Apoptosis

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

<p>EGFR/BRAFV600E-IN-3 is an inhibitor targeting EGFR, BRAFV600E, and EGFRT790M with IC50 values of 57 nM, 68 nM, and 9.70 nM, respectively.</p>

<p>DiPT-4, a dual TOP1/PARP1 inhibitor, effectively induces DNA double-strand breaks (DSBs), cell cycle arrest, and apoptosis in cancer cells, with potential to</p>

<p>eIF4E-IN-3: potent eIF4e inhibitor with promise for cancer study.</p>

<p>EGFR/VEGFR2-IN-1 (Compound 10e) serves as an inhibitor for VEGFR-2 and EGFR, with respective IC50 values of 0.26 and 0.14 μM. It inhibits microtubule protein polymerization with an IC50 of 40.9 μM and induces cell apoptosis (Apoptosis). EGFR/VEGFR2-IN-1 is applicable in research related to anti-leukemia and anti-lymphoma treatments.</p>

<p>PROTAC 20S proteasome subunit β5 degrader 1 (compound 12f) serves as a targeted degrader of the 20S proteasome subunit β5, exhibiting a DC50 value of 0.11 μM in FaDu cells. This compound disrupts the cell cycle and promotes apoptosis (apoptosis), while inhibiting cell proliferation and migration in both FaDu and KM3/BTZ cells. It is applicable for research into resistance to Bortezomib in pharyngeal carcinoma and multiple myeloma.</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>Vonlerizumab (Anti-TNFRSF4/OX40/CD134 Antibody) is a humanized monoclonal antibody targeting OX40, used in tumor research.</p>

<p>VEGFR-2-IN-64 (Compound 28) is an inhibitor of VEGFR2 with an IC50 of 27.8 nM. It suppresses the proliferation of cancer cells A549, T-47D, and Caco-2, exhibits anti-migration and anti-colony formation activities in T-47D cells, and induces apoptosis in T-47D cells.</p>

<p>CDK-IN-14 (B34) is a CDK2 inhibitor (IC50=0.097 μM) that exhibits anti-hepatocellular carcinoma activity. It inhibits the cell cycle in HepG-2 cancer cells and induces apoptosis (apoptosis) through a caspase-mediated mechanism.</p>

<p>CDK/HDAC-IN-4 is a highly selective dual inhibitor of cyclin-dependent kinase (CDK) and histone deacetylase (HDAC), with IC50 values of 88.4 nM and 168.9 nM, respectively. This compound exhibits antiproliferative effects in both hematologic and solid tumor cells. Additionally, CDK/HDAC-IN-4 induces apoptosis and S-phase cell cycle arrest in MV-4-11 cells. It has also demonstrated significant antitumor efficacy in an MV-4-11 xenograft model.</p>

U7D-1: First-class USP7 PROTAC degrader, DC50 33 nM, anticancer, induces apoptosis in Jeko-1.

<p>Topoisomerase II inhibitor 14: powerful anticancer agent that induces apoptosis, halts S phase, and lowers GSH, MDA, and NO levels.</p>

<p>Bcl-2-IN-22 (compound 1), a gold (I) NHC complex, exhibits anticancer activity. It induces cell death (apoptosis) via the mitochondrial pathway with an IC50 value of 0.014 μM. Additionally, Bcl-2-IN-22 targets members of the BCL-2 family, promoting apoptosis and sensitization in multidrug-resistant leukemia cells overexpressing BCL-2.</p>

<p>NMC-001 is a human IgG1 monoclonal antibody (mAb) that targets MDM2. It is useful for pancreatic cancer research. The recommended isotype control is HumanIgG1kappa, Isotype Control.</p>

<p>Cathepsin B, a cysteine protease located within the subcellular endosomes and lysosomal compartments, mediates apoptosis and can be used in cancer research.</p>

<p>S-Adenosyl-L-methionine (Ademetionine) is an intermediate metabolite of methionine,for treatment of primary biliary cirrhosis and major depressive disorder.</p>

<p>SA-VA, an intracellular self-assembled PROTAC featuring azide and alkyne groups, selectively degrades VEGFR-2 and EphB4 proteins within U87 cells.</p>

<p>β-Glucuronide-dPBD-PEG5-NH2 is a β-glucuronide-linked pyrrolobenzodiazepine dimer that functions as a proagent for the synthesis of the antibody-drug conjugate</p>

