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 >
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 >
Autophagy LRRK2 ULK Mitophagy
Cell Cycle/DNA Damage >
Antifolate APC ATM/ATR Aurora Kinase Casein Kinase CDK Checkpoint Kinase (Chk) CRISPR/Cas9 Deubiquitinase DNA Alkylator/Crosslinker DNA-PK DNA/RNA Synthesis Eukaryotic Initiation Factor (eIF) G-quadruplex Haspin Kinase HDAC HSP IRE1 Kinesin LIM Kinase (LIMK) Microtubule/Tubulin Mps1 Nucleoside Antimetabolite/Analog p97 PAK PARP PERK Polo-like Kinase (PLK) PPAR RAD51 ROCK Sirtuin SRPK Telomerase TOPK Topoisomerase Wee1
Cytoskeleton >
Arp2/3 Complex Dynamin Gap Junction Protein Integrin Kinesin Microtubule/Tubulin Mps1 Myosin PAK
Epigenetics >
AMPK Aurora Kinase DNA Methyltransferase Epigenetic Reader Domain HDAC Histone Acetyltransferase Histone Demethylase Histone Methyltransferase JAK MicroRNA PARP PKC Sirtuin Protein Arginine Deiminase
GPCR/G Protein >
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ERK JNK KLF MAP3K MAP4K MAPKAPK2 (MK2) MEK Mixed Lineage Kinase MNK p38 MAPK Raf Ribosomal S6 Kinase (RSK)
Membrane Transporter/Ion Channel >
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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 >
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 >
Akt AMPK ATM/ATR DNA-PK GSK-3 MELK mTOR PDK-1 PI3K PI4K PIKfyve PTEN
PROTAC >
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Protein Tyrosine Kinase/RTK >
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
TGF-beta/Smad >
TGF-beta/Smad PKC ROCK TGF-β Receptor
Vitamin D Related >
VD/VDR
Others >
Androgen Receptor Aromatase Estrogen Receptor/ERR Progesterone Receptor Thyroid Hormone Receptor Others

GSK-J2

GSK-J2 is an isomer of GSK-J1 that does not have any specific activity. GSK-J1 is a potent inhibitor of H3K27me3/me2-demethylases JMJD3/KDM6B and UTX/KDM6A.

  • CAS Number: 1394854-52-4
  • MF: C22H23N5O2
  • MW: 389.45
  • Catalog: Histone Demethylase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

KX-01-191

KX-01-191, a Boronic Ester Precursor, is a potent PARP inhibitor[1].

  • CAS Number: 2211903-84-1
  • MF: C28H39N3OSn
  • MW: 552.34
  • Catalog: PARP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Chelerythrine chloride

Chelerythrine Chloride is a potent, cell-permeable inhibitor of protein kinase C, with an IC50 of 660 nM.

  • CAS Number: 3895-92-9
  • MF: C21H18ClNO4
  • MW: 383.825
  • Catalog: Autophagy
  • Density: 1.36g/cm3
  • Boiling Point: 711.4ºC at 760 mmHg
  • Melting Point: 195-205ºC
  • Flash Point: 219.3ºC

NMS-P515

NMS-P515 is a potent and stereospecific PARP-1 inhibitor, with an IC50 of 27 nM in hela cells. Anti-tumor activity[1].

  • CAS Number: 1262395-13-0
  • MF: C21H29N3O2
  • MW: 355.47
  • Catalog: PARP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

RET-IN-19

RET-IN-19 (compound 59) is a potent RET inhibitor, with IC50 values of 6.8 and 13.51 nM against RET-wt and RET V804M, respectively. RET-IN-19 shows anticancer activity. RET-IN-19 can be used for non-small cell lung cancer (NSCLC) research[1].

  • CAS Number: 2484919-71-1
  • MF: C28H28N6O4S
  • MW: 544.62
  • Catalog: Aurora Kinase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

JAK1-IN-8

JAK1-IN-8, a potent JAK1 inhibitor (IC50<500 nM), compound 28, extracted from patent WO2016119700A1[1].

  • CAS Number: 1973485-18-5
  • MF: C22H23FN4O3S
  • MW: 442.51
  • Catalog: JAK
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

RNAENFDRF

RNAENFDRF (βIIPKC624-632) is conjugated to the cell permeable peptide TAT47-57, which can be used to form an inhibitory peptide SAMβA. SAMβA, a rationally designed selective antagonist of Mfn1-βIIPKC association. SAMβA is a selective inhibitor of mitofusin 1-βIIPKC association improves heart failure outcome in rats[1].

  • CAS Number: 2429946-75-6
  • MF: C50H73N17O16
  • MW: 1168.22
  • Catalog: PKC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

LSD1-IN-20

LSD1-IN-20 (compound 1) is a potent dual non-covalent LSD1/G9a inhibitor, with Ki values of 0.44 and 0.68 μM, respectively. LSD1-IN-20 shows antiproliferative activity in THP-1 leukemia cells and MDA-MB-231 breast cancer cells, with IC50 (72 h) of 0.51 and 1.60 μM, respectively[1].

