NAH-C3-GPKK is a potent, selective protein N-terminal methyltransferase 1 (NTMT1) bisubstrate inhibitor with Kiapp of 7 nM in endogenous proteomes.NAH-C3-GPKK also potently inhibit a methyltransferase complex HemK2-Trm112 (also known as KMT9-Trm112, IC50=0.3 uM).NAH-C3-GPKK is the first potent inhibitor for HemK2/KMT9.

MV1035 (MV-1035) is a novel small molecule that reduce U87 GBM cells migration and invasiveness, targeting m6A demethylase ALKBH5, also inhibits ALKBH2; MV1035 directly inhibits active recombinant ALKBH5 protein and, consequently, negatively regulates CD73 protein expression without affecting CD73 mRNA transcription. In PD-GSCs, MV1035 has a synergistic effect with TMZ in reducing cell viability and their ability to form spheres. MV1035 is able both to reduce the expression of MGMT and to inhibit ALKBH2 activity.

MU1656 (MU 1656 ) is a potent, highly selective inhibitor of histone methyltransferase DOT1L with IC50 of 2 nM; MU1656 displays highly selectively against a panel of 37 methyltransferases. MU1656 is more metabolically stable and significantly less toxic in vivo than pinometostat.

MO-I-500 is a pharmacological inhibitor of m6A demethylase FTO, inhibits purified FTO demethylase catalyzing demethylation with IC50 of 8.7 uM.MO-I-500 treated cells exhibited a global increase in RNA methylation.HeLa cells treated with 25 μM MO-I-500 for 24 hours showed a 9.3% increase in N6-methyl-adenosine content in total RNA.MO-I-500 treatment caused a dramatic (>95%) inhibition in colony formation in SUM149-Luc cells.MO-I-500 modulates various microRNA in treated (25uM) HeLa cells.MO-I-500 treatment also led to decreased levels of FTO and IRX3 proteins in the SUM149 cells, with relatively little effect on cell growth.MO-I-500 can strongly reduce the adverse effects of streptozotocin (STZ) model of AD in human astrocytoma CCF-STTG1 cells.

MJM-1 is a small-molecule brain-penetrant HDAC inhibitor that increases the overall level of histone 3 (H3) acetylation in prostate cancer cell line.MJM-1 injected intraperitoneally (i.p.) crossed the BBB in mice and could be detected in the hippocampus, a brain region that mediates memory.MJM-1 (post-training i.p. administration) enhanced hippocampus-dependent spatial memory consolidation in male mice.

MINA53 inhibitor 9 is a first in class, potent, selective MINA53 inhibitor with IC50 of 1.6 uM, selective over NO66, KDM4-6 and other JmjC oxygenases.

LSH-A54 is a potent, class I selective HDAC inhibitor with IC50 of 26.2 nM (HDAC1) and 59.3 nM (HDAC2); LSH-A54 displays no significant inhibition against HADC3/6 (IC50>10 uM). LSH-A54 exhibits antiproliferative properties against breast cancer cell lines T-47D (IC50=1.58 uM), MCF-7 (IC50=1.32 uM) and BT-474 (IC50=2.55 uM). LSH-A54 attenuates cell migration significantly in wound healing assay and comparably to the pan-HDACi vorinostat, whereas the HDAC1-3 selective HDACi entinostat has no significant effect on cell migration. LSH-A54 reduced the number of colonies significantly in clonogenic survival assay compared to entinostat and showed comparable activity to pan-HDACi vorinostat.

LM146 (LM-146) is a potent and selective inhibitor of pan-PB1 bromodomains (Polybromo-1 protein, PBRM1 or BAF180), binds to PB1(2), PB1(5), and SMARCA2B with KD values of 110, 61, and 2100 nM, respectively.LM146 displayed 34-fold selectivity profile for PB1(5) over SMARCA2, showed no binding to any bromodomains outside the sub-family VIII at 10 uM.PB1 (Polybromo-1 protein) is a component of the BRG1/BRM-associated factor (PBAF) complex, a human analog of the yeast switch/sucrose non-fermenting (SWI/SNF) complex. PB1 is a unique epigenetic reader that contains six distinct bromodomains, while other known bromodomain-containing proteins possess at most two bromodomains. The multi-subunit PBAF complex contains three bromodomain-containing proteins (BCPs): BRD7, a member of the sub-family IV, and SMARCA4 (also known as BRG1) and PB1, two members of the sub-family VIII.

