Cromatina/Epigenetica

PRO-HD1, a PROTAC (proteolysis-targeting chimera) HDAC6 degrader, effectively degrades HDAC6 in A549 cells and inhibits Jurkat cell proliferation with an IC50

Biguanide can reduce oxidative stress in rats with hyperglycemia.

BRD3067, a Tubacin derivative, inhibits HDAC6 (IC50 15 nM) and acts as a negative control for Tubacin A, showing anticancer and anti-inflammatory effects.

Bryostatin 3 is a protein kinase C activator.

<p>MSC2504877 inhibits tankyrase, boosts CDK4/6 inhibitors, blocks Cyclin D2/E2 upregulation, and strengthens phospho-Rb suppression.</p>

Pan-BET/BD2-IN-1 (compound 6b) is a selective BET protein inhibitor with BRDT-1Ki of 1.05 μM and BRD4-1Ki of 0.68 μM. It effectively inhibits the growth of MM.1S cancer cells with an IC50 value of 2.6 μM.

POI ligand 1 serves as a template for the non-selective HDAC inhibitor Vorinostat. It functions as a target protein ligand (PROTAC target protein ligand) in the creation of PROTAC HDAC degraders with anti-tumor properties. Additionally, POI ligand 1 is utilized in the synthesis of FF2049.

<p>SJ1008030, a JAK2 PROTAC, degrades JAK2; EC50: 5.4 nM, IC50: 32.09 nM in MHH-CALL-4 cells for leukemia research.</p>

CPI-1328 is an EZH2 inhibitor with a K i value of 63 fM.

Malantide, a synthetic dodecapeptide, boosts and measures PKA activity by undergoing PKA-induced phosphorylation.

JQ1-TCO, a BET inhibitor derivative, enables click chemistry for molecular probing in vivo and in vitro.

EPZ020411 is an effective and specific small molecule PRMT6 inhibitor (IC50=10 nM).

<p>LSD1-IN-32 (compound 11e) is a potent inhibitor of LSD1, with an IC50 value of 0.99 µM. It effectively impedes RANKL-induced osteoclastogenesis, bone resorption, and F-actin ring formation, indicating its potential use in osteoporosis research.</p>

HDAC1/2-IN-3 is an inhibitor of both HDAC1 and HDAC2, demonstrating IC50 values of 0-5 nM and 5-10 nM, respectively.

HDAC-IN-26 is a highly selective class I HDAC inhibitor with an EC 50 value of 4.7 nM.

Tazemetostat de(methylene morpholine)-O-C3-O-C-COOH (Compound 21b), an EZH2 degrader, is employed in lymphoma research [1].

MZP-55 is a selective BRD3/4 degrader based on PROTAC technology(Brd4BD2 with Kd of 8 nM)

TDI-012804 is a TNKS2 inhibitor that selectively inhibits endogenous TNKS2 protein within cells. It enhances the expression of AXIN1 protein in Tnks1 heterozygous (Tnks1HET) and knockout (Tnks1KO) cells. TDI-012804 suppresses the proliferation of ApcQ1405X/Tnks1KO organoids with an EC50 of 59.1 nM and exhibits selective toxicity towards Tnks1KO AKP-G12D and AKP-G13D organoids.

PROTAC SMARCA2/4-degrader-26 is a PROTAC targeting the SMARCA2/4 proteins. It is composed of the ligand for PROTAC targeting proteins, 2-(4-(3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl)piperazin-1-yl)acetic acid, an E3 ligase component (2S,4R)-4-Hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide, and a PROTAC linker (S)-2-Amino-3,3-dimethylbutanoic acid. The coupled complex of the E3 ubiquitin ligase ligand + Linker is referred to as (S,R,S)-AHPC.

Protein kinase C (PKC) activator

BI01826025 (pArg-JQ1), a BRDT BD1 bromodomain PROTAC degrader, tests ClpC2's effect on ClpC1P1P2 protease.

Bisindolylmaleimide XI hydrochloride (Ro 32-0432) is an orally active pan-PKC inhibitor that inhibits PKCα, PKCβI, PKCβII, and PKCγ.

