Epigeneics include any process that alters gene activity without changing the DNA sequence, and leads to modifications that can be transmitted to daughter cells. Many types of epigenetic processes have been identified—they include DNA methylation, alteration in the structure of histone proteins and gene regulation by small noncoding microRNAs.

Many different DNA and histone modifications have been identified to determine the epigenetic landscape. DNA methylation is mainly mediated by DNA-methyl transferase (DNMT), there are two known types of DNMT, namely DNMT1, which preserves preexisting pattern of methylation after cell replication, and DNMT3A/B, so-called “de novo” DNMT, which methylate previously unmethylated DNA. Histone modifications mainly include acetylation, methylation, phosphorylation, and ubiquitination. The acetylation of histones can be mediated by histone acetyltransferases (HATs) and histone deacetyltransferases (HDACs), while Histhone demethylation is performed by two classes of histone demethylases: lysine-specific demethylase (LSD) family proteins (LSD1 and LSD2) and JmjC domaincontaining histone demethylase (JHDM). Furthermore, enzymes involved in epigenetic modifications can also be governed by miRNAs. For example, miR-34a can directly inhibit the activities of SIRT1 to regulate cholesterol homeostasis.

The accumulated evidence indicates that many genes, diseases, and environmental substances are part of the epigenetics picture. At the FDA, scientists are investigating many drugs that function through epigenetic mechanisms. Drugs that inhibit DNA methylation or histone deacetylation have been studied for the reactivation of tumor suppressor genes and repression of cancer cell growth. Epigenetic inhibitors can also work alone or in combination with other therapeutic agents.

References:
[1] Bob Weinhold. Environ Health Perspect. 2006 Mar; 114(3): A160–A167.
[2] Xu W, et al. Genet Epigenet. 2016 Sep 25;8:43-51.
[3] Biswas S, et al. Pharmacol Ther. 2017. doi: 10.1016/j.pharmthera.2017.02.011.
[4] Perri F, et al. Crit Rev Oncol Hematol. 2017 Mar;111:166-172.


Anti-infection >
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Antibody-drug Conjugate >
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Apoptosis >
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Autophagy >
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15-PGDH 5 alpha Reductase 5-Lipoxygenase Acetyl-CoA Carboxylase Acyltransferase Adenosine Deaminase Adenosine Kinase Aldehyde Dehydrogenase (ALDH) Aldose Reductase Aminopeptidase Angiotensin-converting Enzyme (ACE) ATGL ATP Citrate Lyase Carbonic Anhydrase Carboxypeptidase Cathepsin CETP COMT Cytochrome P450 Dipeptidyl Peptidase Dopamine β-hydroxylase E1/E2/E3 Enzyme Elastase Enolase FAAH FABP Factor Xa Farnesyl Transferase Fatty Acid Synthase (FAS) FXR Glucokinase GSNOR Gutathione S-transferase HCV Protease Hexokinase HIF/HIF Prolyl-Hydroxylase HIV Integrase HIV Protease HMG-CoA Reductase (HMGCR) HSP Indoleamine 2,3-Dioxygenase (IDO) Isocitrate Dehydrogenase (IDH) Lactate Dehydrogenase LXR MAGL Mineralocorticoid Receptor Mitochondrial Metabolism MMP Nampt NEDD8-activating Enzyme Neprilysin PAI-1 PDHK PGC-1α Phosphatase Phosphodiesterase (PDE) Phospholipase Procollagen C Proteinase Proteasome Pyruvate Kinase RAR/RXR Renin ROR Ser/Thr Protease SGK Stearoyl-CoA Desaturase (SCD) Thrombin Tryptophan Hydroxylase Tyrosinase Xanthine Oxidase
Neuronal Signaling >
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Flufenamic acid-d4

Flufenamic acid-d4 is deuterium labeled Flufenamic acid. Flufenamic acid is a non-steroidal anti-inflammatory agent, inhibits cyclooxygenase (COX), activates AMPK, and also modulates ion channels, blocking chloride channels and L-type Ca2+ channels, modulating non-selective cation channels (NSC), activating K+ channels. Flufenamic acid binds to the central pocket of TEAD2 YBD and inhibits both TEAD function and TEAD-YAP-dependent processes, such as cell migration and proliferation.

