Potent Uncompetitive Inhibitors of Nicotinamide Methyltransferase (NNMT) as In Vivo Chemical Probes was written by Barrows, Robert D.;Jeffries, Daniel E.;Vishe, Mahesh;Tukachinsky, Hanna;Zheng, Shao-Liang;Li, Fanfan;Ma, Zhenjie;Li, Xiaolei;Jin, Shujuan;Song, Haobin;Zhang, Ruonan;Zhang, Shaofeng;Ni, Jing;Luan, Haofei;Wen, Lei;Rongshan, Yan;Ying, Chen;Shair, Matthew D.. And the article was included in Journal of Medicinal Chemistry in 2022.HPLC of Formula: 454248-53-4 This article mentions the following:
NNMT uses SAM as a cofactor to catalyze the methylation of nicotinamide, producing 1-methylnicotinamide. Recent studies have shown that NNMT upregulation in cancer-associated fibroblasts (CAFs) is required to maintain the CAF phenotype in high-grade serous carcinoma. These observations suggest that NNMT should be evaluated as a therapeutic target, especially in cancer. Although several small-mol. inhibitors of NNMT have been identified, there remains a need for highly potent and selective inhibitors with excellent in vivo activity and ADME properties that can be used as reliable chem. probes. We have identified azaindoline carboxamide as a selective and potent NNMT inhibitor with favorable PK/PD and safety profiles as well as excellent oral bioavailability and pharmaceutical properties. Our mechanistic studies indicate that 38 binds uncompetitively with SAM but competitively with nicotinamide consistent with its binding in the nicotinamide binding site and likely forming a pos. interaction with SAM. In the experiment, the researchers used many compounds, for example, (R)-3-Boc-4-methyl-1,2,3-oxathiazolidine 2,2-Dioxide (cas: 454248-53-4HPLC of Formula: 454248-53-4).
(R)-3-Boc-4-methyl-1,2,3-oxathiazolidine 2,2-Dioxide (cas: 454248-53-4) belongs to thiazolidine derivatives. Thiazolidine derivatives have been found to exhibit very prominent anti-inflammatory and anti-nociceptive activity. Thiazolidines are also used in peptide and protein modification, protein chemical synthesis, as activators to innate immunity and also act as immunostimulating agents.HPLC of Formula: 454248-53-4
Referemce:
Thiazolidine – Wikipedia,
Thiazolidine – ScienceDirect.com