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Review

A patent review of PRMT5 inhibitors to treat cancer (2018 - present)

ORCID Icon, ORCID Icon, ORCID Icon, , ORCID Icon & ORCID Icon
Pages 265-292 | Received 24 Feb 2023, Accepted 06 Apr 2023, Published online: 27 Apr 2023

References

  • Antonysamy S, Bonday Z, Campbell RM, et al. Crystal structure of the human PRMT5:MEP50 complex. Proc Natl Acad Sci U S A. 2012 Oct;109(44):17960–17965.
  • Yang Y, Bedford MT. Protein arginine methyltransferases and cancer. Nat Rev Cancer. 2013 Jan;13(1):37–50.
  • Morettin A, Baldwin RM, Côté J. Arginine methyltransferases as novel therapeutic targets for breast cancer. Mutagenesis. 2015 Mar;30(2):177–189.
  • Sun L, Wang M, Lv Z, et al. Structural insights into protein arginine symmetric dimethylation by PRMT5. Proc Natl Acad Sci U S A. 2011 Dec;108(51):20538–20543.
  • Schapira M, Ferreira de Freitas R. Structural biology and chemistry of protein arginine methyltransferases. Medchemcomm. 2014 Dec;5(12):1779–1788.
  • Zhang X, Cheng X. Structure of the predominant protein arginine methyltransferase PRMT1 and analysis of its binding to substrate peptides. Structure. 2003 May;11(5):509–520.
  • Ancelin K, Lange UC, Hajkova P, et al. Blimp1 associates with Prmt5 and directs histone arginine methylation in mouse germ cells. Nat Cell Biol. 2006 Jun;8(6):623–630.
  • Guderian G, Peter C, Wiesner J, et al. RioK1, a new interactor of protein arginine methyltransferase 5 (PRMT5), competes with pICln for binding and modulates PRMT5 complex composition and substrate specificity. J Biol Chem. 2011 Jan;286(3):969–977.
  • Friesen WJ, Paushkin S, Wyce A, et al. The methylosome, a 20S complex containing JBP1 and pICln, produces dimethylarginine-modified Sm proteins. Mol Cell Biol. 2001 Dec;21(24):8289–8300.
  • Le Guezennec X, Vermeulen M, Brinkman AB, et al. MBD2/NuRD and MBD3/NuRD, two distinct complexes with different biochemical and functional properties. Mol Cell Biol. 2006 Feb;26(3):843–851.
  • Friesen WJ, Wyce A, Paushkin S, et al. A novel WD repeat protein component of the methylosome binds Sm proteins. J Biol Chem. 2002 Mar;277(10):8243–8247.
  • Krause CD, Yang ZH, Kim YS, et al. Protein arginine methyltransferases: evolution and assessment of their pharmacological and therapeutic potential. Pharmacol Ther. 2007 Jan;113(1):50–87.
  • Harris DP, Bandyopadhyay S, Maxwell TJ, et al. Tumor necrosis factor (TNF)-α induction of CXCL10 in endothelial cells requires protein arginine methyltransferase 5 (PRMT5)-mediated nuclear factor (NF)-κB p65 methylation. J Biol Chem. 2014 May;289(22):15328–15339.
  • Wei H, Wang B, Miyagi M, et al. PRMT5 dimethylates R30 of the p65 subunit to activate NF-κB. Proc Natl Acad Sci U S A. 2013 Aug;110(33):13516–13521.
  • Zheng S, Moehlenbrink J, Lu YC, et al. Arginine methylation-dependent reader-writer interplay governs growth control by E2F-1. Mol Cell. 2013 Oct;52(1):37–51.
  • Jansson M, Durant ST, Cho EC, et al. Arginine methylation regulates the p53 response. Nat Cell Biol. 2008 Dec;10(12):1431–1439.