  • CAS Number: 1185071-99-1
  • MF: C14H6D4F3NO2
  • MW: 285.25
  • Catalog: AMPK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Pacritinib

Pacritinib is a potent inhibitor of both wild-type JAK2 (IC50=23 nM) and JAK2V617F mutant (IC50=19 nM). Pacritinib also inhibits FLT3 (IC50=22 nM) and its mutant FLT3D835Y (IC50=6 nM).

  • CAS Number: 937272-79-2
  • MF: C28H32N4O3
  • MW: 472.579
  • Catalog: JAK
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 711.4±70.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 384.0±35.7 °C

SIRT1-IN-2

SIRT1-IN-2 (compound 3h) is a potent and selective SIRT1 (silent information regulator 1) inhibitor, with an IC50 of 1.6 μM[1].

  • CAS Number: 2470969-89-0
  • MF: C13H15ClN2O
  • MW: 250.72
  • Catalog: Sirtuin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ZXH 3-26

ZXH-3-26 is a selective BRD4 degrader with a DC50/5h (DC50/5h referring to half-maximal degradation after 5 hours of treatment) of ~ 5 nM[1].

  • CAS Number: 2243076-67-5
  • MF: C38H37ClN8O7S
  • MW: 785.27
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PF-956980

PF-00956980 is a reversible pan-JAK inhibitor with IC50 values of 2.2, 23.1 and 59.9 μM for JAK1, JAK2 and JAK3, respectively. PF-00956980 can be used in the research of lung and skin inflammatory diseases[1].

  • CAS Number: 1262832-74-5
  • MF: C18H26N6O
  • MW: 342.439
  • Catalog: JAK
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MI-192 HCl

MI-192 is a selective HDAC2 and HDAC3 inhibitor with IC50s of 30 nM and 16 nM, respectively. MI-192 is more selective for HDAC2/3 than other HDAC isomers.MI-192 induces myeloid leukaemic cells apoptosis. Anticaner and neuroprotective activities[1][2].

  • CAS Number: 1415340-63-4
  • MF: C24H21N3O2
  • MW: 383.44
  • Catalog: Apoptosis
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 565.0±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 295.5±30.1 °C

UNC1021

UNC1021 is a selective L3MBTL3 inhibitor with an IC50 of 0.048 μM[1].

  • CAS Number: 1322591-19-4
  • MF: C26H38N4O2
  • MW: 438.61
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

HYDAMTIQ

HYDAMTIQ is a PARP-1/2 inhibitor (IC50: 29-38 nM) with anticancer, anti-inflammatory, and ischemic protective effects. HYDAMTIQ inhibits pulmonary PARP activity, is effective against allergen-induced cough and dyspnea, and inhibits bronchial hyperresponsiveness to methacholine. HYDAMTIQ has broad-spectrum tumor suppressor effects, including ovarian and breast cancers, prostate and pancreatic tumors, and glioblastoma multiforme. HYDAMTIQ has demonstrated in vivo efficacy in animal models of cerebral ischemia, asthma, cancer, and more[1].

  • CAS Number: 1201832-32-7
  • MF: C14H14N2O2S
  • MW: 274.34
  • Catalog: PARP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CrBKA

CrBKA is a fluorogenic small-molecule substrate of SIRT6 with weak activity[1].

  • CAS Number: 2260810-48-6
  • MF: C28H31N3O6
  • MW: 505.56
  • Catalog: Sirtuin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PLX51107

PLX51107 is a potent and selective BET inhibitor, with Kds of 1.6, 2.1, 1.7, and 5 nM for BD1 and 5.9, 6.2, 6.1, and 120 nM for BD2 of BRD2, BRD3, BRD4, and BRDT, respectively; PLX51107 also interacts with the bromodomains of CBP and EP300 (Kd, in the 100 nM range).

  • CAS Number: 1627929-55-8
  • MF: C26H22N4O3
  • MW: 438.48
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

I-BET762

GSK 525762A is a BET bromodomain inhibitor with IC50 of 32.5-42.5 nM.

