Antitumor agent-69 (compound 12) is a potent inhibitor of protein-protein interaction between DOT1L and MLL-AF9/MLL-ENL, with Kis of 9 nM and 109 nM for AF9 and ENL, respectively. Antitumor agent-69 exhibits anticancer cellular activitiy[1].
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].
WDR5-0103 is a potent and selective WD repeat-containing protein 5 (WDR5) antagonist with Kd of 450 nM.IC50 value: 450 nM (Kd)Target: WDR5in vitro: WDR5-0103 inhibits MLL catalytic activity with an IC50 value of 39±10 μM. An increase in MLL complex concentration resulted in proportional increase in IC50 values for WDR5-0103 (83±10 and 280±12 μM at concentrations of 500 and 1000 nM of the core trimeric MLL complex respectively). These data are consistent with a mechanism of action in which WDR5-0103 antagonizes the interaction of WDR5 with MLL by competing with MLL for their mutual binding site on WDR5.
PF-06821497 (compound 23a) is a potent, selective and orally active Enhancer of Zeste Homolog 2 (EZH2) inhibitor, with a Ki value <0.1 nM against mutant Y641N EZH2. Exhibits robust tumor growth inhibition[1].
AZ505 ditrifluoroacetate is a potent and selective SMYD2 inhibitor with IC50 of 0.12 μM.
Amodiaquine (Amodiaquin), a 4-aminoquinoline class of antimalarial agent, is a potent and orally active histamine N-methyltransferase inhibitor. Amodiaquine is also a Nurr1 agonist and specifically binds to Nurr1-LBD (ligand binding domain) with an EC50 of ~20 μM. Anti-inflammatory effect[1][2][3][4].
MM-401 (TFA) is a MLL1 H3K4 methyltransferase inhibitor. MM-401 inhibits MLL1 activity (IC50 = 0.32 µM) by blocking MLL1-WDR5 interaction. MM-401 can induce cell cycle arrest, Apoptosis and differentiation. MM-401 can be used for the research of MLL leukemia[1].
PRMT5-IN-11 is a promising structure-dependent inhibition of the protein methyltransferase PRMT5:MEP50 complex in the (sub)micromolar range.
UNC0646 is a potent and selective G9a inhibitor with IC50 of 6 nM.IC50 value: 6 nM [1]Target: G9aUNC0646 is a potent and selective inhibitor of the homologous protein lysine methyltransferases, G9a and GLP (IC50 values are 6 nM and 15 nM for G9a and GLP, respectively). UNC0646 potently blocks G9a/GLP methyltransferase activity in cells (IC50 = 10 nM in MCF7 cells); exhibits low cellular toxicity (EC50 = 4.7 μM in MCF7 cells). UNC0646 is selective for G9a/GLP over a range of other protein lysine methyltransferases and protein arginine methyltransferases.
PRMT5-IN-13 is a selective inhibitor of protein arginine methyltransferase 5 (prmt5).
G9a-IN-1 (Compound 113) is a G9a protein inhibitor. G9A/EHMT2 is a nuclear histone lysine methyltransferase that catalyzes histone H3 lysine 9 dimethylation (H3K9me2), which is a reversible modification generally associated with transcriptional gene silencing. G9a-IN-1 can be used for the research of autoimmune disorders or cancer[1].
GSK343 is a highly potent and selective EZH2 inhibitor with an IC50 of 4 nM.
DC_C66 is a cell-permeable, selective coactivator associated arginine methyltransferase 1 (CARM1) inhibitor with an IC50 of 1.8 μM. DC_C66 has a good selectivity for CARM1 against PRMT1 (IC50=21 μM), PRMT6 (IC50= 47μM), and PRMT5[1].
EI1 is a potent and selective EZH2 inhibitor with IC50 of 15 nM and 13 nM for EZH2 (WT) and EZH2 (Y641F), respectively.
SGC0946 is a highly potent and selective DOT1L methyltransferase inhibitor with IC50 of 0.3 nM; selectively kill mixed lineage leukaemia cells.IC50 value: 0.3 nM(DOT1L) [1]Target: selective DOT1L inhibitorSGC 0946 is over 100-fold selective for other histone methyltransferases/HMTs. SGC 0946 potently reduces H3K79 dimethylation with IC50 of 2.6 nM in A431 cells, and 8.8 nM in MCF10A cells, which potently and selectively kills cells containing an MLL translocation. SGC 0946 is much more potent than its close analog EPZ004777, and serves as an excellent chemical probe for investigating DOT1L and further development of DOT1L inhibitors for cancer therapy.
PRMT5-IN-16 (Compound 20) 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].
