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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EZH2 PROTAC Degrader
PROTAC EZH2 Degrader-19 is a potent PROTAC compound that targets the enhancing zeste homolog 2 (EZH2) with an IC50 of 15.00 nM. This reagent effectively induces degradation of all Polycomb Repressive Complex 2 (PRC2) subunits, including EZH2, SUZ12, EED, and RbAp48, in a concentration- and time-dependent manner. PROTAC EZH2 Degrader-19 demonstrates significant antiproliferative effects in cancer cell lines, making it a valuable tool for cancer research and therapeutic applications. -
EZH2 PROTAC Degrader
PROTAC EZH2 Degrader-34 is a targeted degrader of EZH2, exhibiting an IC50 of 6.30 μM in human EZH2 inhibition. This compound is designed to selectively induce the degradation of EZH2, a key enzyme involved in histone methylation. Its applications are primarily in the study of malignancies such as Pfeiffer and prostate cancer, facilitating investigations into the molecular mechanisms of oncogenesis and potential therapeutic interventions. -
EZH2 PROTAC Degrader
PROTAC EZH2 Degrader-11 is a targeted protein degrader designed to selectively degrade the EZH2 protein through a PROTAC mechanism. This compound effectively reduces tumor size and viability in three-dimensional spheroid models, demonstrating potential for cancer research applications. The technology leverages a dual-ligand system, incorporating an EZH2 ligand and a Cereblon ligand, connected by a linker to facilitate the targeted degradation process. -
EZH2 PROTAC Degrader
PROTAC EZH2 Degrader-45 is a specialized PROTAC protein degrader designed to target EZH2, exhibiting an IC50 of 22.97 μM in SU-DHL-6 cells. This compound is primarily utilized in research focused on diffuse large B-cell lymphoma, providing insights into epigenetic regulation through targeted protein degradation. The product includes a histone methyltransferase ligand and a VHL ligand, linked for enhanced efficacy in cellular studies. -
EZH2 PROTAC Degrader
PROTAC EZH2 Degrader-40 is a PROTAC protein degrader specifically designed to target the enhancer of zeste homolog 2 (EZH2), exhibiting an IC50 value of 15.35 μM in SU-DHL-6 cells. This compound is valuable for researching diffuse large B-cell lymphoma and related epigenetic mechanisms. Its structure consists of a histone methyltransferase ligand, an aminopeptidase ligand, and a linker, facilitating targeted degradation of EZH2 to explore therapeutic potential in cancer treatment. -
EZH2 PROTAC Degrader
PROTAC EZH2 Degrader-29 is a targeted protein degrader that specifically engages the EZH2 protein, exhibiting an IC50 of 24.53 μM in diffuse large B-cell lymphoma cells. This compound serves as a valuable tool for investigating the degradation of EZH2 in both basic and translational research settings related to diffuse large B-cell lymphoma and other malignancies. -
Molecule Glue
HuR degrader 2 is a molecular glue that specifically targets the RNA-binding protein Hu antigen R (HuR), leading to a significant degradation of approximately 30% of HuR at a concentration of 0.1 μM. This compound effectively inhibits the proliferation of the Colo-205 cancer cell line, demonstrating an IC50 of ≤200 nM. Additionally, HuR degrader 2 shows a high affinity for cereblon, with an HTRF ratio of less than 0.02, making it a valuable tool for studying HuR's role in cancer biology. -
Molecular Glue
MG-HuR2 is a molecular glue degrader that specifically targets the oncogenic RNA-binding protein HuR, exhibiting an IC50 of 0.5 μM. This compound is particularly relevant for research involving HuR-overexpressing malignancies, such as breast cancer, providing a valuable tool for investigating therapeutic strategies aimed at modulating HuR activity in cancerous tissues. -
HuR Inhibitor
SRI-43265 is a selective inhibitor of human antigen R (HuR) dimerization, a crucial process impacting HuR's role in post-transcriptional regulation of target mRNAs. By disrupting HuR multimers, SRI-43265 demonstrates potential in studying cancer and inflammatory processes, where HuR's activity contributes to pathogenesis. This reagent is valuable for investigating the molecular mechanisms underlying these diseases and for exploring therapeutic strategies targeting HuR functions. -
HuR Inhibitor
