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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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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PI3K/Akt/mTOR >
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PROTAC >
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Ack1 ALK Bcr-Abl BMX Kinase Btk c-Fms c-Kit c-Met/HGFR Discoidin Domain Receptor DYRK EGFR Ephrin Receptor FAK FGFR FLT3 IGF-1R Insulin Receptor IRAK Itk PDGFR PKA Pyk2 ROS Src Syk TAM Receptor Trk Receptor VEGFR
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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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TPOP146

TPOP146 is a selective CBP/P300 benzoxazepine bromodomain inhibitor with Kd values of 134 nM and 5.02 μM for CBP and BRD4.

  • CAS Number: 2018300-62-2
  • MF: C27H35N3O5
  • MW: 481.584
  • Catalog: Epigenetic Reader Domain
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 641.8±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 341.9±31.5 °C

Oroxin A

Oroxin A is the major component of an ethanol-water Oroxylum indicum (L.) Kurz (Bignoniaceae) seed extract (OISE), activates peroxisome proliferator-activated receptor γ (PPARγ) by docking into the PPARγ protein ligand-binding domain. Oroxin A exhibits an inhibitory activity against α-glucosidase and an antioxidant capacity[1]. Oroxin A exerts anti-breast cancer effects by inducing ER stress-mediated senescence[2].

  • CAS Number: 57396-78-8
  • MF: C21H20O10
  • MW: 432.378
  • Catalog: PARP
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 784.0±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 279.0±26.4 °C

OTS193320

OTS193320 (OTS-193320) is a potent inhibitor of protein methyltransferase SUV39H2 with IC50 of 22.2 nM; significantly reduces global H3K9 tri-methylation (H3K9me3) in breast cancer cells in vitro and induces apoptotic cell death, attenuates γ-H2AX levels in combination with doxorubicin compared with the DOX treatment alone, and causes a significant reduction in breast cancer cell viability when compared to the treatment with a single agent; causes growth suppressive effect of SUV39H2-positive A549 lung cancer cells with IC50 of 0.38 uM.

  • CAS Number: 2093401-33-1
  • MF: C28H30ClN5O4
  • MW: 536.029
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

DB0614

DB0614 (Example 21) is a bifunctional compound targeted protein degradation of kinases. DB0614 degrades AAK1, AURKA, BMP2K, CAMKK1, CDK16, CML, CDK6, EIF2AK2, FER, GAK, LCK, LIMK2, MAP3KH, MAPK8, MAPK9, NEK9, PLK4, PTK2B, SIK2, STK17A, STK17B, ULK1, ULK3, and WEE1. DB0614 can be used for research of disease or disorder mediated by aberrant kinase activity[1].

  • CAS Number: 2769753-47-9
  • MF: C41H42N8O7S2
  • MW: 822.95
  • Catalog: Ferroptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

XF056-132

XF056-132 is a potent WDR5 (WD40 repeat domain protein 5) PROTAC degrader[1].

  • CAS Number: 2407450-73-9
  • MF: C51H57F4N9O7S
  • MW: 1016.11
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

RBN012759

RBN012759 is a potent, selective and orally active inhibitor of PARP14, with an IC50 of <3 nM. RBN012759 displays 300-fold selectivity over the monoPARPs and 1000-fold selectivity over the polyPARPs. RBN012759 decreases pro-tumor macrophage function and elicits inflammatory responses in tumor explants[1].

  • CAS Number: 2360851-29-0
  • MF: C19H23FN2O3S
  • MW: 378.46
  • Catalog: PARP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BRD 9757

BRD9757 is a potent, capless and selective HDAC6 inhibitor with an IC50 of 30 nM. BRD9757 shows excellent selectivity toward HDAC6 versus the class I (>20-fold) and class II (>400-fold) HDACs[1].

  • CAS Number: 1423058-85-8
  • MF: C6H9NO2
  • MW: 127.14100
  • Catalog: HDAC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Bempedoic Acid

ETC-1002 is an activator of hepatic AMP-activated protein kinase (AMPK).

  • CAS Number: 738606-46-7
  • MF: C19H36O5
  • MW: 344.48600
  • Catalog: AMPK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tyk2-IN-9

Tyk2-IN-9 (Compound 26) is a selective Tyk-2 inhibitor with IC50s of 0.076 and 1.8 nM for TYK2-JH2 and JAK1-JH2, respectively. Tyk2-IN-9 can be used for the research of inflammatory or autoimmune disease[1].

