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 >
Arenavirus Bacterial CMV Enterovirus Filovirus Fungal HBV HCV HIV HSV Influenza Virus Parasite Reverse Transcriptase RSV SARS-CoV
Antibody-drug Conjugate >
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Apoptosis >
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Autophagy >
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Metabolic Enzyme/Protease >
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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NF-κB >
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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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Staurosporine

Staurosporine is a potent and non-selective inhibitor of protein kinases with IC50s of 6 nM, 15 nM, 2 nM, and 3 nM for PKC, PKA, c-Fgr, and Phosphorylase kinase respectively.

  • CAS Number: 62996-74-1
  • MF: C28H26N4O3
  • MW: 466.531
  • Catalog: PKC
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 677.5±55.0 °C at 760 mmHg
  • Melting Point: 270ºC
  • Flash Point: 363.6±31.5 °C

Alisertib (MLN8237)

Alisertib (MLN 8237) is a selective Aurora A inhibitor with an IC50 of 1.2 nM.

  • CAS Number: 1028486-01-2
  • MF: C27H20ClFN4O4
  • MW: 518.924
  • Catalog: Autophagy
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 729.1±70.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 394.8±35.7 °C

Igermetostat

Igermetostat is EZH2 inhibitor, used in cancer research in vivo and in vitro[1].

  • CAS Number: 2409538-60-7
  • MF: C32H46N4O4
  • MW: 550.73
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Menin-MLL inhibitor 20

Menin-MLL inhibitor 20 is an irreversible menin-MLL interaction inhibitor with antitumor activities (WO2020142557A1, compound 6)[1].

  • CAS Number: 2448173-47-3
  • MF: C33H40N8O4
  • MW: 612.72
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Epsilon-V1-2

Epsilon-V1-2 (ε-V1-2), a PKCε-derived peptide, is a selective PKCε inhibitor. Epsilon-V1-2 inhibits the translocationof PKCε, but not α-, β-, and δPKC[1].

  • CAS Number: 182683-50-7
  • MF: C37H65N9O13
  • MW: 843.964
  • Catalog: PKC
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 1280.1±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 728.0±34.3 °C

SIRT6-IN-5

SIRT6-IN-2 (Compound 5) is a selective SIRT6 inhibitor (IC50: 34 μM). SIRT6-IN-2 increases acetylation of H3K9 and increases glucose uptake in cultured cells. SIRT6-IN-2 also reduces T cell proliferation. SIRT6-IN-2 has immunosuppressive and chemosensitizing effects[1].

  • CAS Number: 891002-11-2
  • MF: C19H14N2O6
  • MW: 366.32
  • Catalog: Sirtuin
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 461.6±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 233.0±28.7 °C

6-Isopropyl-7-oxo-5-phenyl-4,7-dihydropyrazolo[1,5-a]pyrimidine-3-carbonitrile hydrochloride

CPI-455 hydrochloride is a specific, pan-KDM5 inhibitor with an IC50 of 10 nM for KDM5A. CPI-455 hydrochloride mediates KDM5 inhibition, elevates global levels of H3K4me3, and decreases the number of drug-tolerant persister cancer cells in multiple cancer cell line models treated with standard chemotherapy or targeted agents[1].

  • CAS Number: 2095432-28-1
  • MF: C16H15ClN4O
  • MW: 314.770
  • Catalog: Histone Demethylase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Broussonin E

Broussonin E is a phenolic compound and shows anti-inflammatory activity. Broussonin E can suppress inflammation by modulating macrophages activation statevia inhibiting the ERK and p38 MAPK and enhancing JAK2-STAT3 signaling pathway. Broussonin E can be used for the research of inflammation-related diseases such as atherosclerosis[1].

  • CAS Number: 90902-21-9
  • MF: C17H20O4
  • MW: 288.338
  • Catalog: JAK
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 464.9±40.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 235.0±27.3 °C

Anemonine

Anemonin (Pulsatilla camphor), a selective iNOS inhibitor, is also a PKC-θ inhibitor. Anemonin can significantly inhibit the translation or protein stability of PKC-θ protein. Anemonin also ameliorates dextran sodium sulfate-induced acute ulcerative colitis (UC) in mice. Anemonin can be used in the research of inflammation-related diseases[1][2].

