Epigenetic regulators of gene expression and chromatin state include so-called writers, erasers, and readers of chromatin modifications.Well-characterized examples of reader domains include bromodomains typically binding acetyllysine and chromatin organization modifier (chromo), malignant brain tumor (MBT), plant homeodomain (PHD), and Tudor domains generally associating with methyllysine. Research on epigenetic readers has been tremendously influenced by the discovery of selective inhibitors targeting the bromodomain and extraterminal motif (BET) family of acetyl-lysine readers. The human genome encodes 46 proteins containing 61 bromodomains clustered into eight families. Distinct experimental approaches are used to identify the first BET inhibitors, GSK 525762A and (+)-JQ-1. The Polycomb group (PcG) protein, enhancer of zeste homologue 2 (EZH2), has an essential role in promoting histone H3 lysine 27 trimethylation (H3K27me3) and epigenetic gene silencing. This function of EZH2 is important for cell proliferation and inhibition of cell differentiation, and is implicated in cancer progression. Cyclin-dependent kinases regulate epigenetic gene silencing through phosphorylation of EZH2. In many types of cancers including lymphomas and leukemia, EZH2 is postulated to exert its oncogenic effects via aberrant histone and DNA methylation, causing silencing of tumor suppressor genes. p300/CBP is not only a transcriptional adaptor but also a histone acetyltransferase.


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ZEN-3219

ZEN-3219 is a BET inhibitor with IC50s of 0.48, 0.16 and 0.47 μM for BRD4(BD1), BRD4(BD2) and BRD4(BD1BD2), respectively. ZEN-3219 can be used to form PROTACs to induce degradation of BRD4[1].

  • CAS Number: 1952264-34-4
  • MF: C19H18N2O3
  • MW: 322.36
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PROTAC BRD4 Degrader-20

PROTAC BRD4 Degrader-20 (compound 195) is an bifunctional compound and an degrader of BRD4[1].

  • CAS Number: 2086300-61-8
  • MF: C55H58ClN9O7S2
  • MW: 1056.69
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SGC-iMLLT

SGC-iMLLT is a potent and selective inhibitor of MLLT1/3-histone interactions, occupies the Kac/Kcr binding site of MLLT1 YD (ENL/YEATS1), with high binding activity at MLLT1 YD (IC50, 0.26 μM; Kd, 0.129 μM) and MLLT3 YD (AF9/YEATS3) (Kd, 0.077 μM)[1].

  • CAS Number: 2255338-25-9
  • MF: C22H24N6O
  • MW: 388.47
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BY27

BY27 is a potent and selective BET BD2 inhibitor, shows 38, 5, 7, and 21-fold BD1/BD2 selectivity for BRD2, BRD3, BRD4, and BRDT. Anti-cancer activity[1].

  • CAS Number: 2247236-59-3
  • MF: C22H21ClN6
  • MW: 404.90
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GNE-886

GNE-886 is a potent and selective CECR2 bromodomain inhibitor with IC50 of 16 nM; shows a wide selectivity over the 40 bromodomains, >100-fold selectivity over BRD9, BRD7, TAF1(2), and BRD4(1); has a highly favorable measured kinetic solubility of 122 uM and is an appropriate in vitro tool compound for the CECR2 bromodomain.

  • CAS Number: 2101957-05-3
  • MF: C28H30N6O3
  • MW: 498.576
  • Catalog: Epigenetic Reader Domain
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 796.3±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 435.4±32.9 °C

Olinone

Olinone is a selective BRD4 BrD1 inhibitor[1]. Olinone accelerates the progression of mouse primary oligodendrocyte progenitors toward differentiation[2].

  • CAS Number: 1770789-37-1
  • MF: C17H21N3O2
  • MW: 299.37
  • Catalog: Epigenetic Reader Domain
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 675.6±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 362.4±31.5 °C

PROTAC BRD4 Degrader-5

PROTAC BRD4 Degrader-5 is a PROTAC-based BRD4 degrader. PROTAC BRD4 Degrader-5 can potent degrade BRD4 in HER2 positive and negative breast cancer cell lines[1].

  • CAS Number: 2409538-70-9
  • MF: C50H62ClN9O8S2
  • MW: 1016.67
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BETd-260

BETd-260 is a potent BET degrader based on PROTAC technology, with an IC50 of 30 pM against BRD4 protein in RS4;11 leukemia cell line.

