doi:10.3969/j.issn.1004-583X.2023.03.015

Abstract

CLC Number:

R730.54

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URL: https://huicui.hebmu.edu.cn/EN/10.3969/j.issn.1004-583X.2023.03.015

https://huicui.hebmu.edu.cn/EN/Y2023/V38/I3/273

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References 65

[1]	Sur I, Taipale J. The role of enhancers in cancer[J]. Nat Rev Cancer, 2016, 16(8):483-493. doi: 10.1038/nrc.2016.62 pmid: 27364481
[2]	Whyte WA, Orlando DA, Hnisz D, et al. Master transcription factors and mediator establish super-enhancers at key cell identity gene[J]. Cell, 2013, 153(2):307-319. doi: 10.1016/j.cell.2013.03.035 URL
[3]	Kimura H. Histone modifications for human epigenome analysis[J]. J Hum Genet, 2013, 58(7):439-445. doi: 10.1038/jhg.2013.66 pmid: 23739122
[4]	Villar D, Berthelot C, Aldridge S, et al. Enhancer evolution across 20 mammalian species[J]. Cell, 2015, 160(3):554-566. doi: 10.1016/j.cell.2015.01.006 pmid: 25635462
[5]	周洋, 施晓敏, 韩澍, 等. SEs的发现与研究进展[J]. 国际生殖健康/计划生育杂志, 2017, 36(2):137-141+159.
[6]	Sengupta S, George RE. Super-enhancer-driven transcriptional dependencies in cancer[J]. Trends Cancer, 2017, 3(4):269-281. doi: S2405-8033(17)30061-4 pmid: 28718439
[7]	吴志强, 米泽云. 超级增强子在肿瘤研究中的进展[J]. 遗传, 2019, 41(1):41-51.
[8]	Loven J, Hoke HA, Lin CY, et al. Selective inhibition of tumor oncogenes by disruption of super-enhancers[J]. Cell, 2013, 153(2):320-334. doi: 10.1016/j.cell.2013.03.036 pmid: 23582323
[9]	Hnisz D, Schuijers J, Lin CY, et al. Convergence of developmental and oncogenic signaling pathways at transcriptional super-enhancers[J]. Mol Cell, 2015, 58(2):362-370. doi: 10.1016/j.molcel.2015.02.014 pmid: 25801169
[10]	Yimlamai D, Fowl BH, Camargo FD. Emerging evidence on the role of the Hippo/YAP pathway in liver physiology and cancer[J]. J Hepatol, 2015, 63(6):1491-1501. doi: 10.1016/j.jhep.2015.07.008 pmid: 26226451
[11]	Nabet B, Broin P, Reyes JM, et al. Deregulation of the Ras-Erk signaling sxis modulates the enhancer landscape[J]. Cell Rep, 2015, 12(8):1300-1313. doi: 10.1016/j.celrep.2015.06.078 URL
[12]	Niederriter AR, Varshney A, Parker SC, et al. Super enhancers in cancers, complex disease, and developmental disorders[J]. Genes, 2015, 6(4):1183-1200. doi: 10.3390/genes6041183 pmid: 26569311
[13]	Hnisz D, Abraham BJ, Lee TI, et al. Super-enhancers in the control of cell identity and disease[J]. Cell, 2013, 155(4):934-947. doi: 10.1016/j.cell.2013.09.053 pmid: 24119843
[14]	Jiang YY, Lin DC, Mayakonda A, et al. Targeting super-enhancer-associated oncogenes in oesophageal squamous cell carcinoma[J]. Gut, 2017, 66(8):1358-1368. doi: 10.1136/gutjnl-2016-311818 URL
[15]	Jiang Y, Jiang YY, Xie JJ, et al. Co-activation of super-enhancer-driven CCAT1 by TP63 and SOX2 promotes squamous cancer progression[J]. Nat Commun, 2018, 9(1):3619. doi: 10.1038/s41467-018-06081-9 pmid: 30190462
[16]	Xie JJ, Jiang YY, Jiang Y, et al. Super-enhancer-driven long non-coding RNA LINC01503, regulated by TP63, is over-expressed and oncogenic in squamous cell carcinoma[J]. Gastroenterology, 2018, 154(8):2137-2151. doi: S0016-5085(18)30213-0 pmid: 29454790
[17]	Lin X, Spindler TJ, de Souza Fonseca MA, et al. A super-enhancer-associated LncRNA UCA1 interacts directly with AMOT to activate YAP target genes in epithelial ovarian cancer[J]. IScience, 2019, 17:242-255. doi: S2589-0042(19)30208-1 pmid: 31307004
[18]	Jiao W, Chen Y, Song H, et al. HPSE enhancer RNA promotes cancer progression through driving chromatin looping and regulating hnRNPU/p300/EGR1/HPSE axis[J]. Oncogene, 2018, 37(20): 2728-2745. doi: 10.1038/s41388-018-0128-0 pmid: 29511351
[19]	程霄, 杨琼, 谭镇东, 等. 增强子RNA研究现状[J]. 遗传, 2017, 39(9):784-797.
