Identification of DHODH as a therapeutic target in small cell lung cancer was written by Li, Leanne; Ng, Sheng Rong; Colon, Caterina I.; Drapkin, Benjamin J.; Hsu, Peggy P.; Li, Zhaoqi; Nabel, Christopher S.; Lewis, Caroline A.; Romero, Rodrigo; Mercer, Kim L.; Bhutkar, Arjun; Phat, Sarah; Myers, David T.; Muzumdar, Mandar Deepak; Westcott, Peter M. K.; Beytagh, Mary Clare; Farago, Anna F.; Vander Heiden, Matthew G.; Dyson, Nicholas J.; Jacks, Tyler. And the article was included in Science Translational Medicine in 2019.Reference of 18423-43-3 The following contents are mentioned in the article:
Small cell lung cancer (SCLC) is an aggressive lung cancer subtype with extremely poor prognosis. No targetable genetic driver events have been identified, and the treatment landscape for this disease has remained nearly unchanged for over 30 years. Here, we have taken a CRISPR-based screening approach to identify genetic vulnerabilities in SCLC that may serve as potential therapeutic targets. We used a single-guide RNA (sgRNA) library targeting ∼5000 genes deemed to encode “”druggable”” proteins to perform loss-of-function genetic screens in a panel ofcell lines derived from autochthonous genetically engineered mouse models (GEMMs) of SCLC, lung adenocarcinoma (LUAD), and pancreatic ductal adenocarcinoma (PDAC). Cross-cancer analyses allowed us to identify SCLC-selective vulnerabilities. In particular, we observed enhanced sensitivity of SCLC cells toward disruption of the pyrimidine biosynthesis pathway. Pharmacol. inhibition of dihydroorotate dehydrogenase (DHODH), a key enzyme in this pathway, reduced the viability of SCLC cells in vitro and strongly suppressed SCLC tumor growth in human patient-derived xenograft (PDX) models and in an autochthonous mouse model. These results indicate that DHODH inhibition may be an approach to treat SCLC. This study involved multiple reactions and reactants, such as Thymidine 5′-(tetrahydrogen triphosphate) xsodium salt (cas: 18423-43-3Reference of 18423-43-3).
Thymidine 5′-(tetrahydrogen triphosphate) xsodium salt (cas: 18423-43-3) belongs to tetrahydrofuran derivatives. Tetrahydrofuran (THF), or oxolane, is mainly used as a precursor to polymers. Being polar and having a wide liquid range, THF is a versatile solvent. THF can also be synthesized by catalytic hydrogenation of furan. This allows certain sugars to be converted to THF via acid-catalyzed digestion to furfural and decarbonylation to furan, although this method is not widely practiced. THF is thus derivable from renewable resources.Reference of 18423-43-3
18423-43-3;Thymidine 5′-(tetrahydrogen triphosphate) xsodium salt;The future of 18423-43-3;New trend of C10H14N2Na3O14P3;function of 18423-43-3