1448191-66-9

Upstream product

• 34306-42-8 Boc-Abu 
• 1448189-90-9 (2S,4R)-4-hydroxy-N-{ [4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl}pyrrolidine-2-carboxamide hydrochloride 
• 1448191-54-5 tert‐butyl (2S,4R)‐4‐hydroxy‐2‐({[4‐(4‐methyl‐1,3‐thiazol‐5‐yl)phenyl]methyl}carbamoyl)pyrrolidine‐1‐carboxylate 
• 1448189-30-7 1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methaneamine 
• 122957-57-7 4-(4-methyl-1,3-thiazol-5-yl)benzonitrile 
• 623-00-7 4-bromobenzenecarbonitrile 

Relevant academic research and scientific papers

Identification and Characterization of von Hippel-Lindau-Recruiting Proteolysis Targeting Chimeras (PROTACs) of TANK-Binding Kinase 1

Proteolysis targeting chimeras (PROTACs) are bifunctional molecules that recruit an E3 ligase to a target protein to facilitate ubiquitination and subsequent degradation of that protein. While the field of targeted degraders is still relatively young, the potential for this modality to become a differentiated and therapeutic reality is strong, such that both academic and pharmaceutical institutions are now entering this interesting area of research. In this article, we describe a broadly applicable process for identifying degrader hits based on the serine/threonine kinase TANK-binding kinase 1 (TBK1) and have generalized the key structural elements associated with degradation activities. Compound 3i is a potent hit (TBK1 DC50 = 12 nM, Dmax = 96%) with excellent selectivity against a related kinase IKK?, which was further used as a chemical tool to assess TBK1 as a target in mutant K-Ras cancer cells.

Compounds & Methods for the Enhanced Degradation of Targeted Proteins & Other Polypeptides by an E3 Ubiquitin Ligase

The present invention relates to bifunctional compounds, which find utility as modulators of targeted ubiquitination, especially inhibitors of a variety of polypeptides and other proteins that are degraded and/or otherwise inhibited by bifunctional compounds of the present invention. In particular, the present invention is directed to compounds, which contain on one end a VHL ligand that binds to the ubiquitin ligase and on the other end a moiety that binds a target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of that protein. The present invention exhibits a broad range of pharmacological activities associated with compounds of the present invention, consistent with the degradation/inhibition of targeted polypeptides.

COMPOUNDS AND METHODS FOR THE INHIBITION OF VCB E3 UBIQUITIN LIGASE

The present invention relates to novel compounds which find utility as modulators, especially inhibitors of VCB E3 Ubiquitin Ligase and as bioactive agents for use as therapeutics for the stimulation of erythropoiesis in a patient or subject including inducement of EPO production in the patient or subject, for the treatment of chronic anemia and ischemia (limits brain injury during episodes of localized anemia, ischemia and/or stroke and damage to cardiovascular tissue during cardiovascular ischemia), as well as enhancing wound healing processes. Pharmaceutical compositions comprising effective amounts of compounds according to the present invention alone or in combination with an additional erythropoieses stimulating agent such as EPO under the tradename procrit or epogen or darbapoietin alfa under the tradename aranesp. Methods of stimulating erythropoiesis in a subject or patient, including increasing the number of red blood cells and/or hematocrit of the patient, treating anemia, including chronic anemia and anemia associated with chronic kidney disease, dialysis, and cancer chemotherapy, ischemia, stroke and damage to cardiovascular tissue during cardiovascular ischemia as well as enhancing wound healing processes and preventing/reducing scarring secondary to healing represent additional aspects of the present invention. Local enhancement of angiogenesis through induction of VEGF including wound healing and reduction of stent occlusion remain additional aspects of the present invention.