  • Scoumanne A, Zhang J, Chen X. PRMT5 is required for cell-cycle progression and p53 tumor suppressor function. Nucleic Acids Res. 2009 Aug;37(15):4965–4976.
  • Xu X, Hoang S, Mayo MW, et al. Application of machine learning methods to histone methylation ChIP-Seq data reveals H4R3me2 globally represses gene expression. BMC Bioinformatics. 2010 Jul;11(1):396.
  • Majumder S, Alinari L, Roy S, et al. Methylation of histone H3 and H4 by PRMT5 regulates ribosomal RNA gene transcription. J Cell Biochem. 2010 Feb;109(3):553–563.
  • Yue M, Li Q, Zhang Y, et al. Histone H4R3 methylation catalyzed by SKB1/PRMT5 is required for maintaining shoot apical meristem. PLoS One. 2013;8(12):e83258.
  • Migliori V, Müller J, Phalke S, et al. Symmetric dimethylation of H3R2 is a newly identified histone mark that supports euchromatin maintenance. Nat Struct Mol Biol. 2012 Jan;19(2):136–144.
  • Pal S, Baiocchi RA, Byrd JC, et al. Low levels of miR-92b/96 induce PRMT5 translation and H3R8/H4R3 methylation in mantle cell lymphoma. The EMBO Journal. 2007 Aug;26(15):3558–3569.
  • Chung J, Karkhanis V, Baiocchi RA, et al. Protein arginine methyltransferase 5 (PRMT5) promotes survival of lymphoma cells via activation of WNT/β-catenin and AKT/GSK3β proliferative signaling. J Biol Chem. 2019 May;294(19):7692–7710.
  • Gullà A, Hideshima T, Bianchi G, et al. Protein arginine methyltransferase 5 has prognostic relevance and is a druggable target in multiple myeloma. Leukemia. 2018 Apr;32(4):996–1002.
  • Zhang B, Dong S, Zhu R, et al. Targeting protein arginine methyltransferase 5 inhibits colorectal cancer growth by decreasing arginine methylation of eIF4E and FGFR3. Oncotarget. 2015 Sep;6(26):22799–22811.
  • Shailesh H, Siveen KS, Sif S. Protein arginine methyltransferase 5 (PRMT5) activates WNT/β-catenin signalling in breast cancer cells via epigenetic silencing of DKK1 and DKK3. J Cell Mol Med. 2021 Feb;25(3):1583–1600.
  • Yang F, Wang J, Ren HY, et al. Proliferative role of TRAF4 in breast cancer by upregulating PRMT5 nuclear expression. Tumour Biol. 2015 Aug;36(8):5901–5911.
  • Jing P, Zhao N, Ye M, et al. Protein arginine methyltransferase 5 promotes lung cancer metastasis via the epigenetic regulation of miR-99 family/FGFR3 signaling. Cancer Lett. 2018 Jul;427:38–48.
  • Li Z, Zhang J, Liu X, et al. The LINC01138 drives malignancies via activating arginine methyltransferase 5 in hepatocellular carcinoma. Nat Commun. 2018 Apr;9(1):1572.
  • Jia Z, Yue F, Chen X, et al. Protein arginine methyltransferase PRMT5 regulates fatty acid metabolism and lipid droplet biogenesis in white adipose tissues. Adv Sci (Weinh). 2020 Dec;7(23):2002602.
  • LeBlanc SE, Konda S, Wu Q, et al. Protein arginine methyltransferase 5 (Prmt5) promotes gene expression of peroxisome proliferator-activated receptor γ2 (PPARγ2) and its target genes during adipogenesis. Mol Endocrinol. 2012 Apr;26(4):583–597.
  • Muhammad AB, Xing B, Liu C, et al. Menin and PRMT5 suppress GLP1 receptor transcript and PKA-mediated phosphorylation of FOXO1 and CREB. Am J Physiol Endocrinol Metab. 2017 Aug;313(2):E148–e166.
