http://chineseinput.net/에서 pinyin(병음)방식으로 중국어를 변환할 수 있습니다.
변환된 중국어를 복사하여 사용하시면 됩니다.
A novel cereblon modulator for targeted protein degradation
Kim, Sung Ah,Go, Ara,Jo, Seung-Hyun,Park, Sun Jun,Jeon, Young Uk,Kim, Ji Eun,Lee, Heung Kyoung,Park, Chi Hoon,Lee, Chong-Ock,Park, Sung Goo,Kim, Pilho,Park, Byoung Chul,Cho, Sung Yun,Kim, Sunhong,Ha, Elsevier 2019 European Journal of Medicinal Chemistry Vol.166 No.-
<P><B>Abstract</B></P> <P>Immunomodulatory drugs (IMiDs) exert anti-myeloma activity by binding to the protein cereblon (CRBN) and subsequently degrading IKZF1/3. Recently, their ability to recruit E3 ubiquitin ligase has been used in the proteolysis targeting chimera (PROTAC) technology. Herein, we design and synthesize a novel IMiD analog TD-106 that induces the degradation of IKZF1/3 and inhibits the proliferation of multiple myeloma cells <I>in vitro</I> as well as <I>in vivo</I>. Moreover, we demonstrate that TD-428, which comprises TD-106 linked to a BET inhibitor, JQ1 efficiently induce BET protein degradation in the prostate cancer cell line 22Rv1. Consequently, cell proliferation is inhibited due to suppressed C-MYC transcription. These results, therefore, firmly suggest that the newly synthesized IMiD analog, TD-106, is a novel CRBN modulator that can be used for targeted protein degradation.</P> <P><B>Highlights</B></P> <P> <UL> <LI> We design and synthesize a novel IMiD analog. </LI> <LI> TD-106 induces the degradation of IKZF1/3 and inhibits the proliferation of multiple myeloma cells. </LI> <LI> BET PROTAC with TD-106 efficiently induces the degradation of BET proteins. </LI> <LI> TD-106 as a novel CRBN modulator can be used for targeted protein degradation. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>
Pyrazolo[3,4‐ d ]pyrimidine derivatives as irreversible Bruton's tyrosine kinase inhibitors
Yeom Hyesu,Achary Raghavendra,Choi Yunha,Park Chi Hoon,Lee Joo‐Youn,Lee Heung Kyoung,Kim Pilho,Cho Sung Yun 대한화학회 2022 Bulletin of the Korean Chemical Society Vol.43 No.4
4,6-Disubstituted pyrazolo[3,4-d]pyrimidine derivatives were explored as irreversible Bruton’s tyrosine kinase (BTK) inhibitors. The structure–activity relationship was established with over 20 derivatives synthesized to determine initial hit compounds, based on activities against BTK enzyme and TMD8 cells. It turned out that introducing 1-acrylamido-4-aminopiperdine (1b) at the C4 position of pyrazolopyrimidine as in 5e, and 3-acrylamido-aniline (1j) as 4-position substituent, such as in 9d, 10d, and 10e, delivered potent in vitro enzyme activities as well as TMD8 cell-based cytotoxicities. Considering kinase selectivity profiles, 5e was selected for in vivo efficacy studies with a murine xenograft model using TMD8 cells, where 5e exhibited moderate tumor growth inhibition activities. Further optimization of 5e and 9d may lead to clinically useful compounds to overcome B-cell-mediated hematologic cancers.
Link, Michael F.,Kim, Jounghwa,Park, Gyutae,Lee, Taehyoung,Park, Taehyun,Babar, Zaeem Bin,Sung, Kijae,Kim, Pilho,Kang, Seokwon,Kim, Jeong Soo,Choi, Yongjoo,Son, Jihawn,Lim, Ho-Jin,Farmer, Delphine K. Elsevier 2017 Atmospheric environment Vol.156 No.-
<P>A vehicle fleet representative of passenger vehicles driven in the Seoul Metropolitan Region was investigated for primary emissions and secondary chemistry. Exhaust was photochemically oxidized in a flow reactor to determine the ammonium nitrate (NH4NO3) aerosol formation potential from vehicles of gasoline, diesel and liquid petroleum gasoline (LPG) fuel types. Secondary formation of aerosol NH4NO3, was larger than primary emissions for all vehicle fuel types except diesel, for which negligible secondary NH4NO3 production was observed. Although diesel vehicles emitted more primary nitrogen oxides than other vehicle types, ammonia emitted from gasoline and liquid petroleum gasoline fuels types limited the secondary production of NH4NO3. The results suggest that gasoline and liquid petroleum gasoline vehicles with three-way catalysts could be an important source of ammonia for NH4NO3 aerosol formation in ammonia-limited environments, including the Seoul Metropolitan Region. (C) 2017 Published by Elsevier Ltd.</P>