[20]	Yang YS, Jin X, Li Q, et al. Superenhancer drives a tumor-specific splicing variant of MARCO to promote triple-negative breast cancer progression[J]. Proc Natl Acad Sci U S A, 2022, 119(46): e2207201119.
[21]	Pajtler KW, Witt H, Sill M, et al. Molecular classification of ependymal tumors across all CNS compartments, histopathological grades, and age groups[J]. Cancer Cell, 2015, 27(5):728-743. doi: 10.1016/j.ccell.2015.04.002 pmid: 25965575
[22]	Adelman K, Lis JT. Promoter-proximal pausing of RNA polymerase II: Emerging roles in metazoans[J]. Nat Rev Genet, 2012, 13(10):720-731. doi: 10.1038/nrg3293 pmid: 22986266
[23]	Wang Y, Shen N, Li S, et al. Synergistic therapy for cervical cancer by codelivery of cisplatin and JQ1 inhibiting Plk1-Mutant Trp53 Axis[J]. Nano Lett, 2021, 21(6): 2412-2421. doi: 10.1021/acs.nanolett.0c04402 pmid: 33705152
[24]	Xu Y, Pachnikova G, Przybilla D, et al. Evaluation of JQ1 combined with docetaxel for the treatment of prostate cancer cells in 2D- and 3D-culture systems[J]. Front Pharmacol, 2022, 13:839620. doi: 10.3389/fphar.2022.839620 URL
[25]	Chen B, Liu X, Li Y, et al. iRGD tumor-penetrating peptide-modified nanodelivery system based on a marine sulfated polysaccharide for enhanced anti-tumor efficiencyagainst breast cancer[J]. Int J Nanomedicine, 2022, 17:617-633. doi: 10.2147/IJN.S343902 URL
[26]	Fourniols T, Maggio V, Rafael D, et al. Colorectal cancer inhibition by BET inhibitor JQ1 is MYC-independent and not improved by nanoencapsulation[J]. Eur J Pharm Biopharm, 2022, 171:39-49. doi: 10.1016/j.ejpb.2021.10.017 pmid: 34998911
[27]	Pelish HE, Liau BB, Nitulescu II, et al. Mediator kinase inhibition further activates super-enhancer-associated genes in AML[J]. Nature, 2015, 526(7572):273-276. doi: 10.1038/nature14904
[28]	Yao Z, Yang S, Zhao H, et al. BET inhibitor I-BET151 sensitizes GBM cells to temozolomide via PUMA induction[J]. Cancer Gene Ther, 2022, 29(10):1528. doi: 10.1038/s41417-022-00536-4
[29]	Guo NH, Zheng JF, Zi FM, et al. I-BET151 suppresses osteoclast formation and inflammatory cytokines secretion by targetting BRD4 in multiple myeloma[J]. Biosci Rep, 2019, 39(5):BSR20181245.
