Chromatin/Epigenetics

<p>NPC26 is a small molecule that disrupts mitochondrial function and exhibits antitumor activity. It shows significant antiproliferative and cytotoxic effects on CRC cell lines (HCT-116, DLD-1, and HT-29). NPC26 induces mitochondrial permeability transition pore (mPTP) opening, generates reactive oxygen species (ROS), and triggers cell death. Additionally, NPC26 kills CRC cells by activating the AMP-activated protein kinase (AMPK) signaling pathway.</p>

<p>Aurora/LIM kinase-IN-1 (Compound F114) is a dual inhibitor targeting aurora and lim kinases, potentially useful in GBM cancer treatment efforts.</p>

<p>BRD4 Inhibitor-32 (example 15), a BRD4 inhibitor, is applicable in research pertaining to both acute and chronic kidney disease [1].</p>

<p>SGC6870N is inactive against PRMT6 and can be used as a negative control. It is the inactive enantiomer of SGC6870.</p>

<p>PF-06726304 acetate is a selective inhibitor of EZH2, with robust antitumor growth activity.</p>

<p>GNE-886 has a wide range of applications in life science related research.</p>

<p>HuRdegrader 2 (Compound 3) is a molecular glue that targets and degrades the RNA-binding protein Hu antigen R (HuR), achieving 30% degradation at 0.1 μM. It inhibits the proliferation of Colo-205 cancer cells with an IC50 of ≤200 nM. HuRdegrader 2 also shows high affinity for cereblon with an HTRF ratio &lt; 0.02.</p>

<p>MAT2A-IN-24 (Compound 9) is an inhibitor of methionine adenosyltransferase 2a (MAT2a), with an IC50 value of 20 nM for MAT2a inhibition and an antiproliferative IC50 value of 10 nM for HAP1MTAP–/– cells. MAT2A-IN-24 is applicable in the research of tumor diseases associated with MTAP deficiency.</p>

<p>M-525, a potent first-in-class menin-MLL inhibitor, binds at 3 nM IC50 and curbs MLL leukemia cell growth &amp; gene expression.</p>

<p>Glycyl-H-1152 is a potent ROCK-II inhibitor (IC50=11.8 nM) with high selectivity over CaMKII, PKG, Aurora A, PKA, and PKC. Better than Y-27632 and HA-1077.</p>

<p>HDAC6-IN-3 (Compound 14) is an oral anti-prostate cancer agent, inhibiting HDACs and MAO-A, with IC50 of 0.02-1.54 μM.</p>

<p>PARP7-IN-23 (compound 56) is a potent PARP7 inhibitor with an EC50 of 0.915 nM for pSTAT1 in NCI-H1373 cells, indicating its potential for cancer research.</p>

<p>JAK-IN-19 inhibits JAK (pIC50: 7.2, 7.7), less so for VEGFR2 (7.0) and Aurora B (5.8).</p>

<p>RK-0080552 (RK-552) is an inhibitor of the NSD2 histone methyltransferase. It demonstrates significant cytotoxicity against multiple myeloma (MM) cells harboring the t(4;14) translocation. This compound suppresses the IRF4 gene and decreases the dimethylation of histone H3 at lysine 36. RK-0080552 holds promise for research in hematologic malignancies.</p>

<p>Octyl-α-hydroxyglutarate (octyl-2-HG) enhances histone methylation and boosts the viability of LMP1-negative nasopharyngeal carcinoma (NPC) cells.</p>

<p>GSK852 is a potent, second bromodomain (BD2)-selective, bromo and extra-terminal domain (BET) inhibitor with pIC50 of 7.9.</p>

<p>iBFAR2, an inhibitor of BFAR, restores the CD8+ tumor-resident memory T cell subset against solid tumors. It promotes the binding of JAK2-STAT1 and enhances the phosphorylation of STAT1.</p>