TCIP3 is a bivalent molecular glue (molecular glue) that can simultaneously bind to both p300/CBP and BCL6. It redirects p300 and CBP to activate programmed cell death genes, which are typically repressed by the oncogenic driver BCL6. TCIP3 is useful for studying diffuse large B-cell lymphoma (DLBCL) and is not toxic to untransformed tonsil lymphocytes or fibroblasts.

HDAC6-IN-42 (compound 2b) is an HDAC6 inhibitor with an IC50 of 0.009 μM, demonstrating significant anti-leukemia activity and synergistic effects with Decitabine, indicating its potential use in the research of Acute Myeloid Leukemia (AML).

E3 ligase ligand-linker '(S,R,S)-AHPC-C5-COOH' for PROTACs, VH032 inhibits VHL/HIF-1α with 185 nM Kd, may aid anemia and ischemic disease research.

PRMT5-IN-41 (compound 130) is an effective orally active inhibitor of PRMT5. It inhibits the hERG ion channel with an IC50 of 1.36 µM.

EPZ028862 is a

PROTAC SMARCA2/4-degrader-27 (PROTAC 2) serves as a targeted degrader, utilizing PROTAC technology to degrade both SMARCA2 and SMARCA4.

TP-472N serves as a negative control probe for TP-472, which is a specific and effective BRD7/9 probe.

<p>PROTACBRD4 Degrader-32 (Compound 22) is a potent BRD4 PROTAC degrader with a DC50 of 0.20 nM. It employs a unique carbon-carbon linker to connect the BRD4 binding domain with the CRBN binding domain, forming a ternary complex that induces BRD4 ubiquitination and facilitates proteasomal degradation. PROTACBRD4 Degrader-32 holds promise for research into BRD4-related cancers, such as hematological malignancies.</p>

Potent SIRT1/2/3-IN-1 inhibits SIRT1/2/3 with IC50: 0.54, 0.25, 0.72 μM; used in cancer research.

PROTAC BRD4 Degrader-15 targets von Hippel-Lindau and BRD4 with IC50s 7.2/8.1 nM and degrades BRD4 in cancer cells.

NF-κB/HIF-1α-IN-1 (compound 9c) effectively inhibits the NF-κB activation pathway and demonstrates selective antifibrotic activity. This compound exhibits no significant cytotoxicity in NCI tumor cell lines. In rat models, NF-κB/HIF-1α-IN-1 successfully ameliorates liver fibrosis, suppresses the expression levels of NF-κB and HIF-1α, and induces Nrf2.

<p>Compound Ac13, also termed AURKA against 1, acts as an inhibitor of the Aurora kinase (AURKA) with an IC50 of less than 0.5 nM, targeting the acetylation of endogenous lysine (K162) and exhibiting anti-tumor cell proliferation activity. The kinase activity of AURKA, acetylated at K162 and induced by AURKA against 1, is reversibly restored in HCT116 cells transfected with SIRT3.</p>

XYD198 (Compound 14h) is an orally active degrader of CBP/p300. It inhibits the CBP/p300 bromodomain with an IC50 of 213.5 nM and exhibits antitumor activity against acute myeloid leukemia.

PARP1-IN-6, a dual-function inhibitor, targets both tubulin and PARP-1, demonstrating inhibitory concentration (IC50) values of 0.94 μM for tubulin and 0.48 μM

Menin–KMT2A-IN-1 (Compound 20) is an inhibitor of menin–KMT2A, binding to menin with an IC50 of 8 nM, and disrupting the interaction between menin and lysine methyltransferase 2A (KMT2A). It inhibits hERG channels with an IC50 of 65 μM and suppresses MV4-11 cells with an IC50 of 74 nM. Furthermore, Menin–KMT2A-IN-1 exhibits favorable pharmacokinetic properties in CD-1 mice, with an oral bioavailability of 74%.