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

<p>TNF-α (31-45), human is a peptide of tumor necrosis factor-α.</p>

<p>Toremifene citrate is a selective estrogen receptor modulator (SERM). It is an estrogen agonist for bone tissue and cholesterol metabolism but is antagonistic on the mammary and uterine tissue.</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>1,2,3,4-Tetrahydronaphthalen-2-ol exhibits weak inhibitory activity against Bcl-xL and is widely used in biochemical experiments and drug synthesis research.</p>

<p>PAK4-IN-3 (compound 27e) is a PAK4 inhibitor exhibiting an IC50 of 10 nM and demonstrates antiproliferative effects on A549 cells with an IC50 of 0.61μM.</p>

<p>MitoTam bromide hydrobromide is an electron transport chain (ETC) inhibitor.</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>1-Alaninechlamydocin, a fungal metabolite from Tolypocladium sp., inhibits HDACs and reduces cell proliferation with GI50s 5.3-14 nM.</p>

Mepacrine (Erion) is an acridine derivative formerly widely used as an antimalarial.

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

<p>BM-1244 is a potent Bcl-xL/Bcl-2 inhibitor with Kis of 134 and 450 nM for Bcl- xL and Bcl-2, respectively.</p>

<p>Thalidomide-PEG2-NH2: synthetic E3 ligase ligand-linker, combines Thalidomide-based cereblon and PROTAC linker.</p>

<p>Thalidomide-O-amido-C4-N3 (Cereblon Ligand-Linker Conjugates 4) is an E3 ligase ligand-linker conjugate incorporating the Thalidomide-based cereblon ligand and</p>

<p>VEGFR2/HDAC1-IN-1 (compound 13) is a potent dual inhibitor of VEGFR-2 and HDAC, with IC50 values of 57.83 nM for VEGFR-2 and 9.82 nM for HDAC.</p>

<p>Irofulven is an agent of DNA-damaging and antitumor. It is used for the treatment of advanced solid tumors, including prostate, ovarian, and pancreatic cancers.</p>

<p>Sincalide ammonium, a CCK analog, stimulates bile release, gallbladder contraction, and sphincter relaxation, aiding in diagnoses.</p>

<p>Akt/NF-κB/MAPK-IN-1 (compound 2m) serves as a potent, orally active inhibitor targeting NO with an IC50 of 7.70 μM and demonstrates low toxicity.</p>

<p>RIPK1-IN-17 is a dual inhibitor of RIPK1 and RIPK3 inhibits necrosis by inhibiting phosphorylation of RIPK1, RIPK3 and MLKL,in a tnf-induced inflammation model.</p>

<p>Tubulin/AKT1-IN-1 (Compound D1-1) serves as an inhibitor of both tubulin polymerization and AKT pathway activation, effectively suppressing proliferation and</p>

<p>Compound 24a, an FPR1 antagonist, demonstrates potent inhibition of the formyl peptide receptor 1 (FPR1) with an IC50 value of 25 nM.</p>

<p>"(±)-Enterodiol, the racemate of Enterodiol, is metabolized from lignans found in whole-grain cereals, nuts, legumes, flaxseed, and vegetables by human intestinal bacteria. This compound exhibits apoptotic effects in colorectal cancer (CRC) cells and has been identified to possess anti-cancer activities [1] [2]."</p>

<p>Ferroptosis-IN-12 (Cpd-A1) is an inhibitor of ferroptosis. It effectively suppresses ferroptosis in mouse renal tubular epithelial cells (mTECs) treated with Erastin and improves renal function in dose-dependent manners in mouse models of acute kidney injury (AKI) induced by ischemia/reperfusion (I/R) or cecal ligation and puncture (CLP). This compound also reduces renal tubular damage and eliminates inflammation. Exhibiting good plasma stability and high distribution in renal tissues during pharmacokinetic studies in mice, Ferroptosis-IN-12 shows promising potential for research in the field of AKI.</p>

ARD-61: potent PROTAC, degrades AR/PR in AR+ cancers, triggers apoptosis, inhibits tumor growth in mice.

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

<p>UZH1, a mix of active METTL3 inhibitor UZH1a (IC50 280 nM) and inactive UZH1b (IC50 28 μM), modifies epitranscriptomics and has antitumor properties.</p>

<p>8-hydroxy Efavirenz, a main efavirenz metabolite by CYP2B6, causes apoptosis in rat neurons at 0.01 μM.</p>

CLEFMA has anti-proliferative activity. CLEFMA inhibits tumor growth associated with NF-κB-regulated anti-inflammatory and anti-metastatic effects.

