Apoptosis

<p>FAK-IN-4 (Compound 7d) has anticancer activities that can induce cell apoptosis. FAK-IN-4 is potential inhibitor of FAK [1].</p>

<p>CRT0066101 is a potent, orally active PKD inhibitor with IC 50 values of 1 nM, 2.5 nM, and 2 nM for PKD1, PKD2, and PKD3, respectively [1]. Additionally, it inhibits PIM2 with an IC 50 of approximately 135.7 nM and demonstrates anticancer effects [2].</p>

<p>Akt/NF-κB/JNK-IN-1 (Compound 2i) is an inhibitor of Akt, NF-κB and JNK signalling pathways.Akt/NF-κB/JNK-IN-1 exhibits an inhibitory effect on nitric oxide</p>

<p>GP130-IN-1 (compound 49) is an effective inhibitor of GP130, demonstrating significant in vitro anti-tumor activity and higher selectivity compared to Bazedoxifene. It induces ultrastructural changes in cells, leading to a time-dependent arrest of the cell cycle at the G0/G1 phase, and triggers both apoptosis and autophagy. GP130-IN-1 is useful for research on triple-negative breast cancer.</p>

<p>Mps-BAY1, an MPS1 inhibitor, exhibits anticancer activity. It inhibits cell proliferation and induces cell apoptosis by activating mitotic aberrations in cancer cells, leading to overall aneuploidy and polyploidy. Mps-BAY1 is used in research pertaining to colorectal and cervical cancer.</p>

<p>Bim-IN-1 is a potent inhibitor of Bim expression with low toxicity, Bim-IN-1 reduces Bim expression levels with little inhibition of protein kinase A.</p>

<p>TI17 is a selective TRIP13 inhibitor with anticancer activity and inhibits proliferation of multiple myeloma (MM) cells</p>

<p>(Rac)-Idroxioleic acid (2-Hydroxyoleic acid) sodium is a synthetic derivative of oleic acid (OA) that binds to the plasma membrane, altering lipid composition. This compound exhibits antitumor properties.</p>

<p>Top/HDAC-IN-3 (Compound 31) is a dual inhibitor of Topoisomerase and HDAC with oral activity. It induces DNA damage by elevating reactive oxygen species (ROS) levels, consequently inhibiting the clonal formation and migration of cancer cells, and triggering apoptosis (Apoptosis) and cell cycle arrest. Top/HDAC-IN-3 demonstrates a significant antitumor effect in NSCLC models, exhibiting a tumor growth inhibition (TGI = 77.5%, 100 mg/kg) superior to that of the HDAC inhibitor SAHA and the combination of SAHA with the topoisomerase inhibitor Irinotecan.</p>

<p>RIP3 Activator 1 (compound C8) is an effective RIP3 activator that inhibits cell growth and induces necroptotic cell death (necroptosis) and autophagy through the RIP3/p62/Keap1 signaling pathway. Additionally, this compound enhances the expression of p-MLKL and promotes the accumulation of LC3-II and p62 proteins.</p>

<p>GNE684 inhibits RIP1; Ki app: 21 nM (human), 189 nM (mouse), 691 nM (rat).</p>

<p>NLRP3-IN-28 (compound N77) serves as a potent inhibitor of NLRP3, effectively blocking Nigericin-induced pyroptosis with an EC50 of 0.07μM. Additionally, it mitigates inflammatory reactions in vivo [1].</p>

<p>Thalidomide-Piperazine-PEG1-NH2 is a synthetic E3 ligase ligand-linker conjugate, featuring a cereblon ligand based on Thalidomide and a single linker.</p>

<p>Apoptosisinducer 25 (Compound 4H) demonstrates potent anticancer capabilities by inhibiting the proliferation of BGC-823 cancer cells with an IC50 of 0.37 μM. It induces apoptosis in BGC-823 cells, causes mitochondrial dysfunction, and arrests the cell cycle at the G2/M phase. Additionally, Apoptosisinducer 25 exhibits favorable pharmacokinetic properties in rats.</p>

