Cromatina/Epigenética

<p>A unique collection of 252 JAK/STAT signaling targeted compounds for high throughput and high content screening;</p>

<p>3β,6α,12β-Dammar-E-20(22)-ene-3,6,12,25-tetraol is a compound that functions as a SIRT1 activator, effectively enhancing SIRT1 activity.</p>

<p>Dot1L-IN-9 (Compound 12) is a DOT1L inhibitor with an IC50 of 125 nM. It effectively reduces H3K79 dimethylation and is utilized in leukemia research.</p>

<p>PROTAC BET Degrader-10 targets and degrades BRD4 with a DC50 of 49 nM, using Cereblon ligands.</p>

<p>GSK-1070916 (GSK-1070916A) is a reversible and ATP-competitive inhibitor of Aurora B/C with IC50 of 3.5 nM/6.5 nM.</p>

<p>DAO-dBET1, a dual-action PROTAC incorporating the PROTAC degrader dBET1, effectively serves as a potent BRD4 degrader and exhibits a DC50 value of 277 nM in the presence of CoCl2. Additionally, DAO-dBET1 inhibits hypoxia and Cath-L activation with an IC50 value of 281 nM.</p>

<p>HDAC6-IN-53 (Compound W28) is an inhibitor targeting histone deacetylase 6 (HDAC6) with an IC50 of 19.65 nM. It reduces the idiopathic pulmonary fibrosis (IPF) phenotype by inhibiting TGF-β1-induced collagen expression and demonstrates therapeutic efficacy in a bleomycin-induced mouse model of pulmonary fibrosis. HDAC6-IN-53 is applicable for research in idiopathic pulmonary fibrosis and related pulmonary fibrotic diseases.</p>

<p>SAMS peptide is a specific substrate for the AMP-activated protein kinase (AMPK).</p>

<p>Sphingosine (d14:1) boosts N. rileyi fungus growth, inhibits PKC, and reduces CHO cell proliferation; found in various sea creatures.</p>

<p>Go6976 is a PKC inhibitor, widely used in research to probe PKC functions in health and disease.</p>

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

<p>Myelin basic protein (MBP) is a protein believed to be important in the process of myelination of nerves in the nervous system.</p>

<p>G9a-IN-3 (compound 16g) is a potent G9a inhibitor with an IC50 of 0.002 μM. It is applicable for research in sickle cell disease.</p>

<p>Synthetic peptide analog of bovine myelin basic protein (MBP). Non-competitive inhibitor of PKC (IC50 = 46 - 145 mM).</p>

<p>CM112 is a selective degrader of protein arginine methyltransferase 1 (PRMT1), which connects a hydrophobic adamantane tag to MS023 via a 5-PEG linker. It induces the degradation of PRMT1 in various solid tumor cell lines. CM112 also targets the non-enzymatic functions of PRMT1 by reducing the stability of the orphan receptor TR3. This compound shows potential for cancer research.</p>

<p>Echinomycin (Quinomycin A) is a quinoxaline antibiotic and a DNA-intercalating peptide that inhibits hypoxia-inducible factor-1 (HIF-1) DNA binding activity.</p>

<p>PROTACBRD4-DCAF1 degrader-1 (I-907) is a PROTAC degrader targeting BRD4-DCAF1, exhibiting a DC50 range of 10~100 nM.</p>

<p>(S,R,S)-AHPC-C2-amide targets Smad3 degradation and boosts HIF-α; it has anti-fibrotic and renal protective roles.</p>

<p>Ep300/CREBBP-IN-2: Potent, oral Ep300 &amp; CREBBP inhibitor; IC50s: 0.052μM &amp; 0.148μM; cancer research.</p>

<p>UNC 0631 is a effectvie histone methyltransferase G9a inhibitor (IC50=4 nM).</p>

<p>PROTAC BRD4 Degrader-20 (compound 195) is a bifunctional degrader of BRD4 [1].</p>

<p>WDR5-MYC-IN-1 (compound 4o) is an effective inhibitor of the WDR5-MYC interaction, demonstrating a Ki value of 1.0 µM and exhibiting antiproliferative activity.</p>

<p>MRK-990 is an inhibitor of PRMT that targets both PRMT5 and PRMT9, with IC50 values of 30 nM and 10 nM, respectively.</p>

<p>GSK097: Potent, selective BD2 inhibitor in BET proteins; 2000x more selective for BD2 than BD1; soluble &gt;1 mg/mL in FaSSIF.</p>

