Cromatina/Epigenética

RMM23 is an inhibitor that targets PfBDP1, exhibiting a Kd of 1.24 μM. In vitro, it shows EC50 values of 18 μM against the 3D7 wild-type strain, 14 μM against the NF54 wild-type strain, and 20 μM against the multidrug-resistant K1 strain during the blood stage.

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.

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.

Mersalyl is an organic mercurial diuretic.

Sirtuin modulator 5 activates SIRT1 (<50 μM DC50), may extend cell lifespan, and could aid in researching various age/stress-related diseases.

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>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>

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.

A-893 is a cell-active inhibitor of Methyltransferase SMYD2 (IC 50 = 2.8 nM) .

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

<p>MS2133 is a DOT1L PROTAC degrader. It facilitates the ubiquitination and degradation of DOT1L in THP-1 and MV4-11 cells, with DC50 values of 56 nM and 25 nM, respectively, and reduces H3K79 methylation. MS2133 also inhibits the growth of MLL-r leukemia cells, demonstrating anticancer activity.</p>

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.

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.

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

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

<p>PROTAC SMARCA2/4-degrader-31 (Compound I-280) serves as a degrader for the catalytic subunits SMARCA2 and SMARCA4 of the SWI/SNF complex. It effectively degrades SMARCA2 in A549 cells and SMARCA4 in MV411 cells, both with a degradation concentration (DC50) of less than 100 nM.</p>

<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>

<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>

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

<p>Hyp-dBET1 is a PROTAC degrader targeting BRD4, with an IC50 value of 3.4 μM in MDA-MB-231 cells. Under hypoxic conditions, Hyp-dBET1 becomes active, recruiting E3 ubiquitin ligase, and facilitates the degradation of BRD4 via the ubiquitin-proteasome system. Hyp-dBET1 is applicable in anti-cancer research.</p>