[30]	Sahni JM, Keri RA. Targeting bromodomain and extraterminal proteins in breast cancer[J]. Pharmacol Res, 2018, 129:156-176. doi: S1043-6618(17)31403-2 pmid: 29154989
[31]	Choi JE, Verhaegen ME, Yazdani S, et al. Characterizing the therapeutic potential of a potent BET degrader in Merkel mell carcinoma[J]. Neoplasia, 2019, 21(3):322-330. doi: S1476-5586(18)30532-3 pmid: 30797188
[32]	Bai L, Zhou B, Yang CY, et al. Targeted degradation of BET proteins in triple-negative breast cancer[J]. Cancer Res, 2017, 77(9):2476-2487. doi: 10.1158/0008-5472.CAN-16-2622 pmid: 28209615
[33]	Kim E, Ten Hacken E, Sivina M, et al. The BET inhibitor GS-5829 targets chronic lymphocytic leukemia cells and their supportive microenvironment[J]. Leukemia, 2020, 34(6):1588-1598. doi: 10.1038/s41375-019-0682-7 pmid: 31862959
[34]	Zeybek B, Lopez S, Santin AD. BET inhibitors: Betting on improved outcomes in uterine serous carcinoma[J]. Oncotarget, 2018, 9(84):35470-35471. doi: 10.18632/oncotarget.26245 pmid: 30464799
[35]	Leal AS, Liu P, Krieger-Burke T, et al. The Bromodomain inhibitor, INCB057643, targets both cancer cells and the tumor microenvironment in two preclinical models of pancreatic cancer[J]. Cancers (Basel), 2020, 13(1):96. doi: 10.3390/cancers13010096 URL
[36]	Deng M, Xu-Monette ZY, Pham LV, et al. Aggressive B-cell lymphoma with MYC/TP53 dual alterations displays distinct clinicopathobiological features and response to novel targeted agents[J]. Mol Cancer Res, 2021, 19(2):249-260. doi: 10.1158/1541-7786.MCR-20-0466 pmid: 33154093
[37]	Vázquez R, Civenni G, Kokanovic A, et al. Efficacy of novel bromodomain and extraterminal inhibitors in combination with chemotherapy for castration-resistant prostate cancer[J]. Eur Urol Oncol, 2021, 4(3):437-446. doi: 10.1016/j.euo.2019.07.013 pmid: 31402217
[38]	Ramsey HE, Greenwood D, Zhang S, et al. BET inhibition enhances the antileukemic activity of low-dose Venetoclax in acute myeloid leukemia[J]. Clin Cancer Res, 2021, 27(2):598-607. doi: 10.1158/1078-0432.CCR-20-1346 pmid: 33148670
[39]	Stubbs MC, Burn TC, Sparks R, et al. The novel bromodomain and extraterminal domain inhibitor INCB054329 induces vulnerabilities in myeloma cells That inform rational combination strategies[J]. Clin Cancer Res, 2019, 25(1):300-311. doi: 10.1158/1078-0432.CCR-18-0098 pmid: 30206163
[40]	Jauset T, Massó-Vallés D, Martínez-Martín S, et al. BET inhibition is an effective approach against KRAS-driven PDAC and NSCLC[J]. Oncotarget, 2018, 9(27):18734-18746. doi: 10.18632/oncotarget.24648 pmid: 29721157
[41]	Huang X, Qiu M, Wang T, et al. Carrier-free multifunctional nanomedicine for intraperitoneal disseminated ovarian cancer therapy[J]. J Nanobiotechnology, 2022, 20(1):93. doi: 10.1186/s12951-022-01300-4
[42]	Gao L, Xia S, Zhang K, et al. Gene expression profile of THZ1-treated nasopharyngeal carcinoma cell lines indicates its involvement in the inhibition of the cell cycle[J]. Transl Cancer Res, 2021, 10(1):445-460. doi: 10.21037/tcr-19-2888 pmid: 35116274
[43]	Yang Y, Jiang D, Zhou Z, et al. CDK7 blockade suppresses super-enhancer-associated oncogenes in bladder cancer[J]. Cell Oncol (Dordr), 2021, 44(4):871-887.
[44]	Christensen CL, Kwiatkowski N, Abraham BJ, et al. Targeting transcriptional addictions in small cell lung cancer with a covalent CDK7 inhibitor[J]. Cancer Cell, 2014, 26(6):909-922. doi: S1535-6108(14)00423-1 pmid: 25490451
[45]	Zhang J, Liu W, Zou C, et al. Targeting super-enhancer-associated oncogenes in osteosarcoma with THZ2, a covalent CDK7 inhibitor[J]. Clin Cancer Res, 2020, 26(11):2681-2692. doi: 10.1158/1078-0432.CCR-19-1418 pmid: 31937612
[46]	Huang JR, Qin WM, Wang K, et al. Cyclin-dependent kinase 7 inhibitor THZ2 inhibits the growth of human gastric cancer?in vitro?and?in vivo[J]. Am J Transl Res, 2018, 10(11):3664-3676.