  • CAS Number: 508-44-1
  • MF: C10H8O4
  • MW: 192.17
  • Catalog: PKC
  • Density: 1.45
  • Boiling Point: 535.7ºC at 760 mmHg
  • Melting Point: 157-158ºC
  • Flash Point: 300.7ºC

Valemetostat tosylate

Valemetostat tosylate (DS-3201 tosylate) is a first-in-class EZH1/2 dual inhibitor, used in the research of relapsed/refractory peripheral T-cell lymphoma[1].

  • CAS Number: 1809336-93-3
  • MF: C33H42ClN3O7S
  • MW: 660.22
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

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

A-769662

A-769662 is a potent, reversible AMPK activator with EC50 of 0.8 μM.

  • CAS Number: 844499-71-4
  • MF: C20H12N2O3S
  • MW: 360.386
  • Catalog: AMPK
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 630.1±55.0 °C at 760 mmHg
  • Melting Point: 268.39° C
  • Flash Point: 334.9±31.5 °C

BamHI Methyltransferase

BamHI Methyltransferase is a DNA methyltransferase which modifies the underlined cytosine (GGATCC)[1].

  • CAS Number: 92228-39-2
  • MF:
  • MW:
  • Catalog: DNA Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Acetaminophen-13C2,15N

Acetaminophen-13C2,15N is the 13C and 15N labeled Acetaminophen[1]. Acetaminophen (Paracetamol) is a selective cyclooxygenase-2 (COX-2) inhibitor with an IC50 of 25.8 μM;is a widely used antipyretic and analgesic agent[2][3][4]. Acetaminophen is a potent hepatic N-acetyltransferase 2 (NAT2) inhibitor[5].

  • CAS Number: 360769-21-7
  • MF: C613C2H915NO2
  • MW: 154.14
  • Catalog: Bacterial
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

UNC 0642

UNC0642 is a potent and selective G9a/GLP inhibitor, with an IC50 of less than 2.5 nM.

  • CAS Number: 1481677-78-4
  • MF: C29H44F2N6O2
  • MW: 546.695
  • Catalog: Histone Methyltransferase
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 679.2±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 364.6±34.3 °C

Ricolinostat (ACY-1215)

Ricolinostat (ACY-1215) is a potent and selective HDAC6 inhibitor, with an IC50 of 5 nM. ACY-1215 also inhibits HDAC1, HDAC2, and HDAC3 with IC50s of 58, 48, and 51 nM, respectively.

  • CAS Number: 1316214-52-4
  • MF: C24H27N5O3
  • MW: 433.503
  • Catalog: HDAC
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

α7 nAchR-JAK2-STAT3 agonist 1

α7 nAchR-JAK2-STAT3 agonist 1 is a potent α7 nAchR-JAK2-STAT3 agonist, with an IC50 value of 0.32 μM for nitric oxide (NO). α7 nAchR-JAK2-STAT3 agonist 1 effectively suppresses the expression of iNOS, IL-1β, and IL-6 in murine RAW264.7 macrophages. α7 nAchR-JAK2-STAT3 agonist 1 can inhibit LPS-induced NO release, NF-κB activation and cytokine production. α7 nAchR-JAK2-STAT3 can be used for researching sepsis[1].

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

A-3 hydrochloride

A-3 hydrochloride is a potent, cell-permeable, reversible, ATP-competitive non-selective antagonist of various kinases. It against PKA (Ki=4.3 µM), casein kinase II (Ki=5.1 µM) and myosin light chain kinase (MLCK) (Ki=7.4 µM). A-3 hydrochloride also inhibits PKC and casein kinase I with Ki values of 47 µM and 80 µM, respectively[1].

  • CAS Number: 78957-85-4
  • MF: C12H14Cl2N2O2S
  • MW: 321.22300
  • Catalog: Casein Kinase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: 173-176ºC
  • Flash Point: N/A

PF-06885249

PF-249 is a potent, selective AMPK β1-containing complexes activator; increases the phosphorylation of the AMPK substrate ACC at S79 with EC50 of 296 nM, potently inhibits de novo lipogenesis (IC50=15 nM) in primary rat hepatocytes.

  • CAS Number: 1467059-70-6
  • MF: C17H16ClN3O3
  • MW: 345.783
  • Catalog: AMPK
  • 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

HL271

HL271, a chemical derivative of metformin (HY-B0627), is a potent AMPK activator that increases AMPK phosphorylation. HL271 attenuates aging-associated cognitive impairment[1][2].

