An article Inhibition of 3-phosphoglycerate dehydrogenase (PHGDH) by indole amides abrogates de novo serine synthesis in cancer cells WOS:000481615900014 published article about ACID; IDENTIFICATION; BIOSYNTHESIS; DERIVATIVES in [Mullarky, Edouard; Robin, Anita D.; Cantley, Lewis C.] Weill Cornell Med Coll, Meyer Canc Ctr, New York, NY 10065 USA; [Mullarky, Edouard; Robin, Anita D.; Cantley, Lewis C.] Weill Cornell Med Coll, Dept Med, New York, NY 10065 USA; [Xu, Jiayi; Huggins, David J.; Miller, Michael; Michino, Mayako; Stamford, Andrew W.; Meinke, Peter T.; Kargman, Stacia] Triinst Therapeut Discovery Inst, 413 East 69th St, New York, NY 10021 USA; [Huggins, David J.] Weill Cornell Med Coll, Dept Physiol & Biophys, New York, NY USA; [Jennings, Andy] Andy Jennings Consulting LLC, San Diego, CA USA; [Noguchi, Naoyoshi; Tomita, Daisuke] Takeda Pharmaceut Co Ltd, Pharmaceut Res Div, Shonan Res Ctr, 26-1 Muraoka Higashi 2 Chome, Fujisawa, Kanagawa 2518555, Japan; [Olland, Andrea; Lakshminarasimhan, Damodharan] Xtal Biostruct, 12 Michigan Dr, Natick, MA 01760 USA; [Su, Taojunfeng; Zhang, Guoan] Weill Cornell Med, Prote & Metabol Core Facil, New York, NY 10021 USA in 2019.0, Cited 30.0. Name: 3-Pyridinecarboxaldehyde. The Name is 3-Pyridinecarboxaldehyde. Through research, I have a further understanding and discovery of 500-22-1
Cancer cells reprogram their metabolism to support growth and to mitigate cellular stressors. The serine synthesis pathway has been identified as a metabolic pathway frequently altered in cancers and there has been considerable interest in developing pharmacological agents to target this pathway. Here, we report a series of indole amides that inhibit human 3-phosphoglycerate dehydrogenase (PHGDH), the enzyme that catalyzes the first committed step of the serine synthesis pathway. Using X-ray crystallography, we show that the indole amides bind the NAD(+) pocket of PHGDH. Through structure-based optimization we were able to develop compounds with low nanomolar affinities for PHGDH in an enzymatic IC50 assay. In cellular assays, the most potent compounds inhibited de novo serine synthesis with low micromolar to sub-micromolar activities and these compounds successfully abrogated the proliferation of cancer cells in serine free media. The indole amide series reported here represent an important improvement over previously published PHGDH inhibitors as they are markedly more potent and their mechanism of action is better defined.
About 3-Pyridinecarboxaldehyde, If you have any questions, you can contact Mullarky, E; Xu, JY; Robin, AD; Huggins, DJ; Jennings, A; Noguchi, N; Olland, A; Lakshminarasimhan, D; Miller, M; Tomita, D; Michino, M; Su, TJF; Zhang, GA; Stamford, AW; Meinke, PT; Kargman, S; Cantley, LC or concate me.. Name: 3-Pyridinecarboxaldehyde
Reference:
Pyridine – Wikipedia,
,Pyridine | C5H5N – PubChem