<p>PARP1/BRD4-IN-3 (compound HF4) is an effective inhibitor of BRD4 and PARP1, with IC50 values of 1210 nM and 2019 nM respectively. The compound exhibits antiproliferative activity, induces apoptosis (apoptosis) and cell cycle arrest at the G0/G1 phase. Additionally, PARP1/BRD4-IN-3 causes DNA damage and reduces the expression of the Rad51 protein, demonstrating anti-tumor activity.</p>

<p>NA-Ir is a ferroptosis (Ferroptosis) inducer that targets mitochondrial DNA (mtDNA) and activates the cGAS-STING pathway to stimulate ferritin autophagy (). It also induces the production of reactive oxygen species (ROS) through photodynamic therapy (PDT), depletes glutathione (GSH), and downregulates glutathione peroxidase 4 (GPX4), thereby triggering lipid peroxidation and ferroptosis. NA-Ir exhibits enhanced anticancer activity under light exposure and selectively inhibits cancer cells with high H2S content.</p>

<p>ZMF-24 is an anti-triple-negative breast cancer (TNBC) agent that exhibits IC50 values of 0.22 μM and 0.44 μM against BT-549 and MDA-MB-231 TNBC cell proliferation, respectively. It targets the eukaryotic translation initiation factor 3 subunit D (EIF3D), disrupting TNBC's energy supply by inhibiting glycolysis. Additionally, ZMF-24 induces TNBC cell apoptosis (apoptosis) by stimulating sustained endoplasmic reticulum stress.</p>

<p>HDAC-IN-79 (compound 4) is an orally active dual inhibitor of xanthine oxidase and HDAC, exhibiting potent anti-hyperuricemia and antitumor activities in vivo (Xanthine oxidase: IC50=6.6 nM; HDAC1: IC50=134 nM; HDAC2: IC50=284 nM; HDAC3: IC50=173 nM; HDAC6: IC50=1.32 nM). Among leukemia cells, it is most effective in inhibiting the growth of HL60 cells (IC50=0.706 μM) and induces both apoptosis and autophagy. HDAC-IN-79 also modulates the expression levels of biomarkers associated with intracellular HDAC inhibition.</p>

<p>Z-VEID-FMK is a selective caspase-6 peptide inhibitor that irreversibly covalently binds to the enzyme, thereby inhibiting apoptosis and DNA breakage.</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>Photosensitizer-6 (Compound 4) is a metal ion complex that inhibits TrxR. It induces apoptosis in 4T1 cells, targeting cancer cells and eliminating tumors through chemophototherapy and immunogenic cell death under illumination. Additionally, Photosensitizer-6 can be utilized for tumor imaging.</p>

Thalidomide-O-PEG4-Boc is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1].

<p>MS41 is a selective eleven-nineteen leukemia (ENL) PROTAC degrader, with DC50s values of 3.50 nM (MV4;11), 2.84 nM (SEMK2), 3.03 nM (Jurkat), and 26.58 nM (KASUMI1). This compound effectively inhibits the growth of ENL-dependent leukemia cells, induces G1 cell cycle arrest, and increases cellular apoptosis (Apoptosis). Additionally, MS41 reduces chromatin occupancy related to ENL-mediated transcription elongation mechanisms and suppresses the expression of oncogenes and the progression of leukemia.</p>

<p>Trichostatin C, a natural glycosylated hydroxamate, is a histone deacetylase inhibitor with antifungal properties and can induce cell differentiation.</p>

<p>RSM3 TFA is a stapled peptide and an inhibitor of METTL3-METTL14, exhibiting a dissociation constant (Kd) of 3.10 μM. It inhibits tumor growth and induces cell apoptosis. RSM3 TFA is utilized in cancer research.</p>

<p>ZS3-046 is a TAF1 PROTAC degrader that facilitates the ubiquitination and subsequent degradation of TAF1. It can activate p53 and induce apoptosis in acute myeloid leukemia (AML) cells. Additionally, ZS3-046 demonstrates anti-tumor efficacy in AML xenograft mouse models.</p>

<p>Indinavir is an HIV protease inhibitor,HAART. inhibits the activation of MMP-2 in endothelial cells and exhibits affinity for α7-nAchR and SARS-CoV-2 Mpro.</p>

<p>ZYH-23 is a potent inhibitor of necroptosis. It targets HSP90 to inhibit the phosphorylation of RIPK1, RIPK3, and MLKL, effectively blocking programmed cell necrosis.</p>