  • CAS Number: 1239589-91-3
  • MF: C27H38N6O2
  • MW: 478.63
  • Catalog: Histone Demethylase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Aprinocarsen sodium

Aprinocarsen (ISIS 3521) sodium, a specific antisense oligonucleotide inhibitor of protein kinase C-alpha (PKC-α). Aprinocarsen sodium is a 20-mer oligonucleotide, it regulates cell differentiation and proliferation. Aprinocarsen sodium inhibits the growth of human tumor cell lines in nude mice. Aprinocarsen sodium shows the value as a chemotherapeutic compound of human cancers[1].

  • CAS Number: 331257-53-5
  • MF: C196H230N68Na19O105P19S19
  • MW: 6852.85
  • Catalog: PKC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

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

JHDM-IN-1

JHDM-IN-1 (Compound 1) is a Jumonji C domain-containing HDMs (JHDM) inhibitor with IC50s of 3.4, 4.3, 5.9, 10 and 43 μM against JMJD2C, JMJD2A, JMJD2E, PHF8 and JMJD3, respectively[1].

  • CAS Number: 1310809-17-6
  • MF: C27H29N3O6
  • MW: 491.54
  • Catalog: Histone Demethylase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

N-Hydroxy-N'-(3-pyridinyl)octanediamide

Pyroxamide is a potent inhibitor of histone deacetylase 1 (HDAC1) with an ID50 of 100 nM. Pyroxamide can induce apoptosis and cell cycle arrest in leukemia.

  • CAS Number: 382180-17-8
  • MF: C13H19N3O3
  • MW: 265.308
  • Catalog: HDAC
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tubulin/HDAC-IN-1

Tubulin/HDAC-IN-1 is a dual tubulin and HDAC-IN-1 inhibitor through CH/π interaction with tubulin and hydrogen bond interaction with HDAC8. Tubulin/HDAC-IN-1 inhibits tubulin polymerization and selectively inhibits HDAC8 (IC50: 150 nM). Tubulin/HDAC-IN-1 has cytotoxicity against various human cancer cells, also arrests cell cycle in the G2/M phase and induces cell apoptosis. Tubulin/HDAC-IN-1 can be used in the research of hematologic and solid tumors such as neuroblastoma, leukemia[1].

  • CAS Number: 2413587-26-3
  • MF: C21H18N4O3
  • MW: 374.39
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

JAK3 Inhibitor VI

JI6 is a potent, selective and orally active FLT3 inhibitor, with IC50s of ∼40, 8, and 4 nM for FLT3-WT, FLT3-D835Y, and FLT3-D835H, respectively. JI6 also inhibits JAK3 and c-Kit, with IC50s of ∼250 and ∼500 nM, respectively. JI6 can be used for the research of acute myeloid leukemia[1].

  • CAS Number: 856436-16-3
  • MF: C19H17N3O4S
  • MW: 383.42100
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

OBP-801

Spiruchostatin A is a potent HDAC inhibitor with an IC50 value of 2 nM. Spiruchostatin A can induce apoptosis, has antitumor activity and may be used in leukemia studies[1][2].

  • CAS Number: 328548-11-4
  • MF: C20H31N3O6S2
  • MW: 473.607
  • Catalog: HDAC
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 865.5±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 477.3±34.3 °C

MOZ-IN-3

WM-8014 is an inhibitor of MOZ, a member of histone acetyltransferases, with an IC50 of 55 nM.

  • CAS Number: 2055397-18-5
  • MF: C20H17FN2O3S
  • MW: 384.42
  • Catalog: Histone Acetyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TC-A 2317 hydrochloride

TC-A 2317 hydrochloride is an orally active Aurora A kinase inhibitor (Ki=1.2 nM). TC-A 2317 hydrochloride exhibits excellent selectivity to Aurora B kinase (Ki=101 nM) and other 60 kinases, good cell permeability and good PK profile. Antitumor activity[1].

  • CAS Number: 1245907-03-2
  • MF: C19H29ClN6O
  • MW: 392.92600
  • Catalog: Aurora Kinase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MT6378

MT 63-78 is a specific and potent direct AMPK activator with an EC50 of 25 μM. MT 63–78 also induces cell mitotic arrest and apoptosis. MT 63-78 blocks prostate cancer growth by inhibiting the lipogenesis and mTORC1 pathways. MT 63-78 has antitumor effects[1].

  • CAS Number: 1179347-65-9
  • MF: C21H14N2O2
  • MW: 326.35
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

HDAC1-IN-4

HDAC1-IN-4 (JX34) is a potent Plasmodium falciparum HDAC1 inhibitor shows antimalarial activity (IC50 < 5 nM) and lower cytotoxicity[1].

