Cromatina/Epigenetica

<p>MAT2A-IN-20 (Compound A49) is an inhibitor of methionine adenosyltransferase 2A (MAT2A) with an IC50 of ≤50 nM. It also inhibits human UGT1A1 with an IC50 of 28.45 μM. Additionally, MAT2A-IN-20 exhibits antitumor activity in mouse models.</p>

<p>MAT2A-IN-21 (compound 28) is a potent inhibitor of methionine adenosyltransferase 2A (MAT2A), with an IC50 of 49 nM. It selectively inhibits cancer cells with MTAP deficiency.</p>

YEATS4 binder-1(4e) is an effective and selective compound that targets the KAc recognition site within the YEATS structural domain, exhibiting a binding

MAT2A-IN-18 (Compound 15) is an inhibitor of methionine adenosyltransferase 2A (MAT2A) with an IC50 of 50 nM or less.

MAT2A-IN-16 is a MAT2A inhibitor that effectively suppresses the proliferation of MTAP-/-HCT-116 cells, with an IC50 value of 20 nM.

<p>MAT2A-IN-19 (Compound I-3) is an inhibitor of methionine adenosyltransferase 2A (MAT2A), with an IC50 of 32.93 nM.</p>

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

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

WIZ degrader 8 (compound 10) is a potent and selective molecular glue degrader of the transcription factor WIZ, effectively inducing HbF expression. It promotes WIZ degradation and HbF induction, suggesting its potential use as an inhibitor for sickle cell disease.

P300-IN-4 (compound 6) is a histone acetyltransferase p300 inhibitor with an IC50 value of 12.2 μM.

GDC-0339: oral Pim kinase inhibitor for multiple myeloma (Kis: Pim1 - 0.03 nM, Pim2 - 0.1 nM, Pim3 - 0.02 nM), well-tolerated.

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

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.

FY-56: potent, selective LSD1/KDM1A inhibitor (IC50=42nM); differentiates MOLM-13/MV4-11 cells; promising for AML research.

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

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.

Itareparib is a PARP inhibitor with demonstrated antitumor activity.

Aurora A inhibitor4 (compound C9) is a potent inhibitor of Aurora A, with GI50 values of 4.26 μM in DU 145 cells and 7.08 μM in HT-29 cells.

Acetylethylcholine mustard hydrochloride is a choline acetyl-transferase inhibitor that decreases muscle contraction frequency by inhibiting the synthesis of acetyl-beta-methylcholine (Ach), with a half-maximal inhibitory concentration (IC50) of 1.22 mM. It serves as an irreversible ligand for the high-affinity choline transport system and functions as a specific presynaptic long-acting cholinergic toxin. Additionally, acetylethylcholine mustard hydrochloride is a precursor to the ethylcholine mustard aziridinium ion.

LSD1-IN-22: potent LSD1 inhibitor, K_i 98 nM, curbs cancer cell growth.

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

PRMT5-IN-32, an inhibitor of PRMT5, inhibits HCT116 cell proliferation with an IC50 of 0.13 μM [1].

(Sodium) (2R)-Octyl-α-hydroxyglutarate is the sodium salt variant of (2R)-Octyl-α-hydroxyglutarate, which has been shown to possess anti-inflammatory properties [1].

Pociredir (FTX-6058), a potent EED inhibitor (KD=0.163 nM), may help in SCD research.

PRMT5-MTA-IN-3 (Compound P2A) is an orally active and selective inhibitor of protein arginine methyltransferase 5 (PRMT5). It inhibits the proliferation of MTAP-deficient colorectal cancer HCT-116 cell line with an IC50 value of 5 nM. PRMT5-MTA-IN-3 holds potential for research in cancers, particularly in MTAP-deficient tumors such as colorectal cancer, non-small cell lung cancer, and pancreatic cancer.

PARP14 inhibitor2 (Compound 3) is an orally active and highly selective PARP14 inhibitor with an IC50 value of less than 30 nM. It effectively inhibits the mono ADP-ribosyltransferase activity of PARP14 and modulates IFN-γ and IL-4 signaling, thereby reversing pro-tumor macrophage polarization and suppressing anti-tumor inflammatory responses. PARP14 inhibitor2 holds potential for research in PARP14-related conditions such as tumors, atopic dermatitis, and autoimmune diseases.

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

ATRkinase-IN-2 (Compound I-G-27) is an inhibitor of the ATR protein kinase, with a Ki value ranging from 0.01 to 1 μΜ. It is utilized in tumor research.

LSD1-IN-15 inhibits LSD1, MAO-A/B with IC50s: 0.149, 0.028, 0.327 μM; arrests LNCaP cancer cell growth, IC50 9.9 μM.

Purinostat is a selective inhibitor of HDACI/IIb with potential anti-leukemic properties. Its mesylate form, Purinostat mesylate, is effective at inhibiting the survival of Ph+ leukemic cells and CD34+ leukemic cells derived from CML patients. Purinostat mesylate targets HDACI/IIb, impacting several crucial factors for leukemia stem cell (LSC) survival, such as c-Myc, β-Catenin, E2f, Ezh2, Alox5, and mTOR. Additionally, Purinostat mesylate enhances glutamate metabolism in LSCs by increasing GLS1.

ER272 is a natural PKC activator, inducing hippocampal neurogenesis.

MU1656 is a selective inhibitor of histone methyltransferase DOT1L, which significantly inhibits cancer cell proliferation in hematological malignancies.

Tyk2-IN-10 acts as an inhibitor of the Tyrosine Kinase 2 (Tyk2)-mediated signaling pathway, which plays a role in inflammation regulation.

CREB-IN-1 TFA: Potent oral CREB inhibitor, IC50 of 0.18 μM, suppresses breast cancer cell growth.

LSD1/2-IN-4, a PCPA derivative, inhibits LSD1 (Ki 0.11 μM) & LSD2 (Ki 130 μM), potentially useful in T-cell leukemia research.

BRD4-IN-9, an orally active BRD4 inhibitor, demonstrates a potent IC50 of 9.4 nM. In a murine melanoma xenograft model, it effectively inhibits tumor growth.

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

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

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.

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.

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

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

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

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

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

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.

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

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

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.

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.

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.

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

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

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).

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>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.

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.

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

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

<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>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>

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>Igermetostat, an EZH2 inhibitor, is utilized both in vivo and in vitro for cancer research [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>

<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>JAK1-IN-10 (compound 9), a cyano-substituted cyclic hydrazine derivative, functions as a potent and selective inhibitor of JAK1 [1].</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>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-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>Lerzeparib is a PARP (ADP-ribose polymerase) inhibitor that exhibits antineoplastic activity [1].</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>BBDDL2059 is a selective covalent inhibitor targeting EZH2, exhibiting an IC50 of 1.5 nM against the EZH2-Y641F mutant.</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>

<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>

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