Apoptosis

RIP2 Kinase Inhibitor 4, a selective RIPK2 PROTAC, degrades RIPK2 (pIC50=8), inhibits TNF-α release.

BY13 is an SRC-3 PROTAC degrader with a DC50 of 0.031 μM. It selectively obstructs the ER signaling pathway by downregulating ERα levels, showing greater selectivity over the androgen receptor (AR). BY13 effectively addresses endocrine resistance in breast cancer by inducing cell cycle arrest at the G1 phase and triggering apoptosis. Additionally, it surpasses Fulvestrant in efficacy and significantly inhibits the growth of resistant breast tumors in LCC2 xenograft mouse models, exhibiting no noticeable toxicity.

Apoptosisinducer 30 (Compound 15a) acts as an anticancer agent. It induces apoptosis in MCF-7 cells through the mitochondrial pathway. This compound elevates intracellular levels of reactive oxygen species (ROS), decreases mitochondrial membrane potential, and arrests the cell cycle at the G0/G1 phase. Apoptosisinducer 30 inhibits cell growth, with an IC50 value of 0.32 μM against MCF-7 cells, and suppresses tumor growth in a mouse breast cancer model.

Tubulin polymerization-IN-70 (compound Q19) is an effective inhibitor of tubulin polymerization. This compound exerts antiproliferative properties by targeting the colchicine binding site on tubulin, thereby inhibiting its polymerization. Tubulin polymerization-IN-70 also induces apoptosis and cell cycle arrest at the G2/M phase. Additionally, it triggers a decrease in mitochondrial membrane potential and elevates levels of reactive oxygen species (ROS). Moreover, Tubulin polymerization-IN-70 possesses anti-angiogenic and anticancer activities.

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

P1D-34 is a Pin1 PROTAC degrader with a DC50 value of 177 nM. It downregulates Pin1 substrate proteins, including Cyclin D1, Rb, Mcl-1, Akt, and c-Myc. Additionally, P1D-34 exhibits antiproliferative activity across various acute myeloid leukemia (AML) cell lines and induces DNA damage and apoptosis by generating reactive oxygen species (ROS).

Ac-LEHD-AMC, a fluorogenic caspase-9 substrate, releases fluorescent AMC upon cleavage, aiding caspase-9 activity measurement.

Calphostin C is a protein kinase C inhibitor.

Quercetin-d3 hydrate, a deuterated form of Quercetin hydrate, acts as a flavonoid that stimulates recombinant SIRT1 and serves as a PI3K inhibitor. The compound specifically exhibits IC50 values of 2.4 μM, 3.0 μM, and 5.4 μM against PI3Kγ, PI3Kδ, and PI3Kβ, respectively.

SLF-amido-C2-COOH is a synthetic ligand for FKBP (SLF), and can be used in the synthesis of PROTACs.

dTAG-7 selectively degrades BRD4 and FKBP12F36V by linking BET bromodomains to E3 ligase CRBN; it's a heterobifunctional degrader.

AMXT-1501 tetrahydrochloride is an inhibitor of polyamine transport.

BT44, a potent second-gen GDNF mimetic, is a lead for treating neurodegeneration.

RIPK1-IN-30 (compound 24) is a potent RIPK1 inhibitor with an IC50 of 2.01 μM. It demonstrates a protective effect in the HT-29 cell model of TSZ-induced necroptosis, with an EC50 of 6.77 μM.

EGFR-IN-131 (compound 3a) is an efficacious EGFR inhibitor capable of crossing the blood-brain barrier, with an IC50 value of 272.9 nM. This compound exhibits anti-proliferative activity, induces cellular apoptosis (apoptosis), and causes cell cycle arrest in the G0/G1 phase. Additionally, EGFR-IN-131 reduces the protein expression of p-EGFR.

PRMT5-IN-45 (compound 36) is a potent and selective inhibitor of PRMT5, exhibiting an IC50 value of 3 nM. This compound effectively reduces the levels of symmetrical dimethylarginine (sDMA) and inhibits the proliferation of the MOLM-13 cell line by inducing apoptosis and causing cell cycle arrest.

c-Fos-IN-1 (Compound P16) acts as a c-Jun inhibitor, effectively reducing the mRNA and protein levels of c-Fos. It also inhibits the phosphorylation activity of ERK and the transcriptional activity of AP-1. This compound demonstrates anticancer properties through the inhibition of the ERK/c-Fos/Jun pathway. c-Fos-IN-1 curbs the proliferation and migration of gastric cancer cells, with an IC50 of 2.31 μM for MGC-803 cells, causing cell cycle arrest at the G2/M phase and inducing apoptosis in cancer cells. Additionally, c-Fos-IN-1 hampers the growth of gastric cancer tumors.

Theophyllol (theophylline sodium acetate) can alter calcium levels in subcellular fractions of rat brain cortex.

PLD-IN-1 (Compound 3r) is an orally effective inhibitor of phospholipase D (phospholipaseD) with an IC50 of 1.97 μM. It reduces the expression of CD24, CD47, and PD-L1 while enhancing the expression of calreticulin, thereby modulating the immune evasion mechanisms of lung cancer cells by promoting the phagocytosis of cancer cells by macrophages. PLD-IN-1 inhibits the viability of lung cancer cell lines A549, HCC44, H460, and HCC15 with IC50 values of 18.44, 22.31, 24.85, and 21.45 μM, respectively. It induces apoptosis (apoptosis) in A549 cells and inhibits cell migration. Additionally, PLD-IN-1 increases pro-inflammatory M1 macrophage levels and decreases anti-inflammatory M2 macrophage levels, exhibiting anti-tumor activity in mouse models.

