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 >
ADC Cytotoxin ADC Linker Drug-Linker Conjugates for ADC PROTAC-linker Conjugate for PAC
Apoptosis >
Apoptosis Bcl-2 Family c-Myc Caspase DAPK Ferroptosis IAP MDM-2/p53 PKD RIP kinase Survivin Thymidylate Synthase TNF Receptor
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 >
5-HT Receptor AChE Adenosine Kinase Amyloid-β Beta-secretase CaMK CGRP Receptor COMT Dopamine Receptor Dopamine Transporter FAAH GABA Receptor GlyT iGluR Imidazoline Receptor mAChR Melatonin Receptor Monoamine Oxidase nAChR Neurokinin Receptor Opioid Receptor Serotonin Transporter γ-secretase
NF-κB >
NF-κB IKK Keap1-Nrf2 MALT1
PI3K/Akt/mTOR >
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PROTAC >
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Casein Kinase ERK Gli GSK-3 Hedgehog Hippo (MST) JAK Notch Oct3/4 PKA Porcupine ROCK sFRP-1 Smo STAT TGF-beta/Smad Wnt YAP β-catenin γ-secretase
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TC-E 5001

TC-E 5001 is an inhibitor of Wnt pathway that inhibits tankyrase 1/2 (TNKS1/2) via novel adenosine pocket binding, with Kds of 79 nM and 28 nM, respectively. TC-E 5001 also inhibits Axin2 and STF, with IC50s of 0.709 μM and 0.215 μM, respectively[1][2].

  • CAS Number: 865565-29-3
  • MF: C20H19N5O3S
  • MW: 409.46
  • Catalog: PARP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Protein Kinase C (19-35) Peptide

Protein Kinase C (19-35) Peptide is the PKC pseudosubstrate inhibitor/region. Protein Kinase C (19-35) Peptide possibly blocks the substrate-binding site in its kinase domain, makes the cytoplasmic form of PKC inactive[1][2].

  • CAS Number: 309247-48-1
  • MF: C89H153N33O22
  • MW: 2037.40
  • Catalog: PKC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MTP

MTP is a PKM2 inhibitor. MTP induces cancer cell apoptosis by modulating caspase-3 activation. MTP induces autophagy and increases ROS generation. MTP also inhibits JAK2 signaling. MTP can be used for research of oral squamous cell carcinoma[1].

  • CAS Number: 2377372-62-6
  • MF: C29H23F3N4O2
  • MW: 516.51
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MPT0E028

MPT0E028 is an orally active and selective HDAC inhibitor with IC50s of 53.0 nM, 106.2 nM, 29.5 nM for HDAC1, HDAC2 and HDAC6, respectively[1]. MPT0E028 reduces the viability of B-cell lymphomas by inducing apoptosis and possesses potent direct Akt targeting ability and reduces Akt phosphorylation in B-cell lymphoma. MPT0E028 has good anticancer activity[2].

  • CAS Number: 1338320-94-7
  • MF: C17H16N2O4S
  • MW: 344.38500
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

EPZ011989 hydrochloride

EPZ011989 hydrochloride is a potent and orally active Zeste Homolog 2 (EZH2) inhibitor, with a Ki value of <3 nM. EPZ011989 shows anti-tumor activity. EPZ011989 is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups[1].

  • CAS Number: 2095432-26-9
  • MF: C35H52ClN5O4
  • MW: 642.271
  • Catalog: Histone Methyltransferase
  • 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

PARP1-IN-9

PARP1-IN-9 (Compound 5c) is a PARP1 inhibitor with an IC50 of 30.51 nM. PARP1-IN-9 induces cell apoptosis and shows anticancer activity. PARP1-IN-9 has higher potency than Olaparib (HY-10162) [1].

  • CAS Number: 2494000-71-2
  • MF: C18H21N3O5
  • MW: 359.38
  • Catalog: PARP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

DS-437

DS-437 is a potent, selective, dual inhibitor of PRMT5 and PRMT7 with IC50 of 6.0 uM for both, DS-437 is inactive against 29 other human protein-, DNA-, and RNA-methyltransferases; inhibits methylation of full-length histone 4 by PRMT5-MEP50 with an IC50 of 37 ± 1.2 μM in a biochemical assay; inhibits symmetrical dimethylation of PRMT5 substrates in cells.

  • CAS Number: 1674364-87-4
  • MF: C15H23N7O4S
  • MW: 397.453
  • Catalog: Histone Methyltransferase
  • Density: 1.7±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Fucosterol

Fucosterol is isolated from E. stolonifera with anti-adipogenic, anti-diabetic and anti-cancer activities. Fucosterol regulates adipogenesis via modulation of PPARαand C/EBPαexpression.

