Epigenetic modification of chromatin includes methylation of genomic DNA as well as post-translational modification of chromatin-associated proteins, mainly histones. Cell-permeable small-molecule modulators have become a valuable tool in the investigation of gene and protein functions. The use of small molecules to modulate cellular and in vivo systems is receiving strong interest among researchers in academia as well as pharma. The discovery of small molecule regulators (activators or inhibitors) of epigenetic modification enzymes provides researchers with pharmacological tools with which to investigate the biological consequences of chromatin modifications. The major classes of inhibitors/modulators are classified based on their activity and use.
DNA Methyltransferase Inhibitors
DNA methyltransferases are a family of enzymes that catalyze the transfer of methyl group to DNA. There are five related DNA cytosine- 5-methyltransferases (DNMTs) that transfer a methyl group from S-adenosylmethionine (AdoMet, SAM) to the C-5 position of cytosine. Inhibitors have been shown to have anti-proliferative activity. They can reactivate the expression of genes that have been repressed by DNA methylation.
Nucleoside analog inhibitors:
Require DNA incorporation for DNMT inhibition.
|5-Azacytidine ≥98% (HPLC)||A2385-100MG|
|5-Azacytidine ≥98% (HPLC)||A2385-250MG|
|5-Azacytidine ≥98% (HPLC)||A2385-1G|
|Zebularine ≥98% (HPLC), solid||Z4775-5MG|
|Zebularine ≥98% (HPLC), solid||Z4775-25MG|
Non-nucleoside analog inhibitors:
Block DNMT directly without DNA incorporation.
|Caffeic acid purum, ≥95.0% (HPLC)||60020-10G-F|
|Caffeic acid purum, ≥95.0% (HPLC)||60020-50G-F|
|(-)-Epigallocatechin gallate ≥95%, from green tea||E4143-50MG|
|Procaine hydrochloride ≥97%||P9879-50G|
|Procaine hydrochloride ≥97%||P9879-100G|
|Procaine hydrochloride ≥97%||P9879-250G|
|Psammaplin A ≥97% (HPLC), solid||P8749-5MG|
|RG108 ≥98% (HPLC), solid||R8279-10MG|
Histone methyltransferases (HMTs), histone-lysine N-methyltransferase and histone-arginine N-methyltransferase, are enzymes which catalyzye the transfer of one to three methyl groups from the cofactor S-Adenosyl methionine to lysine and arginine residues of histone proteins.
Histone Lysine Methyltransferase (HKMT) inhibitors
|BIX 01294 trihydrochloride hydrate ≥98% (HPLC), white solid||B9311-5MG|
|BIX 01294 trihydrochloride hydrate ≥98% (HPLC), white solid||B9311-25MG|
|Chaetocin from Chaetomium minutum >95% (HPLC), >98% (TLC)||C9492-1MG|
Histone Lysine Demethylase inhibitors:
Lysine specific demethylase I (LSDI, KIA0601, BHC10) has close homology to monoamine oxidases (MAOs), and hence the classic MAO inhibitors pargyline and tranylcypromine have been found to inhibit LSD1, although not with high potency (>100µM).
Protein Arginine Methyltransferase (PRMT) modulators:
Most of the PRMT inhibitors mentioned in literature are nonselective and may also inhibit DNMTs and HKMTs.
|AMI-1 sodium salt hydrate ≥98% (HPLC)||A9232-5MG|
|AMI-1 sodium salt hydrate ≥98% (HPLC)||A9232-25MG|
|AMI-5 (eosin Y)||119830-25G|
|AMI-5 (eosin Y)||119830-100G|
Histone deacetylases (HDACs) are enzymes that remove acetyl groups from lysines of histones and a number of other regulatory and structural proteins. They play critical roles in chromatin remodeling and are involved in transcription regulation, cell-cycle progression, cell survival and differentiation. So far, 18 HDACs have been identified and divided into 3 distinct enzyme classes.
Class I and II HDACs are zinc dependent. Class I, homologous to yeast Rpd3, includes HDAC1, 2, 3, and 8. Class II (HDAC4, 5, 6, 7, 9, 10) resembles yeast Hda1. Class I and II HDACs are associated with malignant transformations and are targets for cancer drugs. Inhibitors of Class I and II HDACs are largely classified into four groups on the basis of their chemical structures.
Short-chain fatty acid inhibitors
Hydroxamic acid inhibitors:
The most widely used HDAC inhibitors are hydroxamic acid- based. They are nonspecific for HDAC subclass.
|Oxamflatin ≥98% (HPLC), solid||O3139-1MG|
|Oxamflatin ≥98% (HPLC), solid||O1319-5MG|
|Scriptaid ≥95% (H-NMR), solid||S7817-1MG|
|Scriptaid ≥95% (H-NMR), solid||S7817-5MG|
|Trichostatin A 5 mM in DMSO (0.2 µm-filtered), from Streptomyces sp.||T1952-200ul|
|Trichostatin A ≥98% (HPLC), from Streptomyces sp.||T8552-1mg|
|Trichostatin A ≥98% (HPLC), from Streptomyces sp.||T8552-5mg|
|CI-994 ≥98% (HPLC), powder||C0621-5MG|
|CI-994 ≥98% (HPLC), powder||C0621-25MG|
Cyclic tetrapeptide and natural product inhibitors:
Most show selectivity for Class I HDACs.
|Apicidin ≥98% (HPLC), from microbial, solid||A8851-1MG|
|Apicidin ≥98% (HPLC), from microbial, solid||A8851-5MG|
|(-)-Depudecin >95% (HPLC), from microbial||D5816-1MG|
Other HDAC inhibitors:
No data suggesting HDAC class selectivity.
|APHA Compound 8 ≥98% (HPLC), solid||A2478-1MG|
|BATCP ≥98% (HPLC), solid||B4061-2MG|
|MOCPAC ≥95% (HPLC), solid||M2195-2MG|
|PTACH ≥98% (HPLC), solid||P5874-2MG|
|Resveratrol >99% (GC)||R5010-100MG|
|Resveratrol >99% (GC)||R5010-500MG|
|Splitomicin ≥98% (HPLC), solid||S4068-5MG|
Histone Acetyltransferases (HAT)
Histone acetyltransferases (HAT) are enzymes that acetylate conserved lysine amino acids on histone proteins by transferring an acetyl group from acetyl CoA to form ε-N-acetyl lysine. Histone acetylation is generally linked to transcriptional activation. These are generally associated with euchromatin.
Histone acetyltransferases (HATs) act as transcriptional coactivators. Histone acetylation plays an important role in regulating the chromatin structure and is tightly regulated by two classes of enzyme, histone acetyltransferases (HAT) and histone deacetylases (HDAC). Deregulated HAT and HDAC activity plays a role in the development of a range of cancers. Consequently, inhibitors of these enzymes have potential as anticancer agents.
|CPTH2 ≥98% (HPLC), powder||C9873-5MG|
|CPTH2 ≥98% (HPLC), powder||C9873-25MG|
|Curcumin from Curcuma longa (Turmeric), powder||C1386-5G|
|Curcumin from Curcuma longa (Turmeric), powder||C1386-10G|
|Curcumin from Curcuma longa (Turmeric), powder||C1386-50G|