<p>SAHA inhibits class I/II HDAC; c-SAHA, a fluorescent derivative, excites at 325 nm and emits at 400 nm.</p>

<p>JWZ-7-7-Neg1, a neighboring transcription chemical inducer (TCIP), serves as a negative control. It exhibits reduced binding capabilities to BRD4 or BCL6 compared to JWZ-7-7, resulting in lower cytotoxicity towards DLBCL cells.</p>

<p>AZD-9574 is a selective inhibitor of PARP1 at the sites of SSBs.</p>

<p>GSK973 is a selective oral BET inhibitor, 1600x more for BRD4 BD2 (pIC50 7.8, pKd 8.7) than BD1, effective against other BD2s.</p>

<p>LLY-284, a less active PRMT5 inhibitor diastereomer of LLY-283, serves as its negative control.</p>

<p>Protein Kinase C (19-31), a PKC inhibitor derived from PKCa, has a serine at position 25 and tests PKC activity.</p>

<p>AUR1545 is a selective KAT2A/KAT2B degradator exhibiting inhibitory activity against cancer models including AML, SCLC, and NEPC, and suppressing tumour growth in the NCI-H1048 xenograft model.</p>

<p>HDAC-IN-89 is an inhibitor of HDAC1 (IC50: 0.95 nM), HDAC2 (IC50: 0.86 nM), HDAC3 (IC50: 1.06 nM), and HDAC8 (IC50: 4.24 nM). It can disrupt the cell cycle and induce apoptosis. Additionally, HDAC-IN-89 exhibits antitumor activity.</p>

<p>JAK-2/3-IN-1 inhibits JAK-2/3 isoforms with sub-250 nM Ki; from US patent US8163732B2.</p>

<p>Fluorescein NAD+ is a non-radioactive PARP assay substrate, enabling direct enzyme measurement by fluorescence. Comes as 81μg in 250μl water.</p>

<p>SJ10542: potent JAK2/3-targeting PG-PROTAC; DC50s: JAK2 - 14 nM, JAK3 - 11 nM, JAK2-fusion ALL - 24 nM; CRBN recruiter.</p>

<p>dBRD9 is a PROTAC.</p>

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

<p>PROTAC SMARCA2/4-degrader-28 (PROTAC 1) functions as a partial degrader of SMARCA2 and SMARCA4 through the PROTAC-based mechanism.</p>

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

<p>iRucaparib-AP6: a specific, non-trapping PARP1 degrader; inhibits the enzyme's activity and scaffolding.</p>

<p>PROTAC HDAC6 degrader4 (Compound 17c) is a PROTAC that targets and degrades HDAC6, with a DC50 of 14 nM. It exhibits inhibitory activity against HDAC1, HDAC2, HDAC3, and HDAC6, with IC50 values of 2.2, 2.37, 0.61, and 0.295 μM, respectively. [Pink: ligand for target protein HDAC6 ligand-3; Black: linker; Blue: ligand for cereblon E3 ligase]</p>

<p>EZH2-IN-4, an oral EZH2 inhibitor, targets WT and mutant forms with IC50s of 0.923 nM and 2.65 nM, showing strong anti-cancer effects.</p>

<p>PRMT5-IN-15 is a PRMT5 inhibitor with an IC 50 value of 0.84 nM.</p>

<p>DNMT1/HDAC-IN-1 (compound (R)-23a), a potent dual inhibitor targeting both DNMT1 and HDAC, exhibits impressive inhibitory effects specifically on HDAC1 (HDAC1:IC50=0.05 μM), a major HDAC isoform that interacts with DNMT1 across multiple protein complexes involved in the transcriptional silencing of TSGs. This compound has been shown to remodel the tumor immune microenvironment and induce tumor regression, effectively reversing cancer-specific epigenetic abnormalities.</p>

<p>CARM1/IKZF3 ligand 1 functions as an inhibitor of CARM1 and serves as a target protein ligand for the synthesis of PROTAC CARM1/IKZF3 degrader-1.</p>

<p>HDAC11-IN-1 (Compound 14-NC6OH) is a macrocyclic inhibitor that selectively targets HDAC11 with a Ki of 40 nM. It demonstrates effective cell permeability and suppresses the expression of YAP1 and SOX2.</p>

