The Tankyrase Inhibitor OM-153 Demonstrates Antitumor Efficacy and a Therapeutic Window in Mouse Models

Overview

Journal Cancer Res Commun

Specialty Oncology

Date 2023 Mar 6

PMID 36873622

Authors

Shoshy A Brinch

Enya Amundsen-Isaksen

Sandra Espada

Clara Hammarstrom

Aleksandra Aizenshtadt

Petter A Olsen

Lone Holmen

Merete Hoyem

Hanne Scholz

Gunnveig Grodeland

Sven T Sowa

Albert Galera-Prat

Lari Lehtio

Ilonka A T M Meerts

Ruben G G Leenders

Anita Wegert

Stefan Krauss

Jo Waaler

Affiliations

Soon will be listed here.

Abstract

Significance: This study uncovers the effectiveness and therapeutic window for a novel tankyrase inhibitor in mouse tumor models.

Citing Articles

From Crypts to Cancer: A Holistic Perspective on Colorectal Carcinogenesis and Therapeutic Strategies.

Gharib E, Robichaud G Int J Mol Sci. 2024; 25(17).

PMID: 39273409 PMC: 11395697. DOI: 10.3390/ijms25179463.

Complex synthetic lethality in cancer.

Ryan C, Devakumar L, Pettitt S, Lord C Nat Genet. 2023; 55(12):2039-2048.

PMID: 38036785 DOI: 10.1038/s41588-023-01557-x.

APC/PIK3CA mutations and β-catenin status predict tankyrase inhibitor sensitivity of patient-derived colorectal cancer cells.

Chen M, Mashima T, Oishi T, Muramatsu Y, Seto Y, Takamatsu M Br J Cancer. 2023; 130(1):151-162.

PMID: 37968472 PMC: 10782021. DOI: 10.1038/s41416-023-02484-8.

A Mouse Model for the Rapid and Binomial Assessment of Putative WNT/β-Catenin Signalling Inhibitors.

Tse J, OKeefe R, Rigopolous A, Carli A, Waaler J, Krauss S Biomedicines. 2023; 11(10).

PMID: 37893093 PMC: 10604108. DOI: 10.3390/biomedicines11102719.

An Evolutionary Perspective on the Origin, Conservation and Binding Partner Acquisition of Tankyrases.

Sowa S, Bosetti C, Galera-Prat A, Johnson M, Lehtio L Biomolecules. 2022; 12(11).

PMID: 36421702 PMC: 9688111. DOI: 10.3390/biom12111688.

References

Mizutani A, Yashiroda Y, Muramatsu Y, Yoshida H, Chikada T, Tsumura T . RK-287107, a potent and specific tankyrase inhibitor, blocks colorectal cancer cell growth in a preclinical model. Cancer Sci. 2018; 109(12):4003-4014. PMC: 6272098. DOI: 10.1111/cas.13805. View

Shultz M, Cheung A, Kirby C, Firestone B, Fan J, Chen C . Identification of NVP-TNKS656: the use of structure-efficiency relationships to generate a highly potent, selective, and orally active tankyrase inhibitor. J Med Chem. 2013; 56(16):6495-511. DOI: 10.1021/jm400807n. View

Troilo A, Benson E, Esposito D, Garibsingh R, Reddy E, Mungamuri S . Angiomotin stabilization by tankyrase inhibitors antagonizes constitutive TEAD-dependent transcription and proliferation of human tumor cells with Hippo pathway core component mutations. Oncotarget. 2016; 7(20):28765-82. PMC: 5045355. DOI: 10.18632/oncotarget.9117. View

Zimmerlin L, Zambidis E . Pleiotropic roles of tankyrase/PARP proteins in the establishment and maintenance of human naïve pluripotency. Exp Cell Res. 2020; 390(1):111935. PMC: 7171895. DOI: 10.1016/j.yexcr.2020.111935. View

Kim S, Han S, Kim Y, Kim H, Gu Y, Kang D . Tankyrase inhibition preserves osteoarthritic cartilage by coordinating cartilage matrix anabolism via effects on SOX9 PARylation. Nat Commun. 2019; 10(1):4898. PMC: 6814715. DOI: 10.1038/s41467-019-12910-2. View

Bregman H, Chakka N, Guzman-Perez A, Gunaydin H, Gu Y, Huang X . Discovery of novel, induced-pocket binding oxazolidinones as potent, selective, and orally bioavailable tankyrase inhibitors. J Med Chem. 2013; 56(11):4320-42. DOI: 10.1021/jm4000038. View

