Chromatin/Epigenetics

<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>

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.

LSD1-IN-35 (Compound Z-1) is a selective inhibitor of LSD1, exhibiting an IC50 of 108 nM. This compound inhibits the demethylation of H3K4me1/2 and acts as an immunomodulator. Additionally, LSD1-IN-35 enhances the responsiveness of gastric cancer cells to T-cell killing by reducing PD-L1 expression, thereby weakening the PD-1/PD-L1 interaction.

CM-414: HDAC/PDE5 inhibitor, targeting Alzheimer’s, IC50s: PDE5 (60 nM), HDAC1/2/3/6. Reduces Aβ, pTau in mice, boosts cognition.

Itareparib is a PARP inhibitor with demonstrated antitumor activity.

TYK2ligand 2 is the TYK2 ligand of PROTACTYD-68. TYD-68 is a highly potent and selective CRBN-recruiting TYK2 PROTAC degrader with a DC50 value of 0.42 nM.

PRMT5-IN-44 (compound 12) is an inhibitor of PRMT5, specifically utilized in cancer research.

ROPA, a potent PKCalpha and PKCgamma activator, promotes tumor growth through PKC-activation.

Trichostatin A S-isomer, a HDAC 1, 3, 4, 6, 10 inhibitor with IC50 ~20 nM, has wide-ranging epigenetic effects.

LSD1-IN-13 hydrochloride (7e) is an oral LSD1 inhibitor (IC50: 24.43 nM), promoting differentiation in AML cell lines.

BPTF-IN-BZ1 is a BPTF inhibitor that possesses a high potency with a Kd of 6.3 nM.

O6BTG-C8-αGlu is an O6-methylguanine-DNA methyltransferase (MGMT) inhibitor with an IC50 of 0.45 μM. At a concentration of 0.1 μM, it fully inhibits MGMT in HeLaS3 cells and demonstrates no cytotoxicity even at prolonged high doses (up to 20 μM). This compound is suitable for research on MGMT-related cancers.

(1-Nitroethene-1,2-diyl)dibenzene (alpha-Nitrostilbene; α-Nitrostilbene) serves as an inhibitor of protein arginine methyltransferase 1 (PRMT1; histone H4 methylation assay with an IC50 of 11 μM). At concentrations of 10 and 100 μM, it also inhibits histone H4 methylation caused by PRMT8 but does not affect methylation of histone H3.1 induced by CARM1 or Set7/9.

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

BAY-3827 is an AMPK inhibitor with antiproliferative activity and antitumor activity. BAY-3827 inhibits the phosphorylation of acetyl CoA carboxylase 1.

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

YTH-IN-1 is an inhibitor of the five YTH structural domains in the human.The YTH family of proteins is an N 6-methyladenosine (m6A) reader in gene expression.

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.

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

Aldometanib (LXY-05-029) is an oral aldolase inhibitor that maintains metabolic balance by blocking FBP and activating lysosomal AMPK.

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

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

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

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.

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

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

EHMT2-IN-2 Used in the research of blood disease or cancer. EHMT2-IN-2 is a potent EHMT inhibitor, with IC50s of all <100 nM for EHMT1 peptide, EHMT2 peptide and cellular EHMT2.

(8R,9S)-Talazoparib is Talazoparib enantiomer , less active than Talazoparib on the inhibition of PARP1 (IC50: 144 nM).

<p>PLK1-IN-6: potent, selective PLK1 inhibitor, IC50 = 0.45 nM, hinders cancer cell growth.</p>

Cercosporin, produced by the plant pathogen Cercospora kikuchii and the elsinochromes, is a potent photosensitizer with a short activation wavelength. Cercosporin contains perylene quinone structural features essential for PKC activity (IC50: 0.6-1.3 μM).

HJB97 is used for the design of potential PROTAC BET degrader. It also has antitumor activity. HJB97 is a high-affinity inhibitor of BET (Kis: 0.9 nM (BRD2 BD1), 0.27 nM (BRD2 BD2), 0.18 nM (BRD3 BD1), 0.21 nM (BRD3 BD2), 0.5 nM (BRD4 BD1), 1.0 nM (BRD4 BD2), respectively).

CARM1-IN-1 hydrochloride is a potent and selective inhibitor of CARM1 (IC50: 8.6 μM) with minimal inhibition of PRMT1 and SET7.

YF-2 hydrochloride is a potent histone acetyltransferase activator that exhibits high selectivity and can pass through the blood-brain barrier. It specifically acetylates H3 in the hippocampus, with EC50 values of 2.75 μM, 29.04 μM, and 49.31 μM for CBP, PCAF, and GCN5, respectively. Notably, it does not affect HDAC activity. Moreover, YF-2 hydrochloride demonstrates promising anti-cancer and anti-Alzheimer's disease properties.

(3R,4S)-Tofacitinib, the less active enantiomer of Tofacitinib, is a JAK3 inhibitor with an IC50 of 1 nM.

