Literature DB >> 33895280

Aminopyrazole based CDK9 PROTAC sensitizes pancreatic cancer cells to venetoclax.

Hannah M King1, Sandeep Rana1, Sydney P Kubica1, Jayapal Reddy Mallareddy1, Smitha Kizhake1, Edward L Ezell1, Muhammad Zahid2, Michael J Naldrett3, Sophie Alvarez3, Henry C-H Law1, Nicholas T Woods4, Amarnath Natarajan5.   

Abstract

Cyclin-dependent kinase 9 (CDK9) is a member of the cyclin-dependent kinase (CDK) family which is involved in transcriptional regulation of several genes, including the oncogene Myc, and is a validated target for pancreatic cancer. Here we report the development of an aminopyrazole based proteolysis targeting chimera (PROTAC 2) that selectively degrades CDK9 (DC50 = 158 ± 6 nM). Mass spectrometry-based kinome profiling shows PROTAC 2 selectively degrades CDK9 in MiaPaCa2 cells and sensitizes them to Venetoclax mediated growth inhibition.
Copyright © 2021 Elsevier Ltd. All rights reserved.

Entities:  

Keywords:  Aminopyrazole; CDK; Cancer; PROTAC; Venetoclax

Mesh：

Substances：

Year:  2021        PMID： 33895280      PMCID： PMC8187316          DOI： 10.1016/j.bmcl.2021.128061

Source DB:  PubMed          Journal:  Bioorg Med Chem Lett        ISSN： 0960-894X            Impact factor:   2.940


  36 in total

1.  Chemically induced degradation of CDK9 by a proteolysis targeting chimera (PROTAC).

Authors:  Caroline M Robb; Jacob I Contreras; Smit Kour; Margaret A Taylor; Mohammad Abid; Yogesh A Sonawane; Muhammad Zahid; Daryl J Murry; Amarnath Natarajan; Sandeep Rana
Journal:  Chem Commun (Camb)       Date:  2017-07-04       Impact factor: 6.222

2.  Selective degradation of CDK6 by a palbociclib based PROTAC.

Authors:  Sandeep Rana; Mourad Bendjennat; Smit Kour; Hannah M King; Smitha Kizhake; Muhammad Zahid; Amarnath Natarajan
Journal:  Bioorg Med Chem Lett       Date:  2019-03-26       Impact factor: 2.823

3.  ABT-263: a potent and orally bioavailable Bcl-2 family inhibitor.

Authors:  Christin Tse; Alexander R Shoemaker; Jessica Adickes; Mark G Anderson; Jun Chen; Sha Jin; Eric F Johnson; Kennan C Marsh; Michael J Mitten; Paul Nimmer; Lisa Roberts; Stephen K Tahir; Yu Xiao; Xiufen Yang; Haichao Zhang; Stephen Fesik; Saul H Rosenberg; Steven W Elmore
Journal:  Cancer Res       Date:  2008-05-01       Impact factor: 12.701

4.  Perturbation of the Bcl-2 network and an induced Noxa/Bcl-xL interaction trigger mitochondrial dysfunction after DNA damage.

Authors:  Hernando Lopez; Liqiang Zhang; Nicholas M George; Xiaoqiong Liu; Xiaming Pang; Jacquelynn J D Evans; Natalie M Targy; Xu Luo
Journal:  J Biol Chem       Date:  2010-03-11       Impact factor: 5.157

Review 5.  A role for CDK9-cyclin K in maintaining genome integrity.

Authors:  David S Yu; David Cortez
Journal:  Cell Cycle       Date:  2011-01-01       Impact factor: 4.534

6.  Cyclin-dependent kinase inhibitor, P276-00 induces apoptosis in multiple myeloma cells by inhibition of Cdk9-T1 and RNA polymerase II-dependent transcription.