  • CAS Number: 1260907-17-2
  • MF: C22H22ClN5O2
  • MW: 423.895
  • Catalog: Epigenetic Reader Domain
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

IHCH-3064

IHCH-3064 is a dual-acting compounds targeting Adenosine A2A Receptor and HDAC. IHCH-3064 exhibits potent binding to A2AR (Ki=2.2 nM) and selective inhibition of HDAC1 (IC50=80.2 nM), with good antiproliferative activity against tumor cell lines in vitro. IHCH-3064 is a tumor immunotherapeutic agent[1].

  • CAS Number: 2420562-65-6
  • MF: C25H21N9O2
  • MW: 479.49
  • Catalog: HDAC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Sirtuin modulator 4

Sirtuin modulator 4 (compound 12) is a sirtuin modulator. Sirtuin modulator 4 shows inhibitory effect to SIRT1 with an EC50 value of 51-100 μM. Sirtuin modulator 4 may be used for the research of increasing the lifespan of a cell, and preventing a wide variety of diseases and disorders including, for example, diabetes, obesity, neurodegenerative diseases, cardiovascular diseases, inflammation and cancer[1].

  • CAS Number: 327104-77-8
  • MF: C18H10N2O2S
  • MW: 318.35
  • Catalog: Sirtuin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

FTX-6058 hydrochloride

FTX-6058 hydrochloride is a potent and orally active inhibitor of Embryonic Ectoderm Development (EED). FTX-6058 hydrochloride can induce HbF protein expression in cell and murine models. FTX-6058 hydrochloride can be used for the research of select hemoglobinopathies, including sickle cell disease and β-thalassemia[1][2].

  • CAS Number: 2490676-19-0
  • MF: C22H19ClFN5O2
  • MW: 439.87
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MS 023 dihydrochloride

MS023 is a potent, selective inhibitor of protein arginine methyltransferases (PRMTs) inhibitor, with IC50s of 30, 119, 83, 4 and 5 nM for PRMT1, PRMT3, PRMT4, PRMT6, and PRMT8, respectively[1].

  • CAS Number: 1992047-64-9
  • MF: C17H27Cl2N3O
  • MW: 360.32
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

HDAC-IN-42

HDAC-IN-42 (compound 14f) is a potent and selective HDAC inhibitor with IC50 values of 0.19 and 4.98 µM for HDAC1 and HDAC6, respectively. HDAC-IN-42 shows anticancer and anti-proliferative activity. HDAC-IN-42 induces apoptosis and cell cycle arrest at G2/M phase[1].

  • CAS Number: 2454024-18-9
  • MF: C20H15NO7
  • MW: 381.34
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

RN-1 dihydrochloride

RN-1 dihydrochloride is a potent, brain-penetrant, irreversible and selective lysine-specific demethylase 1 (LSD1) inhibitor with an IC50 of 70 nM. RN-1 dihydrochloride exhibits selectivity for LSD1 over MAO-A and MAO-B with IC50 values of 0.51 μM and 2.785 μM respectively[1][2].

  • CAS Number: 1781835-13-9
  • MF: C23H31Cl2N3O2
  • MW: 452.42
  • Catalog: Histone Demethylase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Hg-7-85-01

HG-7-85-01 is a type II ATP competitive inhibitor of wild-type and gatekeeper mutations forms of Bcr-Abl, PDGFRα, Kit, and Src kinases. HG-7-85-01 inhibits T315I mutant Bcr-Abl kinase, KDR and RET with IC50s of 3 nM, 20 nM and 30 nM, and is only weak or no inhibition of other kinases (IC50>2 μM). HG-7-85-01 inhibits the cell proliferation, which is mediated by the induction of apoptosis, and inhibition of cell-cycle progression[1].

  • CAS Number: 1258391-13-7
  • MF: C31H31F3N6O2S
  • MW: 608.68
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tofacitinib-d3 citrate

Tofacitinib-d3 (citrate) is deuterium labeled Tofacitinib (citrate). Tofacitinib citrate is an orally available JAK1/2/3 inhibitor with IC50s of 1, 20, and 112 nM, respectively. Tofacitinib citrate has antibacterial, antifungal and antiviral activities.

  • CAS Number: 2701680-77-3
  • MF: C22H25D3N6O8
  • MW: 507.51
  • Catalog: Bacterial
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Dihydrochlamydocin

Dihydrochlamydocin is a Putative HDAC inhibitor.