<p>ZSNI-21 is a dual inhibitor targeting ADAM17 and HDAC2. It effectively suppresses the proliferation of Bel-7402 cells and exhibits significant anti-metastatic properties against HCC-LM3 cells, making it a promising candidate for hepatocellular carcinoma (HCC) research.</p>

<p>UNC10013 is an allosteric modulator of SETDB1, exhibiting negative allosteric regulation through covalent bond formation with Cys385 on the 3TD domain. It has a kinact/KI value of 1.0 × 10^6 M^-1*s^-1. UNC10013 effectively disrupts SETDB1-mediated Akt methylation, holding potential for application in cancer and neurodegenerative disease research.</p>

<p>PRMT5ligand 1 is a ligand of PRMT5, used as a target protein ligand in the synthesis of the PROTAC degrader MS4322.</p>

<p>Biotin-JQ1 is a bromodomain BRD4 binder; inhibits MM1.S cell growth with EC50 of 0.4μM.</p>

<p>(R)-SKBG-1 is an inhibitor of the RNA-binding protein NONO, effectively downregulating androgen receptor expression by targeting both AR-FL mRNA and AR-V7 mRNA</p>

<p>ML234 is a dual inhibitor targeting EZH2/LSD1, with IC50 values of 0.09 and 0.12 μM, respectively. It demonstrates strong antiproliferative effects on prostate cancer cell lines LNCAP, PC3, and 22RV1. Additionally, ML234 inhibits tumor growth in a 22RV1 xenograft mouse model, showing potential as a research agent in prostate cancer therapeutics.</p>

<p>JAK1/STAT3-IN-1 (compound 4f) functions as an anti-atopic dermatitis (AD) agent by inhibiting the JAK1/STAT3 signaling pathway. It has an IC50 value of 2.17 μM for inhibiting NO production. Additionally, JAK1/STAT3-IN-1 improves skin conditions in AD-like mice by reducing inflammatory infiltration, suppressing the expression of p-JAK1/JAK1 and p-STAT3/STAT3, and alleviating the hyperimmune response induced by MC903 (Calcipotriol).</p>

<p>QA-68 is a potent BRD9 degrader, inhibits cell growth, and has anti-leukemic properties.</p>

<p>MACTIDE-V is an orally active and selective peptide-drug conjugate targeting CD206. This compound delivers Verteporfin to CD206+ tumor-associated macrophages (TAM), thereby inhibiting the YAP/TAZ signaling pathway. It facilitates YAP exclusion from the nucleus, induces TAM polarization toward an anti-tumor phenotype, enhances phagocytosis and antigen presentation, and promotes T cell infiltration and NK cell activity. MACTIDE-V suppresses primary tumor growth and lung metastasis in triple-negative breast cancer (TNBC) mouse models.</p>

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

<p>HDAC6ligand-3 serves as a ligand for HDAC6 and can be utilized as a target protein ligand in the synthesis of [PROTAC] HDAC6 degrader4.</p>

<p>Malantide TFA: synthetic dodecapeptide, PKA-specific with Km 15 μM, &gt;90% PKI blockage, also PKC substrate, Km 16 μM.</p>

<p>Delcasertib acetate is a selective δ protein kinase C (δPKC) inhibitor for the study of acute myocardial infarction and pain.</p>

<p>GNE-064: Oral SMARCA4/2, PBRM1 inhibitor; IC50 (SMARCA4)=0.035µM, EC50 (SMARCA2)=0.1µM; High solubility; Research probe.</p>

<p>Antidiabetic agent 7 (Compound 5m) functions as a potent hyperglycemia inhibitor. It effectively stimulates GLUT4 translocation in skeletal muscle cells by activating the AMPK-dependent pathway. Additionally, this compound is capable of reducing blood glucose levels and exhibits favorable pharmacokinetic properties. Antidiabetic agent 7 is suitable for research related to antihyperglycemic treatments.</p>

<p>NCT-TFP is PARP probe used to identifying Poly(ADP-ribose) polymerases (PARP) inhibitors[1].</p>

<p>MS479 is a BRD4 PROTAC degrader that binds with high affinity to BRD4-BD2 and GLP (BRD4-BD2: Kd = 200 nM; GLP: Kd = 306 nM). It effectively reduces the protein levels of BRD4 short isoforms. By directly binding to its substrate GLP, MS479 recruits the E3 ligase SPOP as a bridging protein. Additionally, MS479 can be utilized to inhibit the proliferation of colorectal cancer cells.</p>

