The important role of the histone acetyltransferases p300/CBP in cancer and the promising anticancer effects of p300/CBP inhibitors

Ansari MSZ, Stagni V, Iuzzolino A, Rotili D, Mai A, Del Bufalo D, Lavia P, Degrassi F, Trisciuoglio D. Pharmacological targeting of CBP/p300 drives a redox/autophagy axis leading to senescence-induced growth arrest in non-small cell lung cancer cells. Cancer Gene Ther. 2023;30:124–36. https://doi.org/10.1038/s41417-022-00524-8.

Article  CAS  PubMed  Google Scholar 

Armstrong AJ, Gordon MS, Reimers MA, Hussain A, Patel VG, Lam ET, Sedkov A, Potter V, Shore N. Initial findings from an ongoing first-in-human phase 1 study of the CBP/p300 inhibitor FT-7051 in men with metastatic castration-resistant prostate cancer [abstract]. In: Proceedings of the AACR-NCI-EORTC virtual international conference on molecular targets and cancer therapeutics; 2021 Oct 7–10. Philadelphia (PA): AACR. Mol Cancer Ther. 2021;20(12 Suppl):Abstract nr P202. https://aacrjournals.org/mct/article/20/12_Supplement/P202/675930/Abstract-P202-Initial-findings-from-an-ongoing.

Asante Y, Benischke K, Osman I, Ngo QA, Wurth J, Laubscher D, Kim H, Udhayakumar B, Khan MIH, Chin DH, Porch J, Chakraborty M, Sallari R, Delattre O, Zaidi S, Morice S, Surdez D, Danielli SG, Schäfer BW, Gryder BE, Wachtel M. PAX3-FOXO1 uses its activation domain to recruit CBP/P300 and shape RNA Pol2 cluster distribution. Nat Commun. 2023;14:8361. https://doi.org/10.1038/s41467-023-43780-4.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Balasubramanyam K, Altaf M, Varier RA, Swaminathan V, Ravindran A, Sadhale PP, Kundu TK. Polyisoprenylated benzophenone, garcinol, a natural histone acetyltransferase inhibitor, represses chromatin transcription and alters global gene expression. J Biol Chem. 2004;279:33716–26. https://doi.org/10.1074/jbc.M402839200.

Article  CAS  PubMed  Google Scholar 

Balasubramanyam K, Swaminathan V, Ranganathan A, Kundu TK. Small molecule modulators of histone acetyltransferase p300. J Biol Chem. 2003;278:19134–40. https://doi.org/10.1074/jbc.M301580200.

Article  CAS  PubMed  Google Scholar 

Bannister AJ, Kouzarides T. The CBP co-activator is a histone acetyltransferase. Nature. 1996;384:641–3. https://doi.org/10.1038/384641a0.

Article  CAS  PubMed  Google Scholar 

Békés M, Langley DR, Crews CM. PROTAC targeted protein degraders: the past is prologue. Nat Rev Drug Discov. 2022;21:181–200. https://doi.org/10.1038/s41573-021-00371-6.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Bordoli L, Hüsser S, Lüthi U, Netsch M, Osmani H, Eckner R. Functional analysis of the p300 acetyltransferase domain: the PHD finger of p300 but not of CBP is dispensable for enzymatic activity. Nucleic Acids Res. 2001;29:4462–71. https://doi.org/10.1093/nar/29.21.4462.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Bosnakovski D, da Silva MT, Sunny ST, Ener ET, Toso EA, Yuan C, Cui Z, Walters MA, Jadhav A, Kyba M. A novel P300 inhibitor reverses DUX4-mediated global histone H3 hyperacetylation, target gene expression, and cell death. Sci Adv. 2019;5:eaaw7781. https://doi.org/10.1126/sciadv.aaw7781

Bosnakovski D, Ener ET, Cooper MS, Gearhart MD, Knights KA, Xu NC, Palumbo CA, Toso EA, Marsh GP, Maple HJ, Kyba M. Inactivation of the CIC-DUX4 oncogene through P300/CBP inhibition, a therapeutic approach for CIC-DUX4 sarcoma. Oncogenesis. 2021;10:68. https://doi.org/10.1038/s41389-021-00357-4.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Bowers EM, Yan G, Mukherjee C, Orry A, Wang L, Holbert MA, Crump NT, Hazzalin CA, Liszczak G, Yuan H, Larocca C, Saldanha SA, Abagyan R, Sun Y, Meyers DJ, Marmorstein R, Mahadevan LC, Alani RM, Cole PA. Virtual ligand screening of the p300/CBP histone acetyltransferase: identification of a selective small molecule inhibitor. Chem Biol. 2010;17:471–82. https://doi.org/10.1016/j.chembiol.2010.03.006.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Cai LY, Chen SJ, Xiao SH, Sun QJ, Ding CH, Zheng BN, Zhu XY, Liu SQ, Yang F, Yang YX, Zhou B, Luo C, Zhang X, Xie WF. Targeting p300/CBP attenuates hepatocellular carcinoma progression through epigenetic regulation of metabolism. Cancer Res. 2021;81:860–72. https://doi.org/10.1158/0008-5472.Can-20-1323.

Article  CAS  PubMed  Google Scholar 

Caligiuri M, Williams GL, Castro J, Battalagine L, Wilker E, Yao L, Schiller S, Toms A, Li P, Pardo E, Graves B, Azofeifa J, Chicas A, Herbertz T, Lai M, Basken J, Wood KW, Xu Q, Guichard SM. FT-6876, a potent and selective inhibitor of CBP/p300, is active in preclinical models of androgen receptor-positive breast cancer. Target Oncol. 2023;18:269–85. https://doi.org/10.1007/s11523-023-00949-7.