<p>17-Demethoxy-reblastatin (17-DR) acts as an inhibitor of heat shock protein 90 (Hsp90). It suppresses the proliferation of HepG2 and SMMC7721 cancer cells, diminishes colony formation, and triggers apoptosis via a mitochondria and caspase-mediated pathway.</p>

<p>tDHU, acid is a dihydropyrimidine cereblon ligand consisting of an E3 ligase ligand and a benzoic acid linker. It serves as an E3 ubiquitin ligase ligand-linker conjugate in the development of PROTACs.</p>

<p>LQB-118, an orally active compound sourced from sandalwood, demonstrates multiple therapeutic capabilities. It has shown proficiency in inhibiting glioblastoma cell migration and inducing apoptosis. Additionally, LQB-118 can curtail both migration and invasion of prostate cancer cells by modulating the AKT/GSK3β pathway and regulating MMP-9/reck gene expression. The compound is also effective against yeast polysaccharide-induced inflammation in both in vivo and in vitro settings. Notably, LQB-118 specifically triggers ROS-mediated and mitochondrial-dependent apoptosis in Leishmania amazonensis, highlighting its potential in studies focusing on inflammation, infections, and various cancers.</p>

<p>Ph-Ph+ is a dimerized phenanthroline derivative with antitumor, antibacterial, and antifungal effects.</p>

<p>VEGFR-IN-3 inhibits cancer cell growth (OVCAR-4, MDA-MB-468) with IC50s: 0.29, 0.35μM. Used in cancer research.</p>

<p>Lepidozin G blocks cancer growth (IC50=4.2-5.7μM) and triggers apoptosis in PC-3 cells via mitochondria.</p>

<p>AKT-IN-3: potent oral Akt inhibitor with low hERG blockage. IC50: 1.4-1.7 nM for Akt1-3. Inhibits AGC kinases like PKA, PKC.</p>

<p>HDL-16 is a highly effective P2Y14R antagonist with anti-colitis effects, targeting P2Y14R in intestinal epithelial cells to alleviate ulcerative colitis.</p>

<p>AZD0424: oral Src/Abl kinase inhibitor; potential anticancer; induces apoptosis, cell cycle arrest in lymphoma.</p>

<p>WK88-1, an inhibitor of Hsp90, effectively induces the degradation of various oncogenic signaling molecules, including EGFR, ErbB2, and ErbB3, in the gefitinib-resistant H1975 cell line. This leads to subsequent growth arrest and apoptosis.</p>

<p>CDK4/6-IN-10: Oral CDK4 (IC50: 22 nM) &amp; CDK6 (IC50: 10 nM) inhibitor with anti-cancer potential for MM research.</p>

<p>Caspase-3 Activator 4 (compound 4o) is an effective caspase-3 activator that can cross the blood-brain barrier. This compound exhibits antiproliferative activity and can induce cell apoptosis (apoptosis). Additionally, Caspase-3 Activator 4 enhances the gene expression of TNF-α and reduces the expression of cleaved caspase-3/caspases 3.</p>

<p>ASTX295 is a selective mouse double minute 2 (MDM2) antagonist with an IC50 value of less than 1 nM. It specifically inhibits the interaction between MDM2 and p53, reactivating wild-type (WT) TP53, which subsequently induces the expression of related transcriptional targets, leading to cell death and cell cycle arrest. ASTX295 holds potential for research in lymphoid malignancies such as diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), and T-cell lymphoma.</p>

<p>BCL6-IN-9 (compound 1) is a potent inhibitor of B-cell lymphoma 6 protein (BCL6) (IC50: 3.9 nM) and can be used to study cancer.</p>

<p>HSP90-IN-10 is a potent HSP90 inhibitor, targeting HCC1954 cells (IC50: 6 μM) and inducing apoptosis, sparing normal cells.</p>

<p>Anticancer agent 65: Effective on A549 cells, IC50 1.07 μM, halts S phase, triggers apoptosis, elevates p53/p21, causes ROS and MMP collapse.</p>