ZM-32 is a potent inhibitor of human antigen R (HuR), a critical regulator of mRNA stability. By downregulating the expression of vascular endothelial growth factor A (VEGF-A) and matrix metalloproteinase 9 (MMP9), ZM-32 effectively inhibits angiogenesis in breast cancer. Demonstrating broad-spectrum anti-proliferative effects across various cancer cell lines, ZM-32 also shows significant antitumor efficacy in mouse models of the MDA-MB-231 breast cancer cell line. -
HuR-ARE Inhibitor
Azaphilone-9 (AZA-9) is a potent inhibitor of the HuR-ARE RNA interaction, demonstrating an IC50 value of 1.2 μM. By binding to the RNA-binding protein Hu antigen R (HuR), Azaphilone-9 disrupts the stabilization of various oncogenic mRNAs in tumor cells. This mechanism suggests that Azaphilone-9 may serve as a valuable tool for investigating cancer cell growth and progression in research applications targeting RNA-protein interactions. -
HuR Inhibitor
Okicenone is an inhibitor of Hu protein R (HuR), a key regulator of messenger RNA stability and translation. By disrupting HuR oligomerization and its RNA binding capabilities, Okicenone modulates HuR trafficking, influencing cytokine expression and T-cell activation. This compound is valuable in research focused on immune response modulation and the role of mRNA-binding proteins in cellular processes. -
METTL3-METTL14 Degrader
WD6305 is a selective PROTAC degrader targeting METTL3 and METTL14, with DC50 values of 140 nM and 194 nM, respectively. This compound effectively inhibits m6A modification and has been shown to suppress proliferation and induce apoptosis in acute myeloid leukemia (AML) cells. WD6305 demonstrates significant antitumor activity, making it a valuable tool for research on RNA modifications and cancer therapeutics. -
METTL3 Inhibitor
METTL3-IN-1 is a potent METTL3 inhibitor designed to selectively inhibit the activity of the METTL3 methyltransferase. This compound demonstrates significant biological activity in modulating RNA methylation, making it a valuable tool for studying the role of METTL3 in various cellular processes. It is applicable in research areas such as epitranscriptomics and cancer biology, where understanding RNA modifications is crucial. -
METTL3 Inhibitor
METTL3-IN-2 is a selective inhibitor of the methyltransferase METTL3, exhibiting an IC50 value of 6.1 nM. This compound effectively inhibits cell proliferation in Caov3 ovarian cancer cells, providing a valuable tool for research into the regulation of RNA methylation and its implications in cancer biology. METTL3-IN-2 can be utilized in studies focused on understanding METTL3's role in tumor growth and the development of targeted cancer therapies. -
METTL3 Inhibitor
METTL3-IN-3 is a selective inhibitor of the methyltransferase METTL3, which plays a critical role in RNA m6A methylation. This compound demonstrates significant inhibition of METTL3 activity, thereby impacting the regulation of gene expression and RNA metabolism. METTL3-IN-3 is valuable for research applications focusing on epitranscriptomics, RNA modifications, and their implications in various biological processes and diseases. -
METTL3 Inhibitor
METTL3-IN-5 is a selective inhibitor of METTL3, a key enzyme involved in N6-methyladenosine (m6A) methylation. This compound demonstrates potent inhibitory effects on the growth of MOLM-13 cells, with an IC50 of less than 2 μM. While exhibiting minimal hERG inhibitory activity (IC50 >30 μM), METTL3-IN-5 is a valuable tool for researching acute myeloid leukemia (AML) and m6A-related biological processes. -
METTL3 Inhibitor
METTL3-IN-13 is a selective inhibitor of the methyltransferase METTL3. This compound exhibits significant biological activity by disrupting RNA methylation, which plays a critical role in various cancer types including hypopharyngeal squamous cell carcinoma and non-small cell lung cancer. It serves as a valuable tool for investigating the role of METTL3 in oncogenic processes and may assist in the development of targeted therapies. -
miR-155 Inhibitor
Cobomarsen sodium is a targeted miR-155 inhibitor that modulates various signaling pathways, including JAK/STAT, MAPK/ERK, and PI3K/AKT, contributing to the regulation of cell survival. This oligonucleotide is primarily employed in research focused on B-cell lymphoma, enabling insights into the molecular mechanisms of this malignancy and potential therapeutic strategies. -
miR-155 Inhibitor
Cobomarsen is an oligonucleotide inhibitor targeting miR-155. This compound modulates various signaling pathways associated with cell survival, including the JAK/STAT, MAPK/ERK, and PI3K/AKT pathways. Cobomarsen is primarily utilized in research focused on B-cell lymphoma, providing insights into miRNA-mediated gene regulation and potential therapeutic approaches. -