<p>BRD4/NAMPT-IN-1 (Compound A2) exhibits strong inhibitory effects on NAMPT and BRD4, with IC50 values of 35 nM (NAMPT) and 58 nM (BRD4). This compound significantly suppresses the growth and migration of liver cancer cells while promoting apoptosis. Additionally, BRD4/NAMPT-IN-1 demonstrates potent anticancer activity in HCCLM3 xenograft mouse models without noticeable toxicity.</p>

<p>RU-0415529 is an orally active inhibitor of SARS-CoV-2 non-structural protein 14 (NSP14), with an IC50 of 356 nM. It inhibits viral RNA methylation and replication by stabilizing the cap-binding pocket through SAH binding. Additionally, RU-0415529 exhibits anti-infective activity in mouse models.</p>

<p>PKCiota-IN-1: Strong PKC-ι inhibitor (IC50=2.7 nM); also blocks PKC-α/ε (IC50s=45/450 nM).</p>

<p>AR/BET protein degrader-1 (Compound 149) is a dual-targeting protein degrader of Androgen Receptor and BET (bromodomain and extra-terminal domain), suitable for cancer research.</p>

<p>HIF-1α-IN-5 is an inhibitor of HIF-1α with an IC 50 value of 24 nM in HEK293T cells that also inhibits the activity of MAO-A.</p>

<p>Hesperadin hydrochloride is an ATP-competitive indolone inhibitor of Aurora A and B, with an IC50 value of 250 nM for Aurora B.</p>

<p>Triciferol is a VDR agonist and HDAC antagonist with 1,25D-like potency, affecting gene targets and tubulin, and shows anti-cancer effects in vitro. IC50=87nM.</p>

<p>NSD2-PWWP1-IN-3 (compound 36) is an effective inhibitor of NSD2-PWWP1, with an IC50 value of 8.05 µM. It has potential applications in cancer research.</p>

<p>CRV431 is a novel Pan-Cyclophilin Inhibitor, potently inhibiting all cyclophilin isoforms tested - A, B, D, and G (IC50 values ranged from 1-7 nM).</p>

<p>TK-129: Oral KDM5B inhibitor, IC50=44 nM, low-toxicity, cardioprotective, aids in heart disease research.</p>

<p>5-Ph-IAA-AM, eggshell-permeable analog of 5-Ph-IAA, boosts protein degradation in embryos, useful for studying proteins in C. elegans.</p>

<p>(Rac)-Nanatinostat ((Rac)-CHR-3996, example 44) is a potent HDAC inhibitor with an IC50 of less than 330 nM. It exhibits anticancer properties, effectively inhibiting the growth of HeLa, U937, and HUT cells.</p>

<p>Sapintoxin D is a fluorescent phorbol ester and selective activator of protein kinase C.</p>

<p>HDAC6-IN-9 is a γ-secretase modulator that can significantly reduce the level of Aβ42 in mouse brain and can be used to study neurological diseases.</p>

<p>EBET-590 is a BET inhibitor utilized in cancer research.</p>

<p>AZ-3 is a potent and selective JAK1 inhibitor (IC50: 34 nM).</p>

<p>AMPTX-1 is a molecular glue functioning as a potent, selective, and reversible covalent degrader of BRD9 by recruiting it to the E3 ligase DCAF16.</p>

<p>EZH2-IN-12 (Compound 5) is a potent inhibitor of EZH2, which has potential for studies of CNS malignancies.</p>

<p>CEE321 is an effective pan-JAK inhibitor with an IC50 of 54 nM. It effectively inhibits biomarkers associated with atopic dermatitis.</p>

<p>PARP1-IN-5 is a potent, selective, orally active, low-toxicity PARP-1 inhibitor with an IC50 value of 14.7 nM. PARP1-IN-5 can be used in cancer research.</p>

<p>Pim-1 kinase inhibitor 3 (Compound H5) is a potent inhibitor of Pim-1 kinase, demonstrating an inhibitory concentration (IC50) of 35.13 nM [1].</p>

<p>EN884 is a BRD4 degrader that functions through an SKP1 and proteasome-dependent degradation pathway. It is utilized in the synthesis of proteolysis-targeting chimeras (PROTAC).</p>