<p>QTX125 TFA: Potent, selective HDAC6 inhibitor with antitumor effects.</p>

<p>EGFR-IN-161 (Compound DD-8) is a potent and reversible inhibitor of the L858R/T790M/C797S mutant EGFR kinase, with an IC50 value of 0.87 nM. EGFR-IN-161 effectively inhibits tumor cell apoptosis, G1 phase arrest, and migration.</p>

<p>VEGFR-2-IN-14 (Compound 5) is a potent inhibitor of VEGFR-2, which inhibits the growth of HepG2 cells in the Pre-G1 phase and induces apoptosis.</p>

<p>GL0388, a Bax activator, induces apoptosis, hinders breast cancer growth, and has IC50 of 0.299-1.57 μM.</p>

<p>MG28 exhibits significant cytotoxic effects, likely stemming from its direct and potent DNA-damaging activity. The compound is utilized in cancer research.</p>

<p>YCW-E11 is an antiapoptotic Bcl-2 family proteins inhibitor.</p>

<p>Pan-Trk-IN-3: potent Trk inhibitor (IC50: 2-26 nM), effective against drug-resistant mutants, induces apoptosis, anti-tumor effects.</p>

<p>RIPK1-IN-23 (compound 19) is an RIPK1 inhibitor with potent anti-necroptotic effects in HT-29 cells (EC50 = 1.7 nM). Additionally, RIPK1-IN-23 exhibits anti-inflammatory properties.</p>

<p>CDK2/9-IN-1 (compound 20a) is an orally active dual inhibitor of CDK2 and CDK9, with IC50 values of 0.004 μM and 0.009 μM for CDK2 and CDK9, respectively. It induces apoptosis by regulating G2/M cell cycle arrest and exhibits antitumor activity.</p>

<p>Tubulin inhibitor 13 (E27), IC50 16.1 μM, blocks tubulin polymerization, cancer cell migration, and invasion, induces apoptosis.</p>

<p>EGFR-IN-62: IC50 of 10-242 nM for various EGFR mutations, blocks A549/H1975 cell cycle, induces apoptosis, and inhibits cell motility and proliferation.</p>

<p>GGTI-2154 hydrochloride: selective GGTase I inhibitor, IC50 21 nM, used in cancer research.</p>

<p>KIRA9 inhibits IRE1 with a 4.8 μM IC50, blocking ER-stress-induced mRNA decay and apoptosis by fully binding IRE1's ATP site.</p>

Topo II/HDAC-IN-1 (7d) demonstrates potent dual inhibitory effects on Topo II and HDAC, while Topo II/HDAC-IN-1 (8d) effectively induces apoptosis [1].

<p>Microtubule stabilizer; halts cancer cell growth (IC50: 3-30 nM); arrests cells in prometaphase; prevents bipolar spindle formation.</p>

<p>mTOR/HDAC6-IN-1 inhibits HDAC6 (IC50: 56 nM) &amp; mTOR (IC50: 133.7 nM), may treat TNBC by inducing autophagy and apoptosis.</p>

<p>Verrucarin A, a mycotoxin from Myrothecium verrucaria, inhibits protein synthesis, leukemia growth, and triggers apoptosis.</p>

<p>Ganoderic acid R: potent anticancer, induces apoptosis, cytotoxic to MDR and sensitive tumor cells.</p>

<p>protease-activated receptor-1 (PAR1) antagonist</p>

<p>Flizasertib is a serine/threonine kinase inhibitor that acts by inhibiting RIPK1, which has anti-inflammatory and therapeutic effects on immune disorders.</p>

<p>eIF4A3-IN-6 is a potent eIF4A inhibitor, potentially used for treating eIF4A-related diseases like cancer. (US20170145026A1)</p>

<p>Decarbamoylmitomycin C, an analog of Mitomycin C (MC), functions as a DNA alkylating agent. It is capable of activating chromatin relaxation by the ataxia-telangiectasia and Rad3-related protein (ATR) in a p53-independent manner.</p>