  • CAS Number: 2093388-62-4
  • MF: C43H46N10O6
  • MW: 798.89
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Bromodomain inhibitor-10

Bromodomain inhibitor-10 (compound 128) is a potent bromodomain inhibitor with Kds of 15.0, 2500 nM for BRD4-1 and BRD4-2, respectively. Bromodomain inhibitor-10 inhibits the production of IL12p40[1].

  • CAS Number: 1870849-58-3
  • MF: C20H20N4O3
  • MW: 364.40
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Amredobresib

Amredobresib is a potent inhibitor of BET. Amredobresib inhibits the binding of bromodomains to acetylated lysines on histone H3 and H4 and thus acts as important regulators of gene transcription. Amredobresib is useful for the research of acute myeloid leukemia (AML) and cancer (extracted from patent WO2019145410A1 and WO2021175824A1)[1].

  • CAS Number: 1610044-98-8
  • MF: C26H29N9
  • MW: 467.57
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PF-06726304

PF-06726304 is a potent and selective EZH2 inhibitor with a Ki of 0.7 nM.

  • CAS Number: 1616287-82-1
  • MF: C22H21Cl2N3O3
  • MW: 446.33
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PROTAC BRD4 Degrader-21

PROTAC BRD4 Degrader-21 (Comp 74) is a PROTAC degrader of BRD4. PROTAC BRD4 Degrader-21 displays significant tumor growth inhibition in tumor -bearing xenograft models in mice and can be used for anticancer research[1].

  • CAS Number: 2503036-46-0
  • MF: C47H54Cl2N10O4S
  • MW: 925.97
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BRM/BRG1 ATP Inhibitor-3

BRM/BRG1 ATP Inhibitor-3 is a BRG1/BRM inhibitor. BRM/BRG1 ATP Inhibitor-3 inhibits BRM and BRG1 with IC50 values of 10.4 nM and 19.3 nM, respectively. BRM/BRG1 ATP Inhibitor-3 can be used for the research of cancers and BAF complex-related disorders[1].

  • CAS Number: 2368901-31-7
  • MF: C26H25N5O2S2
  • MW: 503.64
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ZL0580

ZL0580, a structurally close analog of ZL0590, induces epigenetic suppression of HIV via selectively binding to BD1 domain of BRD4. ZL0580 induces HIV suppression by inhibiting Tat transactivation and transcription elongation as well as by inducing repressive chromatin structure at the HIV promoter[1][2][3].

  • CAS Number: 2377151-10-3
  • MF: C25H23F3N4O4S
  • MW: 532.53
  • Catalog: HIV
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CPI203

CPI-203 is a novel potent, selective and cell permeable inhibitor of BET bromodomain, with an IC50 value of appr 37 nM (BRD4 α-screen assay).

  • CAS Number: 1446144-04-2
  • MF: C19H18ClN5OS
  • MW: 399.897
  • Catalog: Epigenetic Reader Domain
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 690.5±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 371.4±34.3 °C

Tz-Thalidomide

Tz-Thalidomide is a tetrazine tagged Thalidomide (HY-14658) (Ligands for E3 Ligase). Tz-Thalidomide has binding affinity for BRD4, with IC50s of 46.25 μM (BRD4-1) and 62.55 μM (BRD4-2)[1].

  • CAS Number: 2087490-42-2
  • MF: C29H29N7O6
  • MW: 571.58
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Y06036

Y06036 is a potent and selective BET inhibitor, which binds to the BRD4(1) bromodomain with Kd value of 82 nM[1]. Antitumor activity[1].

  • CAS Number: 1832671-96-1
  • MF: C16H15BrN2O5S
  • MW: 427.27
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

JQ1-TCO

JQ1-TCO (JQ1-trans-cyclooctene) is a derivative of JQ1 (HY-13030), an inhibitor of BET. JQ1-TCO is suitable for click chemistry and can be used as molecular probes in vitro and in vivo[1][2].

  • CAS Number: 2087490-43-3
  • MF: C31H37ClN6O3S
  • MW: 609.18
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GNE-064

GNE-064 (compound 5) is a selective, orally active and highly soluble inhibitor of SMARCA4, SMARCA2 and PBRM1 bromodomains 5. GNE-064 inhibits SMARCA4 with an IC50 of 0.035 μM and inhibits SMARCA2 with an EC50 of 0.10 μM. GNE-064 possess Kds with 0.01, 0.016, 0.018 and 0.049 μM for SMARCA4, SMARCA2, PBRM1 bromodomains 5 and PBRM1 bromodomains 2, repectively. GNE-064 can be used as a chemical probe for the research of drug synthesis[1].

