Cromatina/Epigenética

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.

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.

O-Desmethyl Midostaurin is the active Midostaurin metabolite via cytochrome P450 liver enzyme metabolism.

<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>NVS-BPTF-1 is a specific inhibitor of bromodomain and PHD finger containing transcription factor (BPTF), exhibiting a dissociation constant (K_D) of 71 nM [1].</p>

CFT8634 degrades BRD9, for synovial sarcoma and SMARCB1 tumor research, from patent WO2021178920A1.

EBET-590 is a BET inhibitor utilized in cancer research.

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

<p>PARP14 inhibitor1 (compound Q22) is a selective inhibitor of PARP14 with an IC50 of 5.52 nM. It also exhibits anti-inflammatory properties and has a half-life of 182 minutes in mouse liver microsomes. This compound is applicable for atopic dermatitis research.</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>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>JAK3 Covalent Inhibitor-1 is a compound characterized by its potent and selective inhibition of Janus kinase 3 (JAK3), possessing an IC50 of 11 nM and</p>

<p>GSK789 is a selective inhibitor of the first bromodomains (BD1) of the bromo and extra terminal domain (BET) proteins.</p>

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

<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>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.</p>

TDI-015051 is an orally active inhibitor of SARS-CoV-2 non-structural protein 14 (SARS-CoV-2 NSP14) with an IC50 of ≤0.15 nM. It effectively inhibits SARS-CoV-2 NSP14 in Huh-7.5 cells (EC50=11.4 nM) and A549 cells expressing ACE2-TMPRSS2 (EC50=64.7 nM). Additionally, TDI-015051 suppresses other coronaviruses such as α-hCoV-NL63, α-hCoV-229E, and β-hCoV-MERS with IC50 values of 1.7, 2.6, and 3.6 nM, respectively. This compound inhibits viral RNA methylation and replication by binding to a stable SAH-cap pocket and demonstrates anti-infection activity in mouse models.

<p>SMARCA2/4-ligand-5 is the target protein ligand of PROTAC SMARCA2/4 degrader-37 (Example 4). PROTAC SMARCA2/4 degrader-37 (Example 4) is a PROTAC degrader of SMARCA2/4, with an IC50 value of ≤0.1 μM.</p>

<p>PARP1-IN-29 is an orally active PARP-1 inhibitor with an IC50 of 6.3 nM. When labeled with [18F], PARP1-IN-29 can be utilized for positron emission tomography (PET) imaging, specifically targeting PARP-1 in tumors. This compound is useful in oncology and imaging studies, particularly for detecting PARP-1 activity in cancer.</p>

<p>XP5 is an oral HDAC6 inhibitor, potent against cancer cells, including YCC3/7 (IC50=31 nM to 2.31 μM).</p>

<p>BRD4 Inhibitor-33 (example 13), a potent inhibitor of BRD4, is applicable in research related to both acute and chronic kidney diseases [1].</p>

Menin-MLL inhibitor 4 has antitumor activity.Menin-MLL inhibitor 4 is an inhibitor of Menin- MLL (mixed-lineage leukemia protein) interaction .

(2S,3R)-LP99 is a less active enantiomer of LP99.

KAT6A-IN-2 (compound 7) is an inhibitor of KAT6A.

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

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

<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>

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.

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

<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>

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

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.

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

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

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

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

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.

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

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).

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

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

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

<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).</p>

<p>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>

<p>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.</p>

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.

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

<p>PARP Protein, Human, Recombinant (His) is expressed in Baculovirus insect cells with His tag.</p>

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

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

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

<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>

AMPK activator C2 is an AMPK allosteric activator.

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

<p>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>

<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>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>

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

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

<p>Igermetostat, an EZH2 inhibitor, is utilized both in vivo and in vitro for cancer research [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>JAK1-IN-10 (compound 9), a cyano-substituted cyclic hydrazine derivative, functions as a potent and selective inhibitor of JAK1 [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>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 &gt;100-fold selectivity over all other bromodomains.</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>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>

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

<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>