<p>EZH2/EPP inhibitor, Kd 320 nM. Reduces EZH2, H3K27me3; halts MLL-AF9 leukemia growth; drives monocyte-macrophage differentiation.</p>

DB008 is a selective PARP16 inhibitor with IC50 of 0.27 μM, has acrylamide, and is membrane-permeable.

TAS-119 (TAS-2104) is an orally available, selective and potent inhibitor of Aurora A with an IC50 of 1.0 nM.TAS-119 also inhibits Aurora B with an IC50 of 95

Compound 1769-24-0 is a natural product for research related to life sciences. The catalog number is TPL0186 and the CAS number is 1769-24-0.

SGC3027 is an inhibitor of histone methyltransferase,also is a first potent, selective and cell active chemical probe for PRMT7.

BB-Cl-Amidine (TFA) is an inhibitor of peptidylarginine deiminase (PAD).

(+)-JQ-1-aldehyde is the aldehyde derivative of (+)-JQ1, commonly used as a precursor for the synthesis of PROTACs targeting the BET bromine domain[1].

AZ9567 is a potent MAT2A inhibitor. It demonstrates antiproliferative activity against MTAPKO HCT116 cells, with a pIC50 of 8.9.

Tanshinol borneol ester stimulates angiogenesis via Akt/MAPK pathways and has anti-ischemic, anti-atherosclerosis effects.

VPC-70063 (Thiourea, N-[3,5-bis(trifluoromethyl)phenyl]-N'-(phenylmethyl)-) is an inhibitor of c-Myc-MAX.

dBET23 is a BRD4 degrader.

Compound I-291, also known as PROTAC SMARCA2/4-degrader-30, targets the catalytic subunits of the SWI/SNF complex, specifically SMARCA2 and SMARCA4. It effectively degrades SMARCA2 in A549 and MV411 cells, as well as SMARCA4 in MV411 cells, with a degradation concentration (DC50) of less than 100 nM.

EPZ-719: Potent SETD2 inhibitor, IC50=0.005μM, high selectivity, potential for targeted epigenetic therapy.

<p>PRMT1-IN-1 is a PRMT1 inhibitor.</p>

<p>NRT is an oral NAD+ precursor, boosts NAD+, activates SIRT1/3, provides vitamin B3, enhances metabolism, and may mitigate Alzheimer's.</p>

<p>EP300/CBP ligand 2 (compound S19) serves as a specific ligand for the bromodomain of CREB binding protein (CBP) and E1A-associated protein (EP300). It plays a critical role in PROTAC technology by acting as a target protein ligand. By linking to an E3 ubiquitin ligase ligand via the PROTAC Linker, it facilitates the synthesis of PROTAC molecules capable of targeted protein degradation. For instance, when EP300/CBP ligand 2 is connected to the conjugate (E3 ubiquitin enzyme ligand + Linker) Thalidomide-NH-C10-Boc, it results in the formation of the PROTAC molecule dCE-2.</p>

ACBI2: potent, oral VHL PROTAC, EC50=7nM; degrades SMARCA2, DC50=1nM in RKO cells; for lung cancer research.

INCB059872: potent, oral, selective LSD1 inhibitor for myeloid leukemia research.

PARP/EZH2-IN-1: Dual PARP (IC50 6.87 nM) & EZH2 (IC50 36.51 nM) inhibitor, potential for BRCA-wild-type triple-negative breast cancer.

HIF-1 inhibitor-5 (Compound 16e) is a potent inhibitor of HIF-1, exhibiting an IC50 value of 2.38 μM and demonstrating significant anti-angiogenic potential [1

PBRM1-BD2-IN-5 is a potent inhibitor of the PBRM1 Bromodomain, demonstrating dissociation constant (Kd) values of 1.5 μM and 3.9 μM for PBRM1-BD2 and PBRM1-BD5

PROTAC SMARCA2/4-degrader-29 (Compound I-279) serves as a degrader for the catalytic subunits SMARCA2 and SMARCA4 of the SWI/SNF complex. In A549 cells, this compound effectively degrades SMARCA2 with a DC50 value of less than 100 nM, and similarly degrades SMARCA4 in MV411 cells with a DC50 under 100 nM.