  • Tsai WW, Niessen S, Goebel N, et al. PRMT5 modulates the metabolic response to fasting signals. Proc Natl Acad Sci U S A. 2013 May;110(22):8870–8875.
  • Chatterjee S, Khunti K, Davies MJ. Type 2 diabetes. Lancet. 2017 Jun;389(10085):2239–2251.
  • Cai S, Liu R, Wang P, et al. PRMT5 prevents cardiomyocyte hypertrophy via symmetric dimethylating HoxA9 and repressing HoxA9 expression. Front Pharmacol. 2020;11:600627.
  • Chen M, Yi B, Sun J. Inhibition of cardiomyocyte hypertrophy by protein arginine methyltransferase 5. J Biol Chem. 2014 Aug;289(35):24325–24335.
  • Harris DP, Chandrasekharan UM, Bandyopadhyay S, et al. PRMT5-mediated methylation of NF-κB p65 at Arg174 is required for endothelial CXCL11 gene induction in response to TNF-α and IFN-γ costimulation. PLoS One. 2016;11(2):e0148905.
  • Quan X, Yue W, Luo Y, et al. The protein arginine methyltransferase PRMT5 regulates Aβ-induced toxicity in human cells and Caenorhabditis elegans models of Alzheimer’s disease. J Neurochem. 2015 Sep;134(5):969–977.
  • Ross CA, Aylward EH, Wild EJ, et al. Huntington disease: natural history, biomarkers and prospects for therapeutics. Nat Rev Neurol. 2014 Apr;10(4):204–216.
  • Ratovitski T, Arbez N, Stewart JC, et al. PRMT5- mediated symmetric arginine dimethylation is attenuated by mutant huntingtin and is impaired in Huntington’s disease (HD). Cell Cycle. 2015;14(11):1716–1729.
  • Zhan X, Stamova B, Sharp FR. Lipopolysaccharide associates with amyloid plaques, neurons and oligodendrocytes in Alzheimer’s disease brain: a review. Front Aging Neurosci. 2018;10:42.
  • Feustel K, Falchook GS. Protein arginine methyltransferase 5 (PRMT5) inhibitors in oncology clinical trials: a review. J Immunother Precis Oncol. 2022 Aug;5(3):58–67.
  • Wang Y, Hu W, Yuan Y. Protein arginine methyltransferase 5 (PRMT5) as an anticancer target and its inhibitor discovery. J Med Chem. 2018 Nov;61(21):9429–9441.
  • Chan-Penebre E, Kuplast KG, Majer CR, et al. A selective inhibitor of PRMT5 with in vivo and in vitro potency in MCL models. Nat Chem Biol. 2015 Jun;11(6):432–437.
  • Epizyme Inc. Arginine methyltransferase inhibitors and uses thereof. WO2016022605. 2016.
  • Siu LL, Rasco DW, Vinay SP, et al. METEOR-1: a phase I study of GSK3326595, a first-in-class protein arginine methyltransferase 5 (PRMT5) inhibitor, in advanced solid tumours. Ann Oncol. 2019;30:v159.
  • Gerhart SV, Kellner WA, Thompson C, et al. Activation of the p53-MDM4 regulatory axis defines the anti-tumour response to PRMT5 inhibition through its role in regulating cellular splicing. Sci Rep. 2018 Jun;8(1):9711.
  • Angel Villalona-Calero AP M, Maki RG, O’Neil B, et al. Design and rationale of a phase 1 dose-escalation study of AMG 193, a methylthioadenosine (MTA)-cooperative PRMT5 inhibitor, in patients with advanced methylthioadenosine phosphorylase (MTAP)-null solid tumors. J Clin Oncol. 2022;TPS3167–TPS3167.
  • Marjon K, Cameron MJ, Quang P, et al. MTAP deletions in cancer create vulnerability to targeting of the MAT2A/PRMT5/RIOK1 Axis. Cell Rep. 2016 Apr;15(3):574–587.