KDOBA67 is a novel cell-permeable inhibitor of H3K27 lysine demethylase KDM6A/B, inhibits TBXT expression chordoma cell lines.KDOBA67 displayed in vitro inhibitory activity in the low micromolar range with IC50 values of 2 to 5 uM in various chordoma cell lines, leading to induction of apoptosis.H3K27 demethylase inhibition via KDOBA67 alters chromatin state at TBXT and inhibits its expression.TBXT was a KDM6A/B target gene, and chromatin changes at TBXT following KDOBA67 treatment were associated with a reduction in TBXT protein levels.KDOBA67 treatment downregulated expression of a network of transcription factors critical for chordoma survival and upregulated pathways dominated by ATF4-driven stress and proapoptotic responses.

IRBM6 (Class I HDAC-IN-6) is a potent, class I selective HDAC inhibitor with EC50 of 50 nM (HeLa cellular), HDAC1/2/3 IC50 of 1.7/2.8/1.1 nM.IRBM6 weakly inhibits HDAC6 (IC50=177 nM) and is inactive at 5 uM against HDACs 4-7.IRBM6 showed a potent inhibitory effect on the growth TC-797s and two additional NUT carcinoma (NC) cell lines, PER-403, and 10-15.IRBM6 induces a transcriptional program of differentiation in NC cells, demonstrated large-scale changes in gene expression that were significantly enriched with differentiation gene sets and depleted of pro-growth gene sets, including those of MYC and E2F targets.IRBM6 repressed growth and induced differentiation of NUT carcinoma (NC) cells in proportion to inhibition of NUT transcriptional activity.

iP300w is a potent p300/CBP inhibitor, inhibits p300-mediated H3K9 acetylation with IC50 of 33 nM in HTRF assay.iP300w diminishes DUX4-induced toxicity and inhibits DUX4-mediated transcription.iP300w blocks DUX4-induced H3 acetylation and prevents the increase in expression of DUX4 target genes, erases the DUX4-mediated transcriptional fingerprint in FSHD myoblasts.iP300w impairs DUX4-mediated transcription in vivo in the iDUX4pA FSHD mouse model.

IMP-1575 (IMP1575) is a potent, selective Hedgehog acyltransferase (HHAT) inhibitor with Ki/IC50 of 38 nM/0.75 uM (Acyl-cLIP assay).IMP-1575 is the first sub-micromolar small-molecule HHAT inhibitor reported to-date.IMP‐1575 (50-0.023 μM) was therefore analyzed for effects on HHAT kinetics at varying Pal‐CoA concentrations (50–0.19 μM).IMP-1575 is a chemical tool and methodology to provide insight into HHAT which may expedite future studies and drug discovery efforts against this important target class.

GSK737 (GSK-737) is a potent, highly selective BET BD2 inhibitor with pIC50 of 7.3 (BRD4 BD2), 200-fold selectivity over BRD4 BD1.

GSK3735967 is a potent, selective, non-nucleoside inhibitor of DNMT1 with IC50 of 40 nM.

GSK3543105 is a potent, selective, non-nucleoside inhibitor of DNMT1 with IC50 of 33 nM.

GSK217 (GSK-217) is a potent, highly selective BET BD2 inhibitor with pIC50 of 7.5 (BRD4 BD2), 300-fold selectivity over BRD4 BD1.

FTO inhibitor CS1 (NSC 337766) is a potent, selective small-molecule inhibitor of m6A demethylase FTO, inhibits m6A demethylation with IC50 of 142.6 nM in vitro (cell-free) assays.CS1 is highly efficacious FTO inhibitors with potent anti-leukemic efficacy againsta panel of leukemia cell lines with high FTO expression in vitro (IC50 range from 20 to 175 nM, MV4-11 IC50=58.9 nM).CS1 blocks the binding of FTO with its known target mRNAs, such as MYC, CEBPA, and RARA, notably increased global m6A abundance in AML cells, does not suppress the enzymatic activity of ALKBH5, or TET1.CS1 treatment resulted in substantially increased apoptosis and cell cycle arrest (at the G0 phase), also significantly promoted myeloid differentiation in human AML cells.FTO inhibitor CS1 substantially delayed AML progression and improved survival in AML PDX mouse model, significantly more effective than FB23-2.

FT108 (FT-108) is a potent, selective HDAC6 inhibitor (IC50=26 nM) relative to other HDAC family members (HDAC3 IC50=6.68 uM and HDAC8 IC50=4.07 uM).