PROTAC BRD4 Degrader-14 binds VHL & BRD4, degrades BRD4 in PC3 cells; IC50: 1.8/1.7 nM BD1/BD2.

HIF-PHD-IN-4 (Compound 13) is an orally active PHD2 inhibitor with an IC50 of 100 nM. At a dose of 2 mg/kg, it effectively enhances G-CSF-induced mobilization of hematopoietic stem cells in mice. HIF-PHD-IN-4 is suitable for research in the oncology field.

HAT-SIL-TG-1&AT: a hypoxia-activated JAK inhibitor that curbs HEL cell growth & STAT3/5 phosphorylation in tumors.

Protein Kinase C (19-36) is a pseudosubstrate peptide inhibitor of protein kinase C (PKC), with an IC50 of 0.18 μM.

PIM-IN-1 is a pan-PIM kinase inhibitor (KG-1, EC 50 = 61 nM; pS6, EC 50 = 71 nM).

SMD-3236 is a PRAOTAC degrader targeting SMARCA2, designed using SMARCA ligand and VHL-1 ligand, and exhibits prolonged anti-tumor activity in vivo. SMARCA2 acts as a synthetic lethal target in cancer cells lacking SMARCA4, with SMD-3236 showing 2000-fold selectivity for SMARCA2 over SMARCA4, having a DC50 of less than 1 nM and a Dmax of over 95%. In the human cancer xenograft models deficient in SMARCA4, notably the H838 model, SMD-3236 effectively induces loss of SMARCA2 in tumor tissue while sparing the SMARCA4 protein, thereby inhibiting tumor growth. The compound consists of a target protein ligand (red part) SMI-1074, a PROTAC linker (black part) (trans-4-Ethynylcyclohexyl)methyl methanesulfonate, and an E3 ligase ligand (blue part) SMARCA2 ligand-14, forming the E3LigaseLigand-linker Conjugate 159.

HDAC1-IN-9 (13c) is an HDAC1 inhibitor. It inhibits the HDAC1 enzyme with an IC50 value of 1.07 µM. This compound exhibits the strongest antiproliferative activity against HT-29 (human colon adenocarcinoma cells), with an IC50 of 1.78 μM. In HCT-116 (human colon cancer cells), HDAC1-IN-9 significantly induces apoptosis. Additionally, HDAC1-IN-9 possesses antiangiogenic properties, reducing the expression levels of VEGFR-2 and phosphorylated VEGFR-2 (pVEGFR-2) by approximately 80%.

PROTAC BRD4 Degrader-1 is an efficacious degrader of BRD4(BRD4 BD1,IC50 of 41.8 nM).

FTX-6058 hydrochloride is a potent EED inhibitor, induces HbF, and aids sickle cell and β-thalassemia research.

SMARCA2 degrader-17 is a degrader of SMARCA2, exhibiting synergistic antiproliferative effects with Adagrasib in cancer cells and capable of inhibiting tumor growth.

PRMT5-IN-13 is a selective inhibitor of protein arginine methyltransferase 5 (prmt5) .

N-Desmethyltamoxifen, tamoxifen's main human metabolite, regulates AML cell ceramide metabolism and is a more potent PKC inhibitor than tamoxifen.

PRMT1 inhibitor, IC50=1.8μM; 5x more selective than PRMT6; >250x over PRMT3, CARM1.

C8 Dihydroceramide is a control for C8 Ceramide, a bioactive, cell-permeable, chemotherapeutic agent that boosts T cell responses and slightly activates PKC.

PRMT3-IN-4 (intermediate 15) is an inhibitor of Protein arginine methyltransferase 3 (PRMT3) and serves as the active control for SGC707. It can be utilized in the synthesis of PROTACs targeting PRMT3 and is applicable in research related to leukemia.

GXH-II-052: Potent BET inhibitor, binds BRD4/BRDT (Kd 0.6-28 nM), anti-proliferative, reduces c-Myc expression.

Tert-butyl compound inhibits human EGLN-1; confirmed by spectrometry after 20 mins.

