Apoptosis

<p>Thrombospondin-1 (1016-1023) (human, bovine, mouse) is part of Thrombospondin-1 (TSP-1), a peptide with CD47 agonism.</p>

<p>Thalidomide-based E3 ligase ligand for PROTAC degrader MI-389 synthesis, linked to cereblon and Boc.</p>

<p>Ferroptosis-IN-3 (Compound 25), a ferroptosis inhibitor, demonstrates potent activity by inhibiting RSL3-induced ferroptosis in HT-1080 cells (EC50: 8.6 nM).</p>

<p>Hematein blocks Akt/PKB, Wnt signaling, promotes apoptosis in lung cancer, is a dye from hematoxylin, and inhibits casein kinase II (IC50: 0.74 μM).</p>

<p>PARP1-IN-27 (Compound 9B) serves as an inhibitor of both PARP1 and PARP2, exhibiting IC 50 values of 2.53 nM and 6.45 nM, respectively, in SUM149PT cells. This compound effectively suppresses the proliferation of BRCA-mutated cancer cell lines such as SUM149PT, HCC1937, and Capan-1, with respective IC 50 values of 0.62, 1.91, and 4.26 μM. Additionally, PARP1-IN-27 exacerbates DNA double-strand breaks, enhances ROS production, causes G2/M phase cell cycle arrest, and triggers apoptosis in SUM149PT cells.</p>

<p>CUR5-8: potent, oral CUR analog, reduces lipid droplets, boosts autophagy, hinders apoptosis, enhances insulin sensitivity.</p>

<p>LH1307 blocks PD-1/PD-L1 interaction, IC50 = 3 nM (HTRF assay), activates Jurkat cells, EC50s: 79 nM (U2OS), 763 nM (CHO).</p>

<p>FF2039 (compound 1j) is a PROTAC degrader specifically targeting HDAC1, HDAC6, and various subtypes of class I, IIa, and IIb HDACs. It induces cell cycle arrest and apoptosis, showing significant antiproliferative activity against both hematological and solid tumor cell lines. The IC50 values for FF2039 against HDAC1, HDAC2, HDAC4, and HDAC6 are 1.03, 2.15, 12.4, and 0.053 μM, respectively. FF2039 exhibits antiproliferative effects on solid tumors such as MM.1S, MDA-MB-231, and U-87MG, with EC50 values of 2.8, 28, and 30 μM, respectively.</p>

<p>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.</p>

<p>RET-IN-4: Oral RET inhibitor, IC50 ~1 nM for variants. Selective over JAK2/FLT3. Potent anticancer use.</p>

<p>Chloranthalactone B, a sesquiterpenoid from Sarcandra glabra, inhibits inflammation via AP-1 &amp; p38 MAPK.</p>

<p>Ferroptosisinducer-4 (Compound 5) is a phospholipid-based ferroptosis inducer featuring a terminal double bond at the sn-2 position. It exhibits significant cytotoxicity towards HT-1080 cells with an IC50 value of 18 μM. The toxicity mechanism involves the generation of lipid peroxides and oxidative damage to the cell membrane induced by the terminal double bond. Ferroptosisinducer-4 can be utilized in studies pertaining to the regulation of ferroptosis.</p>

<p>Compound 13b, a potent EGFR degrader, inhibits and induces apoptosis in NSCLC cells with a DC50 of 13.2 nM.</p>

<p>Caerin 1.1 TFA, a host defense peptide derived from the Australian tree frog Litoria's glandular secretions, exhibits anti-proliferative effects on HeLa cells</p>

<p>8-Aminoadenosine reduces ATP, blocks mRNA synthesis, and Akt/mTOR signaling, triggering autophagy and apoptosis independently of p53, with antitumor effects.</p>

<p>Milademetan tosylate hydrate, an oral MDM2 inhibitor targeting AML and solid tumors, induces G1 arrest and apoptosis.</p>