<p>BRD4 Inhibitor-17: Potent with 0.33 μM IC50; modulates gene expression, may counter arsenic toxicity.</p>

<p>O-Desmethyl Midostaurin is the active Midostaurin metabolite via cytochrome P450 liver enzyme metabolism.</p>

<p>SMARCA2-IN-6 is a potent inhibitor of SMARCA2 (also known as BRM), exhibiting an IC50 of less than 5 nM against both SMARCA2 and SMARCA4. Additionally, this compound suppresses the expression of the KRT80 gene in H1299 cells with an IC50 of 26 nM and inhibits the proliferation of SKMEL5 cells carrying a BRG1 mutation with an IC50 value of 13 nM.</p>

<p>MS8511: Selective, irreversible G9a/GLP inhibitor. IC50: 100 nM (G9a), 140 nM (GLP). Lowers H3K9me2, anti-proliferative. Useful in cancer/AD/PWS research.</p>

<p>PARP7-IN-12, a potent inhibitor targeting PARP7, exhibits an IC50 of 7.836 nM. This compound is applicable in cancer research.</p>

<p>FNDR-20123: First safe, effective anti-malarial HDAC inhibitor for Plasmodium (IC50: 31 nM) &amp; human HDACs, with nanomolar potency across several subtypes.</p>

<p>CBP/p300-IN-16 (compound 1) is a potent inhibitor of EP300/CBP HAT, acting on HAT EP300 (IC50: 0.61 μM) and LK2 H3K27 (IC50: 2.24 μM).</p>

<p>SIRT1-IN-5 (215) is a modulator of the NAD-dependent protein deacetylase SIRT1.</p>

<p>Tyk2-IN-3 is an inhibitor of Tyk2 pseudokinase (IC50: 485 nM).</p>

<p>BET-IN-1 is a potent inhibitor of BET, exhibiting good brain permeability and a reasonable metabolic stability.</p>

<p>JAK3-IN-11: potent oral JAK3 inhibitor (IC50=1.7 nM), noncytotoxic, &gt;588-fold selectivity, blocks T-cell growth; useful in autoimmune research.</p>

<p>CARM1-IN-3 dihydrochloride (17b) is a potent CARM1 inhibitor (IC50: 0.07 μM) with selectivity over CARM3 (IC50 &gt;25 μM).</p>

<p>KDOAM-25 trihydrochloride selectively inhibits KDM5 enzymes, boosts H3K4 methylation, and suppresses MM1S cell growth.</p>

<p>LSD1-IN-19 is a potent, selective LSD1 inhibitor with Ki of 0.108 μM and 72h IC50 values of 0.17-0.40 μM.</p>

<p>CFT8634 degrades BRD9, for synovial sarcoma and SMARCB1 tumor research, from patent WO2021178920A1.</p>

<p>P300 bromodomain-IN-1 blocks c-Myc, induces G1/G0 arrest, apoptosis. Potent EP300 inhibitor (IC50: 49 nM).</p>

<p>SCH-1473759 is an inhibitor of the aurora (IC50s: 4 and 13 nM for Aurora A and B, respectively).</p>

<p>QCA570 is an effective BET degrader based on PROTAC (IC50: 10 nM for BRD4 BD1 Protein).</p>

<p>Londamocitinib (JAK1-IN-7) is a selective and potent JAK1 inhibitor with anti-inflammatory activity.</p>

<p>MAO A/HDAC-IN-1 is an effective monoamine oxidase A (MAO A) and HDAC dual inhibitor, which can be used for glioma research.</p>

<p>BRD4 D1-IN-2 (compound 26), a BRD4 D1 inhibitor, IC50 &lt;0.092 μM, 15 nM affinity, &gt;500x selectivity over BRD2 D1/BRD4 D2.</p>

<p>HDAC6-IN-12 is a potent inhibitor of HDAC6 that binds in the DNA chain, causing DNA damage and exhibiting anticancer effects that can be used in cancer research</p>

