Epigenetics
Epigenetics research delves into the molecular mechanisms that control gene expression and cellular traits without altering the underlying DNA sequence. One crucial aspect of this field is the role of small molecules, which act as powerful regulators of epigenetic modifications. These small compounds, typically comprising a few dozen to a few hundred atoms, have emerged as essential tools in understanding and manipulating the epigenome.
- DNA Methylation Inhibitors: Small molecules like 5-azacytidine and 5-aza-2'-deoxycytidine are DNA methyltransferase inhibitors. They block the addition of methyl groups to DNA, leading to DNA demethylation. This can reactivate silenced genes, potentially offering therapeutic avenues for conditions like cancer.
- HDAC inhibitors: HDACs remove acetyl groups from histone proteins, contributing to gene repression. Small molecule HDAC inhibitors, such as Vorinostat and Romidepsin, can reverse this process by increasing histone acetylation, allowing genes to be more accessible for transcription. These inhibitors are being explored for cancer therapy and other conditions.
- Histone Methyltransferase Inhibitors: Small molecules like GSK126 inhibit specific histone methyltransferases, affecting histone methylation patterns. This can alter gene expression, making them promising candidates for cancer and other diseases with epigenetic dysregulation.
- RNA Modulators: Small molecules can also target non-coding RNAs involved in epigenetic regulation. For instance, small molecules called small interfering RNAs (siRNAs) can be designed to target and degrade specific long non-coding RNAs, influencing gene expression.
- Epigenetic Reader Domain Inhibitors: These small molecules target proteins that recognize and bind to specific epigenetic marks. Examples include inhibitors of bromodomain-containing proteins (BET inhibitors), which can disrupt gene regulation by interfering with protein-DNA interactions.
Small molecules in epigenetics research not only provide insights into the fundamental biology of gene regulation but also hold immense promise for developing novel therapeutics. Their ability to selectively modulate specific epigenetic marks and pathways has led to ongoing clinical trials and drug development efforts for various diseases, including cancer, neurological disorders, and inflammatory conditions. Understanding and harnessing the power of these small molecules is at the forefront of modern epigenetics research, offering new hope for precision medicine and targeted therapies.
3 key components involved in the regulation of epigenetic modifications
Epigenetics Writer
Epigenetics writers are enzymes responsible for adding chemical marks or modifications to DNA or histone proteins. These marks include DNA methylation (addition of methyl groups to DNA) and histone modifications (such as acetylation, methylation, phosphorylation, etc.).
Epigenetics Reader
Function: Epigenetics readers are proteins that can recognize and bind to specific epigenetic marks on DNA or histones. These reader proteins interpret the epigenetic code and facilitate downstream cellular processes, such as gene activation or repression.
Epigenetics Eraser
Function: Epigenetics erasers are enzymes responsible for removing or reversing epigenetic marks on DNA or histones. This process allows for the dynamic regulation of gene expression and the resetting of epigenetic states during various stages of development and in response to environmental changes.
Catalog No.
Product Name
Application
Product Information
Citations
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JAK2/STAT3 inhibitor
Cucurbitacin I, Cucumis sativus L. has been found to suppress levels of phosphotyrosine Stat3 (signal transducer and activator of transcription 3) in v-Src-transformed NIH 3T3 cells. -
MBT Domain (L3MBTL1) Inhibitor
UNC 926 is a methyl lysine reader domain inhibitor. -
PIM-1 Inhibitor
PIM-1 inhibitor 2 is a potent Pim-1 kinase inhibitor (Ki = 91 nM). -
Pim-1 Kinase Inhibitor
TCS PIM-1 1 is a potent and selective ATP-competitive Pim-1 kianse inhibitor with IC50 of 50 nM, displays good selectivity over Pim-2 and MEK1/MEK2(IC50s >20,000 nM). -
PARP-1 inhibitor
BYK204165 is a cell-permeable isoquinolinedione compound that potently and selectively inhibits poly (ADP-ribose) polymerase 1 (PARP1). -
PARP1 Inhibitor
EB 47 is a potent inhibitor of PARP1 with IC50 of 45 nM. - Calcineurin inhibitory peptide is a selective inhibitor of Ca2+-calmodulin-dependent protein phosphatase (calcineurin) (IC50 ~ 10 uM). Does not inhibit PP1, PP2A or CaM kinase II (IC50 > 100 mM).