<p>Boc-AEVD-CHO, a selective Caspase 8 inhibitor, facilitates apoptosis research and the investigation of immune and inflammatory diseases [1] [2].</p>

<p>PB28: A potent σ2 agonist (Ki 0.68 nM), σ1 antagonist (Ki 0.38 nM), with anti-tumor properties and inhibits SARS-CoV-2 interactions.</p>

<p>sEH inhibitor-19 (Compound (R)-14i) is an orally active soluble epoxide hydrolase (sEH) inhibitor with an IC50 of 1.2 nM. This compound suppresses the expression of TNF-α and IL-6 and exhibits anti-inflammatory effects in mouse models of acute pancreatitis and Carrageenan-induced edema.</p>

<p>Lincydomine relaxes smooth muscles, treats unstable angina, and opens human and guinea pig respiratory tracts.</p>

<p>Thalidomide-NH-C8-NH2 is a synthetic E3 ligase ligand-linker for PROTAC, combining cereblon ligand and a specific linker.</p>

<p>AZD1152 is a pro-drug of Barasertib (AZD1152)-hQPA. Which is a highly selective Aurora B inhibitor with IC50 of 0.37 nM in a cell-free assay.</p>

<p>Anti-inflammatory agent 42 has anti-inflammatory activity and inhibits the expression of TNF-α and IL-6 in LPS-stimulated macrophages.</p>

<p>NSC90616 is a mutant p53 rescue compound [1] .</p>

<p>OICR12694 (JNJ-65234637) TFA, an orally active B cell lymphoma 6 (BCL6) inhibitor [1], demonstrates effectiveness in targeting BCL6 pathways.</p>

<p>Compound 7, also known as RAR/RXR agonist-1, is a chlorinated isomer of retinoic acid and acts as a selective RARα agonist and a partial RXRα agonist. It is capable of activating RXRα, thereby inducing G2/M arrest and apoptosis in cancer cells.</p>

<p>PARP1-IN-17 is an inhibitor that targets PARP-1 (IC50=19.24 nM ) with a slightly reduced affinity for PARP-2 (IC50=32.58 nM ) and induces apoptosis.</p>

<p>KRAS inhibitor-40 (Compound 41) is an inhibitor of KRAS, disrupting the KRAS G12C-BRAF complex and suppressing the phosphorylation of the downstream ERK signaling pathway. This compound also inhibits the proliferation of tumor cells with various KRAS mutations, exhibiting antitumor activity.</p>

<p>Enniatin A1, a cyclic hexadepsipeptide from Fusarium, induces apoptosis and disrupts ERK, inhibiting ACAT (IC50: 49 μM).</p>

<p>Potent PROTAC degrader for FLT3/CDK9, induces apoptosis, and shows promise for FLT3-ITD mutated AML research.</p>

<p>TNF/IFNγ-IN-1 (TGA) is a TNF and IFN-γ inhibitor with antioxidant and anti-inflammatory activities for neurodegenerative diseases such as Alzheimer.</p>

<p>Lodapolimab (LY3300054) is an IgGλ anti- PD-1 monoclonal antibody [1] .</p>

<p>Asparanin A, an apoptosis inducer with anticancer properties, arrests the cell cycle in the G0/G1 phase via the mitochondria and PI3K/AKT signaling pathways.</p>

<p>PAA5, a polynuclear Au(I) cluster, triggers ferroptosis and has anticancer effects by increasing pH2AX over time.</p>

<p>Anticancer agent 130 (compound 8d) significantly induces apoptosis in A549 cells [1].</p>

<p>BK60106 is a selective and direct inhibitor of the transmembrane protein CD99, which causes cell death in Ewing Sarcoma cells.</p>

<p>PERK-IN-6 is a novel and highly potent PERK inhibitor (IC50:2.5 nM).</p>

<p>PARP-1/2-IN-2-IN-1 (Compound 12e) effectively inhibits PARP1/2 and CDK12 with IC 50 values of 34 nM, 30 nM, and 285 nM respectively, impairing DNA damage repair</p>

