Apoptosis

PROTACERα Degrader-9 (Compound 18c) is a dual-targeting PROTAC degrader designed to diminish estrogen receptor α (ERα) and aromatase (ARO). It demonstrates a Ki of 0.25 μM for ERα binding and an IC50 of 4.6 μM for ARO inhibition. This compound curbs proliferation in wild-type MCF-7 cells (IC50=0.54 μM) and ERα mutant variants MCF-7EGFR (IC50=0.075 μM), MCF-7D538G (IC50=0.31 μM), and MCF-7Y537S (IC50=2.3 μM), while also downregulating ERS1 and MYC expression. PROTACERα Degrader-9 arrests the cell cycle at the G2/M phase and induces apoptosis in MCF-7 cells, exhibiting antitumor efficacy in mouse models.

PROTACFLT-3degrader 4 is an orally active CRBN-based FLT3-PROTAC degrader that efficiently induces the degradation of FLT3-ITD via the ubiquitin-proteasome system. It demonstrates high selectivity for FLT3-ITD mutant acute myeloid leukemia (AML) cells. [Blue: CRBN ligand, Black: linker; Pink: FLT3 inhibitor].

MK-4166 is a humanized IgG1 agonistic monoclonal antibody targeting GITR. It is capable of enhancing the proliferation of both naive T lymphocytes and tumor-infiltrating T lymphocytes.

<p>GPX4-IN-7 (Compound 31), an indirubin derivative, serves as a ferroptosis inducer in colon cancer treatment.</p>

Narasin (sodium salt) (HainanMycin) induces tumor necrosis factor-related apoptosis-induced ligand (TRAIL)-mediated apoptosis by ER stress in glioma cells and

<p>PROTAC FLT-3 degrader 1 is a PROTAC FLT-3 degrader of internal tandem duplication (ITD)(IC50 0.6 nM),with anti-proliferative activity.</p>

HQY1428 is an orally active CDK12 inhibitor. It impedes DNA replication, causing cell cycle arrest at the G2/M phase in SKOV3 cells, and induces DNA double-strand breaks as well as apoptosis. In the SKOV3 xenograft mouse model, HQY1428 demonstrates antitumor activity. Additionally, when combined with the HER2 inhibitor Lapatinib in the NCI-N87 xenograft mouse model, HQY1428 produces a synergistic therapeutic effect.

<p>Caspase-3 activator 3 (compound 2h) effectively induces apoptosis in HL-60 and K562 cells by substantially activating caspase-3, demonstrating antileukemic</p>

Ub4ix, a DUB/26S proteasome inhibitor, safeguards K48-linked Ub chains against cleavage by deubiquitinating enzymes (DUBs) and inhibits the proteasomal degradation of Ub-tagged proteins. Additionally, it diminishes the viability of Hela cells and triggers apoptosis, exhibiting an IC 50 value of 1.6 μM.

Antiproliferative agent-59 (Compound 14u) acts as an inhibitor of tubulin polymerization. Demonstrating anticancer activity in Huh7, SGC-7901, and MCF-7 cell lines, this compound achieves IC50 values of 0.03, 0.18, and 0.13 μM, respectively. Additionally, it arrests the cell cycle at the G2/M phase and induces apoptosis in Huh7 cells. In a xenograft mouse model utilizing Huh7 cells, Antiproliferative agent-59 exhibits antitumor effects against hepatocellular carcinoma without significant toxicity.

PROTAC FGFR2 degrader 1 (compound N5) is a potent PROTAC that efficiently targets FGFR2, boasting a DC 50 value of 6.46 nM and an FGFR2 IC 50 of 0.08 nM. This compound exhibits significant anti-proliferative effects and high selectivity. It induces G0/G1 arrest in the cell cycles of KATOIII and SNU16 and inhibits apoptosis by diminishing the activation of p-ERK and p-PLCγ, the downstream proteins of FGFR2. Additionally, PROTAC FGFR2 degrader 1 maintains over 50% inhibition of gastric cancer cells at a concentration of 0.17 nM and effectively suppresses the growth of SNU16 xenograft tumors in a mouse model.

FGFR1/VEGFR2-IN-2 (compound 6) is a dual inhibitor targeting both VEGFR2 and FGFR1 with IC50 values of 0.025 µM and 0.026 µM, respectively. This compound also exhibits inhibitory effects on EGFR and PDGFR-β, with IC50 values of 0.106 µM and 0.077 µM, respectively. FGFR1/VEGFR2-IN-2 demonstrates significant anticancer activity in the NCI-60 cell lines, showing a growth inhibition (GI) of 60.38%. In T-47D cell lines, it achieves an IC50 of 8.51 µM, exhibits anti-migratory properties, induces cell cycle arrest in the G1 phase, and promotes both apoptosis and necrosis. Additionally, while it has an IC50 greater than 100 µM in MCF-7 cell lines, it does so with an IC50 of 69.17 µM in MDA-MB-231 cell lines and shows no toxicity to normal cells.

ADH-6 TFA disrupts mutant p53 self-assembly in cancer, restores function, and induces cell cycle arrest and apoptosis.

Tengonermin (ARENEGYR), a vascular agent, is TNF-α fused with CNGRCG peptide, enhancing chemo and T-cell access in tumors.

NecroIr2, an iridium(III) compound, induces necroptosis in Cisplatin-resistant A549R lung cancer cells and disrupts mitochondria.

CQ-ER is a Coumarin-quinazolinone-based photosensitizer targeting the endoplasmic reticulum (ER). It induces ferroptosis, thereby enhancing photodynamic therapy (PDT).

AMXT-1501 tetrahydrochloride is an inhibitor of polyamine transport.

ECDD-S18 (compound ECDD-S18) induces apoptosis in a dose-dependent manner, effectively targeting the vacuolar ATPase (V-ATPase) and impairing lysosomal acidification.

<p>TNF-α-IN-6 is an orally efficacious allosteric inhibitor of TNFα ( K D = 6.8 nM).</p>

Fisetin quarterhydrate, a natural flavonol present in numerous fruits and vegetables, exhibits benefits including antioxidant, anticancer, and neuroprotective