TET Inhibitor
TETi76 is a potent inhibitor of TET family enzymes, demonstrating IC50 values of 1.5 μM for TET1, 9.4 μM for TET2, and 8.8 μM for TET3. By competitively binding to the active site of these enzymes, TETi76 effectively decreases cytosine hydroxymethylation and inhibits the clonal growth of TET2 mutant cells both in vitro and in vivo, while sparing normal hematopoietic precursor cells. This selective activity makes TETi76 a valuable tool for investigating leukemia and studying TET-related pathways in cancer research. -
TET1 Inhibitor
NSC-311068 is a potent inhibitor of TET1, targeting the enzyme's transcriptional activity and its role in modifying 5-hydroxymethylcytosine (5hmC). This compound effectively reduces TET1 expression levels and attenuates global 5hmC levels. NSC-311068 demonstrates significant cytotoxicity in acute myeloid leukemia (AML) cells characterized by elevated TET1 expression, making it a valuable tool for studying TET1-related pathways and potential therapeutic approaches in AML. -
GT1b Ligand
Tet1-Cys peptide is a specifically designed peptide that targets the GT1b ligand. It demonstrates the ability to bind to the neuronal ganglioside receptor GT1b, facilitating neuronal targeting in research applications. The inclusion of a cysteine residue in the Tet1-Cys peptide allows for efficient drug conjugation, making it a valuable tool for studies focused on drug delivery mechanisms and neuronal interactions. -
Neuron-Specific Ligand for GT1B
Tet1 peptide (HLNILSTLWKYR) is a neuron-specific ligand that selectively targets GT1B gangliosides. This peptide plays a crucial role in studies related to neuronal function and cell signaling. A commonly used variant includes a cysteine residue at the C-terminus (HLNILSTLWKYRC), facilitating peptide conjugation for drug delivery studies and enhancing research applications in neurobiology. -
Anxiolytic Agent
Succinic acid sodium functions as an effective anxiolytic agent. It has demonstrated inhibitory effects on colonic epithelial cell proliferation in vivo and can down-regulate the expression of key genes such as KCNMB1 and TET1. This compound is particularly useful for research involving gestational hypertension and related physiological studies. -
WDR5 Inhibitor
WDR5-IN-5 is a selective inhibitor targeting the WIN site of the WD repeat domain 5 (WDR5). This compound demonstrates significant anti-proliferative activity against various cancer cell lines and possesses favorable pharmacokinetic properties in murine models. With a high binding affinity to WDR5, the Ki value is recorded at less than 0.02 nM, making it a valuable tool for research into cancer biology and potential therapeutic applications. -
WDR5 Inhibitor
WDR5-IN-6 is a selective inhibitor of WDR5, acting primarily at the WBM site. This compound demonstrates significant anti-tumor activity by inhibiting cell proliferation in neuroblastoma cell lines. Additionally, WDR5-IN-6 exhibits notable synergy with OICR-9429, another WDR5 inhibitor that targets the WIN site. This compound is valuable for research applications focused on neuroblastoma and related oncological studies. -
WDR5 Inhibitor
WM-586 is a covalent inhibitor of WDR5, effectively disrupting the interaction between WDR5 and MYC with an IC50 value of 101 nM. This compound demonstrates significant potential in cancer research, particularly in the study of neuroblastoma, breast cancer, bladder cancer, and colorectal cancer. Its ability to target the WDR5-MYC complex makes it a valuable tool for exploring therapeutic strategies in various malignancies. -
WDR5-MYC Interaction Inhibitor
WM-662 is an inhibitor targeting the WDR5-MYC interaction, exhibiting an IC50 of 18 μM. This compound is particularly relevant for investigations into cancer biology, aging processes, and neurodegenerative disorders. Its ability to disrupt the WDR5-MYC interaction positions WM-662 as a valuable tool in studying dysregulated gene expression associated with these conditions. -
WDR5-MYC Interaction Inhibitor
Anticancer agent 126 is a specific inhibitor of the WDR5-MYC interaction, targeting the critical role of this complex in oncogenic signaling. This compound effectively disrupts the binding of WDR5 to MYC, leading to a reduction in MYC target gene expression. It is suitable for research applications focused on elucidating the mechanisms of cancer biology and developing therapeutic strategies against MYC-driven malignancies. -
