Chromatin/Epigenetics

GNE-987 is a potent chimeric BET degrader, binding BRD4 BD1/BD2 at IC50: 4.7/4.4 nM & has a DC50: 0.03 nM in EOL-1 AML cells.

Strong PRMT5 inhibitor with 4 nM IC50, surpassing other PRMTs; halts MCL growth in lab tests.

JPS036, a benzamide-based VHL E3-ligase PROTAC, potently degrades HDAC1/2, increasing gene expression and apoptosis in HCT116 cells.

PAD2-IN-2 (cis-isomer of 1) TFA is an inhibitor of protein arginine deiminase 2 (PAD2). This molecule features an azobenzene photoswitch, enabling the optical regulation of PAD activity. Additionally, PAD2-IN-2 TFA inhibits the citrullination of histone H3.

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

PROTACBRD4 degrader-30 is an ISOX-DUAL-based PROTAC degrader, targeting BRD4 with an IC50 value of 65 nM. It is used in research studies related to c-Myc oncoproteins and the pathophysiology of cancer cells.

EXQ-2d is an inhibitor of tankyrase, effectively targeting TNKS1 and TNKS2 with IC50 values of 48.8 nM and 13.8 nM (pIC50=7.31 and 7.86), respectively. Additionally, EXQ-2d suppresses the WNT/β-catenin signaling pathway with an IC50 of 515 nM. It demonstrates antiproliferative activity in cancer cells COLO 320DM and RKO, with GI50 values of 4.9 μM and 77 μM, respectively.

Wnt/β-catenin-IN-5 (Compound 4) functions as an inhibitor of the Wnt/β-catenin signaling pathway. This compound effectively eradicates colorectal cancer stem cells and inhibits tumor growth by suppressing the Wnt signaling pathway. Additionally, Wnt/β-catenin-IN-5 promotes the degradation of KDM3A and KDM3B.

1,4-DPCA is an inhibitor of prolyl-hydroxylase with an IC50 of 2.4 µM for collagen hydroxylation in human foreskin fibroblasts and 60 μM for factor inhibiting

HD-TAC7 is a PROTAC degrader targeting HDAC, with IC50 values of 3.6/4.2/1.1 μM for HDAC1/HDAC2/HDAC3. It can reduce the expression of NF-κB p65.

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

PROTAC BET degrader-2 is a highly potent degrader of Bromodomain and Extra-Terminal (BET) proteins (IC50 of 9.6 nM ).

Dot1L-IN-8 (Compound 15) is an effective Dot1L inhibitor. It suppresses the viability of HL-60, K562, MV4-11, HH, and KG-1 cells, with IC50 values of 0.45, 1.03, 0.68, 1.66, and 1.12 μM, respectively.

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.

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

PROTAC SMARCA2 degrader-20 (Compound I-40) is a potent degrader of PROTAC SMARCA2, showing potential for cancer research applications.

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.

Adenosine receptor modulator 1 acts as an inducer of collagen VII (C7). It enhances the expression of COL7A1 mRNA in donor-derived keratinocytes and, in synergy with Gentamicin, increases the overall levels of C7.

MAT2A-IN-14 (compound H3) is a MAT2A inhibitor that generates reactive oxygen species (ROS) following ultrasound treatment, leading to the specific degradation of MAT2A in cells through rapid oxidation reactions. When combined with ultrasound, MAT2A-IN-14 induces an 87% reduction of MAT2A in human colon cancer cells.

CEM114 is a potent chemical compound known as a chemical epigenetic modifier (CEM).

mUNO is a tumor-homing peptide (mUNO, sequence: "CSPGAK") that specifically binds to murine CD206, targeting tumor-associated macrophages that express CD206/MRC1. Additionally, mUNO can interact with human recombinant CD206.

MD6a is a melatonin derivative with inhibitory activity against poly(ADP-ribose) polymerase (PARP-1). It maintains protein homeostasis and improves mitochondrial function via the TOR/HSF-1 signaling pathway, providing neuroprotective effects.

UNC4976 is a positive allosteric modulator (PAM) peptidomimetic of CBX7 chromodomain binding to nucleic acids.

TYK2activator-1 (16b) is a TYK2 activator with an EC50 value of 1.78 μM. It inhibits JAK2 and JAK3 with IC50 values of 6.8 μM and 6.3 μM, respectively.

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%.

PROTAC Sirt2 Degrader-1 is a SirReal-based PROTAC, acts as a Sirt2 degrader, composed of a highly potent and isotype-selective Sirt2 inhibitor, a linker, and a

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

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.

(rel)-Tranylcypromine D5 hydrochloride is a deuterium labeled (rel)-Tranylcypromine hydrochloride.

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.

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

E67-2: Low-toxic, KIAA1718 inhibitor with IC50 of 3.4μM, targets H3K9/H3K4 demethylases.

WDR5ligand 2 is a ligand for WDR5 and can be utilized in the synthesis of PROTAC WDR5degrader 1.

Martinostat is an HDAC inhibitor that can be radiolabeled for quantitative imaging of HDACs within the central nervous system and major peripheral organs.

SIRT-IN-5, a selective inhibitor of SIRT3 with an IC50 of 2.88 μM, facilitates the differentiation of multiple myeloma cells. This differentiation is associated with increased expression of the differentiation antigens CD49e and human immunoglobulin light chains λ and κ.

Aurothiomalate tetramer sodium, a tetrameric form of Aurothiomalate sodium, functions as an anti-arthritis gold agent. It also acts as a potent and selective inhibitor of the oncogenic PKCι signaling pathway.

HIF1-IN-3 (Benzenepropanamide, N-[(8-hydroxy-7-quinolinyl)(4-methoxyphenyl)methyl]-) is an effective inhibitor of HIF-1 (EC50 = 0.9 μM) and can be used in

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

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

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.

Dihydrochlamydocin, an inhibitor of histone deacetylases (HDAC), exhibits potent cytostatic activity against mastocytoma cells.

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

PARP/HDAC-IN-1 is a PARP and HDAC inhibitor that inhibits PARP1, PARP2, and HDAC1, and may be used to study pancreatic cancer.

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%.

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

PAD2-IN-1 is a selective benzimidazole-derived inhibitor with a 95-fold and 79-fold higher affinity for PAD2 over PAD4 and PAD3, respectively.

WQQ-345, a BCAT1 inhibitor, exhibits an IC50 of 10.8 mM. In 67R cells, it reduces α-KG levels and upregulates H3K27me3 expression while downregulating the expression of glycolytic enzymes (PFKP and LDHA), leading to impaired glycolytic activity. Additionally, WQQ-345 demonstrates tumor-suppressive activity in a 67R subcutaneous xenograft model.