<p>Antiangiogenic agent 6 (Pt-1) effectively inhibits angiogenesis and induces necroptosis in tumor cells.</p>

<p>Thalidomide-NH-PEG7, a chemical for creating PROTAC iRucaparib-AP6, selectively degrades PARP1 and is used in ADCs.</p>

<p>Liensinine is the active constituent of plumula nelambinis with anti-hypertension.</p>

<p>HDAC6-IN-16 (compound 5c), a quinazolin-4(3H)-one-based inhibitor of histone deacetylase 6 (HDAC6), demonstrates an anticancer effect by inhibiting colony</p>

<p>SI-2, a SRC-3 inhibitor, triggers breast cancer cell death (IC50: 3-20 nM), sparing normal cells.</p>

<p>PRLX-93936 HCL is an analog of erastin and demonstrated synergistic effects against non-small cell lung cancer (NSCLC) cells with cisplatin.</p>

<p>Ganoderic acid T1, a derivative of Ganoderic acid T, triggers cancer cell apoptosis by boosting ROS and activating caspases.</p>

<p>Eldecalcitol, orally active vitamin D analog, boosts bone density and treats osteoporosis.</p>

<p>LIB3S0280 is a potent inhibitor of TBK1, with an IC50 of 493.9 nM. It suppresses TBK1 downstream signaling by reducing the phosphorylation of IκBα and AKT. LIB3S0280 causes G2/M phase arrest and induces apoptosis in pancreatic cancer cells. Notably, it exhibits significant inhibitory effects on pancreatic cancer cell lines with high TBK1 expression, with a 96-hour IC50 value ranging from 6.64-10.98 μM. LIB3S0280 shows potential for research in pancreatic ductal adenocarcinoma (PDAC).</p>

<p>A-1155905 is an MCL-1 inhibitor with anticancer activity, demonstrating a half maximal inhibitory concentration (IC50) of 33.5 Nm and a dissociation constant (Ki) of 0.58 nM. This compound selectively binds to MCL-1 and possesses sufficient affinity to disrupt the MCL-1-Bim complex in live cells. The induction of death in MCL-1-dependent cell lines by A-1155905 is reliant on caspase proteins and occurs through apoptosis.</p>

<p>NL13, a Polo-like kinase 4 (PLK4) inhibitor, exhibits an IC 50 value of 2.32 μM. It demonstrates the ability to suppress the viability of PC3 and DU145 prostate cancer cells with respective IC 50 values of 3.51 μM and 2.53 μM. NL13 also inhibits tumor growth in prostate cancer mice. Additionally, it deactivates the AKT signaling pathway by reducing CCNB1/CDK1 levels, leading to G2/M cell cycle arrest and initiating apoptosis through caspase-9/caspase-3 cleavage.</p>

<p>Thalidomide-based E3 ligase ligand linked to a PROTAC piperazine-piperidine chain.</p>

<p>EATC, a tetracycline byproduct, combats Pseudomonas to E. coli with MIC50s of 0.75-16 mg/L.</p>

<p>CWI1-2 HCL: Potent IGF2BP2 inhibitor, induces apoptosis/differentiation, targets leukemia therapy.</p>

<p>Nrf2 activator-11 (compound M11) is a Nrf2 activator that possesses blood-brain barrier permeability and offers anti-oxidation, anti-inflammation, anti-ferroptosis, and anti-apoptosis properties. It is applicable for use in studying cerebral ischemia-reperfusion (CI/R) injury models.</p>

<p>Z-Asp-CH2-DCB is an irreversible inhibitor of broad spectrum caspase.</p>

<p>2,2'-Dihydroxy chalcone inhibits β-glucuronidase (IC50=1.6 μM) and lysozyme (IC50=1.4 μM), and fights E. coli, S. fowleri, S. albicans, S. aureus.</p>