WDR5 Inhibitor
WDR5-IN-7 is a potent inhibitor of WD repeat domain 5 (WDR5), utilizing a benzoxazepinone structure. This compound exhibits significant anti-cancer activity and is particularly useful in the study of various tumor models. WDR5-IN-7 serves as a valuable tool for elucidating the role of WDR5 in oncogenic processes and for exploring therapeutic strategies in cancer research. -
WDR5-MLL1 Inhibitor
DDO-2213 is a potent inhibitor of the WDR5-MLL1 complex, exhibiting an IC50 of 29 nM and a Kd value of 72.9 nM for WDR5. This compound selectively targets MLL histone methyltransferase activity, effectively inhibiting the proliferation of cells containing MLL translocations. DDO-2213 is a valuable tool for research focused on MLL fusion leukemia and its underlying mechanisms. -
CRBN Degrader
WDR5 Degrader-1 is a cereblon (CRBN)-recruiting compound designed to selectively induce degradation of the WDR5 protein. This degrader effectively targets WDR5 while sparing the CRBN neo-substrate IKZF1, facilitating precise manipulation of WDR5 levels in cellular systems. It is a valuable tool for investigating the biological roles of WDR5 in transcriptional regulation and potential therapeutic strategies in diseases associated with dysregulated WDR5 expression. -
WDR5-MLL1 Inhibitor
WDR5-0102 is a selective inhibitor of the WDR5-MLL1 complex, exhibiting a dissociation constant (Kd) of 4 μM and a competitive inhibition constant (Kdis) of 7 μM. This compound effectively suppresses the H3K4 methyltransferase activity of MLL1 without affecting other human methyltransferases, including SETD7 and several others such as G9a, EHMT1, SUV39H2, SETD8, PRMT3, and PRMT5. WDR5-0102 is a valuable tool for investigating the role of MLL1 in various biological processes and its implications in cancer research. -
MLL1-WDR5 PPI Inhibitor
DDO-2093 is a selective inhibitor of the MLL1-WDR5 protein-protein interaction, exhibiting a potent IC50 of 8.6 nM and a dissociation constant (Kd) of 11.6 nM. This compound demonstrates significant antitumor activity by selectively targeting and inhibiting the catalytic function of the MLL complex. DDO-2093 is useful in research focused on understanding MLL-related oncogenesis and potential therapeutic strategies in cancer treatment. -
WDR5 Ligand
OICR-9429-N-C2-NH2 is a selective ligand for WDR5, a key protein involved in the regulation of gene expression and crucial in oncogenic pathways. This compound facilitates the design and synthesis of PROTACs (Proteolysis Targeting Chimeras), allowing for targeted protein degradation. Its unique properties make it a valuable tool for cancer research and the development of innovative therapeutic strategies. -
PROTAC WDR5 Degrader
XF067-68 is a PROTAC designed for the targeted degradation of the WD40 repeat domain protein 5 (WDR5). This compound facilitates the specific elimination of WDR5, making it a valuable tool for investigating diseases associated with WDR5 dysregulation. Researchers can employ XF067-68 to elucidate the biological roles of WDR5 and explore potential therapeutic interventions in related disorders. -
WDR5 Antagonist
WDR5-47 is a potent WDR5 antagonist that specifically disrupts the WDR5-MLL1 interaction. This compound demonstrates significant biological activity with a dissociation constant (Kd) of 0.3 μM, showcasing its effectiveness in inhibiting WDR5-mediated functions. WDR5-47 is ideal for research applications focusing on epigenetic regulation and will aid in the investigation of oncogenic processes involving the MLL1 complex. -
WDR5 Degrader
XF056-132 free base is a potent WDR5 (WD40 repeat domain protein 5) degrader that utilizes the proteolysis-targeting chimeric (PROTAC) mechanism. This compound effectively promotes the selective degradation of WDR5, which is implicated in various cancers and transcriptional regulation processes. XF056-132 serves as a valuable tool for research into targeted protein degradation and its therapeutic potential in oncological studies. -
WDR5-MLL1 Ligand
Z88418521 is a ligand targeting the WDR5-MLL1 complex, acting to disrupt its interaction. This compound demonstrates potential inhibitory effects on pathways associated with oncogenesis, particularly in leukemia research. Z88418521 serves as a valuable tool for investigating the molecular mechanisms underlying various cancer pathologies. -
WDR5 PROTAC Degrader
