BROWSE

Related Scientist

lim,sangmin's photo.

lim,sangmin
분자활성촉매반응연구단
more info

ITEM VIEW & DOWNLOAD

Identification of β-lapachone analogs as novel MALT1 inhibitors to treat an aggressive subtype of diffuse large B-cell lymphoma

Cited 30 time in webofscience Cited 30 time in scopus
1,204 Viewed 195 Downloaded
Title
Identification of β-lapachone analogs as novel MALT1 inhibitors to treat an aggressive subtype of diffuse large B-cell lymphoma
Author(s)
Sang Min Lim; Yujeong Jeong; Suhyun Lee; Honggu Im; Hyun Seop Tae; Kim, B.G.; Park, H.D.; Park, J.; Sungwoo Hong
Publication Date
2015-11
Journal
JOURNAL OF MEDICINAL CHEMISTRY, v.58, no.21, pp.8491 - 8502
Publisher
AMER CHEMICAL SOC
Abstract
The treatment of activated B cell-like DLBCL (ABC-DLBCL) is one of the urgent unmet medical needs because it is the most resistant DLBCL subtype to current therapies eagerly awaiting effective therapeutic strategies. Recently, the paracaspase MALT1 has emerged as a promising therapeutic target for the treatment of ABC-DLBCL. Herein, we report a new class of MALT1 inhibitors developed by high-throughput screening and structure-based drug design. The original hit, 4-amino-1,2-naphthoquinone series inhibited MALT1 activity but suffered from poor cellular activity. The extensive pharmacophore search led to the discovery of structurally similar β-lapachone that is a direct inhibitor of MALT1 and possesses favorable physicochemical properties. Molecular simulation studies suggested the possibility of the formation of a covalent bond between MALT1 and β-lapachone, which was corroborated by experimental wash-out studies. Inspired by this, we explored the structure-activity relationships by incorporating electron-withdrawing substituents at C8 position of β-lapachone. These MALT1 inhibitors exhibited potent antiproliferative activity to OCI-LY3 cell line and inhibited the cleavage of CYLD mediated MALT1. © 2015 American Chemical Society
URI
https://pr.ibs.re.kr/handle/8788114/1836
DOI
10.1021/acs.jmedchem.5b01415
ISSN
0022-2623
Appears in Collections:
Center for Catalytic Hydrocarbon Functionalizations(분자활성 촉매반응 연구단) > 1. Journal Papers (저널논문)
Files in This Item:
2015-acs.jmedchem.pdfDownload

qrcode

  • facebook

    twitter

  • Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.
해당 아이템을 이메일로 공유하기 원하시면 인증을 거치시기 바랍니다.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse