of cells and preventing apoptosis, PYCR1 is emerging as an attractive oncol. target. Previous PYCR1 knockout studies led to a reduction in tumor growth. Accordingly, a small mol. inhibitor of PYCR1 could lead to new treatments for cancer, and a focused screening effort identified pargyline as a fragment-like hit. Herein the design and synthesis of the first tool compounds as PYCR1 inhibitors, derived from pargyline, which were assayed to assess their ability to attenuate the production of proline, are reported. Structural activity studies have revealed the key determinants of activity, with the most potent compound, 4-bromobenzyl(propargyl)methylamine, showing improved activity in vitro in enzyme (IC50 = 8.8μM) and pathway relevant effects in cell-based assays. In the experiment, the researchers used many compounds, for example, 2-Bromo-4-fluorobenzylbromide (cas: 61150-57-0Reference of 61150-57-0).
2-Bromo-4-fluorobenzylbromide (cas: 61150-57-0) belongs to organobromine compounds. Most organobromine compounds, like most organohalide compounds, are relatively nonpolar. One prominent application of synthetic organobromine compounds is the use of polybrominated diphenyl ethers as fire-retardants, and in fact fire-retardant manufacture is currently the major industrial use of the element bromine.Reference of 61150-57-0
Referemce:
Bromide – Wikipedia,
bromide – Wiktionary