Development of selective mono or dual PROTAC degrader probe of CDK isoforms.
Sign Up to like & getrecommendations! Published in 2019 at "European journal of medicinal chemistry"
DOI: 10.1016/j.ejmech.2019.111952
Abstract: Cyclin-dependent kinase (CDK) family members are promising molecular targets in discovering potent inhibitors in disease settings, they function differentially. CDK2, CDK4 and CDK6, directly regulate the cell cycle, while CDK9 primarily modulates the transcription regulation.… read more here.
Keywords: degrader; development selective; protac; selective mono ... See more keywords
Potent and Selective Mitogen-Activated Protein Kinase Kinase 1/2 (MEK1/2) Heterobifunctional Small-molecule Degraders.
Sign Up to like & getrecommendations! Published in 2020 at "Journal of medicinal chemistry"
DOI: 10.1021/acs.jmedchem.0c01609
Abstract: Previously, we reported a first-in-class von Hippel-Lindau (VHL)-recruiting mitogen-activated protein kinase kinases 1 and 2 (MEK1/2) degrader, MS432. To date, only two MEK1/2 degrader papers have been published and very limited structure-activity relationships (SAR) have… read more here.
Keywords: degrader; kinase; activated protein; mek1 degrader ... See more keywords
Development of Human Carbonic Anhydrase II Heterobifunctional Degraders
Sign Up to like & getrecommendations! Published in 2023 at "Journal of Medicinal Chemistry"
DOI: 10.1021/acs.jmedchem.2c01843
Abstract: Human carbonic anhydrase II (hCAII) is a metalloenzyme essential to critical physiological processes in the body. hCA inhibitors are used clinically for the treatment of indications ranging from glaucoma to epilepsy. Targeted protein degraders have… read more here.
Keywords: human carbonic; development human; carbonic anhydrase; heterobifunctional degraders ... See more keywords
Discovery of LL-K8-22: A Selective, Durable, and Small-Molecule Degrader of the CDK8-Cyclin C Complex.
Sign Up to like & getrecommendations! Published in 2023 at "Journal of medicinal chemistry"
DOI: 10.1021/acs.jmedchem.2c02045
Abstract: The CDK8-cyclin C complex is an important anti-tumor target, but unlike CDK8, cyclin C remains undruggable. Modulators regulating cyclin C activity directly are still under development. Here, a series of hydrophobic tagging-based degraders of the… read more here.
Keywords: cdk8 cyclin; molecule; degrader; cyclin complex ... See more keywords
Discovery of a First-in-class Mitogen-Activated Protein Kinase Kinase 1/2 (MEK1/2) Degrader.
Sign Up to like & getrecommendations! Published in 2019 at "Journal of medicinal chemistry"
DOI: 10.1021/acs.jmedchem.9b01528
Abstract: MEK1 and MEK2 (also known as MAP2K1 and MAP2K2) are the "gatekeepers" of the ERK signaling output with redundant roles in controlling ERK activity. Numerous inhibitors targeting MEK1/2 have been developed including three FDA-approved drugs.… read more here.
Keywords: degrader; kinase; discovery first; mek1 ... See more keywords
Proximity-Induced Nucleic Acid Degrader (PINAD) Approach to Targeted RNA Degradation Using Small Molecules
Sign Up to like & getrecommendations! Published in 2023 at "ACS Central Science"
DOI: 10.1021/acscentsci.3c00015
Abstract: Nature has evolved intricate machinery to target and degrade RNA, and some of these molecular mechanisms can be adapted for therapeutic use. Small interfering RNAs and RNase H-inducing oligonucleotides have yielded therapeutic agents against diseases… read more here.
Keywords: proximity induced; pinad; degrader; small molecules ... See more keywords
CRISPR Screen Reveals BRD2/4 Molecular Glue-like Degrader via Recruitment of DCAF16.
Sign Up to like & getrecommendations! Published in 2023 at "ACS chemical biology"
DOI: 10.1021/acschembio.2c00747
Abstract: Molecular glues (MGs) are monovalent small molecules that induce an interaction between proteins (native or non-native partners) by altering the protein-protein interaction (PPI) interface toward a higher-affinity state. Enhancing the PPI between a protein and… read more here.
Keywords: compound; screen; degrader; molecular glue ... See more keywords
PROTAC Linkerology Leads to an Optimized Bivalent Chemical Degrader of Polycomb Repressive Complex 2 (PRC2) Components.
Sign Up to like & getrecommendations! Published in 2023 at "ACS chemical biology"
DOI: 10.1021/acschembio.2c00804
Abstract: Bivalent chemical degraders, otherwise known as proteolysis-targeting chimeras (PROTACs), have proven to be an efficient strategy for targeting overexpressed or mutated proteins in cancer. PROTACs provide an alternative approach to small-molecule inhibitors, which are restricted… read more here.
Keywords: linkerology leads; protac linkerology; bivalent chemical; degrader ... See more keywords
SJPYT-195: A Designed Nuclear Receptor Degrader That Functions as a Molecular Glue Degrader of GSPT1.
Sign Up to like & getrecommendations! Published in 2022 at "ACS medicinal chemistry letters"
DOI: 10.1021/acsmedchemlett.2c00223
Abstract: We previously reported a specific inverse agonist (SPA70) of the nuclear receptor pregnane X receptor (PXR). However, derivatization of SPA70 yielded only agonists and neutral antagonists, suggesting that inverse agonism of PXR is difficult to… read more here.
Keywords: nuclear receptor; sjpyt 195; degrader; molecular glue ... See more keywords
Discovery and resistance mechanism of a selective CDK12 degrader
Sign Up to like & getrecommendations! Published in 2021 at "Nature Chemical Biology"
DOI: 10.1038/s41589-021-00765-y
Abstract: Cyclin-dependent kinase 12 (CDK12) is an emerging therapeutic target due to its role in regulating transcription of DNA-damage response (DDR) genes. However, development of selective small molecules targeting CDK12 has been challenging due to the… read more here.
Keywords: bsj 116; discovery resistance; mechanism; degrader ... See more keywords
Emerging degrader technologies engaging lysosomal pathways
Sign Up to like & getrecommendations! Published in 2022 at "Chemical Society Reviews"
DOI: 10.1039/d2cs00624c
Abstract: Targeted protein degradation (TPD) provides unprecedented opportunities for drug discovery. While the proteolysis-targeting chimera (PROTAC) technology has already entered clinical trials and changed the landscape of small-molecule drugs, new degrader technologies harnessing alternative degradation machineries,… read more here.
Keywords: emerging degrader; degrader technologies; technologies engaging; lysosomal pathways ... See more keywords