[47]	Hu S, Marineau JJ, Rajagopal N, et al. Discovery and characterization of SY-1365, a selective, covalent inhibitor of CDK7[J]. Cancer Res, 2019, 79(13):3479-3491. doi: 10.1158/0008-5472.CAN-19-0119 pmid: 31064851
[48]	Lei H, Wang Z, Jiang D, et al. CRISPR screening identifies CDK12 as a conservative vulnerability of prostate cancer[J]. Cell Death Dis, 2021, 12(8):740. doi: 10.1038/s41419-021-04027-6 pmid: 34315855
[49]	Zhang T, Kwiatkowski N, Olson CM, et al. Covalent targeting of remote cysteine residues to develop CDK12 and CDK13 inhibitors[J]. Nat Chem Biol, 2016, 12(10):876-884. doi: 10.1038/nchembio.2166 pmid: 27571479
[50]	Geng M, Yang Y, Cao X, et al. Targeting CDK12-mediated transcription regulation in anaplastic thyroid carcinoma[J]. Biochem Biophys Res Commun, 2019, 520(3):544-550. doi: 10.1016/j.bbrc.2019.10.052 URL
[51]	Tripathy D, Bardia A, Sellers WR. Ribociclib (LEE011): Mechanism of action and clinical impact of this selective cyclin-dependent kinase 4/6 inhibitor in various solid tumors[J]. Clin Cancer Res, 2017, 23(13):3251-3262. doi: 10.1158/1078-0432.CCR-16-3157 pmid: 28351928
[52]	Kennedy AL, Vallurupalli M, Chen L, et al. Functional, chemical genomic, and super-enhancer screening identify sensitivity to cyclin D1/CDK4 pathway inhibition in Ewing sarcoma[J]. Oncotarget, 2015, 6(30):30178-30193. doi: 10.18632/oncotarget.4903 pmid: 26337082
[53]	Ghosh C, Paul S, Dandawate P, et al. Super-enhancers: novel target for pancreatic ductal adenocarcinoma[J]. Oncotarget, 2019, 10(16):1554-1571. doi: 10.18632/oncotarget.26704 pmid: 30899425
[54]	Choi J, Bordeaux ZA, McKeel J, et al. GZ17-6.02 02 inhibits the growth of EGFRvIII+ Glioblastoma[J]. Int J Mol Sci, 2022, 23(8):4174. doi: 10.3390/ijms23084174 URL
[55]	McKeown MR, Johannessen L, Lee E, et al. Antitumor synergy with SY-1425, a selective RARα agonist, and hypomethylating agents in retinoic acid receptor pathway activated models of acute myeloid leukemia[J]. Haematologica, 2019, 104(4):e138-e142. doi: 10.3324/haematol.2018.192807 URL
[56]	Noguchi-Yachide T. BET bromodomain as a target of epigenetic therapy[J]. Chem Pharm Bull (Tokyo), 2016, 64(6):540-547. doi: 10.1248/cpb.c16-00225 URL
[57]	柳克俊, 张智敏, 冉挺, 等. BET bromodomain蛋白小分子抑制剂研究进展[J]. 中国医科大学学报, 2015, 46 (3):264 -271.