PI3K/HDAC-IN-4 (Compound 31f) is a dual inhibitor targeting PI3K and HDAC, with an IC50 of 0.2μM. It demonstrates high selectivity for HDAC1-3, with IC50 values of 75.5 nM, 70.9 nM, and 1.9 nM, respectively. As a potent pan-PI3K inhibitor, PI3K/HDAC-IN-4 has IC50 values of 2.5 nM, 80.5 nM, 10.0 nM, and 57.2 nM for PI3Kα, β, δ, and γ, respectively. This compound effectively induces apoptosis in tumor cells by concurrently inhibiting the PI3K/AKT/mTOR signaling pathway and HDAC1-3. It shows significant antiproliferative activity across various tumor cell lines, such as MV4-11, Jeko-1, HL60, and MCF-7, with IC50 values of 0.2, 0.9, 0.8, and 1.5 μM, respectively. PI3K/HDAC-IN-4 is applicable in the study of lymphoma and leukemia.

12-Deoxyphorbol 13-palmitate, a monomer derived from the roots of Euphorbia fischeriana, exhibits notable antitumor activity. This compound induces cell cycle arrest and apoptosis in gastric cancer cells by modulating key cell cycle regulators, such as cyclin B, cyclin A, and CDC2. Additionally, 12-Deoxyphorbol 13-palmitate significantly diminishes liver fibrosis by targeting APOL2 and impairing the APOL2–SERCA2–PERK–HES1 signaling pathway.

SF1126 is a first-in-class PI3K/BRD4 inhibitor and RGDS-conjugated LY294002 prodrug, enhancing solubility and targeting tumor integrins.

Asaretoclax is an effective inhibitor of B-cell lymphoma 2 (Bcl-2), demonstrating potential for use in cancer research.

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

LSD1-IN-27 inhibits LSD1 (IC50=13 nM), blocks gastric cancer cell stemness/migration, reduces PD-L1, and boosts T-cell response.

Mcl-1 antagonist 1 is a Mcl-1 protein antagonist.

MD-265 is a PROTAC degrader that targets and degrades MDM2, leading to the activation of p53 in cancer cells with wild-type p53. MD-265 achieves complete tumor regression and enhances long-term survival in leukemic mice.

KGYY15 (Mouse KGYY15), a peptide that targets CD40, exhibits weak inhibition of the CD40-CD40L interaction, with an IC50 exceeding 1 mM. At a concentration of 100 μM, KGYY15 activates the NF-κB pathway by 33%.

Hexapeptide-11 is a novel proteostasis network modulator in human diploid fibroblasts.

KTX-582: potent IRAK4/Ikaros degrader (DC50=4/5nM), induces MYD88 MT DLBCL apoptosis & tumor regression in lymphoma.

Targaprimir-96 is a potent microRNA-96 (miR-96) processing inhibitor.

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].

intestinal epithelium-specific growth factor

Aromatase-IN-5 (Compound 10) is a potent inhibitor of aromatase with an IC50 value of 0.06 μM. It effectively blocks estrogen production and inhibits the proliferation of breast cancer cell lines such as MCF-7, arresting the cell cycle in the G1 phase and inducing apoptosis. Aromatase-IN-5 shows promise for breast cancer research.

Ferroptosis-IN-16 (Compound 13l) acts as a specific inhibitor of ferroptosis, demonstrating EC50 values of 0.7 nM in ES-2 cells and 0.9 nM in LX-2 cells. It effectively alleviates acute liver injury induced by Acetaminophen in mouse models and shows excellent metabolic stability in mouse liver microsomes.

SL-01, an oral gemcitabine derivative, potently induces apoptosis to hinder breast cancer more effectively than gemcitabine.

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.

Acetyl tetrapeptide-2 is a skin conditioner, by soothing and nourishing the skin through similar mechanisms as other peptides.

Cannflavin A, isolated from Cannabis sativa L., exhibits anti-cancer, neuroprotective, and anti-inflammatory activities by inhibiting Aβ1-42 aggregation and

XZ338 is a highly selective degrader targeting BCL-XL without degrading BCL-2. It exhibits an IC50 value of 3.7 nM against MOLT-4 cells and possesses antiproliferative properties, making it useful for cancer research.

Antitumor photosensitizer-5 (Ru2) is an effective photosensitizing agent that targets tumor mitochondria, with an IC50 of 0.3 μM for phototoxicity against A549 cells. Upon exposure to 460 nm light, it induces reactive oxygen species production and NADH depletion, leading to mitochondrial damage, caspase-3 activation, apoptosis induction, and inhibition of cell migration. Antitumor photosensitizer-5 shows potential for preventing malignant tumor growth and may be applicable in photodynamic therapy.

Sarglaroids F (compound 6), an anti-inflammatory agent extracted from the roots of Grass Coral, suppresses LPS/ATP-induced IL-1β secretion by modulating K+

CDD-2807 is a serine/threonine kinase 33 (STK33) inhibitor with an IC50 of 9.2 nM. In mice, CDD-2807 demonstrates no significant toxicity and can cross the blood-testis barrier without accumulating in the brain. It offers reversible contraceptive effects, indicating potential for development as a male contraceptive.

AlPcS2 disodium: a photosensitizer for cancer therapies, isomeric mix, and used as a dye, reagent, and luminescent agent.

LP23, a non-arylmethylamine PD-1/PD-L1 inhibitor (IC 50: 16.7 nM), exhibits anti-tumor activity through the restoration of immune cell function in HepG2/Jurkat

Stem bromelain: cysteine protease from pineapple stem with fibrinolytic, anti-inflammatory, antitumoral properties.