Li N, Zhang Y, Han X, Liang K, Wang J, Feng L . Poly-ADP ribosylation of PTEN by tankyrases promotes PTEN degradation and tumor growth. Genes Dev. 2014; 29(2):157-70. PMC: 4298135. DOI: 10.1101/gad.251785.114. View

Solberg N, Waaler J, Lund K, Mygland L, Olsen P, Krauss S . TANKYRASE Inhibition Enhances the Antiproliferative Effect of PI3K and EGFR Inhibition, Mutually Affecting β-CATENIN and AKT Signaling in Colorectal Cancer. Mol Cancer Res. 2017; 16(3):543-553. DOI: 10.1158/1541-7786.MCR-17-0362. View

Waaler J, Leenders R, Sowa S, Brinch S, Lycke M, Nieczypor P . Preclinical Lead Optimization of a 1,2,4-Triazole Based Tankyrase Inhibitor. J Med Chem. 2020; 63(13):6834-6846. PMC: 8008393. DOI: 10.1021/acs.jmedchem.0c00208. View

10.

Haikarainen T, Krauss S, Lehtio L . Tankyrases: structure, function and therapeutic implications in cancer. Curr Pharm Des. 2014; 20(41):6472-88. PMC: 4262938. DOI: 10.2174/1381612820666140630101525. View

11.

Bhardwaj A, Yang Y, Ueberheide B, Smith S . Whole proteome analysis of human tankyrase knockout cells reveals targets of tankyrase-mediated degradation. Nat Commun. 2017; 8(1):2214. PMC: 5738441. DOI: 10.1038/s41467-017-02363-w. View

12.

Tian H, Biehs B, Warming S, Leong K, Rangell L, Klein O . A reserve stem cell population in small intestine renders Lgr5-positive cells dispensable. Nature. 2011; 478(7368):255-9. PMC: 4251967. DOI: 10.1038/nature10408. View

13.

Plummer R, Dua D, Cresti N, Drew Y, Stephens P, Foegh M . First-in-human study of the PARP/tankyrase inhibitor E7449 in patients with advanced solid tumours and evaluation of a novel drug-response predictor. Br J Cancer. 2020; 123(4):525-533. PMC: 7434893. DOI: 10.1038/s41416-020-0916-5. View

14.

Muller P, Milton M . The determination and interpretation of the therapeutic index in drug development. Nat Rev Drug Discov. 2012; 11(10):751-61. DOI: 10.1038/nrd3801. View

15.

Donato E, Biagioni F, Bisso A, Caganova M, Amati B, Campaner S . YAP and TAZ are dispensable for physiological and malignant haematopoiesis. Leukemia. 2018; 32(9):2037-2040. PMC: 6127083. DOI: 10.1038/s41375-018-0111-3. View

16.

Zhang Y, Liu S, Mickanin C, Feng Y, Charlat O, Michaud G . RNF146 is a poly(ADP-ribose)-directed E3 ligase that regulates axin degradation and Wnt signalling. Nat Cell Biol. 2011; 13(5):623-9. DOI: 10.1038/ncb2222. View

17.

Waaler J, Machon O, von Kries J, Wilson S, Lundenes E, Wedlich D . Novel synthetic antagonists of canonical Wnt signaling inhibit colorectal cancer cell growth. Cancer Res. 2011; 71(1):197-205. DOI: 10.1158/0008-5472.CAN-10-1282. View

18.

Norum J, Skarpen E, Brech A, Kuiper R, Waaler J, Krauss S . The tankyrase inhibitor G007-LK inhibits small intestine LGR5 stem cell proliferation without altering tissue morphology. Biol Res. 2018; 51(1):3. PMC: 5759193. DOI: 10.1186/s40659-017-0151-6. View

19.

McGonigle S, Chen Z, Wu J, Chang P, Kolber-Simonds D, Ackermann K . E7449: A dual inhibitor of PARP1/2 and tankyrase1/2 inhibits growth of DNA repair deficient tumors and antagonizes Wnt signaling. Oncotarget. 2015; 6(38):41307-23. PMC: 4747407. DOI: 10.18632/oncotarget.5846. View

20.

Leenders R, Brinch S, Sowa S, Amundsen-Isaksen E, Galera-Prat A, Murthy S . Development of a 1,2,4-Triazole-Based Lead Tankyrase Inhibitor: Part II. J Med Chem. 2021; 64(24):17936-17949. PMC: 8713164. DOI: 10.1021/acs.jmedchem.1c01264. View