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.
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].
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].
XY1 is a very close analogue of SGC707 (a potent, selective, and non-competitive inhibitor of PRMT3 with IC50 of 31 nM), but XY1 is completely inactive.Target: PRMT3XY1 is a close analogue of SGC707, is completely inactive againstPRMT3 at concentrations as high as 100 μM. XY1 contains a naphthyl group replacing the isoquinoline group, lacks the key hydrogen bond with T466. The naphthyl ring of XY1 could act as a weak hydrogen-bond acceptor, but this should come with a substantial enthalpic penalty. The more than 1000-fold potency loss of XY1 compared with SGC707 supports this analysis. It is unclear whether other factors such as electronic effects also contributed to the potency loss of XY1 compared with SGC707. SGC707 and XY1 are a pair of excellent tools for the biomedical community to further elucidate biological functions and disease associations of PRMT3.
UNC 0631 is a potent G9a inhibitor with IC50 value of 4 nM.IC50 value: 4 nM [1]Target: G9aUNC 0631, which had high in vitro potency versus G9a and improved lipophilicity, was highly potent (IC50 < 0.06 μM) in reducing H3K9me2 levels in MDA-MB-231 cells and had low cell toxicity. In particular, compounds 7 was more potent than compound 5 and had a similar tox/function ratio in MDAMB-231 cells. UNC 0631 showed excellent separation of functional potency versus cell toxicity in MDA-MB-231 cells, thecompound was further evaluated in a variety of cell lines to characterize it's cellular potency and cell toxicity. UNC 0631 had excellent tox/functionratios in these cell lines.
RK-701 is an highly selective and non-genotoxic inhibitor of G9a with IC50 value of 23-27 nM. RK-701 selectively up-regulates HbF, γ- Globin, BGLT3 expression, down-regulates H3K9me2 expression. RK-701 also has inhibition for BCL11A and ZBTB7A[1].
PFI-2 hydrochloride is a a first-in-class, potent, highly selective, and cell-active inhibitor of the methyltransferase activity of SETD7 with IC50 of 2 nM, 500 fold active than (S)-PFI-2.IC50 value: 2 nM [1]Target: SETD7(R)-PFI-2 is highly selective (>1,000-fold) for SETD7, over a panel of 18 other human protein methyltransferases and DNMT1, and was shown to be inactive against 134 additional ion channel, GPCR, and enzyme targets (<35% inhibition at 10 μM). (R)-PFI-2 binds to SETD7 only in the presence of SAM. PFI-766, a biotinylated variant of (R)-PFI-2 that retains the ability to bind and inhibit SETD7 (IC50 110 ± 26 nM in our in vitro enzymatic assay). PFI-766 engagement of endogenous SETD7 was also confirmed by mass spectrometry that supported the high specificity of the compound for endogenous SETD7.
PF-06726304 acetate is a potent and selective EZH2 inhibitor. PF-06726304 acetate inhibits wild-type and Y641N mutant EZH2 with Kis of 0.7 and 3.0 nM, respectively. PF-06726304 acetate displays robust antitumor growth activity[1].
BIX-01338 hydrate is a histone lysine methyltransferase inhibitor.
MS023 is a potent, selective, and cell-active inhibitor of human type I PRMTs with IC50 of 4-119 nM.IC50 value: 4-119 nMTarget: type I PRMTs in vitro: MS023 potently inhibits PRMT1 (IC50 = 30 ± 9 nM), PRMT3 (IC50 = 119 ± 14 nM), PRMT4 (IC50 = 83 ± 10 nM), PRMT6 (IC50 = 4 ± 0.5 nM), and PRMT8 (IC50 = 5 ± 0.1 nM). Importantly, MS023 does not inhibit any type II PRMTs (PRMT5 and 9) and type III PRMT (PRMT7) at concentrations up to 10 μM. MS023 displays high potency for type I PRMTs including PRMT1, -3, -4, -6, and -8 but is completely inactive against type II and type III PRMTs, protein lysine methyltransferases and DNA methyltransferases. MS023 potently decreases cellular levels of histone arginine asymmetric dimethylation. It also reduces global levels of arginine asymmetric dimethylation and concurrently increased levels of arginine monomethylation and symmetric dimethylation in cells. [1]
MRK-740 is a potent, selective and substrate-competitive PRDM9 histone methyltransferase inhibitor with an IC50 of 80 nM. MRK-740 is more selective for PRDM9 than other histone methyltransferases and other non-epigenetic targets. MRK-740 reduces PRDM9-dependent trimethylation of H3K4 (IC50 = 0.8 µM)[1].
