Smil, David; Wong, Jong Fu; Williams, Eleanor P.; Adamson, Roslin J.; Howarth, Alison; McLeod, David A.; Mamai, Ahmed; Kim, Soyoung; Wilson, Brian J.; Kiyota, Taira; Aman, Ahmed; Owen, Julie; Poda, Gennady; Horiuchi, Kurumi Y.; Kuznetsova, Ekaterina; Ma, Haiching; Hamblin, J. Nicole; Cramp, Sue; Roberts, Owen G.; Edwards, Aled M.; Uehling, David; Al-awar, Rima; Bullock, Alex N.; O’Meara, Jeff A.; Isaac, Methvin B. published the artcile< Leveraging an Open Science Drug Discovery Model to Develop CNS-Penetrant ALK2 Inhibitors for the Treatment of Diffuse Intrinsic Pontine Glioma>, Reference of 916791-62-3, the main research area is preparation ALK2 inhibitor diffuse intrinsic pontine glioma.
There are currently no effective chemotherapeutic drugs approved for the treatment of diffuse intrinsic pontine glioma (DIPG), an aggressive pediatric cancer resident in the pons region of the brainstem. Radiation therapy is beneficial but not curative, with the condition being uniformly fatal. Anal. of the genomic landscape surrounding DIPG has revealed that activin receptor-like kinase-2 (ALK2) constitutes a potential target for therapeutic intervention given its dysregulation in the disease. An open science approach has been adopted to develop a series of potent, selective, orally bioavailable, and brain-penetrant ALK2 inhibitors based on the lead compound LDN-214117. Modest structural changes to the C-3, C-4, and C-5 position substituents of the core pyridine ring afforded compounds M4K2009, M4K2117, and M4K2163, each with a superior potency, selectivity, and/or blood-brain barrier (BBB) penetration profile. Robust in vivo pharmacokinetic (PK) properties and tolerability mark these inhibitors as advanced preclin. compounds suitable for further development and evaluation in orthotopic models of DIPG.
Journal of Medicinal Chemistry published new progress about Activin receptor ACVRLK2 Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 916791-62-3 belongs to class pyridine-derivatives, and the molecular formula is C5H2Cl2FN, Reference of 916791-62-3.