[58]	Shin HY. Targeting super-enhancers for disease treatment and diagnosis[J]. Mol Cells, 2018, 41(6):506-514. doi: 10.14348/molcells.2018.2297 pmid: 29754476
[59]	Nakamura Y, Hattori N, Iida N, et al. Targeting of super-enhancers and mutant BRAF can suppress growth of BRAF-mutant colon cancer cells via repression of MAPK signaling pathway[J]. Cancer Lett, 2017, 402:100-109. doi: S0304-3835(17)30353-1 pmid: 28576751
[60]	Zhu X, Zhang T, Zhang Y, et al. A super-enhancer controls TGF- β signaling in pancreatic cancer through downregulation of TGFBR2[J]. Cell Signal, 2020, 66: 109470. doi: 10.1016/j.cellsig.2019.109470 URL
[61]	Cheng W, Yang Z, Wang S, et al. Recent development of CDK inhibitors: An overview of CDK/inhibitor co-crystal structures[J]. Eur J Med Chem, 2019, 164:615-639. doi: S0223-5234(19)30003-0 pmid: 30639897
[62]	Nagaraja S, Vitanza NA, Woo PJ, et al. Transcriptional dependencies in diffuse intrinsic pontine glioma[J]. Cancer Cell, 2017, 31(5):635-652. doi: S1535-6108(17)30107-1 pmid: 28434841
[63]	Zheng C, Liu M, Fan H. Targeting complexes of super-enhancers is a promising strategy for cancer therapy[J]. Oncol Lett, 2020, 20(3):2557-2566. doi: 10.3892/ol.2020.11855 pmid: 32782573
[64]	Gao Y, Volegova M, Nasholm N, et al. Synergistic anti-tumor effect of combining selective CDK7 and BRD4 inhibition in neuroblastoma[J]. Front Oncol, 2022, 11:773186. doi: 10.3389/fonc.2021.773186 URL
[65]	Ma X, Kuang X, Xia Q, et al. Covalent CDK7 inhibitor THZ1 inhibits myogenic differentiation[J]. J Cancer, 2018, 9(17):3149-3155. doi: 10.7150/jca.25395 pmid: 30210638

抑制剂	靶点	肿瘤
JQ1	BRD4	前列腺癌^[24],乳腺癌^[25],结肠癌^[26]等
I-BET151	BRD4	急性髓性白血病^[27],多形性胶质母细胞瘤^[28],多发性骨髓瘤^[29]等
BETd-246	BRD2,BRD3,BRD4	三阴性乳腺癌^[30],默克尔细胞癌^[31],乳腺癌^[32]等
GS-5829	BRD2,BRD3,BRD4	慢性淋巴细胞性白血病^[33],子宫浆液性癌^[34]等
INCB057643	BRD2,BRD3,BRD4	胰腺癌^[35],弥漫大B细胞淋巴瘤^[36],前列腺癌^[37]等