Y16524 is a potent inhibitor of the CBP/p300 bromodomain (CBP/p300bromodomain) with an IC50 value of 0.01 μM. It shows potential for research in acute myeloid leukemia (AML).

N,N-Didesethyl Sunitinib Hydrochloride is a potent AMPK inhibitor with IC50 of 393 nM and 141 nM for AMPKα1 and AMPK2,respectively.

Axltide mimics mouse Insulin receptor substrate 1, amino acids 979-989 with sequence KKSRGDYMTMQIG.

PRMT5-IN-11 demonstrates potent structure-dependent inhibition against the protein methyltransferase PRMT5:MEP50 complex at submicromolar concentrations.

Foenumoside B, a triterpene saponin extracted from Lysimachia foenum-graecum, stimulates AMPK signaling, suppresses PPARγ-induced adipogenesis, and promotes

BBDDL2204 (compound 13) is a potent and selective covalent inhibitor of EZH2, demonstrating an IC50 of 2.5 nM against EZH2Y641F.

Cath-L-dBET1 is a PROTAC degrader targeting BRD4. It has an IC50 value of 2.8 μM in MDA-MB-231 cells. Activated by cathepsin L (Cath-L), Cath-L-dBET1 recruits E3 ubiquitin ligase to degrade BRD4 via the ubiquitin-proteasome system. Hyp-dBET1 is applicable for antitumor research.

<p>WL12 (ZINC6733033): First-in-class JMJD6 inhibitor; halts JMJD6-dependent cervical/liver cancer cell growth.</p>

FTX-6058 is an oral inhibitor of EED that induces HbF and may treat hemoglobinopathies like sickle cell and β-thalassemia.

Sirt2-IN-7, a selective SIRT2 inhibitor, has IC50 and Ki values of 178.2 nM and 154.3 nM, useful in cancer research.

NPC-15437 dihydrochloride is a PKC inhibitor blocking enzyme activity and phorbol ester binding, selective over other kinases, in cellular signaling research.

TO-1187 is a selective HDAC6 PROTAC degrader with a DC50 of 5.81 nM. It enhances the ubiquitination and subsequent degradation of HDAC6, making it useful for research in hematological malignancies and solid tumors.

<p>Pim-1 kinase inhibitor 11 (10f) is an inhibitor of PIM-1 with an IC50 value of 0.18 μM. It exhibits anticancer activity by inducing apoptosis and causing cell cycle arrest.</p>

dBAZ2 is a pioneering PROTAC degrader targeting BAZ2A and BAZ2B, with DC50 values of 180 nM for BAZ2A and 250 nM for BAZ2B.

PROTAC BRD9-binding moiety 1 that binds to BRD9, and used for inhibiting BRD9 activity, based on PROTAC.

AZD1152 is a pro-drug of Barasertib (AZD1152)-hQPA. Which is a highly selective Aurora B inhibitor with IC50 of 0.37 nM in a cell-free assay.

TNKS-2-IN-2 is a TNKS2 selective inhibitor (IC50: 22 nM) with potential anti-tumour activity for the study of colon cancer lung cancer and breast cancer.

XF056-132 is a potent WDR5 (WD40 repeat domain protein 5) PROTAC degrader [1] .

MT1, a bivalent chemical probe targeting BET bromodomains, demonstrates an IC50 value of 0.789 nM for BRD4(1).

Larsucosterol ammonium salt is a derivative of 25HC3S. It is a DNMT inhibitor, a LXR antagonist, an endogenous epigenetic modulator of lipid metabolism.

mTOR/HDAC-IN-1, a dual inhibitor for mTOR & HDAC1 with IC50s 0.49 & 0.91 nM, potential anti-cancer agent.

JAK-IN-15 is a JAK inhibitor. WO2016119700A1 (Compound 15).

OARV-771: VHL-based PROTAC targeting BET; DC50: Brd4-6nM, Brd2-1nM, Brd3-4nM; enhanced cell permeability.

DW71177 is a BET inhibitor with potent anti-leukemic activity for the study of leukemia.