K. Howard
4 Papers
K. Howard is an academic researcher. The author has contributed to research in topics: Medicine & Chemistry. The author has an hindex of 1, co-authored 3 publications.
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Papers
Regulated Induced Proximity Targeting Chimeras (RIPTACs): a Novel Heterobifunctional Small Molecule Therapeutic Strategy for Killing Cancer Cells Selectively
Kanak Raina,C.D. Forbes,Rebecca Stronk,Jonathan P. Rappi,Kyle J. Eastman,Samuel Gerritz,Xinheng Yu,Hao Li,Amit Bhardwaj,Mia E. Forgione,Abigail Hundt,Madeline P. King,Zoe M. Posner,Allison Denny,Andrew McGovern,David E. Puleo,Ethan Garvin,Rebekka Chenard,Nilesh Zaware,James J. Mousseau,Jen Macaluso,Michael Martin,Kyle Bassoli,Kelli Jones,Marco Garcia,K. Howard,Levi M. Smith,Jinshan Chen,Cesar A. De Leon,John Hines,Katherine J. Kayser-Bricker,Craig M. Crews +31 more
TL;DR: In this article , the authors describe a proof-of-concept study using novel heterobifunctional small molecules called Regulated Induced Proximity Targeting Chimeras or RIPTACs, which elicit a stable ternary complex between a target protein selectively expressed in cancer tissue and a pan-expressed protein essential for cell survival.
Abstract 1629: Prostate cancer RIPTAC™ therapeutics demonstrate activity in preclinical models of Enzalutamide-resistant prostate cancer
Xinheng Yu,Kyle J. Eastman,Kanak Raina,Kelli Jones,C.D. Forbes,Abigail Hundt,Marco Garcia,Rebecca Stronk,K. Howard,Andrew McGovern,Rebekka Chenard,Allison Denny,Mia E. Forgione,Kyle Bassoli,Ethan Garvin,James J. Mousseau,Hao Li,Madeline P. King,Amit Bhardwaj,Katherine J. Kayser-Bricker,Craig M. Crews +20 more
TL;DR: In this paper , the Androgen Receptor (AR) was used as a tumor specific protein to selectively inhibit an essential protein involved in transcriptional regulation and provide in vivo efficacy coupled with a therapeutic index.
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Abstract 1764: Development of an alphalex™-auristatin low pH targeting conjugate for the treatment of solid tumors
Sophia Gayle,Robert A. Aiello,J R Bechtold,Patricia-Ann Bourassa,Johanna Csengery,Connor J Hagen,K. Howard,Kelli Jones,Lori L. Lopresti-Morrow,Robert B. Maguire,T H M Paradis,Theresa Pasqualini,Joseph Tweed,Laurie Tylaska,Ning Zhang,Vishwas M. Paralkar +15 more
TL;DR: The ability of alphalex-MMAE to display potent in vitro and in vivo efficacy in colorectal, non-small cell lung, and prostate carcinoma cell lines is demonstrated and Cybrexa will move forward with the goal of initiating IND-enabling studies in 2022.
Regulated induced proximity targeting chimeras-RIPTACs-A heterobifunctional small molecule strategy for cancer selective therapies.
Kanak Raina,Chris D. Forbes,Rebecca Stronk,Jonathan P. Rappi,Kyle J. Eastman,Nilesh Zaware,Xinheng Yu,Hao Li,Amit Bhardwaj,Samuel W. Gerritz,Mia E. Forgione,Abigail Hundt,Madeline P. King,Zoe M. Posner,Allison D. Correia,Andrew McGovern,David E. Puleo,Rebekka Chenard,James J. Mousseau,J. I. Vergara,Ethan Garvin,Jennifer Macaluso,Michael Martin,Kyle Bassoli,Kelli Jones,Marco Garcia,K. Howard,Madeleine Yaggi,Jinshan M. Chen,Andrew B. Mayfield,Cesar A. De Leon,John Hines,Katherine J. Kayser-Bricker,Craig M Crews +33 more
Abstract: We describe a protein proximity inducing therapeutic modality called Regulated Induced Proximity Targeting Chimeras or RIPTACs: heterobifunctional small molecules that elicit a stable ternary complex between a target protein (TP) selectively expressed in tumor cells and a pan-expressed protein essential for cell survival. The resulting co-operative protein-protein interaction (PPI) abrogates the function of the essential protein, thus leading to death selectively in cells expressing the TP. This approach leverages differentially expressed intracellular proteins as novel cancer targets, with the advantage of not requiring the target to be a disease driver. In this chemical biology study, we design RIPTACs that incorporate a ligand against a model TP connected via a linker to effector ligands such as JQ1 (BRD4) or BI2536 (PLK1) or CDK inhibitors such as TMX3013 or dinaciclib. RIPTACs accumulate selectively in cells expressing the HaloTag-FKBP target, form co-operative intracellular ternary complexes, and induce an anti-proliferative response in target-expressing cells.