<p>Balanol is an ATP-competitive Protein Kinase C and Protein Kinase A inhibitor.</p>

<p>Tyk2-IN-17 (compound 185) effectively inhibits TYK2 [1].</p>

<p>Tyk2-IN-14, a small molecule inhibitor of TYK2, is significant in treating inflammatory diseases and conditions linked to hypersecretion of IFNa and interferons [1].</p>

<p>PARP-1-IN-1: Selective, oral PARP-1 inhibitor with 0.96 nM IC50; well-tolerated and effective in single-dose MDA-MB-436 model.</p>

<p>B026: Oral p300/CBP HAT inhibitor, IC50: p300 1.8 nM, CBP 9.5 nM; targets AR+ prostate cancer cells.</p>

<p>Pim-1 kinase inhibitor 6 (Compound 4d) is a robust inhibitor of Pim-1 kinase, demonstrating an IC 50 of 0.46 μM. It significantly exhibits cytotoxic effects on cancer cells [1].</p>

<p>DS44470011 is an inhibitor of hypoxia-inducible factor prolyl hydroxylase (HIF-PHD) with oral bioavailability. It enhances the release of erythropoietin (EPO) from cells and is utilized in research related to renal anemia.</p>

<p>IBL-302 (AMU302), an orally available dual-signaling inhibitor targeting PIM and PI3K/AKT/mTOR, is effective against breast cancer and neuroblastoma. It has shown in vivo efficacy in a nude mouse xenograft model by combating trastuzumab resistance. Additionally, IBL-302 augments the effectiveness of widely used cytotoxic chemotherapy drugs such as cisplatin, doxorubicin, and etoposide [1] [2] [3].</p>

<p>SE-7552, a derivative of 2-(difluoromethyl)-1,3,4-oxadiazole (DFMO), serves as an orally active, highly selective non-hydroxamate HDAC6 inhibitor, boasting an IC50 of 33 nM. It exhibits over 850-fold selectivity against all other known HDAC isozymes. Demonstrating efficacy in vivo, SE-7552 effectively inhibits the growth of multiple myeloma. Additionally, it functions as an anti-obesity agent in diet-induced obese mice [1] [2].</p>

<p>Menin-MLL inhibitor 26: Active reference, inhibits cell growth, used in leukemia research.</p>

<p>EED ligand 1: potent PRC2 inhibitor targeting EED subunit.</p>

<p>MDH1/2-IN-1 is an MDH1/2 inhibitor with IC50 values of 1.07 nM and 1.06 nM, respectively. It suppresses mitochondrial respiration and the HIF-1α pathway. MDH1/2-IN-1 exhibits significant antitumor potential and offers new avenues for developing drugs targeting cancer metabolism.</p>

<p>JAK1/TYK2-IN-4 serves as a dual inhibitor targeting both JAK and TYK2, displaying IC50 values of 39 nM and 21 nM, respectively. It is also orally bioavailable [1].</p>

<p>WDR5-IN-5: Selective oral inhibitor for WDR5's WIN site with high affinity (Ki&lt;0.02 nM) and anti-cancer properties. Good pharmacokinetics.</p>

<p>Aurora inhibitor 1 is a potent Aurora inhibitor (IC50: ≤ 4 nM and ≤13 nM for Aurora A and Aurora B kinase).</p>

<p>BET-IN-8 (Compound 27) is a potent inhibitor of BET (Ki: 0.83 μM, Kd: 0.571 μM), which ameliorates LPS-induced sepsis in vivo.BET-IN-8 has shown potential in</p>

<p>GSK8814 is a selective and ATAD2/2B bromodomain chemical probe and inhibitor (binding constant pKd=8.1 and a pKi=8.9 in BROMOscan).</p>

<p>Basroparib is an inhibitor of ribose polymerase (PARP) and has shown antitumour effects.</p>

<p>BRD-7880 is a potent and highly specific inhibitor of aurora kinases B and C.</p>

