5413-84-3Relevant academic research and scientific papers
Discovery of AB680: A Potent and Selective Inhibitor of CD73
Lawson, Kenneth V.,Kalisiak, Jaroslaw,Lindsey, Erick A.,Newcomb, Eric T.,Leleti, Manmohan Reddy,Debien, Laurent,Rosen, Brandon R.,Miles, Dillon H.,Sharif, Ehesan U.,Jeffrey, Jenna L.,Tan, Joanne B. L.,Chen, Ada,Zhao, Sharon,Xu, Guifen,Fu, Lijuan,Jin, Lixia,Park, Tim W.,Berry, Wade,Moschütz, Susanne,Scaletti, Emma,Str?ter, Norbert,Walker, Nigel P.,Young, Stephen W.,Walters, Matthew J.,Schindler, Uli,Powers, Jay P.
, p. 11448 - 11468 (2020/11/26)
Extracellular adenosine (ADO), present in high concentrations in the tumor microenvironment (TME), suppresses immune function via inhibition of T cell and NK cell activation. Intratumoral generation of ADO depends on the sequential catabolism of ATP by two ecto-nucleotidases, CD39 (ATP → AMP) and CD73 (AMP → ADO). Inhibition of CD73 eliminates a major pathway of ADO production in the TME and can reverse ADO-mediated immune suppression. Extensive interrogation of structure-activity relationships (SARs), structure-based drug design, and optimization of pharmacokinetic properties culminated in the discovery of AB680, a highly potent (Ki = 5 pM), reversible, and selective inhibitor of CD73. AB680 is further characterized by very low clearance and long half-lives across preclinical species, resulting in a PK profile suitable for long-acting parenteral administration. AB680 is currently being evaluated in phase 1 clinical trials. Initial data show AB680 is well tolerated and exhibits a pharmacokinetic profile suitable for biweekly (Q2W) iv-administration in human.
IMAGING AGENTS FOR NEURAL FLUX
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Page/Page column 129; 130, (2016/02/10)
Provided herein are radiolabeled compounds useful for non-invasive imaging techniques. An exemplary radiolabeled compound provided herein is useful as a radiotracer for positron emission tomography. The present application also provides unlabeled compounds useful in methods of treating diseases of the central nervous system or disease of the peripheral nervous system. Methods for preparing radiolabeled compounds, preparing unlabeled compounds, and diagnostic methods using labeled or unlabeled compounds are also provided.
