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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Bromosporine

Bromosporine is a broad spectrum inhibitor for bromodomains with IC50 of 0.41 μM, 0.29 μM, 0.122 μM and 0.017 μM for BRD2, BRD4, BRD9 and CECR2, respectively.IC50 value: 0.41/0.29/0.122/0.017 uM (BRD2/BRD4/BRD9/CECR2) [1]Target: BRD inhibitorIn cell-based assays, Bromosporine (1 μM) accelerates FRAP recovery of BRD4 and CREBBP, while shows no activities against TIF1α, BAZ2A, and SMARCA2 even at 10 μM. Bromosporine shows moderate cytotoxicity in HeLa cells at 18 μM. Bromosporine, as a chemical probe for bromodomain functional assays, will be very useful in elucidating further biological roles of reader domains.

  • CAS Number: 1619994-69-2
  • MF: C17H20N6O4S
  • MW: 404.444
  • Catalog: Epigenetic Reader Domain
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PBRM1-BD2-IN-6

PBRM1-BD2-IN-6 is a potent PBRM1 bromodomain inhibitor with an IC50 value of 0.22 µM. PBRM1-BD2-IN-6 shows antiproliferation activity. PBRM1-BD2-IN-6 has the potential for the research of PBRM1-dependent cancer[1].

  • CAS Number: 2819989-67-6
  • MF: C16H15ClN2O
  • MW: 286.76
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

dBET23

dBET23 is a BRD4 heterobifunctional small-molecule ligand (PROTAC), exhibits significant and selective degradation of BRD4 BD1 (DC50/5h=50 nM) in cellular degradation assays.

  • CAS Number: 1957234-83-1
  • MF: C43H45ClN8O9S
  • MW: 885.39
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BAY-299

BAY-299 is a very potent, dual inhibitor with IC50s of 67 nM for BRPF2 bromodomains (BD), 8 nM for TAF1 BD2, and 106 nM for TAF1L BD2.

  • CAS Number: 2080306-23-4
  • MF: C25H23N3O4
  • MW: 429.468
  • Catalog: Epigenetic Reader Domain
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 688.7±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 370.3±31.5 °C

CBP/p300-IN-14

CBP/p300-IN-14 is a potent inhibitor of CBP/EP300 (lysine acetyltransferase) with an IC50 of 3.3 nM (extracted from patent WO2021213521A1, compound 27)[1].

  • CAS Number: 2725036-10-0
  • MF: C30H31F2N7O2
  • MW: 559.61
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

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

PLK1/BRD4-IN-1

PLK1/BRD4-IN-1 (9b) is an orally active dual PLK1 and BRD4 inhibitor with IC50 values of 22 nM and 109 nM against PLK1 and BRD4, respectively. PLK1/BRD4-IN-1 induces cell cycle arrest and apoptosis, downregulates the transcription of several proliferation-related oncogenes, and exhibits favorable in vivo antitumor activity[1].

  • CAS Number: 2412707-81-2
  • MF: C31H43N9O2
  • MW: 573.73
  • Catalog: Apoptosis
  • 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

PROTAC BRD4 Degrader-17

PROTAC BRD4 Degrader-17 (compound 13i) is a potent PROTAC BRD4 Degrader, with IC50 values of 29.54 nM (BRD4 (BD1)) and 3.82 nM (BRD4 (BD2)). PROTAC BRD4 Degrader-17 significantly attenuates G2/M progression associated Cyclin B1 expression. PROTAC BRD4 Degrader-17 significantly induces apoptosis in MV-4-11 cells[1].

  • CAS Number: 2585561-49-3
  • MF: C49H47N7O9
  • MW: 877.94
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tazemetostat (EPZ-6438)

Tazemetostat (EPZ-6438) is a potent, selective and orally available EZH2 inhibitor with Ki and IC50 of 2.5 and 11 nM, respectively.

  • CAS Number: 1403254-99-8
  • MF: C34H44N4O4
  • MW: 572.738
  • Catalog: Epigenetic Reader Domain
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 750.8±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 407.9±32.9 °C

A 485

A-485 is a potent and selective catalytic inhibitor of p300/CBP with IC50s of 9.8 nM and 2.6 nM for p300 and CBP, respectively.

  • CAS Number: 1889279-16-6
  • MF: C25H24F4N4O5
  • MW: 536.48
  • 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

Bromodomain inhibitor-9

Bromodomain inhibitor-9 is a Bromodomains inhibitor that selectively inhibits BRD4-1 (Kd: 12 nM). Bromodomain inhibitor-9 can be used in the research of diseases or conditions associated with systemic or tissue inflammation, lipid metabolism, fibrosis or chronic autoimmune diseases[1].