MS40 is a WDR5 PROTAC degrader with a Kd of 125 nM, which facilitates the ubiquitination and subsequent degradation of the WDR5 protein. The degradation of WDR5 causes the dissociation of the MLL/KMT2A complex from chromatin, leading to reduced levels of H3K4me2. This compound is instrumental in investigating the mechanistic pathways involved in primary leukemia. -
WDR5 Ligand
WDR5 ligand 2 is a specific ligand for the WDR5 protein, which plays a crucial role in regulating gene expression and chromatin dynamics. This compound can be utilized in the synthesis of PROTAC WDR5 degrader 1, facilitating targeted protein degradation studies. Its application is valuable in research focusing on epigenetic regulation and cancer biology. -
YTHDF2 Ligand
YTHDF2 ligand-1 is a selective and high-affinity ligand that targets YTHDF2, with an IC50 of 11 μM and a Kd of 1.3 μM. This compound effectively competes with m6A-RNA for the binding site on YTHDF2, making it a valuable tool for studies involving RNA methylation and its implications in cancer research. Researchers can utilize YTHDF2 ligand-1 to explore the role of YTHDF2 in various cellular processes and potential therapeutic interventions. -
PARP-1 Inhibitor
PARP-1-IN-32 is a potent inhibitor of poly(ADP-ribose) polymerase-1 (PARP-1). This compound is utilized in cancer research to investigate the mechanisms of DNA repair and cellular response to genotoxic stress. Its ability to selectively inhibit PARP-1 makes it a valuable tool for studying the role of this enzyme in tumor biology and therapeutic resistance. -
SIRT6 Inhibitor
SIRT6-IN-6 is a selective inhibitor of SIRT6, demonstrating a potent IC50 of 4.93 μM and a Ki of approximately 10 μM. This compound shows significant selectivity against other histone deacetylases, including SIRT1-3 and HDAC1-11. Research findings indicate that SIRT6-IN-6 effectively elevates the expression of the glucose transporter GLUT-1, which contributes to the reduction of blood glucose levels in mouse models of type 2 diabetes. This reagent is valuable for studies focused on the mechanistic pathways associated with type 2 diabetes and metabolic regulation. -
Sirtuin Inhibitor
MC3482 is a selective inhibitor of sirtuin 5 (SIRT5), known for its role in mitochondrial metabolism and deacylation processes. This compound effectively modulates SIRT5 activity, making it valuable for studies examining the implications of SIRT5 in cellular energy regulation and metabolic disorders. Its use in research can contribute to understanding SIRT5's role in various physiological and pathological conditions, including cancer and neurodegeneration. -
SIRT5 Inhibitor
MC3138 is a selective SIRT5 inhibitor, demonstrating notable antitumor activity in human pancreatic ductal adenocarcinoma (PDAC) cells, with IC50 values ranging from 25.4 to 236.9 μM. In preclinical studies, MC3138 enhances the efficacy of Gemcitabine, significantly inhibiting tumor growth in murine models. This compound is valuable for research into targeted cancer therapies and the modulation of metabolic pathways related to SIRT5 activity. -
SIRT3 Activator
2-APQC is a selective activator of Sirtuin-3 (SIRT3), exhibiting an affinity of Kd=2.756 μM. This compound enhances mitochondrial proline metabolism through the SIRT3-PYCR1 axis and mitigates ROS-induced cytotoxicity by inhibiting the mTOR-p70S6K, JNK, and TGF-β/Smad3 signaling pathways. Additionally, 2-APQC activates the AMPK-Parkin axis, providing a protective effect against myocardial hypertrophy and fibrosis, making it a valuable tool for researching heart failure and related cardiac dysfunctions. -
Sirtuin Activator
ADTL-SA1215 is a novel small-molecule activator of SIRT3, targeting the regulation of autophagy pathways. This compound has demonstrated potential in inducing autophagy in triple-negative breast cancer cells, presenting opportunities for cancer research and therapeutic development. Its specificity for SIRT3 makes it an essential tool for studying the role of sirtuins in cellular metabolism and cancer progression. -
SIRT5 Inhibitor
Et-29 is a potent inhibitor of SIRT5, with a reported Ki value of 40 nM, demonstrating selectivity for this target. By modulating the activity of SIRT5, Et-29 plays a significant role in the study of metabolic processes and post-translational modifications. This reagent is ideal for research applications focused on the regulation of cellular metabolism and potential therapeutic strategies in metabolic diseases.
