Cromatina/Epigenética

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.

Tubulin/PARP-IN-1 (compound 14) is a dual PARP-tubulin inhibitor with anti-endometrial cancer activity. It exhibits inhibitory concentration (IC50) values of 74 nM for PARP1, 109 nM for PARP2, and 1.4 μM for microtubules/tubulin. Tubulin/PARP-IN-1 induces apoptosis and autophagy, causing cell cycle arrest at the G2/M phase.

Curcuphenol in concentrations in the range of 29-116 μg/ml inhibited cell proliferation and DNA replication and induced cell death in a dose-dependent manner.

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

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

M 1121 is a covalent and orally active inhibitor of the menin-MLL interaction capable of achieving complete and persistent tumor regression.

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%.

RX-37, a potent BET inhibitor (Ki: 3.2-24.7 nM for BRD2/3/4), selectively hinders growth in leukemia cells with MLL1 gene rearrangement.

AZ9567 is a potent MAT2A inhibitor. It demonstrates antiproliferative activity against MTAPKO HCT116 cells, with a pIC50 of 8.9.

EZH2-IN-5, potent EZH2 inhibitor; IC50: 1.52 nM (wild-type), 4.07 nM (Tyr641 mutant).

Ethyl 2-amino-4-methyl-5-thiophene carboxylate is a SETD7 inhibitor (IC50=4.59μM) with anticancer properties.

JPS014: A potent benzamide-based VHL E3-ligase PROTAC that degrades HDAC1/2, altering gene expression and inducing apoptosis in HCT116 cells.

Eldocasiran, a micro-RNA-193a-3p analogue, exhibits anticancer properties. It is utilized in cancer research [1].

PROTAC BRD9 binder moiety 5 selectively binds BRD9 with IC50 4.20μM, used in PROTAC synthesis, shows cancer cell antiproliferative activity.

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.

VPC-70063 (Thiourea, N-[3,5-bis(trifluoromethyl)phenyl]-N'-(phenylmethyl)-) is an inhibitor of c-Myc-MAX.

HDAC-IN-65 (compound 6) is a selective histone deacetylase (HDAC) inhibitor with an IC50 value of 2.5 μM. It is a prodrug offering excellent bioreductive properties.

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%.

PRO-HD2 is a selective, PROTAC-based degrader of HDAC6 [1].

(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