ENL YEATS Domain inhibitor 7 is a selective, small molecule inhibitor of ENL YEATS Domain with IC50 of 0.62 uM in inhibiting the ENL-acetyl-H3 interaction.ENL YEATS Domain inhibitor 7 displayed strong selectivity toward the ENL YEATS domain over all other human YEATS domains.ENL YEATS Domain inhibitor 7 exhibited on-target inhibition of ENL in cultured cells and a synergistic effect with the bromodomain and extraterminal domain inhibitor JQ1 in killing leukemia cells.

DK1-04 is a potent, selective, cell-permeable small-molecule SIRT5 inhibitor with IC50 of 0.34 uM, shows no inhibition on SIRT1-3/6 at 83 uM.

DC-CBi-22 is a highly potent, selective CECR2 bromodomain inhibitor with IC50 of 8.0 nM, 24.9-fold selectivity over BPTF BRD.

DC541 (DC 541) is a potent, selective peptidomimetic inhibitor of Protein N-terminal methyltransferase NTMT1 with IC50 of 0.34 uM; DC541 exhibits over 300-fold selectivity to several methyltransferases. DC541 inhibited funtions the cellular α-N-terminal methylation level of regulator of chromosome condensation 1 (RCC1, IC50 value of 30 μM) in human colorectal cancer HT29 cells.

CRCM5484 is a potent, BET BDII-selective inhibitor with IC50 of 130/20/71 nM for BRD4-BD2/BRD3-BD2/BRD2-BD2, respectively.CRCM5484 displays 475-fold selectivity over its first bromodomain (BRD3-BD2 vs BRD3-BD1).CRCM5484 demonstrates very low activity in various cell-based assays.CRCM5484 modulates the anti-leukemic activity in combination with various FDA-approved and/or in-development drugs in a cell- and context-dependent differential manner.

BY27 (BD2 inhibitor BY27) is a potent, highly selective BET BD2 inhibitor with Ki of 8.9/8.2/14.2 nM for BRD2/3/4-BD2 respectively.BY27 displays 38-fold selectivity for BRD2-BD2 over BRD2-BD1.BY27 showed good antitumor activity in the MV4-11 xenograft model with an improved in vivo tolerance in mice compared with I-BET762.

BRD8 inhibitor DN02 is a first-in-class selective and cellularly active probe for NuA4 factor BRD8 (BD1) with IC50 of 34 nM, no affinity for BRD8 {BD2}, CBP, and p300.

BRD4 D1 inhibitor 30 is a high-affinity, BRD4 D1-selective chemical probe with Kd of 18 nM, 500-fold selectivity against BRD2 D1 and BRD4 D2.BRD4 D1 inhibitor 30 down regulated inflammation, IL-8 and chemokine in cell based assays, but was unable to reduce c-Myc expression at low concentration in multiple myeloma cells.

BR-001 (BR001) is a potent, selective, allosteric inhibitor of EED subunit of PRC2 complex, disrupts EED-H3K27me3 interaction (IC50=4.5 nM).BR-001 directly binds to EED in the H3K27me3-binding pocket, BR-001 significantly increases the thermal stability of EED in thermal shift assay.BR-001 is selective for EED, has no activity against 371 wild-type kinases.BR-001 significantly reduced the cellular H3K27me3 level and also exhibited a strong antiproliferative effect in Karpas 422 cells.BR-001 inhibited proliferation of DLBCL cells and tumor growth, and upregulated target genes expression.BR-001 has potent antitumor efficacy in vivo, modulates immune response to suppress syngeneic CT26 colon tumor.

BAY-155 (BAY155) is a novel, potent and selective menin-MLL inhibitor with binding IC50 of 8 nM, 10-fold better compared to that of MI-503; BAY-155 demonstrated a significantly enhanced selectivity profile compared to MI-503 in a panel of assays covering numerous safety pharmacology-relevant targets including GPCRs, ion channels and transporters. BAY-155 shows anti-proliferative activity in a large cell line panel, exhibits specific therapeutic activityin AML/ALL models.

ALKBH5 inhibitor 6 is a small molecule inhibitor of RNA 6-N-methyladenosine (m6A) demethylase ALKBH5, inhibits ALKBH5 RNA m6A demethylation activity with IC50 of 1.79 uM.

ALKBH5 inhibitor 3 is a small molecule inhibitor of RNA 6-N-methyladenosine (m6A) demethylase ALKBH5, inhibits ALKBH5 RNA m6A demethylation activity with IC50 of 0.84 uM.