CM-579 is a first-in-class reversible, dual inhibitor of G9a and DNMT, with IC50 values of 16 nM, 32 nM for G9a and DNMT, respectively. Has potent in vitro cellular activity in a wide range of cancer cells[1].
MM-102 is a potent WDR5/MLL interaction inhibitor, achieves IC50 = 2.4 nM with an estimated Ki < 1 nM in WDR5 binding assay, which is >200 times more potent than the ARA peptide.IC50 value: 2.4 nMTarget: MLLin vitro: MM-102 inhibits MLL1 methyltransferase activity and MLL-1-induced HoxA9 and Meis-1 gene expression in leukemia cells expressing the MLL1-AF9 fusion gene. Also inhibits cell growth and induces apoptosis in leukemia cells harbouring MLL1 fusion proteins. MM-102, with the highest binding affinities to WDR5, also show the most potent inhibitory activity in the HMT assay with IC50 = 0.4-0.9 μM. MM-102 dose-dependently inhibits cell growth in the MV4;11 and KOPN8 leukemia cell lines, which carry MLL1-AF4 and MLL1-ENL fusion proteins, respectively. MM-102 has IC50 = 25 μM in both cell lines and completely inhibits cell growth in these cell lines at 75 μM. MM-102 effectively and selectively inhibits cell growth and induces apoptosis in leukemia cells harboring MLL1 fusion proteins and has minimal effect in leukemia cells with wild-type MLL1 protein.[1]
C21 is a potent, irreversible, and selective PRMT1 inhibitor with an IC50 of 1.8 μM. C21 inhibits PRMT6 with an IC50 of 8.8 μM[1].
NSD3-IN-2 is a potent NSD3 inhibitor with an IC50 value of 17.97 μM. NSD3-IN-2 inhibits the growth and proliferation of non-small cell lung cancer cell lines H460, H1299 and H1650 with anti-cancer activity[1].
EZH2-IN-8 is a potent inhibitor of EZH2. EZH2 overexpression or mutations in the SET region (Y641F, Y641N, A687V, A677G point mutations) all lead to abnormal elevation of H3K27me3 and promote the growth and development of many types of tumors, such as breast cancer, prostate cancer, leukemia, etc. EZH2-IN-8 has the potential for the research of cancer diseases (extracted from patent WO2021129629A1, compound 265)[1].
Piribedil hydrochloride is a potent and orally active dopamine D2 and dopamine D3 agonist. Piribedil hydrochloride is also a α2-adrenoceptors antagonist. Piribedil hydrochloride can inhibit MLL1 methyltransferase activity (EC50: 0.18 μM). Piribedil hydrochloride has the potential for the research of parkinson's disease, circulatory disorders, cancers[1][2][3][4].
PRMT5-IN-27 (compound 481) is an inhibitor of PRMT5. PRMT5-IN-27 inhibits HCT116 cell proliferation with an IC 50 of 0.13 μM[1].
MM-102 (HMTase Inhibitor IX) TFA is a potent WDR5/MLL interaction inhibitor, achieves IC50 = 2.4 nM with an estimated Ki < 1 nM in WDR5 binding assay, which is >200 times more potent than the ARA peptide.
MAK683-CH2CH2COOH binds to EED (embryonic ectoderm development protein). MAK683-CH2CH2COOH and a VHL ligand for the E3 ubiquitin ligase have been used to design PROTAC EED degrader-1 (HY-130614) and PROTAC EED degrader-2 (HY-130615)[1].
DZNep (3-Deazaneplanocin A) is a potent histone methyltransferase EZH2 inhibitor.
DC-S239 is a selective histone methyltransferase SET7 inhibitor with an IC50 value of 4.59 μM. DC-S239 also displays selectivity for DNMT1, DOT1L, EZH2, NSD1, SETD8 and G9a. DC-S239 has anticancer activity[1].
HLCL-61 hydrochloride is a first-in-class small-molecule inhibitor of PRMT5. Target: PRMT5in vitro: HLCL-61 shows effective inhibition of symmetric arginine dimethylation (me2) of histones H3 and H4 in AML samples, starting at 12 h post-treatment and persisting after 48 h. Treatment of AML cell lines (MV4-11 and THP-1) and primary blasts with HLCL-61 also resulted in a decrease of cell viability. HLCL-61 is also effective in promoting apoptosis in MV4-11 and THP-1 cells after 48 h.[1]
PRMT5-IN-2 is a rotein arginine methyltransferase 5 (PRMT5) inhibitor extracted from patent WO2018130840A1, compound 3[1].
MS-0124 is a potent and selective inhibitor of G9a-like Protein (GLP) lysine methyltransferase with IC50 of 13 nM, shows >30-fold selectivity for GLP over G9a and other methyltransferases.