INCB054329	BRD2,BRD3,BRD4	卵巢癌^[38],前列腺癌^[39],急性髓系白血病^[40]等
THZ1	CDK7	卵巢癌^[41],鼻咽癌^[42],膀胱癌^[43],小细胞肺癌^[44]等
THZ2	CDK7	骨肉瘤^[45],胃癌^[46]等
SY-1365	CDK7	卵巢癌和乳腺癌^[47]等
THZ531	CDK12,CDK13	前列腺癌^[48],急性T细胞淋巴瘤^[49],甲状腺未分化癌^[50]等
Lee011	CDK4, CDK6	乳腺癌^[51],黑色素瘤^[51],神经母细胞瘤^[51],尤因肉瘤^[52]等
GZ17-6.02	-	胰腺导管腺癌^[53],恶性胶质瘤^[54]等
SY-1425	RARα	急性髓性白血病^[55]等

抑制剂	靶点	肿瘤
JQ1	BRD4	前列腺癌^[24],乳腺癌^[25],结肠癌^[26]等
I-BET151	BRD4	急性髓性白血病^[27],多形性胶质母细胞瘤^[28],多发性骨髓瘤^[29]等
BETd-246	BRD2,BRD3,BRD4	三阴性乳腺癌^[30],默克尔细胞癌^[31],乳腺癌^[32]等
GS-5829	BRD2,BRD3,BRD4	慢性淋巴细胞性白血病^[33],子宫浆液性癌^[34]等
INCB057643	BRD2,BRD3,BRD4	胰腺癌^[35],弥漫大B细胞淋巴瘤^[36],前列腺癌^[37]等
INCB054329	BRD2,BRD3,BRD4	卵巢癌^[38],前列腺癌^[39],急性髓系白血病^[40]等
THZ1	CDK7	卵巢癌^[41],鼻咽癌^[42],膀胱癌^[43],小细胞肺癌^[44]等
THZ2	CDK7	骨肉瘤^[45],胃癌^[46]等
SY-1365	CDK7	卵巢癌和乳腺癌^[47]等
THZ531	CDK12,CDK13	前列腺癌^[48],急性T细胞淋巴瘤^[49],甲状腺未分化癌^[50]等
Lee011	CDK4, CDK6	乳腺癌^[51],黑色素瘤^[51],神经母细胞瘤^[51],尤因肉瘤^[52]等
GZ17-6.02	-	胰腺导管腺癌^[53],恶性胶质瘤^[54]等
SY-1425	RARα	急性髓性白血病^[55]等

抑制剂	靶点	肿瘤	临床试验
OTX-015	BRD2, BRD3, BRD4	急性髓系白血病,弥漫大B细胞淋巴瘤,急性淋巴细胞白血病,多发性骨髓瘤	Ⅰ/Ⅱ期,NCT02303782,撤销
		急性髓系白血病	Ⅰ/Ⅱ期,NCT02303782,撤销
		多形性胶质母细胞瘤	Ⅱ期,NCT02296476,终止
		NUT中线癌,三阴性乳腺癌,非小细胞肺癌,去势抵抗性前列腺癌	Ⅰ期,NCT02698176,终止
		NUT中线癌,三阴性乳腺癌,非小细胞肺癌,去势抵抗性前列腺癌,胰腺导管腺癌	Ⅰ期,NCT02259114,完成
		急性髓性白血病,弥漫大B细胞淋巴瘤	Ⅰ期,NCT02698189,终止
CPI-0610	BRD4	周围神经肿瘤	Ⅱ期,NCT02986919,撤销
		多发性骨髓瘤	Ⅱ期,NCT04603495,招募
		多发性骨髓瘤	Ⅰ期,NCT02157636,完成
		淋巴瘤	Ⅰ期,NCT01949883,完成
I-BET762	BRD2, BRD3 BRD4	复发性或难治性血液系统恶性肿瘤	Ⅰ期,NCT01943851,完成
		激素受体阳性(HR+)/人表皮生长因子受体2阴性(HER2-)晚期或转移性乳腺癌	Ⅱ期,NCT02964507,完成
	实体瘤	Ⅱ期,NCT03266159,撤销
		去势抵抗性前列腺癌	Ⅱ期,NCT03150056,招募
		NUT中线癌、小细胞肺癌、非小细胞肺癌、结直肠癌、神经母细胞瘤、去势抵抗性前列腺癌、三阴性乳腺癌、雌激素受体阳性(ER阳性)乳腺癌、MYCN驱动的实体瘤	Ⅰ期,NCT01587703,完成
		晚期或难治性实体瘤或淋巴瘤	Ⅰ期,NCT03925428,撤销
		转移性或不可切除性NUT中线癌	Ⅰ/Ⅱ期,NCT04116359,撤销
		NUT中线癌	NCT03702036,已失效
TEN-010	BRD2, BRD3 BRD4	NUT中线癌,弥漫大B细胞淋巴瘤	Ⅰ期,NCT01987362,完成
		急性髓系白血病,骨髓增生异常综合征	Ⅰ期,NCT02308761,完成
		弥漫大B细胞淋巴瘤,高级别B细胞淋巴瘤	Ⅰ期,NCT03255096,完成