<p>PRMT5 IN-1 hydrochloride is a potent PRMT5 inhibitor (IC50: 11 nM), forms covalent adduct with C449, and converts to an aldehyde in vivo.</p>

<p>DS17701585: Oral EP300/CBP inhibitor; potent on CBP, EP300, H3K27, &amp; SOX2; useful for cancer research.</p>

<p>Tyk2-IN-15 (Compound 97) is a selective inhibitor of tyrosine kinase 2 (Tyk2) with an IC50 value ≤ 10 nM for Tyk2-JH2. It is utilized in the research of inflammatory and autoimmune diseases [1].</p>

<p>BRD4-BD1/2-IN-2 inhibits BRD4 BD1/BD2 with IC50 &lt;300 nM/&lt;0.5 nM (WO2021233371A1).</p>

<p>HDAC2-IN-1 is an oral HDAC2 inhibitor (IC50: 0.5 μM), crosses the blood-brain barrier, and inhibits HDAC1 and HDAC8.</p>

<p>PRMT5-IN-18 (Compound 002) is a potent inhibitor of PRMT5 and can be used in the study of PRMT5-mediated diseases, such as tumours.</p>

<p>HDAC-IN-33 inhibits HDAC1/2/6 (IC50: 24/46/47 nM), exhibits potent antitumor activity in vitro and in vivo, and activates antitumor immunity.</p>

<p>MTL-CEPBA is a small activating RNA that targets C/EBPα upregulation and exhibits anti-inflammatory and anti-cancer effects.</p>

<p>Aurora A inhibitor 1: potent, selective, targets cancer-linked Aurora A overexpression, potential for cancer research. (WO2021147974A1, 49)</p>

<p>ORIC-944 is an orally available, selective variant of PRC2 with anticancer activity for the study of prostate cancer.</p>

<p>Pocenbrodib (FT-7051) is a potent inhibitor of the bromodomain of the CBP/p300 family with potential antitumour activity and is palatable for cancer research.</p>

<p>GSK3368715 dihydrochloride (EPZ019997 dihydrochloride) is a PRMTs inhibitor , with anticancer activity, for the study of advanced solid tumors.</p>

<p>LLY-283, PRMT5 inhibitor, IC50 22 nM, Kd 6 nM, oral, selective, with antitumor effects.</p>

<p>DN02: a potent, selective BRD8(1) bromodomain probe; Ki=32 nM; 30x more affine than BRD8(2).</p>

<p>EZM0414 is a potent, selective, orally bioavailable inhibitor of SETD2 with IC50 of 18 nM in SETD2 biochemical assay and IC50 of 34 nM in a cellular assay.</p>

<p>INCB054329 is a BET inhibitor targeting BRD2/3/4 and BRDT with IC50s ranging from 1-119 nM.</p>

<p>AMG-193 is an inhibitor of the MTA-PRMT5 complex and is used in the study of cancer, respiratory diseases and digestive disorders.</p>

<p>BRD0639 is a first-in-class PRMT5-substrate interaction inhibitor for PBM-dependent PRMT5 activity studies.</p>

<p>Sinefungin (Adenosyl-Ornithine) is an effective inhibitor of virion mRNA(guanine-7-)-methyltransferase, mRNA(nucleoside-2'-)-methyltransferase, and viral</p>

<p>JDTic, a 4-phenylpiperidine derivative distantly related to analgesics like meperidine and ketobemidone and more closely to the mu opioid antagonist alvimopan, exhibits a notably long duration of action, maintaining effects in animals for weeks following a single dose. This duration is not due to irreversible binding to the kappa opioid receptor but rather to altered activity of c-Jun N-terminal kinases. As a highly selective antagonist for the κ-opioid receptor, without influencing the μ- or δ-opioid receptors, JDTic has shown potential in animal studies for producing antidepressant and anxiolytic effects. It also demonstrates promise in treating addiction to substances such as cocaine and morphine, distinguishing itself structurally from other kappa antagonists like norbinaltorphimine.</p>