  • CAS Number: 52574-64-8
  • MF: C28H40N4O6
  • MW: 528.64
  • Catalog: HDAC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Leucosceptoside A

Leucosceptoside A is a phenylethanoid glycoside with anti-hyperglycemic and anti-hypertensive activities. Leucosceptoside A shows inhibitory activity against α-glucosidase and PKCα (IC50 of 19.0 μM)[1][2][3].

  • CAS Number: 83529-62-8
  • MF: C30H38O15
  • MW: 638.61400
  • Catalog: PKC
  • Density: 1.545g/cm3
  • Boiling Point: 884.547ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 283.993ºC

5-Aza-4'-thio-2'-deoxycytidine

5-Aza-4'-thio-2'-deoxycytidine (5-Aza-T-dCyd) is an orally active DNA methyltransferase I (DNMT1) inhibitor. 5-Aza-4'-thio-2'-deoxycytidine, a sulfur-containing deoxy-cytidine analog, has the potential for DNA hypomethylating and has antitumor effects[1].

  • CAS Number: 169514-76-5
  • MF: C8H12N4O3S
  • MW: 244.27
  • Catalog: DNA Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Ac-Arg-Gly-Lys(Ac)-MCA

Ac-Arg-Gly-Lys(Ac)-AMC is a substrate for HDAC[1].

  • CAS Number: 660846-97-9
  • MF: C28H40N8O7
  • MW: 600.667
  • Catalog: HDAC
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

UNC1999

UNC1999 is a SAM-competitive, potent and selective inhibitor of EZH1/2 with IC50s of 10 nM and 45 nM, repectively.

  • CAS Number: 1431612-23-5
  • MF: C33H43N7O2
  • MW: 569.740
  • Catalog: Autophagy
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 804.7±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 440.4±34.3 °C

Sirtinol

Sirtinol is a sirtuin inhibitor, with IC50s of 48 μM, 57.7 μM and 131 μM for ySir2, hSIRT2 and hSIRT2, respectively.

  • CAS Number: 410536-97-9
  • MF: C26H22N2O2
  • MW: 394.465
  • Catalog: Autophagy
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 659.2±50.0 °C at 760 mmHg
  • Melting Point: 119-120℃
  • Flash Point: 352.5±30.1 °C

4-Phenylbutyric acid-d5

4-Phenylbutyric acid-d5 is the deuterium labeled 4-Phenylbutyric acid[1]. 4-Phenylbutyric acid (4-PBA) is an inhibitor of HDAC and endoplasmic reticulum (ER) stress, used in cancer and infection research[2][3][4].

  • CAS Number: 64138-52-9
  • MF: C10H7D5O2
  • MW: 169.23
  • Catalog: HDAC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Protein Kinase C (661-671)

Protein Kinase C (661-671) is a fragment peptide of β1 subspecies of protein kinase C (PKC). PKC plays a role in cellular growth control and tumor promotion[1][2].

  • CAS Number: 149839-93-0
  • MF: C59H87N13O19
  • MW: 1282.40
  • Catalog: PKC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Antitumor agent-69

Antitumor agent-69 (compound 12) is a potent inhibitor of protein-protein interaction between DOT1L and MLL-AF9/MLL-ENL, with Kis of 9 nM and 109 nM for AF9 and ENL, respectively. Antitumor agent-69 exhibits anticancer cellular activitiy[1].

  • CAS Number: 2417651-42-2
  • MF: C43H62N8O5
  • MW: 771.00
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tubastatin A

Tubastatin A (TSA) TFA is a potent and selective?HDAC6?inhibitor with?IC50?of 15 nM in a cell-free assay, and is selective (1000-fold more) against all other isozymes except HDAC8 (57-fold more). Tubastatin A TFA also inhibits HDAC10 and metallo-β-lactamase domain-containing protein?2 (MBLAC2).

  • CAS Number: 1239262-52-2
  • MF: C22H22F3N3O4
  • MW: 449.42
  • Catalog: Apoptosis
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BET bromodomain inhibitor 2

BET bromodomain inhibitor 2 is a potent BET bromodomain inhibitor with an IC50 of 14.1 µM[1].

  • CAS Number: 2414195-69-8
  • MF: C23H30N2O5S
  • MW: 446.56
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A