  • JNJ-64619178. NCI drug dictionary, national institutes of health–national cancer institute. 2023. Comprehensive Cancer Information - NCI (date:10-02-2023)
  • Tao H, Yan X, Zhu K, et al. Discovery of novel PRMT5 inhibitors by virtual screening and biological evaluations. Chem Pharm Bull. 2019;67(4):382–388.
  • Jensen-Pergakes K, Tatlock J, Maegley KA, et al. SAM-competitive PRMT5 Inhibitor PF-06939999 demonstrates antitumor activity in splicing dysregulated NSCLC with decreased liability of drug resistance. Mol Cancer Ther. 2022 Jan;21(1):3–15.
  • Tango therapeutics announces clearance of TNG908 IND by FDA and recent pipeline progress updates. 2022.
  • Prelude therapeutics announces third quarter 2022 financial results and provides business update. 2022.
  • Egloff S. CDK9 keeps RNA polymerase II on track. Cell Mol Life Sci. 2021 Jul;78(14):5543–5567.
  • Smith CR, Aranda R, Bobinski TP, et al. Fragment-based discovery of MRTX1719, a synthetic lethal inhibitor of the PRMT5*MTA complex for the treatment of MTAP-deleted cancers. J Med Chem. 2022 Feb;65(3):1749–1766.
  • Asberry AM, Cai X, Deng X, et al. Discovery and Biological Characterization of PRMT5:MEP50 Protein-Protein Interaction Inhibitors. J Med Chem. 2022 Oct;65(20):13793–13812.
  • Amgen Inc. Tricyclic-amide-bicyclic PRMT5 inhibitors. WO2022169948. 2022.
  • Angex pharmaceutial, Inc. Heterocyclic compounds as PRMT5 inhhibitors. WO2020243178A1. 2020.
  • Angex pharmaceutial, Inc. Heterocyclic compounds as PRMT5 inhhibitors. WO2019112719A1. 2019.
  • Aurigene discovery tech limited. Imidazolidin-2-one compounds as PRMT5 modulators. WO2019180628. 2019.
  • Aurigene Discovery Tech Ltd. Substituted imidazolidin-2-one derivatives as PRMT5 inhibitors. WO2019180631A1. 2019.
  • Aurigene Discovery Tech Ltd. Substituted imidazolidin-2-one deri vatives as PRMT5 inhibitors. CN112105609A. 2020.
  • Bayer AG Thiazole compounds useful as PRMT5 inhibitors. WO2019002074A1. 2019.
  • Bayer Aktiengesellschaft Thiazole compounds useful as PRMT5 inhibitors. US20200123147A1. 2020.
  • Shoda T, Ohoka N, Tsuji G, et al. Targeted protein degradation by chimeric compounds using hydrophobic E3 ligands and adamantane moiety. Pharmaceuticals (Basel). 2020 Feb;13(3):34.
  • Janssen Pharmaceutica NV. Novel 6-6 bicyclic aromatic ring substituted nucleoside analogues for use as PRMT5 inhibitors. CN107922413A. 2018.
  • Janssen Pharmaceutica NV. Novel 6-6 bicyclic aromatic ring substituted nucleoside analogues for use as PRMT5 inhibitors. WO2017032840A1. 2017.
  • Janssen Pharmaceutica NV. Novel Spirobicyclic analogue. WO2019110734A1. 2019.
  • Janssen Pharmaceutica NV. Novel monocyclic and bicyclic ring system substituted carbanucleoside analogues for use as PRMT5 inhibitors. WO2018065365A1. 2018.
  • Lupin limited substituted bicyclic heterocyclic compounds as PRMT5 inhibitors. CN111712498A. 2020.
  • Lupin limited PRMT5 inhibitors. CN114026094A. 2022.
  • Lupin limited substituted nucleoside analogs as PRMT5 inhibitors. WO2021111322A1. 2021.
