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. 2021 Jul 19;13(14):3606. doi: 10.3390/cancers13143606

Table 1.

Summary of bromodomain (BRD) inhibitors with potential in the clinical setting.

BRD Inhibitor
(Molecule Images Created with JSME [279]) 		Target Cancer Type/Results Clinical Trial ID/Reference
graphic file with name cancers-13-03606-i001.jpg JQ1 BET’s The first generation of BET inhibitors which has proven to be a valuable tool for understanding BET BRDs in numerous cancers, but demonstrated toxicities in the clinic. As a result derivatives of JQ1 have had greater clinical success. [27,280,281]
graphic file with name cancers-13-03606-i002.jpg OTX015*
(Birabresib)		 BET’s Identifiers and resulting publications for ongoing and completed clinical trials for OTX015 as an exclusive therapy or in combination treatment.
This JQ1 derivative used in combination with PROTACs has shown promise in cell models of prostate cancer, lymphoma, and leukemia.		 NCT02698176, NCT02259114, NCT01713582, NCT02698189,
NCT02296476
[282,283,284,285,286,287,288]
graphic file with name cancers-13-03606-i003.jpg I-BET762
GSK525762A, (Molibresib)		 BET’s Phase 1 clinical trial of this orally available compound initially showed that daily dosing with molibresib was well tolerated and showed efficacy for patients with nuclear protein in testis (NUT) carcinoma. [28,288,289,290]
graphic file with name cancers-13-03606-i004.jpg I-BET151
GSK1210151A		 BET’s This BET inhibitor demonstrates strong anti-proliferative effects, and xenograft models indicate repression of proliferation in myeloma cells. However, this drug has not made progressed to clinical trials. [291]
graphic file with name cancers-13-03606-i005.jpg ABBV-744 Pan-BET
(Selective for the 2nd bromodo-main)		 Selective for the 2nd bromodomain of the BET-bromodomain proteins, and has demonstrated anti-proliferative effects for numerous acute myeloid leukemia and prostate cancer cell lines. NCT04454658
[110,111]
Not available ZEN-3694 BET’s A current phase 2 clinical trial using ZEN-3694 in combination with the enzalutamide is recruiting for castration resistant prostate cancer (CRPC), where the compound has shown efficacy in a phase 1 clinical trial. NCT04471974
[292]
graphic file with name cancers-13-03606-i006.jpg ACBI1 SMARCA2/4 This PROTAC degrader resulted in reduced protein levels and apoptosis of acute myeloid leukemia (AML) cells. [293]
graphic file with name cancers-13-03606-i007.jpg GSK2801 BAZ2A/B The selective acetyl-lysine competitive inhibitor induces apoptosis in triple negative breast cancer (TNBC) cells in combination with BET inhibitors. [144,294]
graphic file with name cancers-13-03606-i008.jpg CCS1477 CBP/p300 Current Phase 1 & 2 clinical trials are recruiting patients for treatment of hematological malignancies and advanced prostate cancer. NCT03568656, NCT04068597
graphic file with name cancers-13-03606-i009.jpg I-CBP112 CBP/p300 Combination therapy with the p300/CBP active site inhibitor (A-485) resulted in reduced p300 chromatin enrichment, and decreased expression of androgen-dependent and pro-oncogenic genes in leukemia and prostate cancer. [154,295]
graphic file with name cancers-13-03606-i010.jpg IACS-9571 BRPF1/TRIM24 This selective inhibitor has provided insights into cellular functions, and may be useful as a potential therapeutic for acute myeloid leukemia (AML) and breast cancer (BCa). [165]
graphic file with name cancers-13-03606-i011.jpg IACS-9571 TRIM24 When developed into a bifunctional degrader linked to the VHL E3 ligase, TRIM24 protein degradation resulted in a greater negative impact on proliferation in leukemia cell lines. [296]
graphic file with name cancers-13-03606-i012.jpg AM879 ATAD2 Treatment with AM879, prevented cell proliferation, and induced apoptosis in triple negative breast cancer (TNBC) cells. [195]
graphic file with name cancers-13-03606-i013.jpg Bromospo-rine Multi-BRD (BET) Shows promise as a therapeutic for colorectal cancer (CRC) when administered in combination with 5-Fluorouracil (5-FU). [12,297]
graphic file with name cancers-13-03606-i014.jpg I-BRD9 BRD9 The selective inhibitor identified cancer associated and immune response genes as possible targets of BRD9 regulation in leukemia cells. [298]
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BI-7273
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BI-9564
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BI-7271
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BI-7189		 BI-7273/BI-9564
BI-7271/BI-7273/BI-7189		 BRD9 These small molecule inhibitors display anti-tumor activity in xenograft models of AML. [299]
graphic file with name cancers-13-03606-i019.jpg PFI-3 SMARCA2/4 and PB1(5) Treatment with PFI-3 has been shown to sensitize cancer cells to chemotherapeutic agents. http://www.thesgc.org/chemical-probes/PFI-3, accessed on 7 July 2021
[300]
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MS2126
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MS7972		 MS2126/MS7972 CBP/p300 Cell based assays in osteosarcoma cells, demonstrated that these molecules can modulate the p53 response to DNA damage. [301]
graphic file with name cancers-13-03606-i022.jpg SGC-CBP30 CBP/p300 Inhibition of CBP is suggested to be a potential method for targeting transcriptional dependencies in multiple myeloma. [302,303,304]
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OF-1
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PFI-4
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NI-57		 OF-1, PFI-4, NI-57 pan-BRPF While these inhibitors have not be linked to anti-proliferative or anti-cancer therapies, they have been suggested as potential therapeutics in bone malignancies. [167]