Article  PubMed  PubMed Central  Google Scholar 

Chan SH, Tang Y, Miao L, Darwich-Codore H, Vejnar CE, Beaudoin JD, Musaev D, Fernandez JP, Benitez MDJ, Bazzini AA, Moreno-Mateos MA, Giraldez AJ. Brd4 and P300 confer transcriptional competency during zygotic genome activation. Dev Cell. 2019;49:867–81.e8. https://doi.org/10.1016/j.devcel.2019.05.037.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Chang Q, Li J, Deng Y, Zhou R, Wang B, Wang Y, Zhang M, Huang X, Li Y. Discovery of novel PROTAC degraders of p300/CBP as potential therapeutics for hepatocellular carcinoma. J Med Chem. 2024;67:2466–86. https://doi.org/10.1021/acs.jmedchem.3c01468.

Article  CAS  PubMed  Google Scholar 

Chapuy B, McKeown MR, Lin CY, Monti S, Roemer MG, Qi J, Rahl PB, Sun HH, Yeda KT, Doench JG, Reichert E, Kung AL, Rodig SJ, Young RA, Shipp MA, Bradner JE. Discovery and characterization of super-enhancer-associated dependencies in diffuse large B cell lymphoma. Cancer Cell. 2013;24:777–90. https://doi.org/10.1016/j.ccr.2013.11.003.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Chen X, Zhang M, Gan H, Wang H, Lee JH, Fang D, Kitange GJ, He L, Hu Z, Parney IF, Meyer FB, Giannini C, Sarkaria JN, Zhang Z. A novel enhancer regulates MGMT expression and promotes temozolomide resistance in glioblastoma. Nat Commun. 2018;9:2949. https://doi.org/10.1038/s41467-018-05373-4.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Crabb S, Plummer R, Greystoke A, Carter L, Pacey S, Walter H, Coyle VM, Knurowski T, Clegg K, Ashby F, Pegg N, West W, Brooks N, Hughes A, de Bono J. A phase I/IIa study to evaluate the safety and efficacy of CCS1477, a first in clinic inhibitor of p300/CBP, as monotherapy in patients with selected molecular alterations. Ann Oncol. 2021;32(Suppl 5):S617. https://doi.org/10.1016/j.annonc.2021.08.1082.

Article  Google Scholar 

Cramer P. Organization and regulation of gene transcription. Nature. 2019;573:45–54. https://doi.org/10.1038/s41586-019-1517-4.

Article  CAS  PubMed  Google Scholar 

Crawford MC, Tripu DR, Barritt SA, Jing Y, Gallimore D, Kales SC, Bhanu NV, Xiong Y, Fang Y, Butler KAT, LeClair CA, Coussens NP, Simeonov A, Garcia BA, Dibble CC, Meier JL. Comparative analysis of drug-like EP300/CREBBP acetyltransferase inhibitors. ACS Chem Biol. 2023;18:2249–58. https://doi.org/10.1021/acschembio.3c00293.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Cui H, Yi H, Bao H, Tan Y, Tian C, Shi X, Gan D, Zhang B, Liang W, Chen R, Zhu Q, Fang L, Gao X, Huang H, Tian R, Sperling SR, Hu Y, Chen W. The SWI/SNF chromatin remodeling factor DPF3 regulates metastasis of ccRCC by modulating TGF-β signaling. Nat Commun. 2022;13:4680. https://doi.org/10.1038/s41467-022-32472-0.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Diesch J, Le Pannérer MM, Winkler R, Casquero R, Muhar M, van der Garde M, Maher M, Herráez CM, Bech-Serra JJ, Fellner M, Rathert P, Brooks N, Zamora L, Gentilella A, de la Torre C, Zuber J, Götze KS, Buschbeck M. Inhibition of CBP synergizes with the RNA-dependent mechanisms of Azacitidine by limiting protein synthesis. Nat Commun. 2021;12:6060. https://doi.org/10.1038/s41467-021-26258-z.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Durbin AD, Wang T, Wimalasena VK, Zimmerman MW, Li D, Dharia NV, Mariani L, Shendy NAM, Nance S, Patel AG, Shao Y, Mundada M, Maxham L, Park PMC, Sigua LH, Morita K, Saur Conway A, Robichaud AL, Perez-Atayde AR, Bikowitz MJ, Quinn TR, Wiest OG, Easton J, Schonbrunn E, Bulyk ML, Abraham BJ, Stegmaier K, Look AT, Qi J. EP300 selectively controls the enhancer landscape of MYCN-amplified neuroblastoma. Cancer Discov. 2022;12:730–51. https://doi.org/10.1158/2159-8290.Cd-21-0385.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Falkenberg KJ, Johnstone RW. Histone deacetylases and their inhibitors in cancer, neurological diseases and immune disorders. Nat Rev Drug Discov. 2014;13:673–91. https://doi.org/10.1038/nrd4360.

Article  CAS  PubMed  Google Scholar 

Garcia-Carpizo V, Ruiz-Llorente S, Sarmentero J, González-Corpas A, Barrero MJ. CREBBP/EP300 bromodomain inhibition affects the proliferation of AR-positive breast cancer cell lines. Mol Cancer Res. 2019;17:720–30. https://doi.org/10.1158/1541-7786.Mcr-18-0719.

Article  CAS  PubMed  Google Scholar 

Garcia-Carpizo V, Ruiz-Llorente S, Sarmentero J, Graña-Castro O, Pisano DG, Barrero MJ. CREBBP/EP300 bromodomains are critical to s

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