@inbook{1883af7f63644ab7920f52fc94dee958,
title = "Conformational control and regulation of the pseudokinase KSR via small molecule binding interactions",
abstract = "Pseudokinases often operate through functionally related enzymes and receptors. A prime example is the pseudokinase KSR (Kinase Suppressor of RAS), which can act as both an amplifier and inhibitor of members in the RAS-MAPK (Mitogen Activated Protein Kinase) signaling pathway. KSR is structurally related to the active RAF kinases over multiple domains; moreover, the pseudokinase domain of KSR forms physical and regulatory complexes with both RAF and MEK through distinct interfaces. Characterization of small molecule interactions on KSR has been used to uncover novel chemical tools and understand the mechanism of action of clinical drugs. Here, we elaborate on assays and structural methods for measuring binding at orthosteric and interfacial binding sites on KSR. These distinct small molecule pockets provide therapeutic paths for targeting KSR1 and KSR2 pseudokinases in disease, including in RAS and RAF mutant cancers.",
keywords = "Activity-based probes, Crystallization, Interfacial sites, KSR, MEK, Molecular glues, Orthosteric site, RAF, SBDD, Target engagement",
author = "Arthur Chow and Khan, {Zaigham M.} and Marsiglia, {William M.} and Dar, {Arvin C.}",
note = "Funding Information: The Dar laboratory gratefully receives funding from the NIH (RO1s CA227636, CA258736, CA256480, and R56 AG066712) and the Mark Foundation for Cancer Research (20-030-ASP, 21-039-ASP). A.C.D. also thanks the Pershing-Square Sohn Cancer Research Alliance and Alex's Lemonade Stand Foundation for Childhood Cancer for support. A.C. and W.M.M. are recipients of NIH 5T32CA078207 and F99/K00 CA212474 awards, respectively. The authors are also supported by NCI grant P30 CA196521 to the Tisch Cancer Institute. A.C.D. is a founder, shareholder, advisory board member, and consultant to Nested Therapeutics. Publisher Copyright: {\textcopyright} 2022 Elsevier Inc.",
year = "2022",
month = jan,
doi = "10.1016/bs.mie.2022.03.039",
language = "English",
isbn = "9780323915410",
series = "Methods in Enzymology",
publisher = "Academic Press Inc.",
pages = "365--402",
editor = "Natalia Jura and Murphy, {James M.}",
booktitle = "Pseudokinases",
address = "United States",
}