Literature DB >> 30108985

N-Acetyl-3-aminopyrazoles block the non-canonical NF-kB cascade by selectively inhibiting NIK.

Agnese C Pippione1, Stefano Sainas1, Antonella Federico1, Elisa Lupino2, Marco Piccinini2, Michael Kubbutat3, Jean-Marie Contreras4, Christophe Morice4, Alessandro Barge1, Alex Ducime1, Donatella Boschi1, Salam Al-Karadaghi5, Marco L Lolli1.   

Abstract

NF-κB-inducing kinase (NIK), an oncogenic drug target that is associated with various cancers, is a central signalling component of the non-canonical pathway. A blind screening process, which established that amino pyrazole related scaffolds have an effect on IKKbeta, led to a hit-to-lead optimization process that identified the aminopyrazole 3a as a low μM selective NIK inhibitor. Compound 3a effectively inhibited the NIK-dependent activation of the NF-κB pathway in tumour cells, confirming its selective inhibitory profile.

Entities:  

Year:  2018        PMID： 30108985      PMCID： PMC6071728          DOI： 10.1039/c8md00068a

Source DB:  PubMed          Journal:  Medchemcomm        ISSN： 2040-2503            Impact factor:   3.597


  20 in total

1.  Structure-Based Design of Tricyclic NF-κB Inducing Kinase (NIK) Inhibitors That Have High Selectivity over Phosphoinositide-3-kinase (PI3K).

Authors:  Georgette M Castanedo; Nicole Blaquiere; Maureen Beresini; Brandon Bravo; Hans Brightbill; Jacob Chen; Hai-Feng Cui; Charles Eigenbrot; Christine Everett; Jianwen Feng; Robert Godemann; Emily Gogol; Sarah Hymowitz; Adam Johnson; Nobuhiko Kayagaki; Pawan Bir Kohli; Kathleen Knüppel; Joachim Kraemer; Susan Krüger; Pui Loke; Paul McEwan; Christian Montalbetti; David A Roberts; Myron Smith; Stefan Steinbacher; Swathi Sujatha-Bhaskar; Ryan Takahashi; Xiaolu Wang; Lawren C Wu; Yamin Zhang; Steven T Staben
Journal:  J Med Chem       Date:  2017-01-12       Impact factor: 7.446

Review 2.  Non-canonical NF-κB signaling pathway.

Authors:  Shao-Cong Sun
Journal:  Cell Res       Date:  2010-12-21       Impact factor: 25.617

3.  Application of Ullmann and Ullmann-Finkelstein reactions for the synthesis of N-aryl-N-(1H-pyrazol-3-yl) acetamide or N-(1-aryl-1H-pyrazol-3-yl) acetamide derivatives and pharmacological evaluation.

Authors:  Rebecca Deprez-Poulain; Nicolas Cousaert; Patrick Toto; Nicolas Willand; Benoit Deprez
Journal:  Eur J Med Chem       Date:  2011-05-30       Impact factor: 6.514

Review 4.  The non-canonical NF-κB pathway in immunity and inflammation.

Authors:  Shao-Cong Sun
Journal:  Nat Rev Immunol       Date:  2017-06-05       Impact factor: 53.106

5.  Design, synthesis, biological evaluation and X-ray structural studies of potent human dihydroorotate dehydrogenase inhibitors based on hydroxylated azole scaffolds.

Authors:  Stefano Sainas; Agnese C Pippione; Marta Giorgis; Elisa Lupino; Parveen Goyal; Cristina Ramondetti; Barbara Buccinnà; Marco Piccinini; Rodolpho C Braga; Carolina H Andrade; Mikael Andersson; Ann-Christin Moritzer; Rosmarie Friemann; Stefano Mensa; Salam Al-Kadaraghi; Donatella Boschi; Marco L Lolli
Journal:  Eur J Med Chem       Date:  2017-02-14       Impact factor: 6.514

6.  Inhibiting NF-κB-inducing kinase (NIK): discovery, structure-based design, synthesis, structure-activity relationship, and co-crystal structures.

Authors:  Kexue Li; Lawrence R McGee; Ben Fisher; Athena Sudom; Jinsong Liu; Steven M Rubenstein; Mohmed K Anwer; Timothy D Cushing; Youngsook Shin; Merrill Ayres; Fei Lee; John Eksterowicz; Paul Faulder; Bohdan Waszkowycz; Olga Plotnikova; Ellyn Farrelly; Shou-Hua Xiao; Guoqing Chen; Zhulun Wang
Journal:  Bioorg Med Chem Lett       Date:  2013-01-11       Impact factor: 2.823

7.  The crystal structure of the catalytic domain of the NF-κB inducing kinase reveals a narrow but flexible active site.