<p>Apoptosis Inducer 5, a lignan enantiomer extracted from Crataegus pinnatifida, demonstrates cytotoxic properties through inducing apoptosis and autophagy in</p>

<p>PD-1/PD-L1-IN-30: Cancer research inhibitor with 0.018 μM IC50.</p>

<p>Anticancer agent 53 exhibits potent in vitro cytotoxicity, triggers apoptosis, halts S/G2/M cycle, and has antitumor effects without toxicity.</p>

<p>D-Cl-amidine hydrochloride is a potent and highly selective inhibitor of PAD1. It exhibits excellent tolerance and does not induce significant toxicity [1].</p>

<p>Thalidomide-NH-C5-NH2 is a synthetic E3 ligase ligand-linker conjugate, consisting of a Thalidomide-based cereblon ligand and a linker, used in the synthesis of PROTACs.</p>

<p>NSC308848 is an effective apoptosis (cell death) inducer that operates in a Myc-dependent manner. It acts by inhibiting Myc transactivation and disrupting the DNA binding activity of Myc family proteins.</p>

<p>MDK-3345 is a reversible covalent inhibitor for Mcl-1.</p>

<p>XPO1-IN-1: an oral MM.1S cell inhibitor (IC50: 24 nM), induces apoptosis, stable metabolism, good pharmacokinetics.</p>

<p>Sabialimon P (compound 16), with an IC50 of 18.12 μM, functions as a NO release inhibitor and exhibits anti-inflammatory properties. It effectively diminishes the secretion of TNF-α, iNOS, IL-6, and NF-κB, and suppresses the expression of COX-2 and NF-κB/p65 in LPS-induced RAW264.7 cells.</p>

<p>Oxamic acid is an inhibitor of LDH-A and exhibits antitumor activity. It demonstrates antiproliferative effects on cancer cells and can induce apoptosis.</p>

<p>NSD2-IN-1: potent, selective NSD2-PWWP1 inhibitor, IC50 0.11 μM, induces gene expression changes, apoptosis, cell cycle arrest.</p>

<p>BHA536 is an orally effective inhibitor of PKCα/β and the NF-kB signaling pathway. This compound inhibits the proliferation of ABC DLBCL cells harboring CD79 mutations by causing cell cycle arrest in the G1 phase and induces apoptosis in TMD8 cells. Additionally, BHA536 exhibits antitumor activity in mice.</p>

<p>BMI-135, a selective estrogen mimic, demonstrates agonist activity for the estrogen receptor and induces a rapid endoplasmic reticulum stress response (UPR) alongside apoptosis in breast cancer cells.</p>

<p>ASK1-IN-8 (Compound 35) is an orally active inhibitor of apoptosis signal-regulating kinase 1 (ASK1) with an IC50 value of 1.8 nM. In a mouse liver injury model induced by Acetaminophen, ASK1-IN-8 significantly reduces plasma alanine aminotransferase (ALT) levels, offering liver protection. This compound is useful for research in liver disease-related fields.</p>

<p>Nenocorilant (Relacorilant) is an orally active glucocorticoid receptor (GR) antagonist (Ki: 0.15 nM). Nenocorilant can be used to study tumours.</p>

<p>DAPK1-IN-1 (compound 10) is an inhibitor of Death-associated protein kinase 1 (DAPK1), with a dissociation constant (Kd) of 0.63 μM. It is utilized in the study of Alzheimer's disease.</p>

<p>Thalidomide-NH-amido-PEG2-C2-NH2 hydrochloride is a synthetic E3 ligase ligand-linker conjugate, comprised of a cereblon ligand based on Thalidomide and a linker, utilized in the synthesis of PROTACs.</p>

<p>GQN-B37-E is an effective selective binder and inhibitor of MCL-1. It binds to the BH3-binding domain of MCL-1. GQN-B37-E demonstrates binding affinity for MCL-1 within the sub-micromolar range (Ki= 0.6 μM), yet shows negligible binding to BCL-2 or BCL-XL.</p>