<p>PPIA-IN-1 (Compound 20b) is an inhibitor of peptidyl-prolyl isomerase A (PPIA) with a KD of 0.52 μM. It demonstrates antiproliferative activity across various cancer cell lines, including an IC50 of 0.69 μM in HCT116 cells, induces cell cycle arrest at the G0/G1 phase, and exhibits antimetastatic effects in HCT116 cells. PPIA-IN-1 elevates ROS levels, causing DNA damage, ER stress, and mitochondrial dysfunction, and induces apoptosis in HCT116 cells via the MAPK pathway. Additionally, PPIA-IN-1 shows antitumor activity in a CT26 xenograft mouse model.</p>

<p>Thalidomide-5-NH-PEG2-NH2 hydrochloride is a cereblon ligand based on Thalidomide, designed to recruit CRBN proteins. It has the capability to be linked with target protein ligands via a linker, facilitating the formation of PROTAC molecules, such as THAL-SNS-032.</p>

<p>Thalidomide-O-PEG4-amine is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1].</p>

<p>RETligand-3 is the ligand for PROTAC QZ2135, which targets RET.</p>

<p>PTD-p65-P1: a NF-kappaB inhibitor blocking activation from multiple inflammatory stimuli.</p>

<p>Thalidomide-based E3 ligase ligand with PEG2-C2 linker; used as an immunomodulatory cancer treatment.</p>

<p>Anticanceragent 272 (Compound 2) is an anticancer agent demonstrating significant activity against bladder cancer cells (T-24) with an IC50 of 2.81 μM. It depletes glutathione (GSH) through a Fenton-like reaction, generating reactive oxygen species (ROS) and hydroxyl radicals (•OH), thereby inducing apoptosis and ferroptosis. Anticanceragent 272 enhances chemodynamic therapy (CDT) and promotes tumor cell death through mitochondrial dysfunction and autophagy. It holds potential for further research in bladder cancer.</p>

<p>Mcl1-IN-26 is an effective and selective myeloid cell leukemia 1 inhibitor.</p>

<p>Compound 5b (Anti-inflammatory agent 61) is a potent anti-inflammatory agent that diminishes TNF-α expression in LPS-induced inflammation within RAW 264.7 cells</p>

<p>YB-0158 ammonium (Wnt pathway inhibitor 2 ammonium) is a reverse-rotation peptidomimetic with translation-enhancing potential and anticancer activity.</p>

GPX4-IN-6 is a GPX4 inhibitor with antitumor activity.GPX4-IN-6 induces iron death and is used for the treatment and prevention of triple-negative breast cancer

<p>(±)-Indoxacarb is a pyrazoline insecticide with insecticidal activity and cytotoxicity, blocks sodium channels in insect neurons, and can induce apoptosis.</p>

<p>Phenamet is a bioactive chemical.</p>

<p>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).</p>

<p>MDMX/MDM2-IN-2 is a potent dual inhibitor of p53-MDM2/MDMX, demonstrating dissociation constants (Kis) of 0.23 μM for MDM2 and 2.45 μM for MDMX.</p>

<p>p53 and MDM2 proteins-interaction-inhibitor (racemic) is an inhibitor of the interaction between p53 and MDM2 proteins.</p>

<p>D-CopA3 is an inhibitor of MDM2 and an activator of the p53 signaling pathway. It exhibits cytotoxicity in colorectal cancer cells HCT-116, LoVo, and RKO with IC50 values of 15-18 μM and induces JNK/Beclin-1 mediated autophagy. D-CopA3 downregulates the expression of the cell cycle inhibitor protein p21Cip1/Waf1, enhances mucosal barrier function, and reduces infiltration of inflammatory mediators. It shows anti-inflammatory properties in mouse models of acute enteritis induced by C. difficile toxin A and chronic colitis induced by DSS. Additionally, D-CopA3 demonstrates antitumor activity in a mouse HCT-116 xenograft model.</p>

<p>SB-1295, an orally active CDK9/T1 inhibitor with an IC50 of 0.17 μM, exhibits antiproliferative effects on HCT 116 and MIA PaCa-2 cells.</p>

<p>DPH: antihistamine for cough, nausea, itching, allergy, Parkinson's, sleep aid, cold remedy.</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>PARP1-IN-15 (Compound 6) is a PARP1 inhibitor that also inhibits tankyrase (TNKS) and promotes DNA double-strand breaks, leading to tumor cell apoptosis.</p>