  • CAS Number: 2694816-85-6
  • MF: C21H25N9O3
  • MW: 451.48
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Psychosine-d5

Psychosine-d5 is deuterium labeled Psychosine. Psychosine, a substrate of the galactocerebrosidase (GALC) enzyme, is a potential biomarker for Krabbe disease. Psychosine is a highly cytotoxic lipid, capable of inducing cell death in a wide variety of cell.

  • CAS Number: 2260670-12-8
  • MF: C24H42D5NO7
  • MW: 466.66
  • Catalog: PKC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SIRT2-IN-9

SIRT2-IN-9 (compound 12) is a selective inhibitor of SRIT2 with an IC50 value of 1.3 μM. SIRT2-IN-9 inhibits proliferative activity of MCF-7 breast cancer cells. SIRT2-IN-9 can be used for the research of cancer[1].

  • CAS Number: 522650-91-5
  • MF: C21H22N6OS2
  • MW: 438.57
  • Catalog: Sirtuin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PROTAC BRD4 Degrader-15

PROTAC BRD4 Degrader-15 is a potent BRD4 degrader, with IC50s of 7.2 nM and 8.1 nM for BRD4 BD1 and BD2, respectively. PROTAC BRD4 Degrader-15 is capable of potently degrading the BRD4 protein in PC3 prostate cancer cells[1].

  • CAS Number: 2417370-67-1
  • MF: C57H62F2N10O10S2
  • MW: 1149.29
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

1,2-Didecanoylglycerol

1,2-Didecanoylglycerol, a synthetic diacylglycerol, is metabolized by platelets to 1,2-didecanoylphosphatidic acid (PA10) and activates protein kinase C (PKC)[1][2].

  • CAS Number: 17863-69-3
  • MF: C23H44O5
  • MW: 400.59
  • Catalog: PKC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

H-PHE-LYS-LYS-SER-PHE-LYS-LEU-NH2

FKKSFKL-NH2 is a protein kinase C-selective peptide. FKKSFKL-NH2 can be used for the research of various biochemical[1].

  • CAS Number: 137168-33-3
  • MF: C45H73N11O8
  • MW: 896.130
  • Catalog: PKC
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 1275.7±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 725.3±34.3 °C

GSK232

GSK232 is a highly selective, cellularly penetrant CECR2 inhibitor with excellent physicochemical properties.

  • CAS Number: 2702984-69-6
  • MF: C21H27ClN6O3S
  • MW: 479.00
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

1-Stearoyl-2-arachidonoyl-sn-glycerol

1-Stearoyl-2-arachidonoyl-sn-glycerol is a diacylglycerol (DAG) containing polyunsaturated fatty acids. 1-Stearoyl-2-arachidonoyl-sn-glycerol can activate PKC. 1-Stearoyl-2-arachidonoyl-sn-glycerol also can augment nonselective cation channel (NSCC) activity[1][2].

  • CAS Number: 65914-84-3
  • MF: C41H72O5
  • MW: 645.007
  • Catalog: PKC
  • Density: 0.9±0.1 g/cm3
  • Boiling Point: 689.2±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 190.3±25.0 °C

PF-03622905

PF-03622905 is a potent and ATP-competitive PKC inhibitor with IC50s of 5.6 nM, 14.5 nM, 13 nM, 37.7 nM, and 74.1 nM for PKCα, PKCβI, PKCβII, PKCγ, and PKCθ, respectively. PF-03622905 shows high specificity for PKC over other protein kinases[1].

  • CAS Number: 1072100-15-2
  • MF: C24H35N7O3
  • MW: 469.58
  • Catalog: PKC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

HDAC6-IN-10

HDAC6-IN-10 is a highly selective HDAC6 inhibitor with the IC50 of 0.73 nM. HDAC6-IN-10 has 144~10941-fold selectivity over other HDAC isoforms. HDAC6-IN-10 shows anti-proliferative activities against multiple myeloma cells[1].

  • CAS Number: 2408286-73-5
  • MF: C21H20N4O4
  • MW: 392.41
  • Catalog: HDAC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BRD4-BD1/2-IN-2

BRD4-BD1/2-IN-2 is a potent BRD4 BD2 inhibitor with IC50s of <0.5 nM and <300 nM for BRD4 BD2 and BRD4 BD1, respectively (WO2021233371A1, compound 2)[1].

  • CAS Number: 2743464-27-7
  • MF: C30H33N5O4
  • MW: 527.61
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

1-Oleoyl-2-acetyl-rac-glycerol

1-Oleoyl-2-acetyl-sn glycerol is a synthetic, cell permeable diacylglycerol analog. 1-Oleoyl-2-acetyl-sn glycerol activates calcium-dependent protein kinase C (PKC) and induces the superoxide-production.

