P3 SAR exploration of biphenyl carbamate based Legumain inhibitors

被引：11

作者：

Higgins, Catherine ^{[1
]}

Bouazzaoui, Samira ^{[1
]}

Gaddale, Kishore ^{[1
]}

D'Costa, Zenobia ^{[1
]}

Templeman, Amy ^{[1
]}

O'Rourke, Martin ^{[2
]}

Young, Andrew ^{[3
]}

Scott, Christopher ^{[1
,3
]}

Harrison, Tim ^{[1
,2
]}

Mullan, Paul ^{[1
]}

Williams, Rich ^{[1
]}

机构：

[1] Queens Univ Belfast, CCRCB Drug Discovery Grp, Ctr Canc Res & Cell Biol, Belfast BT9 7BL, Antrim, North Ireland

[2] Almac Discovery, Craigavon BT63 5QD, North Ireland

[3] Queens Univ Belfast, Sch Pharm, Belfast BT9 7BL, Antrim, North Ireland

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2014年 / 24卷 / 11期

关键词：

Legumain; Cancer; Cyano warhead; Protease inhibitor; ASPARAGINE ENDOPEPTIDASE; IDENTIFICATION;

D O I：

10.1016/j.bmcl.2014.04.002

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

This Letter describes the further development and SAR exploration of a novel series of Legumain inhibitors. Based upon a previously identified Legumain inhibitor from our group, we explored the SAR of the carbamate phenyl ring system to probe the P3 pocket of the enzyme. This led to the identification of a sub-nanomolar inhibitor of Legumain. (C) 2014 Elsevier Ltd. All rights reserved.

引用

页码：2521 / 2524

页数：4

共 18 条

[11] Genome-wide array-based comparative genomic hybridization analysis of pancreatic adenocarcinoma: Identification of genetic indicators that predict patient outcome
Loukopoulos, Panayiotis
Shibata, Tatsuhiro
Katoh, Hiroto
Kokubu, Akiko
Sakamoto, Michiie
Yamazaki, Ken
Kosuge, Tomoo
Kanai, Yae
Hosoda, Fumie
Imoto, Issei
Ohki, Misao
Inazawa, Jyoji
Hirohashi, Setsuo
[J]. CANCER SCIENCE, 2007, 98 (03): : 392 - 400
[12] Asparagine endopeptidase is not essential for class II MHC antigen presentation but is required for processing of cathepsin L in mice
Maehr, R
Hang, HC
Mintern, JD
Kim, YM
Cuvillier, A
Nishimura, M
Yamada, K
Shirahama-Noda, K
Hara-Nishimura, I
Ploegh, HL
[J]. JOURNAL OF IMMUNOLOGY, 2005, 174 (11) : 7066 - 7074
[13] Asparagine endopeptidase can initiate the removal of the MHC class II invariant chain chaperone
Manoury, B
Mazzeo, D
Li, DTN
Billson, J
Loak, K
Benaroch, P
Watts, C
[J]. IMMUNITY, 2003, 18 (04) : 489 - 498
[14] Nishimura M., 2003, J BIOL CHEM, V278, P33194
[15] Ohno Y., 2013, WORLD J UROL
[16] Invasion suppressor cystatin E/M (CST6): high-level cell type-specific expression in normal brain and epigenetic silencing in gliomas
Qiu, Jingxin
Ai, Lingbao
Ramachandran, Cheppail
Yao, Bing
Gopalakrishnan, Suhasni
Fields, C. Robert
Delmas, Amber L.
Dyer, Lisa M.
Melnick, Steven J.
Yachnis, Anthony T.
Schwartz, Philip H.
Fine, Howard A.
Brown, Kevin D.
Robertson, Keith D.
[J]. LABORATORY INVESTIGATION, 2008, 88 (09) : 910 - 925
[17] Legumain: A biomarker for diagnosis and prognosis of human ovarian cancer
Wang, Lina
Chen, Si
Zhang, Mingna
Li, Na
Chen, Yanan
Su, Weijun
Liu, Yanhua
Lu, Dan
Li, Sanglin
Yang, Yixuan
Li, Zongjin
Stupack, Dwayne
Qu, Pengpeng
Hu, Huaidong
Xiang, Rong
[J]. JOURNAL OF CELLULAR BIOCHEMISTRY, 2012, 113 (08) : 2679 - 2686
[18] Cystatin M: A novel candidate tumor suppressor gene for breast cancer
Zhang, J
Shridhar, R
Dai, Q
Song, J
Barlow, SC
Yin, LJ
Sloane, BF
Miller, FR
Meschonat, C
Li, BDL
Abreo, F
Keppler, D
[J]. CANCER RESEARCH, 2004, 64 (19) : 6957 - 6964

← 1 2 →