GS-5829	BRD2,BRD3,BRD4	晚期实体瘤,淋巴瘤	Ⅰ期,NCT02392611,完成
		晚期雌激素受体阳性HER2阴性乳腺癌	Ⅰ/Ⅱ期,NCT02983604,终止
		转移性去势抵抗性前列腺癌	Ⅰ/Ⅱ期,NCT02607228,终止
ODM207	BRD4	晚期实体瘤	Ⅰ/Ⅱ期,NCT0303559,完成
INCB057643	BRD2,BRD3,BRD4	晚期实体瘤	Ⅰ/Ⅱ期,NCT02711137,终止
		晚期实体瘤	Ⅰ/Ⅱ期,NCT02959437,完成
INCB054329	BRD2,BRD3,BRD4	晚期实体瘤	Ⅰ/Ⅱ期,NCT02431260,终止
BMS-986158	BRD2,BRD3,BRD4	小儿实体肿瘤,淋巴瘤,小儿脑瘤	Ⅰ期,NCT03936465,招募
		晚期肿瘤	Ⅰ/Ⅱ期,NCT02419417,招募
ZEN003694	BRD2,BRD3,BRD4	转移性去势抵抗性前列腺癌	Ⅰ期,NCT04986423,招募
		转移性去势抵抗性前列腺癌	Ⅰ/Ⅱ期,NCT04145375,招募
		转移性去势抵抗性前列腺癌	Ⅰ/Ⅱ期,NCT02711956,完成
		转移性去势抵抗性前列腺癌	Ⅰ期,NCT02705469,完成
		复发性卵巢、输卵管癌或原发性腹膜癌	Ⅱ期,NCT05071937,未招募
		三阴性乳腺癌	Ⅱ期,NCT03901469,未招募
		晚期和难治性实体肿瘤和淋巴瘤	Ⅰ/Ⅱ期,NCT05053971,未招募
		转移性或复发性恶性实体瘤,复发性铂耐药卵巢癌,难治性卵巢癌	Ⅰ期, NCT04840589,招募
		进展期/转移性/不可切除的NUT中线癌	Ⅰ/Ⅱ期,NCT05019716,未招募
		去势抵抗性前列腺癌/转移性前列腺癌/转移性前列腺小细胞癌	Ⅱ期,NCT04471974,招募
PLX2853	PLX2853	妇科恶性肿瘤,卵巢恶性肿瘤	Ⅰ/Ⅱ期,NCT04493619,招募
		小细胞肺癌,葡萄膜黑色素瘤,卵巢透明细胞癌,非霍奇金淋巴瘤,晚期恶性肿瘤,实体瘤,弥漫性大B细胞淋巴瘤,滤泡淋巴瘤	Ⅰ/Ⅱ期,NCT03297424,完成
		复发性或难治性急性髓性白血病(AML),骨髓增生异常综合征(MDS)	Ⅱ期,NCT03787498,完成
		转移性去势性前列腺癌	Ⅰ期,NCT04556617,完成
BI 894999	BRD4	晚期恶性肿瘤,NUT中线癌	Ⅰ期,NCT02516553,完成
GSK2820151	BRD2,BRD3,BRD4	复发或晚期实体瘤	Ⅰ期,NCT02630251,终止
BAY 1238097	BRD2,BRD3,BRD4	晚期实体瘤	Ⅰ期,NCT02369029,终止
SY-1365	CDK7	晚期实体瘤,乳腺癌,卵巢癌	Ⅰ期,NCT03134638,终止
THZ531	CDK12,CDK13	卵巢癌	肿瘤活检,NCT04555473,招募
Lee011	CDK4, CDK6	晚期实体瘤,巨块型肿瘤	Ⅰ期,NCT02934568,招募
		晚期实体肿瘤,转移性激素受体阳性乳腺癌	Ⅰ/Ⅰb期,NCT03775525,招募
SY-1425	RARα	急性髓系白血病,骨髓增生异常综合征	Ⅱ期,NCT02807558,未招募

抑制剂	靶点	肿瘤	临床试验
OTX-015	BRD2, BRD3, BRD4	急性髓系白血病,弥漫大B细胞淋巴瘤,急性淋巴细胞白血病,多发性骨髓瘤	Ⅰ/Ⅱ期,NCT02303782,撤销
		急性髓系白血病	Ⅰ/Ⅱ期,NCT02303782,撤销
		多形性胶质母细胞瘤	Ⅱ期,NCT02296476,终止
		NUT中线癌,三阴性乳腺癌,非小细胞肺癌,去势抵抗性前列腺癌	Ⅰ期,NCT02698176,终止
		NUT中线癌,三阴性乳腺癌,非小细胞肺癌,去势抵抗性前列腺癌,胰腺导管腺癌	Ⅰ期,NCT02259114,完成
		急性髓性白血病,弥漫大B细胞淋巴瘤	Ⅰ期,NCT02698189,终止
CPI-0610	BRD4	周围神经肿瘤	Ⅱ期,NCT02986919,撤销
		多发性骨髓瘤	Ⅱ期,NCT04603495,招募
		多发性骨髓瘤	Ⅰ期,NCT02157636,完成
		淋巴瘤	Ⅰ期,NCT01949883,完成
I-BET762	BRD2, BRD3 BRD4	复发性或难治性血液系统恶性肿瘤	Ⅰ期,NCT01943851,完成