<p>PROTAC GPX4 Degrader-1 (DC-2) is a PROTAC-based compound that efficiently degrades GPX4, demonstrating a degradation concentration (DC 50) of 0.03 μM in HT1080</p>

<p>c-Met-IN-24 (compound 3g) serves as a dual-target inhibitor for STAT-3 (=4.7 μM) and c-MET (=12.67 μM), exhibiting anticancer properties. It arrests the G2/M cell cycle and induces apoptosis in SNB-75 cells, making it applicable in the research of central nervous system cancers.</p>

<p>Thalidomide-O-C6-NH2 is a synthesized E3 ligase ligand-linker conjugate used in the PROTAC dTAG-13, a degrader of FKBP12F36V and BET[1].</p>

<p>HDAC6-IN-22 (compound 30), an HDAC6 inhibitor, exhibits an IC50 of 4.63 nM and demonstrates antiproliferative effects against multiple myeloma both in vitro and</p>

<p>Disitertide (P144) is an inhibitor of TGF-β1.</p>

<p>PRMT5-IN-31 (Compound 3m), a selective PRMT5 inhibitor (IC50: 0.31 μM), increases hnRNP E1 protein levels by occupying the substrate site of PRMT5 and</p>

<p>S65487 (VOB560) hydrochloride, a potent and selective Bcl-2 inhibitor, is effective against BCL-2 mutations, including G101V and D103Y.</p>

<p>Enterodiol is a natural product that can be used as a reference standard.</p>

<p>Thalidomide-based cereblon ligand linked to PROTAC technology as E3 ligase ligand-linker.</p>

<p>FGA139 is an inhibitor of cysteine proteases, specifically targeting cathepsin B and L with IC50 values of 4.98 μM and 3.14 μM, respectively. It reduces the production of NO in LPS-induced RAW264.7 cells and lowers TNFα levels in microglia, demonstrating antioxidant and anti-inflammatory properties. Additionally, FGA139 enhances the secretion of neuroprotective metabolites such as purines and linoleic acid in LPS-stimulated microglia. This compound is applicable in the study of neuroinflammatory diseases.</p>

<p>YN14-H is a PROTAC degrader that targets KRASG12C. It effectively inhibits the growth of NCI-H358 and MIA PaCa-2 cells, with IC50 values of 0.042 μM and 0.021 μM, respectively, and DC50 values of 28.9 nM and 18.1 nM. YN14-H significantly induces apoptosis and suppresses cell migration. It demonstrates favorable pharmacokinetics and excellent in vivo antitumor activity.</p>

<p>Albanol B, from mulberries, combats Alzheimer's, bacteria, and oxidation, hinders cancer growth, and triggers cell arrest and apoptosis.</p>

<p>dTAG-47 targets FKBP12 F36V for protein degradation, useful in basal-like breast cancer research.</p>

<p>Apoptosisinducer 32 (Compound 7g) is an apoptosis inducer with a KD of 42 μM, demonstrating antitumor activity by causing significant morphological changes, such as membrane blebbing, nuclear fragmentation, and apoptotic body formation, in MDA-MB-231 cells. The IC50 values for Apoptosisinducer 32 are 4.77 μM in MCF-7 cells, 6.56 μM in MDA-MB-231 cells, and 337.8 μM in HEK cells.</p>

<p>FA4-Cu is a compound formed from the effective pancreatic cancer inhibitor FA4 and Cu(II), which can induce apoptosis by triggering ER and mitochondrial stress.</p>

<p>N-Stearoyltyrosine (N-(1-Oxooctadecyl)-L-tyrosine) is an analog of Anandamide. It exhibits neuroprotective effects by safeguarding the CA1 region of the hippocampus in a gerbil ischemia-reperfusion model. Additionally, N-Stearoyltyrosine inhibits free radical generation, enhances antioxidant capacity, and reduces IR-induced apoptosis (cell apoptosis).</p>