  • Lupin limited pharmaceutical combination of PRMT5 inhibitor. CN114599361A. 2022.
  • Lupin limited pharmaceutical combination of PRMT5 inhibitor. WO2021079302A1. 2021.
  • Merck sharp & Dohme PRMT5 inhibitors. WO2019094311A1. 2019.
  • Merck Sharp & Dohme PRMT5 inhibitors. WO2019094312A1. 2019.
  • Merck Sharp & Dohme PRMT5 inhibitors. WO2021126728A1. 2021.
  • Merck Sharp & Dohme PRMT5 inhibitors. WO2021126729A1. 2021.
  • Merck Sharp & Dohme PRMT5 inhibitors. WO2020033285. 2020.
  • Merck Sharp & Dohme PRMT5 inhibitors. WO2020033288. 2020.
  • MIRATI THERAPEUTICS INC. MTA-cooperative PRMT5 inbihitors. WO2021050915A1. 2021.
  • MIRATI THERAPEUTICS INC. Aminopyridine-based MTA-cooperative PRMT5 inbihitors. WO2023278564A1. 2023.
  • PRELUDE THERAPEUTICS INC. Selective inhibitors of protein arginine methyl transferase 5 (PRMTS). WO2018085833. 2018.
  • PRELUDE THERAPEUTICS INC. Selective inhibitors of protein arginine methyl transferase 5 (PRMTS). WO2018152501. 2018.
  • PRELUDE THERAPEUTICS INC. Selective inhibitors of protein arginine methyltransferase 5 (PRMTS). WO2018152548. 2018.
  • PRELUDE THERAPEUTICS INC. Selective inhibitors of protein arginine methyl transferase 5 (PRMTS). WO2019178368. 2019.
  • PRELUDE THERAPEUTICS INC. Selective inhibitors of protein arginine methyl transferase 5 (PRMTS). WO2018160855. 2018.
  • Jiangsu Simcere Pharm Co Ltd. Tetrahydroisoquinoline compounds and use thereof. WO2022002142A1. 2022.
  • Nanjing Sanhome Pharmaceutical Res And Development Co Ltd. Tricyclic compound as prmt5 inhibitor and application thereof. CN112645946A. 2021.
  • Zhengzhou University Arginine methyltransferase 5 small molecule inhibitor and preparation method and use thereof. CN111592522. 2020.
  • Shanghai Apeiron Biotechnology Co Ltd. Used as a nucleoside analogue of PRMT5 inhibitors. CN113234079. 2021.
  • California Inst of Tech PRMT5 inhibitors and their uses. CN114127072. 2020.
  • Indian University research technology small molecule protein arginine methyltransferase 5 (PRMT5) inhibitors and therapeutics. WO2018081451. 2018.
  • Gao H, Sun X, Rao Y. PROTAC technology: opportunities and challenges. ACS Med Chem Lett. 2020 Mar;11(3):237–240.
  • Sun X, Gao H, Yang Y, et al. PROTACs: great opportunities for academia and industry. Signal Transduct Target Ther. 2019;4:64.
  • Lai AC, Crews CM. Induced protein degradation: an emerging drug discovery paradigm. Nat Rev Drug Discov. 2017 Feb;16(2):101–114.
  • Schapira M, Calabrese MF, Bullock AN, et al. Targeted protein degradation: expanding the toolbox. Nat Rev Drug Discov. 2019 Dec;18(12):949–963.
  • Shen Y, Gao G, Yu X, et al. Discovery of first-in-class protein arginine methyltransferase 5 (PRMT5) degraders. J Med Chem. 2020 Sep;63(17):9977–9989.
  • McKinney DC, McMillan BJ, Ranaghan MJ, et al. Discovery of a first-in-class inhibitor of the PRMT5-substrate adaptor interaction. J Med Chem. 2021 Aug;64(15):11148–11168.

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