Chromatine/Épigénétique

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

<p>JAK2-IN-6: A potent JAK2-specific inhibitor (IC50=22.86μg/mL), blocks JAK2 signaling, has anticancer properties, and is inactive against JAK1/3.</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>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>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>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>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>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>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>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>Tert-butyl compound inhibits human EGLN-1; confirmed by spectrometry after 20 mins.</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>

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