Authors:  Sonal M Manohar; Maggie J Rathos; Vinay Sonawane; Shalini V Rao; Kalpana S Joshi
Journal:  Leuk Res       Date:  2011-01-08       Impact factor: 3.156

7.  Transcriptional regulation by targeted recruitment of cyclin-dependent CDK9 kinase in vivo.

Authors:  B Majello; G Napolitano; A Giordano; L Lania
Journal:  Oncogene       Date:  1999-08-12       Impact factor: 9.867

Review 8.  Recent Advances in Cancer Drug Development: Targeting Induced Myeloid Cell Leukemia-1 (Mcl-1) Differentiation Protein.

Authors:  Mohammad Abid; Yogesh A Sonawane; Jacob I Contreras; Sandeep Rana; Amarnath Natarajan
Journal:  Curr Med Chem       Date:  2017       Impact factor: 4.530

9.  3-Aminopyrazole inhibitors of CDK2/cyclin A as antitumor agents. 1. Lead finding.

Authors:  Paolo Pevarello; Maria Gabriella Brasca; Raffaella Amici; Paolo Orsini; Gabriella Traquandi; Luca Corti; Claudia Piutti; Pietro Sansonna; Manuela Villa; Betsy S Pierce; Maurizio Pulici; Patrizia Giordano; Katia Martina; Edward L Fritzen; Richard A Nugent; Elena Casale; Alexander Cameron; Marina Ciomei; Fulvia Roletto; Antonella Isacchi; GianPaolo Fogliatto; Enrico Pesenti; Wilma Pastori; Aurelio Marsiglio; Karen L Leach; Paula M Clare; Francesco Fiorentini; Mario Varasi; Anna Vulpetti; Martha A Warpehoski
Journal:  J Med Chem       Date:  2004-06-17       Impact factor: 7.446

10.  Synthesis of aminopyrazole analogs and their evaluation as CDK inhibitors for cancer therapy.

Authors:  Sandeep Rana; Yogesh A Sonawane; Margaret A Taylor; Smitha Kizhake; Muhammad Zahid; Amarnath Natarajan
Journal:  Bioorg Med Chem Lett       Date:  2018-10-15       Impact factor: 2.823
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  5 in total

Review 1.  CDK9 inhibitors in cancer research.

Authors:  Zhi Huang; Tianqi Wang; Cheng Wang; Yan Fan
Journal:  RSC Med Chem       Date:  2022-04-20

Review 2.  PROTACs: great opportunities for academia and industry (an update from 2020 to 2021).

Authors:  Ming He; Chaoguo Cao; Zhihao Ni; Yongbo Liu; Peilu Song; Shuang Hao; Yuna He; Xiuyun Sun; Yu Rao
Journal:  Signal Transduct Target Ther       Date:  2022-06-09

Review 3.  Recent advancements in the discovery of cereblon-based protease-targeted chimeras with potential for therapeutic intervention.

Authors:  Harbinder Singh; Devendra K Agrawal
Journal:  Future Med Chem       Date:  2022-09-01       Impact factor: 4.767

4.  Spirocyclic dimer SpiD7 activates the unfolded protein response to selectively inhibit growth and induce apoptosis of cancer cells.

Authors:  Smit Kour; Sandeep Rana; Sydney P Kubica; Smitha Kizhake; Mudassier Ahmad; Catalina Muñoz-Trujillo; David Klinkebiel; Sarbjit Singh; Jayapal Reddy Mallareddy; Surabhi Chandra; Nicholas T Woods; Adam R Karpf; Amarnath Natarajan
Journal:  J Biol Chem       Date:  2022-04-01       Impact factor: 5.486

Review 5.  Inhibitors, PROTACs and Molecular Glues as Diverse Therapeutic Modalities to Target Cyclin-Dependent Kinase.

Authors:  Sandeep Rana; Jayapal Reddy Mallareddy; Sarbjit Singh; Lidia Boghean; Amarnath Natarajan
Journal:  Cancers (Basel)       Date:  2021-11-02       Impact factor: 6.639
  5 in total

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