<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.</p>

<p>PROTACSMARCA2/4 degrader-38 is a SMARCA2/4 PROTAC degrader with DC50 values of 3.0 nM and 4.0 nM, respectively. It facilitates the ubiquitination and degradation of SMARCA2/4 and can block the G0/G1 phase of the cell cycle, leading to the induction of apoptosis. PROTACSMARCA2/4 degrader-38 is applicable in acute myeloid leukemia (AML) research.</p>

<p>Compound A6, a potent PROTAC HDAC6 degrader, has a DC50 of 3.5 nM and induces apoptosis in myeloid leukemia cells.</p>

<p>FW-1 is a type I inhibitor of FLT3, with an IC50 of approximately 1 μM. It exhibits cytotoxic effects in FLT3-mutant AML cells, causes cell cycle arrest at the G0/G1 phase, and induces apoptosis in MV4-11 and MOLM-13 cells.</p>

<p>Thalidomide-NH-C6-NH2 is a synthetic conjugate compound designed as an E3 ligase ligand-linker.</p>

<p>MET/PDGFRA-IN-2 (compound 8h) serves as an inhibitor of MET and PDGFRA proteins, promoting apoptosis in cells and impeding the proliferation of MET-positive</p>

<p>Fluoxetine-Conjugated Platinum(IV) prodrug-1 is an eEF2K inhibitor that can hinder the proliferation of cancer cells, induce DNA damage, and cause cell cycle arrest at the S phase, leading to apoptosis (Apoptosis). It also promotes the accumulation of reactive oxygen species (ROS) and disrupts mitochondrial function. This prodrug inhibits the migration and invasion of TNBC cells by suppressing MMP-2 activity and induces autophagy in TNBC cells through AMPK activation. In the 4T1-Luc mouse model, it exhibits antitumor activity and triggers immune suppression. Fluoxetine-Conjugated Platinum(IV) prodrug-1 is relevant for research in triple-negative breast cancer (TNBC).</p>

<p>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.</p>

<p>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.</p>

<p>Etoposide phosphate disodium, a prodrug of etoposide, is a powerful anticancer drug inhibiting DNA topoisomerase II.</p>

<p>DPP-4-IN-8 (compound 27) is a potent and selective inhibitor of dipeptidyl peptidase 4 (DPP4), with an inhibition constant (Ki) of 0.96 μM.</p>

<p>ROTACMNK1degrader-1 is a selective MNK1 PROTAC degrader with a DC50 of 11.92 nM and a Dmax greater than 96% in MV4-11 cells. It significantly reduces p-eIF4E levels with an IC50 of 22.07 nM, induces apoptosis, and causes cell cycle arrest at the G1 phase. This compound exhibits potent antitumor activity, demonstrating strong anti-leukemic effects in MV4-11 xenograft mouse models with acceptable drug safety.</p>

<p>Apoptosisinducer 24 (Compound 4) inhibits the proliferation of gastric cancer cells with an IC50 range of 1.2-4.8 μM. It arrests the cell cycle at the G2/M phase, induces apoptosis in BGC-823 cells, and causes mitochondrial dysfunction. In mice, Apoptosisinducer 24 exhibits antitumor activity without significant toxicity, having an LD50 of 91.2 mg/kg.</p>

<p>Thalidomide-O-C5-acid, a synthesized E3 ligase linker, merges cereblon and PROTAC tech.</p>

<p>EGFR-IN-83 (Compound 9), an EGFR inhibitor with an IC50 of 2.53 nM, exhibits antiproliferative effects on MCF-7 and MDA-MB-231 cell lines, with respective IC50</p>

<p>MPP hydrochloride is a selective estrogen receptor (ERR) modulator.</p>

<p>FOXO4-DRI: a peptide blocking FOXO4/p53 interaction; induces senescent cells' apoptosis.</p>