<p>RIPK3-IN-3 (compound 20) is a selective RIPK3 inhibitor that demonstrates potent activity with an IC50 value of 10 nM.</p>

<p>Nrf2 activator-9 (compound D-36) is an agent that mitigates oxidative stress by inhibiting the apoptosis of HUVEC cells induced by oxidized low-density</p>

<p>JGB1741, a SIRT1 inhibitor (IC50=15µM), modulates apoptosis markers and p53 acetylation in breast cancer research.</p>

<p>Thalidomide-O-amido-PEG1-(C1-PEG)2-C2-NH2 is a synthetic conjugate compound that combines a Thalidomide-based cereblon ligand and a linker, which is commonly</p>

<p>Cereblon ligand for PROTAC R&amp;D; has E3 ligase, alkylC1-PEG3-alkylC3 linker, terminal amine. Part of Arvinas-licensed tool molecules.</p>

<p>TG101209 analog 1 (Compound 8h) serves as an inhibitor of BUB1B, exhibiting an IC50 of 10.36 μM. It also possesses cytotoxic properties, demonstrated by an IC50 of 1.347 μM against Caki-1 cells, and can induce necrosis and apoptosis.</p>

<p>Compound (Ra)-10, also known as Mcl-1 inhibitor 14, is a potent inhibitor of myeloid cell leukemia-1 (MCL-1), exhibiting a K_i of 0.018 nM, and holds potential</p>

<p>HC Toxin: cyclic tetrapeptide, reversible HDAC inhibitor (IC50=30 nM), upregulates 15-lipoxygenase-1, induces fetal hemoglobin, from C. carbonum.</p>

<p>Enpp/Carbonic anhydrase-IN-1 (compound 1e) is a potent inhibitor of Enpp and carbonic anhydrase.</p>

<p>RIPK2-IN-2, a RIP2 kinase PROTAC inhibitor, blocks proinflammatory signaling in autoinflammatory diseases.</p>

<p>CAY10726, an arylurea fatty acid, cuts ATP by 28% and promotes apoptosis in breast cancer cells by depleting mitochondrial lipids.</p>

<p>Anticanceragent 273 (Compound 9q) is an effective anticancer compound identified from matrine. It inhibits cancer cell proliferation, with an IC50 of 4.48 μM against HeLa cells. Anticanceragent 273 exerts its anticancer effects by modulating PI3K/AKT expression and activating activating transcription factor 4 (ATF4), which induces endoplasmic reticulum stress and triggers apoptosis. It holds potential for cancer research, including cervical cancer.</p>

<p>Multi-kinase-IN-4 (compound 5d) is a multi-targeted kinase inhibitor active against VEGFR2, EGFR, HER2, and CDK2, with respective IC50 values of 0.33, 0.22, 0.</p>

<p>P53/TLR2 modulator-1 (Compound Z9) is an agent that targets both the P53 pathway and TLR2, exhibiting radioprotective properties. It mitigates apoptosis by inhibiting radiation-induced expression of P53 and Bax. Concurrently, it enhances the TLR2 pathway by upregulating downstream proteins MyD88 and P65, which promotes secretion of cytokines like IL-6, providing radioprotective effects. P53/TLR2 modulator-1 shows significant radioprotective activity in AHH-1 and HUVECs cells, enhances survival rates in C57BL/6J mice exposed to lethal radiation doses, and alleviates radiation-induced damage to their hematopoietic system, intestinal villi, and spleen. It is applicable for research on radiation-related diseases.</p>

<p>HDAC-IN-57 is an orally active pan-inhibitor of histone deacetylase (HDAC), inhibiting HDAC1, HDAC2, HDAC6, and HDAC8 with IC50 values of 2.07 nM, 4.71 nM, 2.4</p>

<p>eIF4E-IN-2 effectively inhibits eIF4e, crucial for research on diseases like cancer.</p>

<p>PL120131 is a PD-1/PD-L1 inhibitory peptide that disrupts the interaction between PD-1 and PD-L1 by binding to PD-1. This compound can inhibit the apoptosis signaling pathway mediated by PD-1, thereby preventing apoptosis (apoptosis) in Jurkat cells and primary lymphocytes. Additionally, PL120131 supports cytotoxic T lymphocytes (CTL) in exhibiting antitumor activity.</p>

Sodium valproate is an anti-epileptic, boosting brain GABA levels and possibly affecting potassium channels for membrane stability.