  • CAS Number: 1997321-20-6
  • MF: C17H21N5O2
  • MW: 327.38
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CBP/p300-IN-15

CBP/p300-IN-15 (compound 13a) is a potent p300/CBP inhibitor, with IC50 values of 2.50 and 28.0 nM, respectively. CBP/p300-IN-15 shows good activity against OVCAR-3 and A2780 cell line, with EC50 values of 0.865 and 2.71 μM, respectively. CBP/p300-IN-15 can be used for ovarian cancer research[1].

  • CAS Number: 2379409-91-1
  • MF: C26H28N4O5
  • MW: 476.52
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BRD4 Inhibitor-23

BRD4 Inhibitor-23 is a potent and orally active BRD4 inhibitor with IC50s of 6.21 nM and 1.44 nM for BRD4 BD-1 and BRD4 BD-2, respectively (WO2022033542A1; Example 1)[1].

  • CAS Number: 2760307-53-5
  • MF: C22H19F2N3O4S
  • MW: 459.47
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CeMMEC1

CeMMEC1 is an inhibitor of BRD4, and also has high affinity for TAF1, with an IC50 of 0.9 μM for TAF1, and a Kd of 1.8 μM for TAF1 (2).

  • CAS Number: 440662-09-9
  • MF: C19H16N2O4
  • MW: 336.341
  • Catalog: DNA/RNA Synthesis
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 590.1±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 310.7±30.1 °C

(R)-BAY1238097

(R)-BAY1238097 is the R-isomer with lower activity of BAY1238097. BAY1238097 is a potent and selective inhibitor of BET binding to histones and has strong anti-proliferative activity in different AML (acute myeloid leukemia) and MM (multiple myeloma) models through down-regulation of c-Myc levels and its downstream transcriptome[1][2].

  • CAS Number: 1564269-85-7
  • MF: C25H33N5O3
  • MW: 451.56
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(Rac)-BAY1238097

(rac)-BAY1238097 is a BET inhibitor, with an IC50 of 1.02 μM for BRD4. Used in cancer research[1].

  • CAS Number: 1564268-19-4
  • MF: C25H33N5O3
  • MW: 451.56
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GSK8814

GSK8814 is a potent, selective, and ATAD2/2B bromodomain chemical probe and inhibitor, with a binding constant pKd=8.1 and a pKi=8.9 in BROMOscan. GSK8814 binds to ATAD2 and BRD4 BD1 with pIC50s of 7.3 and 4.6, respectively. GSK8814 shows 500-fold selectivity for ATAD2 over BRD4 BD1[1].

  • CAS Number: 1997369-78-4
  • MF: C28H35F2N5O3
  • MW: 527.61
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

OARV-771

OARV-771 is a VHL-based BET degrader (PROTAC) with improved cell permeability. OARV-771 shows DC50s of 6, 1, and 4 nM for Brd4, Brd2 and Brd3, respectively[1].

  • CAS Number: 2683008-37-7
  • MF: C49H59ClN8O8S2
  • MW: 987.62
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

VinSpinIn

VinSpinIn is a Spindlin1 inhibitor (KD: 9.9 nM for SPIN149-262). VinSpinIn is a chemical probe for tudor domain of Spindlin1. VinSpinIn can be used to study chromatin function[1].

  • CAS Number: 2380021-98-5
  • MF: C42H58N8O4
  • MW: 738.96
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

JQ-1 carboxylic acid

JQ-1 carboxylic acid is a highly potent, selective and cell-permeable BRD4 inhibitor with IC50s of 77 nM and 33 nM for BRD4(1) and BRD4(2), respectively.

  • CAS Number: 202592-23-2
  • MF: C19H17ClN4O2S
  • MW: 400.882
  • Catalog: Epigenetic Reader Domain
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 661.6±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 353.9±34.3 °C

MI-3454

MI-3454 is an orally active, highly potent and selective menin-MLL1 interaction inhibitor with an IC50 of 0.51 nM. MI-3454 inhibits proliferation, induces differentiation and complete remission or regression of leukemia in mouse models of MLL1-rearranged or NPM1-mutated leukemia through downregulation of key genes involved in leukemogenesis[1].

  • CAS Number: 2134169-43-8
  • MF: C32H35F3N8OS
  • MW: 636.73
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ZEN-3694

ZEN-3694 is a bromo-structural domain extra-terminal inhibitor (BETi) with activity in androgen signaling inhibitor (ASI) resistance models and can be used in combination with enzalutamide to study metastatic desmoplasia-resistant prostate cancer.

  • CAS Number: 1643947-30-1
  • MF: C19H19N5O
  • MW: 333.39
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A