  • CAS Number: 2482998-39-8
  • MF: C21H24BrClN6O2
  • MW: 507.81
  • Catalog: HDAC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SRTCX1002

SRTCX1002 (SRTCX-1002) is a small molecule activator of SIRT1 (STAC) with EC1.5 of 0.4 uM, enhances deacetylation of cellular p65 protein with IC50 of 0.84 uM in cellular p65 acetylation assay; suppresses TNFα-induced NF-κB transcriptional activation and reduction of LPS-stimulated TNFα secretion in a SIRT1-dependent manner.

  • CAS Number: 1203479-63-3
  • MF: C21H19N5O2S
  • MW: 405.473
  • Catalog: Sirtuin
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GSK1070916

GSK-1070916 is a potent and selective ATP-competitive inhibitor of aurora B and aurora C with Kis of 0.38 and 1.5 nM, respectively, and is >250- fold selective over Aurora A.

  • CAS Number: 942918-07-2
  • MF: C30H33N7O
  • MW: 507.629
  • Catalog: Aurora Kinase
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

γ-Oryzanol

γ-Oryzanol is a potent DNA methyltransferases (DNMTs) inhibitor in the striatum of mice. γ-Oryzanol significantly inhibits the activities of DNMT1 (IC50=3.2 μM), DNMT3a (IC50=22.3 μM).

  • CAS Number: 11042-64-1
  • MF: C40H58O4
  • MW: 602.886
  • Catalog: DNA Methyltransferase
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 663.2±40.0 °C at 760 mmHg
  • Melting Point: 135-137°C
  • Flash Point: 193.8±20.8 °C

(±)-1,2-Diolein

(±)-1,2-Diolein (1,2-Dioleoyl-rac-glycerol) is a PKC activator[1].

  • CAS Number: 2442-61-7
  • MF: C39H72O5
  • MW: 620.99
  • Catalog: PKC
  • Density: 0.9±0.1 g/cm3
  • Boiling Point: 670.8±35.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 186.3±19.4 °C

Ainsliadimer C

Ainsliadimer C, a potential activator of SIRT1, ameliorates inflammatory responses in adipose tissue.

  • CAS Number: 1365995-73-8
  • MF: C30H36O7
  • MW: 508.60
  • Catalog: Sirtuin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Sangivamycin

Sangivamycin (NSC 65346), a nucleoside analog, is a potent inhibitor of protein kinase C (PKC) with an Ki of 10 μM. Sangivamycin has potent antiproliferative activity against a variety of human cancers[1][2].

  • CAS Number: 18417-89-5
  • MF: C12H15N5O5
  • MW: 309.28
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: 880.6ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 486.4ºC

PKC-theta inhibitor 1

PKC-theta inhibitor 1 is the PKCθ inhibitor with an Ki value of 6 nM, inhibits IL-2 production in vivo with an IC50 of 0.19 μM. PKC-theta inhibitor 1 demonstrates a reduction of symptoms in a mouse model of multiple sclerosis[1].

  • CAS Number: 1160501-81-4
  • MF: C17H15F3N4O
  • MW: 348.32
  • Catalog: PKC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Namoline

Namoline, a γ-pyrone, is a selective and reversible Lysine-specific demethylase 1 (LSD1) inhibitor with an IC50 of 51 μM in a HRP-coupled enzymatic assay. Namoline impairs LSD1 demethylase activity and blocks cell proliferation. Namoline has the potential for androgen-dependent prostate cancer research[1].

  • CAS Number: 342795-11-3
  • MF: C10H3ClF3NO4
  • MW: 293.58
  • Catalog: Histone Demethylase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

LMK 235

LMK-235 is a potent and selective HDAC4/5 inhibitor, inhibits HDAC5, HDAC4, HDAC6, HDAC1, HDAC2, HDAC11 and HDAC8, with IC50s of 4.22 nM, 11.9 nM, 55.7 nM, 320 nM, 881 nM, 852 nM and 1278 nM, respectively, and is used in cancer research.

  • CAS Number: 1418033-25-6
  • MF: C15H22N2O4
  • MW: 294.346
  • Catalog: HDAC
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ZIKV-IN-3

ZIKV-IN-3 (compound 5a), an andrographolide derivatives, is a potent ZIKV NS5 methyl transferase (MTase) inhibitor with an IC50 value of 18.34 μM. ZIKV-IN-3 inhibits ZIKV replication and infection. ZIKV-IN-3 can be used in research of Zika virus (ZIKV)[1].

  • CAS Number: 947699-46-9
  • MF: C39H41NO4
  • MW: 587.75
  • Catalog: DNA Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Cenisertib

Cenisertib (AS-703569) is a multi-kinase inhibitor that blocks the activity of Aurora-kinase-A/B, ABL1, AKT, STAT5 and FLT3. Cenisertib induces major growth-inhibitory effects by blocking the activity of several different molecular targets in neoplastic mast cells (MC)[1]. Cenisertib inhibits tumor growth in xenograft models of pancreatic, breast, colon, ovarian, and lung tumors and leukemia[2].

  • CAS Number: 871357-89-0
  • MF: C24H30FN7O
  • MW: 451.540
  • Catalog: Aurora Kinase
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 708.3±70.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 382.2±35.7 °C