  • CAS Number: 17605-67-3
  • MF: C29H48O
  • MW: 412.69100
  • Catalog: PARP
  • Density: 0.98 g/cm3
  • Boiling Point: 504.2ºC at 760 mmHg
  • Melting Point: 118-120ºC
  • Flash Point: 220.3ºC

HDAC-IN-56

HDAC-IN-56 ((S)-17b) is an orally active class I histone deacetylase (HDAC) inhibitor with IC50 values of 56.0 ± 6.0, 90.0 ± 5.9, 422.2 ± 105.1, >10000 nM for HDAC1, HDAC2, HDAC3, and HDAC4-11, respectively. HDAC-IN-56 has potent inhibitory activity while strongly increasing intracellular levels of acetylhistone H3 and P21 and effectively inducing G1 cell cycle arrest and apoptosis.HDAC-IN-56 has antitumor activity [1].

  • CAS Number: 2814571-89-4
  • MF: C28H28FN5O2
  • MW: 485.55
  • Catalog: HDAC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PAD4-IN-3

PAD4-IN-3 (compound 4B) is a PAD4 inhibitor with antitumor activity in vitro and in vivo. PAD4-IN-3 was covalently linked to RGD sequence peptide-modified chitosan (K-CRGDV), resulting in an enhanced oxidative stress-responsive nanoagent. K-CRGDV-PAD4-IN-3 can actively target tumors, inhibit PAD4 activity, block the formation of neutrophil extracellular traps (NETs), and improve the tumor immune microenvironment in response to the tumor microenvironment[1].

  • CAS Number: 2642327-44-2
  • MF: C21H26BClN4O4
  • MW: 444.72
  • Catalog: Cancer
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SP-2-225

SP-2-225 is a selective HDAC6 inhibitor. SP-2-225 enhance the production of cancer-associated antigens and macrophage antigen cross-presentation to T cells. SP-2-225 reduces the tumor volume in a syngeneic SM1 melanoma model[1].

  • CAS Number: 2364448-93-9
  • MF: C28H34N2O3
  • MW: 446.58
  • Catalog: HDAC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

vanicoside A

Vanicoside A is a protein kinase C(PKC) inhibitor from Polygonum pensylvanicum[1].

  • CAS Number: 155179-22-9
  • MF: C51H50O21
  • MW: 998.930
  • Catalog: PKC
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 1155.8±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 332.6±27.8 °C

MI-3

MI-3 is a Menin-MLL interaction inhibitor with IC50 value of 648 ± 25 nM.IC50 value: 648 ± 25 nM [1]Target: Menin-MLLin vitro: The menin-MLL inhibitors very effectively blocked proliferation of MLL-AF9 and MLL-ENL transduced BMC, with GI50 values of about 5 μM for MI-2 and MI-3. MI-2 and MI-3 showed only a small effect on the cell growth of E2A-HLF transduced BMC (GI50 > 50 μM). MI-2 and MI-3 substantially and specifically reduce the immortalization potential of cells transformed with MLL fusion oncoproteins [1].in vivo: MLL-AF9 transformed BMC that remained viable after 7 days of treatment with MI-2 and MI-3 showed substantial changes in morphology, indicative of monocytic differentiation, as evidenced by increased cell size, lower nuclear to cytoplasmic ratio and highly vacuolated cytoplasm. Consistent with the change in cell morphology, the expression of CD11b was substantially increased on MLL-AF9 transformed BMC after 7 days of treatment with MI-2 and MI-3 [1].

  • CAS Number: 1271738-59-0
  • MF: C18H25N5S2
  • MW: 375.555
  • Catalog: Histone Methyltransferase
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 527.9±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 273.1±32.9 °C

TNG-462

TNG-462 (Compound 1143) is an orally active PRMT5 inhibitor for investigation of MTAP-deficient and/or MTA-accumulating cancers[1].

  • CAS Number: 2760483-96-1
  • MF: C28H36N6O2S
  • MW: 520.69
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Kazinol B

Kazinol B, a prenylated flavan with a dimethyl pyrane ring, is an inhibitor of nitric oxide (NO) production. Kazinol B improves insulin sensitivity by enhancing glucose uptake via the insulin-Akt signaling pathway and AMPK activation. Kazinol B has the potential for diabetes mellitus research[1][2].

  • CAS Number: 99624-27-8
  • MF: C25H28O4
  • MW: 392.487
  • Catalog: AMPK
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 556.6±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 290.4±30.1 °C

Demethyleneberberine

Demethyleneberberine is a natural mitochondria-targeted antioxidant. Demethyleneberberine alleviates mice colitis and inhibits the inflammatory responses by inhibiting NF-κB pathway and regulating the balance of Th cells. Demethyleneberberine could serve as a AMPK activator for treating non-alcoholic fatty liver disease (NAFLD)[1][2][3].

  • CAS Number: 25459-91-0
  • MF: C19H18NO4+
  • MW: 323.34300
  • Catalog: AMPK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Etilefrin

Etilefrine (3-[2-(ethylamino)-1-hydroxyethyl]phenol) is an α adrenergic agonist[2]. Etilefrine also is an AMPK activator[1]. Etilefrine can be used for the research of postural hypotension[3].