Amredobresib is a potent BET inhibitor that impedes the interaction between bromodomains and acetylated lysines on histone H3 and H4, thereby serving as crucial regulators of gene transcription. It proves valuable in the investigation of acute myeloid leukemia (AML) and cancer.

BD-9136, a highly selective BRD4 degrader, demonstrates the capability to inhibit tumor growth without inducing adverse effects in mice, showing potential for

HIF-PHD-IN-1 is a pharmacological compound that acts as an orally active inhibitor of the hypoxia-inducible factor prolyl hydroxylase domain (HIF-PHD), displaying an IC50 of 54 nM for hHIF-PHD2. Its potential as a therapeutic agent for renal anemia is highly promising.

<p>20-HETE is a CYP450 product, vasoconstrictor, modulates K+ channels, affects NADPH, ROS, NF-κB, NO synthase, and cell apoptosis/proliferation.</p>

<p>CTB (Cholera Toxin B subunit) is an activator of p300 histone acetyltransferase and induces apoptosis in MCF-7 cells.</p>

<p>Desidustat is an inhibitor of HIF hydroxylase.</p>

PF-03814735 is a novel, potent and reversible inhibitor of Aurora A/B with IC50of 0.8 nM/5 nM, is less potent to Flt3, FAK, TrkA, and minimally active to Met and FGFR1. Phase 1.

AMPK activator C2 is an AMPK allosteric activator.

Bisindolylmaleimide I HCl is a specific ATP-competitive PKC inhibitor.

BLL5 Maleate is a first-in-class selective PRMT5 inhibitor, it blocks EBV-driven B lymphocyte transformation and survival while leaving normal B cells unaffected.

<p>BET-IN-15 (compound 1) is a potent, orally active inhibitor of BET, demonstrating inhibitory IC50 values of 0.64 nM for BRD4-BD1 and 0.25 nM for BRD4-BD2.</p>

<p>Compound A8, known as JAK2-IN-9, is a selective JAK2 inhibitor with an IC50 of 5 nM.</p>

<p>JAK1-IN-11 (compound 11) serves as a potent inhibitor of Janus kinases, exhibiting nanomolar inhibitory concentrations with IC50 values of 0.02 nM (JAK1) and 0.</p>

<p>BBDDL2059 is a selective covalent inhibitor targeting EZH2, exhibiting an IC50 of 1.5 nM against the EZH2-Y641F mutant.</p>

<p>Igermetostat, an EZH2 inhibitor, is utilized both in vivo and in vitro for cancer research [1].</p>

<p>JAK1-IN-10 (compound 9), a cyano-substituted cyclic hydrazine derivative, functions as a potent and selective inhibitor of JAK1 [1].</p>

<p>DPP, a Platinum(IV) complex with a pterostilbene-derived axial ligand, inhibits the JAK2-STAT3 pathway in breast cancer (BC) cells, demonstrating</p>

<p>Lerzeparib is a PARP (ADP-ribose polymerase) inhibitor that exhibits antineoplastic activity [1].</p>

<p>JAK-IN-27, also known as compound 1, is an orally active, potent inhibitor of the JAKS family kinases, displaying inhibitory concentrations (IC50s) of 3.0 nM</p>

<p>BET-IN-14 is a pan BET inhibitor with an IC50 of 5.35 nM, demonstrating oral activity and anticancer properties [1].</p>

<p>STAT3-IN-18 (compound SPP), a platinum (IV) complex featuring an axial ligand from sandalwood, suppresses the JAK2-STAT3 pathway in breast cancer (BC) cells and</p>

<p>Antitumor Agent-104 (Compound 9) serves as an antineoplastic by impeding DNA repair mechanisms in tumor cells, primarily through the inhibition of PARP1 enzyme</p>

BAZ2-ICR is an epigenetic chemical probe and it also is a potent, selective, cell active and orally active BAZ2A/B bromodomains inhibitor with IC50s of 130 nM and 180 nM, and Kds of 109 nM and 170 nM, respectively. BAZ2-ICR shows 10-15-fold selectivity for binding BAZ2A/B over CECR2 and >100-fold selectivity over all other bromodomains.

<p>JAK-IN-34 (compound 11n) is a potent inhibitor of Janus kinases (JAKs), demonstrating IC50 values of 0.40 nM for JAK1, 0.83 nM for JAK2, 2.10 nM for JAK3,</p>

<p>PARP7-IN-16 free base is the freebase form of PARP7-IN-16. As a selective oral inhibitor of PARP-1/2/7, it demonstrates IC50 values of 0.94, 0.87, and 0.21 nM, respectively. This compound is utilized in the research of breast and prostate cancer.</p>

<p>BET BD2-IN-3 (compound I-58), a BET inhibitor specifically targeting the BD2 domain, can be radiolabeled with [11C] for use in positron emission tomography (PET) imaging. PET studies with [11C]BD2-IN-3 in mice have demonstrated appropriate biodistribution in peripheral organs and tissues.</p>

BB-Cl-Amidine hydrochloride is an inhibitor of peptidylarginine deminase (PAD) [1].