  • CAS Number: 1422365-52-3
  • MF: C13H17ClF3N5O
  • MW: 351.76
  • Catalog: AMPK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(E/Z)-AG490

(E/Z)-AG490 ((E/Z)-Tyrphostin AG490) is a racemic compound of (E)-AG490 and (Z)-AG490 isomers. (E)-AG490 (HY-12000) is a tyrosine kinase inhibitor that inhibits EGFR, Stat-3 and JAK2/3.

  • CAS Number: 134036-52-5
  • MF: C17H14N2O3
  • MW: 294.30500
  • Catalog: JAK
  • Density: 1.337g/cm3
  • Boiling Point: 615.2ºC at 760mmHg
  • Melting Point: 215ºC
  • Flash Point: 325.9ºC

ME 0328

ME0328 is a potent and selective ARTD3/PARP3 inhibitor with an IC50 of 0.89±0.28 μM.

  • CAS Number: 1445251-22-8
  • MF: C19H19N3O2
  • MW: 321.37300
  • Catalog: PARP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CBB1007

CBB1007 is a cell-permeable amidino-guanidinium compound that acts as a potent, reversible and substrate competitive LSD1 selective inhibitor (IC50 = 5.27 μM for hLSD1).IC50 Value: 5.27 uMTarget: hLSD1CBB1007 efficiently can block LSD1-mediated demethylation of H3K4Me2 and H3K4Me (IC50 ≤ 5 μM) with no effect on H3K4Me3 and H3K9Me2, and LSD2 and JARID1A activities. Increases H3K4Me2 and H3K4Me contents (IC50 ≤ 5 μM), and causes activation of epigenetically suppressed CHRM4/M4-ArchR and SCN3A genes in F9 cells (IC50 ≤ 3.74 μM). CBB1007 was Shown to preferentially arrest the growth of pluripotent tumors with minimal effect on non-pluripotent cancer or normal somatic cells (IC50 ≥ 100 μM).

  • CAS Number: 1379573-92-8
  • MF: C27H34N8O4
  • MW: 534.610
  • Catalog: Histone Demethylase
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 763.8±70.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 415.7±35.7 °C

Iniparib (BSI-201)

Iniparib (BSI-201) is an irreversible inhibitor of PARP1, used in the research of triple negative breast cancer.

  • CAS Number: 160003-66-7
  • MF: C7H5IN2O3
  • MW: 292.031
  • Catalog: PARP
  • Density: 2.1±0.1 g/cm3
  • Boiling Point: 344.8±32.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 162.3±25.1 °C

Go6976

Go6976 is a Protein Kinase C (PKC) inhibitor, with an IC50 of 20 nM.

  • CAS Number: 136194-77-9
  • MF: C24H18N4O
  • MW: 378.426
  • Catalog: PKC
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 652.3±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 348.3±31.5 °C

Sinefungin

Sinefungin is a potent inhibitor of virion mRNA(guanine-7-)-methyltransferase, mRNA(nucleoside-2'-)-methyltransferase, and viral multiplication[1]. Sinefungin, a SET7/9 inhibitor, ameliorates renal fibrosis by inhibiting H3K4 methylation [2].

  • CAS Number: 58944-73-3
  • MF: C15H23N7O5
  • MW: 381.39
  • Catalog: Histone Methyltransferase
  • Density: 1.9±0.1 g/cm3
  • Boiling Point: 783.2±70.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 427.5±35.7 °C

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

MS67

MS67 is a potent and selective WD40 repeat domain protein 5 (WDR5) degrader with a Kd of 63 nM. MS67 is inactive against other protein methyltransferases, kinases, GPCRs, ion channels, and transporters. MS67 shows potent acticancer effects[1].

  • CAS Number: 2407452-77-9
  • MF: C52H59F4N9O7S
  • MW: 1030.14
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

LSD1-IN-5

LSD1-IN-5 (Compound 4e) is a potent and reversible inhibitor of lysine-specific demethylase 1 (LSD1), with an IC50 of 121 nM. LSD1-IN-5 increases dimethylated Lys4 of histone H3, shows no effect on expression of LSD1[1].

  • CAS Number: 2035912-55-9
  • MF: C15H13BrN2O3
  • MW: 349.18
  • Catalog: Histone Demethylase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A