  • CAS Number: 709-55-7
  • MF: C10H15NO2
  • MW: 181.23200
  • Catalog: AMPK
  • Density: 1.127 g/cm3
  • Boiling Point: 351.7ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 155.5ºC

Bisindolylmaleimide XI hydrochloride

Bisindolylmaleimide XI hydrochloride (Ro 32-0432) is a potent, selective and orally active PKC inhibitor with IC50s of 9 nM, 28 nM, 31 nM, 37 nM, and 108 nM for PKCα, PKCβI, PKCβII, PKCγ, and PKCε, respectively[1][2].

  • CAS Number: 145333-02-4
  • MF: C28H29ClN4O2
  • MW: 489.01
  • Catalog: PKC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SZUH280

SZUH280 is a potent and selective PROTAC HDAC8 degrader with a DC50 of 0.58 μM in A549 cells. SZUH280 induces cancer cell apoptosis. SZUH280 hampers DNA damage repair in cancer cells, promoting cellular radiosensitization[1].

  • CAS Number: 2770263-77-7
  • MF: C36H34N8O8
  • MW: 706.70
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

c-Met/HDAC-IN-3

c-Met/HDAC-IN-3 (Compound 15f) is a dual c-Met and HDAC inhibitor with IC50 values of 12.50 nM and 26.97 nM against c-Met and HDAC1, respectively. c-Met/HDAC-IN-3 induces apoptosis and cause cell cycle arrest in G2/M phase[1].

  • CAS Number: 2439175-23-0
  • MF: C34H35FN4O7
  • MW: 630.66
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Roy-Bz

Roy-Bz is a selecive PKCδ activator. Roy-Bz potently inhibits the proliferation of colon cancer cells by inducing a PKCδ-dependent mitochondrial apoptotic pathway involving caspase-3 activation[1].

  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Methyl cinnamate

Methyl cinnamate (Methyl 3-phenylpropenoate), an active component of Zanthoxylum armatum, is a widely used natural flavor compound. Methyl cinnamate (Methyl 3-phenylpropenoate) possesses antimicrobial activity and is a tyrosinase inhibitor that can prevent food browning. Methyl cinnamate (Methyl 3-phenylpropenoate) has antiadipogenic activity through mechanisms mediated, in part, by the CaMKK2-AMPK signaling pathway[1].

  • CAS Number: 103-26-4
  • MF: C10H10O2
  • MW: 162.185
  • Catalog: Bacterial
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 261.9±0.0 °C at 760 mmHg
  • Melting Point: 34-38 °C(lit.)
  • Flash Point: 141.3±9.9 °C

SGC2085

SGC2085 is a potent and selective coactivator associated arginine methyltransferase 1 (CARM1) inhibitor with an IC50 of 50 nM.

  • CAS Number: 1821908-48-8
  • MF: C19H24N2O2
  • MW: 312.406
  • Catalog: Histone Methyltransferase
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 498.3±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 255.2±28.7 °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

S2116

S2116, a N-alkylated tranylcypromine (TCP) derivative, is a potent lysine-specific demethylase 1 (LSD1) inhibitor. S2116 increases H3K9 methylation and reciprocal H3K27 deacetylation at super-enhancer regions. S2116 induces apoptosis in TCP-resistant T-cell acute lymphoblastic leukemia (T-ALL) cells by repressing transcription of the NOTCH3 and TAL1 genes. S2116 significantly retardes the growth of T-ALL cells in xenotransplanted mice[1].

  • CAS Number: 2262489-89-2
  • MF: C22H26ClF2N3O2
  • MW: 437.91
  • 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

Marein

Marein has the neuroprotective effect due to a reduction of damage to mitochondria function and activation of the AMPK signal pathway. Marein improves insulin resistance induced by high glucose in HepG2 cells through CaMKK/AMPK/GLUT1 to promote glucose uptake, through IRS/Akt/GSK-3β to increase glycogen synthesis, and through Akt/FoxO1 to decrease gluconeogenesis. Marein is a HDAC inhibitor with an IC50 of 100 µM. Marein has beneficial antioxidative, antihypertensive, antihyperlipidemic and antidiabetic effects[1][2][3].

  • CAS Number: 535-96-6
  • MF: C21H22O11
  • MW: 450.393
  • Catalog: HDAC
  • Density: 1.7±0.1 g/cm3
  • Boiling Point: 835.4±65.0 °C at 760 mmHg
  • Melting Point: 197-202ºC
  • Flash Point: 293.5±27.8 °C

SGC2085

SGC2085 hydrochloride is a potent and selective inhibitor of coactivator associated arginine methyltransferase 1 (CARM1) with an IC50 of 50 nM. SGC2085 hydrochloride also selectively inhibits PRMT6 with an IC50 value of 5.2 μM, but not other PRMT proteins[1].

  • CAS Number: 1821908-49-9
  • MF: C19H24N2O2*ClH
  • MW: 348.8717
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

INCB059872

INCB059872 is a potent, orally active, selective and irreversible Lysine-Specific Demethylase 1 (LSD1) inhibitor. INCB059872 can be used for the research of myeloid leukemia[1].

  • CAS Number: 1802909-49-4
  • MF: C23H34N2O3
  • MW: 386.53
  • Catalog: Histone Demethylase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A