<p>SJ988497: PROTAC JAK2 degrader, inhibits CRLF2r cell growth, degrades GSPT1, combines Ruxolitinib, linker, Pomalidomide; researched for ALL.</p>

<p>EPZ028862 is a</p>

<p>SP-96: Aurora B inhibitor, IC50=0.316 nM, selectively hinders MDA-MD-468 growth, GI50=107 nM, for triple-negative breast cancer research.</p>

<p>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>

<p>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.</p>

<p>SIRT1-IN-1 is a selective inhibitor of SIRT1 with an IC50 of 205 nM.Cost-effective and quality-assured.</p>

<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.</p>

<p>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>

<p>VinSpinIn is a probe for the Spin family proteins.</p>

<p>SIRT5 inhibitor 9 (compound 14) is a moderately selective and substrate-competitive SIRT5 inhibitor with IC50=4.07 μM and has potential anticancer effects.</p>

<p>(rel)-Tranylcypromine D5 hydrochloride is a deuterium labeled (rel)-Tranylcypromine hydrochloride.</p>

<p>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.</p>

<p>SIRT5 inhibitor 8 (compound 10) is a moderately selective and substrate-competitive SIRT5 inhibitor with IC50=5.38 μM, with potential anticancer effects.</p>

<p>HDAC8-IN-10 (compound 15) serves as a potent inhibitor of HDAC8, exhibiting an IC50 value of 7.6 nM. It also acts as a ligand for the HDAC8 target protein, utilized in the synthesis of PROTAC YX862.</p>

<p>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.</p>

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

<p>BRD4-binding moiety 1 links to cereblon, forming a PROTAC that degrades BRD4 efficiently.</p>

<p>Mz325 serves as a dual inhibitor of both HDAC and Sirt2, exhibiting an IC50 of 9.7 µM against Sirt2, which are implicated in the pathogenesis of cancer and</p>

<p>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%.</p>

<p>Compound 8b, a dual-ligand PROTAC, targets VHL &amp; BRD4, degrades BRD4 in PC3 cells; conjugates with STEAP1/CLL1, DC50: 1.3/18 nM.</p>

<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>

<p>Uzansertib (INCB053914) is a potent pan-PIM kinase inhibitor with low IC50s: 0.24, 30, 0.12 nM for PIM1, 2, 3; hinders hematologic tumor growth.</p>

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

<p>α-Hydroxyglutaric Acid is a natural product for research related to life sciences. The catalog number is T36624 and the CAS number is 2889-31-8.</p>

<p>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.</p>

<p>R 8605 is a third-generation retinoid.</p>

<p>PROTAC BRM degrader-1 (compound 17) serves as a PROTAC-based degrader targeting both BRM and BRG1, exhibiting DC50 values of 93 pM and 4.9 nM, respectively [1].</p>

<p>TB22 is a non-nucleoside inhibitor of DOT1LR231Q with anticancer activity. It inhibits the malignant phenotype of lung cancer cells harboring the R231Q mutation via the MAPK/ERK signaling pathway, making it useful for lung cancer research.</p>

<p>UNC10142 (Compound 44) is a small-molecule antagonist of CHD1, with a binding IC50 value of 1.7 μM. It induces a dose-dependent reduction in the viability of PTEN-deficient prostate cancer cells.</p>

<p>SW2_152F: Potent CBX2 ChD inhibitor, Kd 80 nM, 24-1000x selective over other CBXs in vitro.</p>

<p>BTR2004 is a selective PROTAC degrader targeting the BET family (BRD2/3/4) proteins. It facilitates the formation of a ternary complex with BRD proteins and KLHL20, leading to ubiquitination and proteasomal degradation via the UPS pathway. BTR2004 shows potential for research in PC3 prostate cancer and MDA-MB-231 breast cancer cell lines.</p>

<p>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>

<p>Biguanide can reduce oxidative stress in rats with hyperglycemia.</p>

<p>BETd-246 is an inhibitor of second-generation and PROTAC-based BET bromodomain (BRD), show antitumor activity.</p>

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

<p>HSP90/LSD1-IN-1 (compound 6) is a dual inhibitor of HSP90 and LSD1. This compound effectively inhibits the proliferation of prostate cancer cell lines PC-3 and DU145, with GI50 values of 0.24 μM and 0.30 μM, respectively.</p>