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PTPMT1 inhibitor
Alexidine is an alkyl bis(biguanide) antiseptic which has been used in mouthwashes to eliminate plaque forming microorganisms. -
HDAC6 inhibitor
TCS HDAC6 20b, selective inhibitor of histone deacetylase 6 (HDAC6). Inhibits HCT116 growth in combination with taxol. Also inhibits growth of MCF-7 cells stimulated by estrogen. -
PTP1B Inhibitor
TCS 401 is a selective inhibitor of protein-tyrosine phosphatase 1B (PTP1B) (Ki values are 0.29, 59, 560, 1100, > 2000, > 2000 and > 2000 μM for PTP1B, CD45 D1D2, PTPβ, PTPε D1, SHP-1, PTPα D1 and LAR D1D2 respectively). -
Calcineurin inhibitor
Cyclosporine is a calcineurin phosphatase pathway inhibitor, used as an immunosuppressant drug to prevent rejection in organ transplantation. -
endothelial barrier enhancer
Ginsenoside Rk1, one of the main elements of Sung Ginseng, has been confirmed as a new endothelial barrier enhancer recently and has anti-cancer activity. -
HDAC/ACE inhibitor
Sinapinic acid (Sinapic acid) is a phenolic compound isolated from Hydnophytum formicarum Jack. Rhizome, acts as an inhibitor of HDAC, with an IC50 of 2.27 mM, and also inhibits ACE-I activity. Sinapinic acid posssess potent anti-tumor activity, induces apoptosis of tumor cells. -
LSD1/BHC110 & MAO inhibitor
Tranylcypromine hydrochloride is a non-selective MAO-A/B inhibitor. -
JAK2/HDAC dual inhibitor
JAK/HDAC-IN-1 is a potent JAK2/HDAC dual inhibitor, exhibits antiproliferative and proapoptotic activities in several hematological cell lines. -
Histone Demethylases Inhibitor
Methylstat is a potent inhibitor of histone demethylases, effectively suppressing the activity of these enzymes. It demonstrates notable anti-proliferative effects with minimal cytotoxicity, inducing apoptosis and causing cell cycle arrest at the G0/G1 phase. Methylstat enhances the expression of key regulatory proteins such as p53 and p21, and it also inhibits cytokine-induced angiogenesis. This compound serves as a valuable chemical probe for investigating the role of histone demethylation in cancer biology and angiogenesis-related research. -
Tip60 HAT Inhibitor
TH1834 dihydrochloride is a selective inhibitor of Tip60 (KAT5), a histone acetyltransferase involved in the regulation of gene expression and DNA repair. This compound has been shown to induce apoptosis and enhance DNA damage in breast cancer cells, demonstrating its potential as a therapeutic agent in cancer research. Importantly, TH1834 dihydrochloride does not inhibit the activity of the structurally related histone acetyltransferase MOF, suggesting a targeted approach in modulating histone acetylation and cellular responses. -
PIM Kinase Inhibitor
PIM-447 dihydrochloride is a potent and selective pan-PIM kinase inhibitor targeting PIM1, PIM2, and PIM3 with Ki values of 6, 18, and 9 pM, respectively. This compound exhibits significant antimyeloma activity and protective effects on bone tissue. PIM-447 dihydrochloride also induces apoptosis, making it a valuable tool for research into cancer therapies and bone disease studies. -
SIRT6 Activator
SIRT6 activator 12q is a potent and selective small molecule that acts as an activator of SIRT6, exhibiting an IC50 of 0.58 μM, while demonstrating much lower activity against other sirtuins such as SIRT1-3 and SIRT5. This compound has been shown to inhibit cell growth and migration, induce apoptosis, and cause cell cycle arrest at the G2 phase. With its potential anticancer properties, SIRT6 activator 12q is a valuable tool for research in cancer biology and therapeutic development targeting SIRT6 pathways. -
MLL1 Inhibitor
MM-401 TFA is a selective inhibitor of the MLL1 H3K4 methyltransferase, functioning primarily by disrupting the interaction between MLL1 and WDR5 (IC50 = 0.32 μM). This compound has demonstrated the capability to induce cell cycle arrest, promote apoptosis, and facilitate differentiation in various cell types. Its unique mechanism makes MM-401 TFA a valuable tool for investigating the role of MLL1 in MLL leukemia research. -
WDR5 Inhibitor
WDR5-IN-1 is a highly selective inhibitor of WD repeat domain 5 (WDR5), demonstrating a binding affinity (Kd) of less than 0.02 nM. It effectively inhibits the MLL1 histone methyltransferase activity with an IC50 of 2.2 nM, leading to reduced MYC recruitment at WDR5-displaced genes. This compound exhibits significant anti-proliferative effects in neuroblastoma (CHP-134) and Burkitt’s lymphoma (Ramos) cell lines, making it a valuable tool for research in cancer biology and epigenetics. -
PAD1 Inhibitor
D-Cl-amidine hydrochloride is a potent and selective inhibitor of protein arginine deiminase 1 (PAD1). This compound effectively modulates citrullination, a post-translational modification involved in various biological processes, including inflammation and autoimmunity. D-Cl-amidine hydrochloride is a valuable tool for research into the roles of PAD1 in disease mechanisms and therapeutic interventions. Its favorable toxicity profile enhances its utility in biochemical and cellular assays. -
