A patent review of MALT1 inhibitors (2013-present)

被引:18
|
作者
Hamp, Isabel [1 ,2 ]
O'Neill, Thomas J. [3 ]
Plettenburg, Oliver [1 ,2 ]
Krappmann, Daniel [1 ]
机构
[1] Helmholtz Zentrum Munchen, Inst Med Chem, German Res Ctr Environm Hlth, D-85764 Neuherberg, Germany
[2] Leibniz Univ Hannover, Ctr Biomol Drug Res BMWZ, Inst Organ Chem, Hannover, Germany
[3] Helmholtz Zentrum Munchen, Res Unit Cellular Signal Integrat, German Res Ctr Environm Hlth, D-85764 Neuherberg, Germany
关键词
MALT1; allosteric inhibition; autoimmunity; cancer immunotherapy; lymphoma; proteases; regulatory T cells; NF-KAPPA-B; T-CELL; PARACASPASE MALT1; ALLOSTERIC INHIBITORS; PROTEASE ACTIVITY; TARGETING BTK; ACTIVATION; CLEAVAGE; IBRUTINIB; MECHANISMS;
D O I
10.1080/13543776.2021.1951703
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Introduction MALT1 is the only human paracaspase, a protease with unique cleavage activity and substrate specificity. As a key regulator of immune responses, MALT1 has attracted attention as an immune modulatory target for the treatment of autoimmune/inflammatory diseases. Further, chronic MALT1 protease activation drives survival of lymphomas, suggesting that MALT1 is a suitable drug target for lymphoid malignancies. Recent studies have indicated that MALT1 inhibition impairs immune suppressive function of regulatory T cells in the tumor microenvironment, suggesting that MALT1 inhibitors may boost anti-tumor immunity in the treatment of solid cancers. Areas covered This review summarizes the literature on MALT1 patents and applications. We discuss the potential therapeutic uses for MALT1 inhibitors based on patents and scientific literature. Expert opinion There has been a steep increase in MALT1 inhibitor patents. Compounds with high selectivity and good bioavailability have been developed. An allosteric binding pocket is the preferred site for potent and selective MALT1 targeting. MALT1 inhibitors have moved to early clinical trials, but toxicological studies indicate that long-term MALT1 inhibition can disrupt immune homeostasis and lead to autoimmunity. Even though this poses risks, preventing immune suppression may favor the use of MALT1 inhibitors in cancer immunotherapies.
引用
收藏
页码:1079 / 1096
页数:18
相关论文
共 50 条
  • [41] Overview of the eruptions of Sinabung Volcano, 2010 and 2013-present and details of the 2013 phreatomagmatic phase
    Gunawan, Hendra
    Surono
    Budianto, Agus
    Kristianto
    Prambada, Oktory
    McCausland, Wendy
    Pallister, John
    Iguchi, Masato
    JOURNAL OF VOLCANOLOGY AND GEOTHERMAL RESEARCH, 2019, 382 : 103 - 119
  • [42] An updated patent review of SOS1 inhibitors (2022-present)
    Zhou, Guizhen
    Zhou, Chuan
    Ma, Xinyi
    Xu, Jiahang
    Zhou, Zehui
    Xu, Tianfeng
    Zheng, Mingyue
    Zhang, Sulin
    EXPERT OPINION ON THERAPEUTIC PATENTS, 2024, 34 (12) : 1199 - 1213
  • [43] Inhibitors of RIP1 kinase: a patent review (2016-present)
    Harris, Philip A.
    EXPERT OPINION ON THERAPEUTIC PATENTS, 2021, 31 (02) : 137 - 151
  • [44] MALT1 Inhibitors and Degraders: Strategies for NF-κB-Driven Malignancies
    Zhang, Ru-Yue
    Wang, Zi-Xuan
    Zhang, Meng-Yuan
    Wang, Yu-Fan
    Zhou, Si-Li
    Xu, Jia-Lu
    Lin, Wen-Xuan
    Ji, Tian-Rui
    Chen, Ya-Dong
    Lu, Tao
    Li, Nian-Guang
    Shi, Zhi-Hao
    JOURNAL OF MEDICINAL CHEMISTRY, 2025, 68 (05) : 5075 - 5096
  • [45] Acyltransferase inhibitors: a patent review (2010-present)
    Ohshiro, Taichi
    Tomoda, Hiroshi
    EXPERT OPINION ON THERAPEUTIC PATENTS, 2015, 25 (02) : 145 - 158
  • [46] Inhibitors of cathepsin G: a patent review (2005 to present)
    Kosikowska, Paulina
    Lesner, Adam
    EXPERT OPINION ON THERAPEUTIC PATENTS, 2013, 23 (12) : 1611 - 1624
  • [47] Acetylcholinesterase inhibitors: a patent review (2008-present)
    Pohanka, Miroslav
    EXPERT OPINION ON THERAPEUTIC PATENTS, 2012, 22 (08) : 871 - 886
  • [48] A patent review of MAPK inhibitors (2018-present)
    Wydra, Valentin R.
    Ditzinger, Raphael B.
    Seidler, Nico J.
    Hacker, Frederik W.
    Laufer, Stefan A.
    EXPERT OPINION ON THERAPEUTIC PATENTS, 2023, 33 (06) : 421 - 444
  • [49] Discovery and optimization of cyclohexane-1,4-diamines as allosteric MALT1 inhibitors
    Schiesser, Stefan
    Hajek, Peter
    Pople, Huw E.
    Kack, Helena
    Oster, Linda
    Cox, Rhona J.
    EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2022, 227
  • [50] Glycosidase inhibitors: a patent review (2008-2013)
    Bras, Natercia F.
    Cerqueira, Nuno M. F. S. A.
    Ramos, Maria J.
    Fernandes, Pedro A.
    EXPERT OPINION ON THERAPEUTIC PATENTS, 2014, 24 (08) : 857 - 874