JNJ-64619178 is a selective and pseudo-irreversible PRMT5 inhibitor[1].
LLY-507 is a potent and selective inhibitor of protein-lysine methyltransferase SMYD2 with an IC50 of 15 nM.
CMP-5 (PRMT5-IN-5)is a first-in-class, small-molecule PRMT5-specific inhibitor that blocks EBV-driven B-lymphocyte transformation and survival, without effect on normal B cells; displays no activity against other type I (PRMT1 and PRMT4) and type II (PRMT7) enzymes; inhibition of PRMT5 leads to lost recruitment of a PRMT5/p65/HDAC3-repressive complex on the miR96 promoter, restored miR96 expression, and PRMT5 downregulation.
EZH2-IN-4 is an orally active, potent EZH2 inhibitor with IC50s of 0.923 nM and 2.65 nM against wild type (WT) 5-membered (5-mer) EZH2 and mutant 5-mer EZH2, respectively. EZH2-IN-4 has anti-cancer activity[1].
BAY-598 is selective small molecule inhibitor of SMYD2 .
DCG066 is a G9a inhibitor in vitro.
LEM-14 is a specific inhibitor of histone lysine methyltransferase NSD2 (MMSET/WHSC1) with in vitro IC50 of 132 uM, and that is inactive against the closely related NSD1 and NSD3.
EPZ-719 is a novel and potent SETD2 inhibitor ( IC50 = 0.005 μM) with a high selectivity over other histone methyltransferases.
EPZ004777 is a potent, selective DOT1L inhibitor with an IC50 of 0.4 nM.
3-Deazaneplanocin A hydrochloride is a potent histone methyltransferase EZH2 inhibitor.
XF067-68 is a PROTAC for targeted degradation of WD40 repeat domain protein 5 (WDR5) (extracted from patent WO2019246570A1)[1].
Igermetostat is EZH2 inhibitor, used in cancer research in vivo and in vitro[1].
Valemetostat tosylate (DS-3201 tosylate) is a first-in-class EZH1/2 dual inhibitor, used in the research of relapsed/refractory peripheral T-cell lymphoma[1].
UNC0642 is a potent and selective G9a/GLP inhibitor, with an IC50 of less than 2.5 nM.
Sinefungin is a potent inhibitor of virion mRNA(guanine-7-)-methyltransferase, mRNA(nucleoside-2'-)-methyltransferase, and viral multiplication[1]. Sinefungin, a SET7/9 inhibitor, ameliorates renal fibrosis by inhibiting H3K4 methylation [2].
MS67 is a potent and selective WD40 repeat domain protein 5 (WDR5) degrader with a Kd of 63 nM. MS67 is inactive against other protein methyltransferases, kinases, GPCRs, ion channels, and transporters. MS67 shows potent acticancer effects[1].
EPZ011989 hydrochloride is a potent and orally active Zeste Homolog 2 (EZH2) inhibitor, with a Ki value of <3 nM. EPZ011989 shows anti-tumor activity. EPZ011989 is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups[1].
DS-437 is a potent, selective, dual inhibitor of PRMT5 and PRMT7 with IC50 of 6.0 uM for both, DS-437 is inactive against 29 other human protein-, DNA-, and RNA-methyltransferases; inhibits methylation of full-length histone 4 by PRMT5-MEP50 with an IC50 of 37 ± 1.2 μM in a biochemical assay; inhibits symmetrical dimethylation of PRMT5 substrates in cells.
MI-3 is a Menin-MLL interaction inhibitor with IC50 value of 648 ± 25 nM.IC50 value: 648 ± 25 nM [1]Target: Menin-MLLin vitro: The menin-MLL inhibitors very effectively blocked proliferation of MLL-AF9 and MLL-ENL transduced BMC, with GI50 values of about 5 μM for MI-2 and MI-3. MI-2 and MI-3 showed only a small effect on the cell growth of E2A-HLF transduced BMC (GI50 > 50 μM). MI-2 and MI-3 substantially and specifically reduce the immortalization potential of cells transformed with MLL fusion oncoproteins [1].in vivo: MLL-AF9 transformed BMC that remained viable after 7 days of treatment with MI-2 and MI-3 showed substantial changes in morphology, indicative of monocytic differentiation, as evidenced by increased cell size, lower nuclear to cytoplasmic ratio and highly vacuolated cytoplasm. Consistent with the change in cell morphology, the expression of CD11b was substantially increased on MLL-AF9 transformed BMC after 7 days of treatment with MI-2 and MI-3 [1].