JAK1 Inhibitor
Ivarmacitinib is a potent inhibitor of the Janus kinase 1 (JAK1) enzyme with notable selectivity against JAK2, JAK3, and Tyk2. This compound effectively inhibits JAK1-STAT3 phosphorylation and promotes apoptosis in hepatic stellate cells, highlighting its potential for anti-proliferative and anti-inflammatory research applications. Ivarmacitinib is valuable for studies focused on diseases involving the JAK-STAT signaling pathway. -
WDR5 Inhibitor
WDR5-IN-4 is a selective inhibitor of the WDR5 protein, which plays a crucial role in chromatin regulation. With a Kd value of 0.1 nM, WDR5-IN-4 effectively displaces WDR5 from chromatin, leading to decreased expression of associated genes and subsequent inhibition of translation, resulting in nucleolar stress. This compound demonstrates potential anti-cancer effects, making it a valuable tool for research into gene regulation and cancer therapeutics. -
WDR5 Inhibitor
WDR5-IN-4 TFA is a potent inhibitor targeting the WIN site of the chromatin-associated protein WDR5, exhibiting a Kd of 0.1 nM. This compound effectively displaces WDR5 from chromatin, leading to a reduction in the expression of WDR5-associated genes, resulting in translational inhibition and nucleolar stress. Its significant anti-cancer activity makes WDR5-IN-4 TFA a valuable tool for research in cancer biology and therapy modulation. -
GBP1:PIM1 Interaction Inhibitor
NSC756093 is a GBP1:PIM1 interaction inhibitor with a binding affinity of 38 nM. This compound demonstrates significant biological activity by suppressing cell proliferation, reducing migration, inducing G1 phase cell-cycle arrest, and promoting apoptosis in ovarian cancer cells. Additionally, NSC756093 decreases proteasomal activity and leads to the accumulation of ubiquitinated proteins, thereby inhibiting tumor progression and lung metastasis in murine ovarian cancer xenograft models. Furthermore, it enhances sensitivity of prostate cancer cells to Docetaxel and sensitizes GBP1-overexpressing ovarian cancer cells to Paclitaxel, making it a valuable reagent for research in prostate and ovarian cancer. -
PLK1/BRD4 Inhibitor
PLK1/BRD4-IN-5 is a potent inhibitor targeting both PLK1 and BRD4, exhibiting IC50 values of 0.3 nM and 60.8 nM, respectively. This compound effectively induces cell cycle arrest in the S phase and promotes apoptosis in MV4-11 cells in a dose-dependent manner. PLK1/BRD4-IN-5 is a valuable tool for cancer research, facilitating studies on mechanisms of tumorigenesis and therapeutic responses. -
HDAC Inhibitor
DL-Sulforaphane N-acetyl-L-cysteine is an orally active inhibitor of histone deacetylases (HDACs) and a stable metabolite of sulforaphane. This compound enhances autophagy-mediated reduction of α-tubulin expression via the ERK signaling pathway, making it a valuable tool in cancer research. Its improved blood-brain barrier permeability and extended half-life support its potential in neurobiological studies and therapeutic applications. -
AKR1C1/JAK2/STAT3/NF-κB Inhibitor
Zingiberen Newsaponin is a potent inhibitor of the AKR1C1/JAK2/STAT3 and NF-κB signaling pathways. This steroid saponin compound demonstrates significant anti-hepatocellular carcinoma (HCC) activity by promoting cancer cell apoptosis through the induction of oxidative stress, as evidenced by the upregulation of ROS and MDA levels. Additionally, Zingiberen Newsaponin mitigates cerebral ischemia-reperfusion injury by reducing pro-inflammatory cytokines and enhancing superoxide dismutase (SOD) activity, thereby protecting neuronal cells. Furthermore, it has been shown to induce platelet aggregation, broadening its application in cardiovascular research. -
JAK2 Inhibitor
G5-7 is an orally active allosteric inhibitor of Janus kinase 2 (JAK2), selectively disrupting JAK2-mediated phosphorylation and activation of epidermal growth factor receptor (EGFR) at Tyr1068 and signal transducer and activator of transcription 3 (STAT3). This compound induces cell cycle arrest and apoptosis, demonstrating significant antiangiogenic effects. G5-7 shows promise for research applications in glioma studies, making it a valuable tool for understanding JAK2-related signaling pathways and their implications in cancer. -
PARP Inhibitor
Niraparib tosylate hydrate is a potent inhibitor of PARP1 and PARP2, exhibiting IC50 values of 3.8 nM and 2.1 nM, respectively. This compound functions by disrupting the DNA repair mechanism, leading to the accumulation of DNA damage and subsequent activation of apoptosis. Niraparib tosylate hydrate demonstrates significant anti-tumor activity, making it a valuable tool for cancer research, particularly in studies focused on DNA repair pathways and therapeutic resistance.
