Chromatin/Epigenetics

<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>HDAC6-IN-56 (compound 18d) is an inhibitor of HDAC6, with an IC50 of 1.3 nM. This compound can inhibit the S phase and induce apoptosis in HCT-116 colon cancer cells.</p>

PROTAC BRD4 Degrader-27 is a selective PROTAC targeting BRD4, distinguished from BRD2/BRD3. This compound is composed of the E3 ubiquitinase ligand Thalidomide-4-OH, the PROTAC Linker γ-Aminobutyric acid, and the PROTAC target protein ligand PROTAC BRD4 ligand-3. The active control for this target protein ligand is Mivebresib, while the conjugate of the E3 ubiquitin ligase ligand and Linker is identified as Pomalidomide 4'-alkylC3-acid.

<p>JQ-1 (carboxylic acid)-NH-C2-NH-AMPRO-222 incorporates a BRD4 ligand and a PROTAC linker, and is used in the synthesis of PROTAC BRD4 Degrader-29.</p>

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

Mersalyl is an organic mercurial diuretic.

<p>PROTAC SMARCA2/4-degrader-25 is a PROTAC that targets SMARCA2/4. It consists of the E3 ligase ligand (2S,4R)-4-Hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide, a PROTAC Linker (S)-2-Amino-3,3-dimethylbutanoic acid, and the target protein ligand SMARCA2/4-ligand-3. The conjugate of the E3 ubiquitin ligase ligand and Linker is (S,R,S)-AHPC.</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>Compound 15: Potent PROTAC, selectively degrades BRD4/BRD2, has low toxicity, and is built of a BET inhibitor, linker, and CRBN ligand.</p>

<p>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.</p>

<p>HIF-1 alpha (556-574) is a 19-mer fragment vital for gene expression in low oxygen; it binds VHL with critical proline 564 for stability.</p>

<p>SW2_110A acetate is a selective, cell-permeable chromobox inhibitor of homologue CBX8 (Kd = 800 nM) bound to CBX8 N-terminal color gamut (ChD).</p>

<p>ZMF-23, a PAK1/HDAC6 dual inhibitor, suppresses PAK1 and HDAC6-mediated aerobic glycolysis and cellular migration while inducing TNF-α-regulated necroptosis and</p>

Lys-arg-ala-lys-ala-lys-thr-thr-lys-lys-arg is a protein kinase C substrate.

<p>JAK3-IN-15 (compound 22) is a JAK3 inhibitor that reduces the secretion of p-JAK3 induced by LPS. It is utilized in research for rheumatoid arthritis.</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>Dihydrochlamydocin, an inhibitor of histone deacetylases (HDAC), exhibits potent cytostatic activity against mastocytoma cells.</p>

HD-TAC7 is a PROTAC HDAC degrader; IC50s: HDAC1 (3.6μM), HDAC2 (4.2μM), HDAC3 (1.1μM); reduces NF-κB p65; researched for asthma, COPD.

<p>LSD1/HDAC6-IN-1 is an oral dual inhibitor of LSD1/HDAC6 with anti-tumor effects, useful for multiple myeloma research.</p>

<p>JAK1/TYK2-IN-1 is a dual inhibitor of TYK2 and JAK1 ( IC 50 = 29 and 41 nM respectively).</p>