		激素受体阳性(HR+)/人表皮生长因子受体2阴性(HER2-)晚期或转移性乳腺癌	Ⅱ期,NCT02964507,完成
	实体瘤	Ⅱ期,NCT03266159,撤销
		去势抵抗性前列腺癌	Ⅱ期,NCT03150056,招募
		NUT中线癌、小细胞肺癌、非小细胞肺癌、结直肠癌、神经母细胞瘤、去势抵抗性前列腺癌、三阴性乳腺癌、雌激素受体阳性(ER阳性)乳腺癌、MYCN驱动的实体瘤	Ⅰ期,NCT01587703,完成
		晚期或难治性实体瘤或淋巴瘤	Ⅰ期,NCT03925428,撤销
		转移性或不可切除性NUT中线癌	Ⅰ/Ⅱ期,NCT04116359,撤销
		NUT中线癌	NCT03702036,已失效
TEN-010	BRD2, BRD3 BRD4	NUT中线癌,弥漫大B细胞淋巴瘤	Ⅰ期,NCT01987362,完成
		急性髓系白血病,骨髓增生异常综合征	Ⅰ期,NCT02308761,完成
		弥漫大B细胞淋巴瘤,高级别B细胞淋巴瘤	Ⅰ期,NCT03255096,完成
GS-5829	BRD2,BRD3,BRD4	晚期实体瘤,淋巴瘤	Ⅰ期,NCT02392611,完成
		晚期雌激素受体阳性HER2阴性乳腺癌	Ⅰ/Ⅱ期,NCT02983604,终止
		转移性去势抵抗性前列腺癌	Ⅰ/Ⅱ期,NCT02607228,终止
ODM207	BRD4	晚期实体瘤	Ⅰ/Ⅱ期,NCT0303559,完成
INCB057643	BRD2,BRD3,BRD4	晚期实体瘤	Ⅰ/Ⅱ期,NCT02711137,终止
		晚期实体瘤	Ⅰ/Ⅱ期,NCT02959437,完成
INCB054329	BRD2,BRD3,BRD4	晚期实体瘤	Ⅰ/Ⅱ期,NCT02431260,终止
BMS-986158	BRD2,BRD3,BRD4	小儿实体肿瘤,淋巴瘤,小儿脑瘤	Ⅰ期,NCT03936465,招募
		晚期肿瘤	Ⅰ/Ⅱ期,NCT02419417,招募
ZEN003694	BRD2,BRD3,BRD4	转移性去势抵抗性前列腺癌	Ⅰ期,NCT04986423,招募
		转移性去势抵抗性前列腺癌	Ⅰ/Ⅱ期,NCT04145375,招募
		转移性去势抵抗性前列腺癌	Ⅰ/Ⅱ期,NCT02711956,完成
		转移性去势抵抗性前列腺癌	Ⅰ期,NCT02705469,完成
		复发性卵巢、输卵管癌或原发性腹膜癌	Ⅱ期,NCT05071937,未招募
		三阴性乳腺癌	Ⅱ期,NCT03901469,未招募
		晚期和难治性实体肿瘤和淋巴瘤	Ⅰ/Ⅱ期,NCT05053971,未招募
		转移性或复发性恶性实体瘤,复发性铂耐药卵巢癌,难治性卵巢癌	Ⅰ期, NCT04840589,招募
		进展期/转移性/不可切除的NUT中线癌	Ⅰ/Ⅱ期,NCT05019716,未招募
		去势抵抗性前列腺癌/转移性前列腺癌/转移性前列腺小细胞癌	Ⅱ期,NCT04471974,招募
PLX2853	PLX2853	妇科恶性肿瘤,卵巢恶性肿瘤	Ⅰ/Ⅱ期,NCT04493619,招募
		小细胞肺癌,葡萄膜黑色素瘤,卵巢透明细胞癌,非霍奇金淋巴瘤,晚期恶性肿瘤,实体瘤,弥漫性大B细胞淋巴瘤,滤泡淋巴瘤	Ⅰ/Ⅱ期,NCT03297424,完成
		复发性或难治性急性髓性白血病(AML),骨髓增生异常综合征(MDS)	Ⅱ期,NCT03787498,完成
		转移性去势性前列腺癌	Ⅰ期,NCT04556617,完成
BI 894999	BRD4	晚期恶性肿瘤,NUT中线癌	Ⅰ期,NCT02516553,完成
GSK2820151	BRD2,BRD3,BRD4	复发或晚期实体瘤	Ⅰ期,NCT02630251,终止
BAY 1238097	BRD2,BRD3,BRD4	晚期实体瘤	Ⅰ期,NCT02369029,终止
SY-1365	CDK7	晚期实体瘤,乳腺癌,卵巢癌	Ⅰ期,NCT03134638,终止
THZ531	CDK12,CDK13	卵巢癌	肿瘤活检,NCT04555473,招募
Lee011	CDK4, CDK6	晚期实体瘤,巨块型肿瘤	Ⅰ期,NCT02934568,招募
		晚期实体肿瘤,转移性激素受体阳性乳腺癌	Ⅰ/Ⅰb期,NCT03775525,招募
SY-1425	RARα	急性髓系白血病,骨髓增生异常综合征	Ⅱ期,NCT02807558,未招募

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