  • CAS Number: 1870849-34-5
  • MF: C24H28N4O5S
  • MW: 484.57
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Thalidomide-NH-CBP/p300 ligand 2

Thalidomide-NH-CBP/p300 ligand 2 (P-007) is a PROTAC-based CBP and p300 degrader (extracted from patent WO2020173440)[1].

  • CAS Number: 2484739-21-9
  • MF: C48H57F2N11O6
  • MW: 922.03
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

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

OF 1

OF-1 is a selective BRPF1B and BRPF2 bromodomain inhibitor with Kd values of 100 nM/500 nM for BRPF1B/BRPF2; 39-fold selectivity over BRD4.

  • CAS Number: 919973-83-4
  • MF: C17H18BrN3O4S
  • MW: 440.311
  • Catalog: Epigenetic Reader Domain
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 573.8±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 300.8±32.9 °C

NSC 228155

NSC 228155 is a potent inhibitor of KIX-KID interaction, inhibits kinase-inducible domain (KID) from CREB and KID-interacting domain (KIX) from CBP, with an IC50 of 0.36 μM. NSC 228155 is not selective against CREB-mediated gene transcription in living HEK 293T cells[1].

  • CAS Number: 113104-25-9
  • MF: C11H6N4O4S
  • MW: 290.255
  • Catalog: Epigenetic Reader Domain
  • Density: 1.7±0.1 g/cm3
  • Boiling Point: 627.3±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 333.2±34.3 °C

PROTAC BRD4 Degrader-6

PROTAC BRD4 Degrader-6 (compound 32a) is a potent small-molecule BRD4 degrader with IC50 value of 2.7 nM for BRD4 BD1. PROTAC BRD4 Degrader-6 potently degrades BRD4 protein and inhibits the expression of c-Myc. PROTAC BRD4 Degrader-6 inhibits the proliferation of pancreatic cancer cell line BxPC3 and induces apoptosis. PROTAC BRD4 Degrader-6 can be used for human pancreatic cancer research[1].

  • CAS Number: 2410947-56-5
  • MF: C43H40F2N10O10S
  • MW: 926.90
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

dBET1

dBET1 is a potent BRD4 protein degrader based on PROTAC technology with an EC50 of 430 nM.

  • CAS Number: 1799711-21-9
  • MF: C38H37ClN8O7S
  • MW: 785.268
  • Catalog: Epigenetic Reader Domain
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

VZ 185

VZ185 is a potent, fast, and selective dual BRD7/9 PROTAC degrader with DC50s of 4.5 and 1.8 nM, respectively.

  • CAS Number: 2306193-61-1
  • MF: C53H67FN8O8S
  • MW: 995.21
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BET-BAY 002

BET-BAY 002 is a potent BET inhibitor; shows efficacy in a multiple myeloma model.

  • CAS Number: 1588521-78-1
  • MF: C22H18ClN5O
  • MW: 403.864
  • Catalog: Epigenetic Reader Domain
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 635.7±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 338.3±34.3 °C

Mivebresib

Mivebresib is a potent and orally available bromodomain and extraterminal domain (BET) bromodomain inhibitor. Mivebresib binds to BRD4 with a Ki of 1.5 nM.

  • CAS Number: 1445993-26-9
  • MF: C22H19F2N3O4S
  • MW: 459.466
  • Catalog: Epigenetic Reader Domain
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 608.9±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 322.0±34.3 °C

L-45

L-45 is the first potent, selective, and cell-active p300/CBP-associated factor (PCAF) bromodomain (Brd) inhibitor with a Kd of 126±15 nM.

  • CAS Number: 2079885-05-3
  • MF: C21H24N6
  • MW: 360.46
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Ziftomenib

Ziftomenib is a menin-MLL interaction inhibitor with antitumor activities (WO2017161028A1, compound 151)[1].

  • CAS Number: 2134675-36-6
  • MF: C33H42F3N9O2S2
  • MW: 717.87
  • 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

PF-CBP1 hydrochloride

PF-CBP1 hydrochloride is a highly selective inhibitor of the CREB binding protein bromodomain.Target: CREBin vitro: PF-CBP1 modulates key inflammatory genes in primary macrophages. PF-CBP1 downregulates RGS4 in neurons, a target linked to Parkinson's disease. PF-CBP1 is 139-fold selective over BRD4 in the biochemical assays and >105-fold selective by ITC. F-CBP1 is also a potent inhibitor of EP300 (a result observed for other CBP inhibitors. [1]

  • CAS Number: 2070014-93-4
  • MF: C29H36N4O3·HCl
  • MW: 525.08
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

E3 Ligase Ligand-Linker Conjugates 19

E3 Ligase Ligand-Linker Conjugates 19 is a degron-linker. The PROTAC linker is bound lo at least one targeting ligand.

  • CAS Number: 1799711-24-2
  • MF: C19H22N4O6
  • MW: 402.4
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A