Authors:  Gladys de Leon-Boenig; Krista K Bowman; Jianwen A Feng; Terry Crawford; Christine Everett; Yvonne Franke; Angela Oh; Mark Stanley; Steven T Staben; Melissa A Starovasnik; Heidi J A Wallweber; Jiansheng Wu; Lawren C Wu; Adam R Johnson; Sarah G Hymowitz
Journal:  Structure       Date:  2012-08-23       Impact factor: 5.006

8.  Frequent engagement of the classical and alternative NF-kappaB pathways by diverse genetic abnormalities in multiple myeloma.

Authors:  Christina M Annunziata; R Eric Davis; Yulia Demchenko; William Bellamy; Ana Gabrea; Fenghuang Zhan; Georg Lenz; Ichiro Hanamura; George Wright; Wenming Xiao; Sandeep Dave; Elaine M Hurt; Bruce Tan; Hong Zhao; Owen Stephens; Madhumita Santra; David R Williams; Lenny Dang; Bart Barlogie; John D Shaughnessy; W Michael Kuehl; Louis M Staudt
Journal:  Cancer Cell       Date:  2007-08       Impact factor: 31.743

9.  NF-kappaΒ-inducing kinase regulates stem cell phenotype in breast cancer.

Authors:  Karla Vazquez-Santillan; Jorge Melendez-Zajgla; Luis Enrique Jimenez-Hernandez; Javier Gaytan-Cervantes; Laura Muñoz-Galindo; Patricia Piña-Sanchez; Gustavo Martinez-Ruiz; Javier Torres; Patricia Garcia-Lopez; Carolina Gonzalez-Torres; Victor Ruiz; Federico Avila-Moreno; Marco Velasco-Velazquez; Mayra Perez-Tapia; Vilma Maldonado
Journal:  Sci Rep       Date:  2016-11-23       Impact factor: 4.379

10.  Targeting the NF-κB Pathway as a Combination Therapy for Advanced Thyroid Cancer.

Authors:  Nikita Pozdeyev; Adam Berlinberg; Qiong Zhou; Kelsey Wuensch; Hiroyuki Shibata; William M Wood; Bryan R Haugen
Journal:  PLoS One       Date:  2015-08-11       Impact factor: 3.240
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  6 in total

1.  Use of the 4-Hydroxytriazole Moiety as a Bioisosteric Tool in the Development of Ionotropic Glutamate Receptor Ligands.

Authors:  Stefano Sainas; Piero Temperini; Jill C Farnsworth; Feng Yi; Stine Møllerud; Anders A Jensen; Birgitte Nielsen; Alice Passoni; Jette S Kastrup; Kasper B Hansen; Donatella Boschi; Darryl S Pickering; Rasmus P Clausen; Marco L Lolli
Journal:  J Med Chem       Date:  2019-04-18       Impact factor: 7.446

Review 2.  Targeting NF-κB-Inducing Kinase (NIK) in Immunity, Inflammation, and Cancer.

Authors:  Kathryn M Pflug; Raquel Sitcheran
Journal:  Int J Mol Sci       Date:  2020-11-11       Impact factor: 5.923

Review 3.  The Therapeutic Potential of Targeting NIK in B Cell Malignancies.

Authors:  Marco V Haselager; Eric Eldering
Journal:  Front Immunol       Date:  2022-07-12       Impact factor: 8.786

Review 4.  Pharmacological inhibition of NF-κB-inducing kinase (NIK) with small molecules for the treatment of human diseases.

Authors:  Jing Cheng; Xuexin Feng; Zhiqiang Li; Feilong Zhou; Jin-Ming Yang; Yujun Zhao
Journal:  RSC Med Chem       Date:  2021-01-22

5.  A New NF-κB Inhibitor, MEDS-23, Reduces the Severity of Adverse Post-Ischemic Stroke Outcomes in Rats.

Authors:  Elina Rubin; Agnese C Pippione; Matthew Boyko; Giacomo Einaudi; Stefano Sainas; Massimo Collino; Carlo Cifani; Marco L Lolli; Naim Abu-Freha; Jacob Kaplanski; Donatella Boschi; Abed N Azab
Journal:  Brain Sci       Date:  2021-12-28

6.  Discovery of novel pyrazole derivatives as a potent anti-inflammatory agent in RAW264.7 cells via inhibition of NF-ĸB for possible benefit against SARS-CoV-2.

Authors:  Anup Masih; Amol K Agnihotri; Jitendra K Srivastava; Nidhi Pandey; Hans R Bhat; Udaya P Singh
Journal:  J Biochem Mol Toxicol       Date:  2020-10-23       Impact factor: 3.568
  6 in total

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