  • CAS Number: 86390-77-4
  • MF: C23H42O5
  • MW: 398.577
  • Catalog: PKC
  • Density: 1.0±0.1 g/cm3
  • Boiling Point: 490.0±15.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 152.3±13.9 °C

MDL-811

MDL-811, an allosteric SIRT6 activator, significantly activates SIRT6 histone H3 deacetylation (H3K9Ac, H3K18Ac, and H3K56Ac). MDL-811 could be used in the study of colorectal cancer[1].

  • CAS Number: 2275619-98-0
  • MF: C25H25BrCl2FN3O5S2
  • MW: 681.42
  • Catalog: Sirtuin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PRMT5-IN-17

PRMT5-IN-17 (Compound 6) is a PRMT5 inhibitor with anti-tumor activity. PRMT5 is a type of protein arginine methyltransferase, and is a new anti-tumor target related to epigenetic modification[1].

  • CAS Number: 2755304-03-9
  • MF: C26H33N7O2
  • MW: 475.59
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

NCGC00247743

NCGC00247743 is a histone lysine demethylase KDM4 inhibitor.

  • CAS Number: 1435192-04-3
  • MF: C24H29N3O2
  • MW: 391.51
  • Catalog: Histone Demethylase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

UCN-02

UCN-02 (7-epi-Hydroxystaurosporine) is a selective protein kinase C (PKC) inhibitor produced by Streptomyces strain N-12, with IC50s of 62 nM and 250 nM for PKC and protein kinase A (PKA), respectively. UCN-02 (7-epi-Hydroxystaurosporine) displays cytotoxic effect on the growth of HeLa S3 cells[1][2].

  • CAS Number: 121569-61-7
  • MF: C28H26N4O4
  • MW: 482.537
  • Catalog: PKC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SK-575

SK-575 is a highly potent and specific proteolysis-targeting chimera (PROTAC) degrader of PARP1. SK-575 potently inhibits the growth of cancer cells bearing BRCA1/2 mutations. SK-575 inhibits cell growth in MDA-MB-436 and Capan-1 cells, with IC50 values of 19 ± 6 nM and 56 ± 12 nM, respectively[1].

  • CAS Number: 2523016-96-6
  • MF: C47H53FN8O8
  • MW: 876.97
  • Catalog: PARP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Hinokitiol

Hinokitiol is a component of essential oils isolated from Chymacyparis obtusa, reduces Nrf2 expression, and decreases DNMT1 and UHRF1 mRNA and protein expression, with anti-infective, anti-oxidative, and anti-tumor activities.

  • CAS Number: 499-44-5
  • MF: C10H12O2
  • MW: 164.201
  • Catalog: DNA Methyltransferase
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 303.4±35.0 °C at 760 mmHg
  • Melting Point: 50-52 °C(lit.)
  • Flash Point: 128.1±18.5 °C

BAY-3827

BAY-3827 is a potent and selective AMPK inhibitor with IC50 values of 1.4 nM at low (10 µM ATP concentration) and 15 nM at high (2 mM ATP concentration). BAY-3827 shows over 500-fold selectivity for most of the 331 kinases. BAY-3827 prevents phosphorylation of acetyl-CoA carboxylase 1 and shows strongest anti-proliferative activity in androgen-dependent prostate cancer cell lines[1].

  • CAS Number: 2377576-35-5
  • MF: C27H25FN6O
  • MW: 468.53
  • Catalog: AMPK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

4-Phenylbutyric acid-d2

4-Phenylbutyric acid-d2 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.

  • CAS Number: 461391-24-2
  • MF: C10H8D4O2
  • MW: 168.22600
  • Catalog: HDAC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

cGAS inhibitor 467

GSK467 is a selective KDM5 (JARID1) inhibitor with a Ki of 10 nM for KDM5B, shows 180-fold selectivity for KDM4C and no measurable inhibitory effects toward KDM6 or other Jumonji family members[1].

  • CAS Number: 1628332-52-4
  • MF: C17H13N5O2
  • MW: 319.32
  • Catalog: Histone Demethylase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PKC-IN-4

PKC-IN-4 (compound 7l) is a potent and orally active aPKC inhibitor with an IC50 of 0.52 µM. PKC-IN-4 inhibits TNF-α induced NF-κB activity in vitro. PKC-IN-4 blocks VEGF- and TNFα-induced permeability across the retinal vasculature[1].

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