927877-48-3Relevant academic research and scientific papers
Development of a Hematopoietic Prostaglandin D Synthase-Degradation Inducer
Yokoo, Hidetomo,Shibata, Norihito,Naganuma, Miyako,Murakami, Yuki,Fujii, Kiyonaga,Ito, Takahito,Aritake, Kosuke,Naito, Mikihiko,Demizu, Yosuke
, p. 236 - 241 (2021)
Although hematopoietic prostaglandin D synthase (H-PGDS) is an attractive target for treatment of a variety of diseases, including allergic diseases and Duchenne muscular dystrophy, no H-PGDS inhibitors have yet been approved for treatment of these diseases. Therefore, the development of novel agents having other modes of action to modulate the activity of H-PGDS is required. In this study, a chimeric small molecule that degrades H-PGDS via the ubiquitin-proteasome system, PROTAC(H-PGDS)-1, was developed. PROTAC(H-PGDS)-1 is composed of two ligands, TFC-007 (that binds to H-PGDS) and pomalidomide (that binds to cereblon). PROTAC(H-PGDS)-1 showed potent activity in the degradation of H-PGDS protein via the ubiquitin-proteasome system and in the suppression of prostaglandin D2 (PGD2) production. Notably, PROTAC(H-PGDS)-1 showed sustained suppression of PGD2 production after the drug removal, whereas PGD2 production recovered following removal of TFC-007. Thus, the H-PGDS degrader - PROTAC(H-PGDS)-1 - is expected to be useful in biological research and clinical therapies.
Modulators of methyl modifying enzymes, compositions and uses thereof
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, (2015/12/26)
Agents for modulating methyl modifying enzymes, compositions and uses thereof are provided herein.
MODULATORS OF METHYL MODIFYING ENZYMES, COMPOSITIONS AND USES THEREOF
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, (2013/06/05)
Agents for modulating methyl modifying enzymes, compositions and uses thereof are provided herein
PYRIMIDINE HYDRAZIDE COMPOUNDS AS PGDS INHIBITORS
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, (2008/12/04)
This invention is directed to a compound wherein R1, R2, R3, R4 and L1 are as defined herein, a pharmaceutical composition comprising the compound, and the use of the compound to treat allergic and/or