<p>PROTAC EGFR degrader 6 effectively degrades EGFR Del19 in HCC827 cells (DC50=45.2 nM) and induces apoptosis and G1 arrest.</p>

<p>CYP51/PD-L1-IN-2 (compound L20), a quinazoline with antifungal properties, is a potent dual inhibitor targeting both CYP51 (IC50: 0.263 μM) and PD-L1 (IC50: 0.</p>

<p>Zapalog: photocleavable dimerizer controlling instant protein interactions.</p>

<p>EM 163是一种 TIR-TIR 相互作用抑制剂，它是MyD88蛋白的TIR（Toll/白细胞介素-1受体）结构域拟态。EM 163针对IL-1受体中的TIR 结构域，阻断与MyD88的相互作用。EM 163抑制葡萄球菌肠毒素B（SEB）引起的体内炎症细胞因子的产生。EM 163能保护小鼠免受SEB 冲击引起的死亡。在体外的大鼠海马神经元中，EM 163阻断p38的激活和IL-1β对化学诱导的长期电位（LTP）引发的蛋白质合成的抑制作用。</p>

<p>Schisandronic acid is a triterpenoid acid isolated from the stems of Schisandra propinqua.</p>

<p>Taccalonolide E is a microtubule stabilizer and induces cancer cell apoptosis .</p>

<p>Citreoviridin from Penicillium citreoviride blocks brain Na+/K+-ATPase; boosts Na+/K+- and Mg2+-ATPase in microsomes dose-dependently.</p>

<p>Sandacanol (Sandranol) is an olfactory receptor (OR10H1) agonist.Sandacanol induces cell cycle arrest and partial apoptosis in bladder cancer cells.</p>

<p>Flavopiridol (Alvocidib) blocks CDK1/2/4/6 by competing with ATP (IC50 ~40 nM); 7.5x selectivity over CDK7; also inhibits EGFR, PKA. In Phase 1/2 trials.</p>

<p>Dynorphin A is a endogenous opioid peptide and a κ-opioid receptor (KOR) agonist,a neurotransmitter and regulator in the central and peripheral nervous systems</p>

<p>Taxamairin B is a potent anti-inflammatory compound that inhibits the expression of proinflammatory cytokines (TNF-α, IL-1β, and IL-6) and reduces the</p>

<p>SH-5, an AKT inhibitor potentiates apoptosis and inhibits invasion through the suppression of anti-apoptotic, proliferative and metastatic gene products</p>

<p>RO5353 is a potent and orally active inhibitor of p53-MDM2.</p>

<p>FKBP12 ligand-1 is the target protein ligand for MC-25B, which is a PROTAC targeting FKBP12.</p>

<p>DD0-2363 (Compound 32d) is a dual-target inhibitor of WDR5-MLL1/HDAC. It can suppress the proliferation of acute myeloid leukemia cells and induce apoptosis. With its antitumor properties, DD0-2363 is applicable for research on acute myeloid leukemia.</p>

<p>IPH10 is an anticancer agent with strong antitumor effects in vivo and exhibits no liver or kidney toxicity. It significantly increases the reactive oxygen species (ROS) levels in tumor cells, decreases mitochondrial membrane potential, and induces apoptosis (apoptosis) in these cells.</p>

<p>Betamethasone (NSC-39470), a glucocorticoid steroid, has immunosuppressive and anti-inflammatory properties.</p>

<p>Acetyl coenzyme A (Acetyl-CoA) is a pivotal molecule connecting multiple cellular metabolic pathways in the tricarboxylic acid cycle, fatty acid synthesis</p>

<p>Etanercept is a fusion protein consisting of the soluble portion of the p75-tumor necrosis factor receptor (TNFR) and the Fc fragment of human IgG1 and is commonly used to treat patients with rheumatoid arthritis.Cost-effective and quality-assured.</p>