<p>AQX-435 activates SHIP1, inhibits PI3K in BCR signaling, induces apoptosis in B cells, and slows lymphoma growth.</p>

<p>AKN-028 acetate: an oral TK inhibitor for AML research, targets FLT3 with IC50 of 6 nM, inhibits autophosphorylation, and induces apoptosis.</p>

<p>Topo II/HDAC-IN-2 (8d) demonstrates remarkable dual inhibitory effects on Topo II and HDAC, and also induces apoptosis [1].</p>

<p>Necrosis Inhibitor 3 (compound B3) effectively inhibits necrosis, demonstrating an IC50 of 0.29 nM in HT29 cells [1].</p>

<p>MA242 free base is a dual MDM2/NFAT1 inhibitor that triggers apoptosis in pancreatic cancer cells.</p>

<p>c-Myc inhibitor16 iodide (Compound W11) is a selective inhibitor of the c-MycG-quadruplex (c-MycG4). It suppresses the transcription and translation of the c-Myc gene, disrupts the tumor cell cycle by halting growth at the G0/G1 phase, and activates mitochondrial apoptotic pathways, leading to early apoptosis in cancer cells. This compound shows potential for research in breast cancer.</p>

<p>TNF-α-IN-2 is orally active TNFα inhibitor that distorts the TNFα trimer, causing abnormal signal transduction when it binds to TNFR1, rheumatoid arthritis.</p>

<p>TRPM7-IN-1 (compound SUD) is a benzamide-urea derivative and an effective inhibitor of TRPM7. This compound induces cell cycle arrest and apoptosis in MCF-7 and BGC-823 cells, reducing their migration capabilities. It decreases vimentin expression while increasing E-cadherin expression. TRPM7-IN-1 reduces TRPM7-like currents and inhibits TRPM7 expression by activating the PI3K/Akt signaling pathway. This compound shows potential as a therapeutic agent for reducing breast and gastric cancer metastasis by targeting TRPM7 expression and activity.</p>

<p>PLK1-IN-15 is a PLK1 inhibitor with an IC50 of 38.5 nM. It exhibits antiproliferative effects on HepG2, Huh7, H1299, and A549 cells, with IC50 values of 2.03, 2.08, 4.79, and 17.11 μM, respectively. Additionally, PLK1-IN-15 can induce cell cycle arrest in the G2/M phase and trigger apoptosis (Apoptosis), demonstrating anticancer activity.</p>

ASCT2-IN-1 (compound 20k) is an inhibitor of ASCT2, demonstrating IC50 values of 5.6 μM in A549 cells and 3.5 μM in HEK293 cells. It induces apoptosis and inhibits tumor growth.

<p>Antitumor agent-37: strong anti-growth, anti-spread, induces DNA damage, apoptosis via Bcl-2/Bax/caspase3, boosts immune response.</p>

<p>HR-19011 (Compound 40) is an inducer of eIF2α phosphorylation that increases expression levels of downstream proteins ATF and CHOP,antiproliferative.</p>

<p>hCAIX/XII-IN-1: potent CAIX inhibitor (KI=0.48μM), CAXII (KI=0.83μM), antiproliferative, induces apoptosis in MCF-7 cells.</p>

<p>ASK1-IN-7 (Compound 4c) is an ASK1 inhibitor and a derivative of the ASK1 inhibitor scaffold 5-(5-Phenyl-furan-2-ylmethylene)-2-thioxo-thiazolidin-4-one. This compound is potentially applicable in research involving ASK1 signaling pathways, including studies on cellular stress response, inflammatory response, neurodegenerative diseases, and cardiovascular diseases.</p>

<p>PD-1-IN-17 TFA is a potent PD-1 inhibitor, blocking 92% of splenocyte growth at 100 nM.</p>

<p>PIM1-IN-3 (HL8) selectively blocks PIM1, induces Colo320 cell apoptosis, and may be researched for cancer.</p>

<p>RSK-IN-2 (Compound 3e) is an inhibitor of RSK, showing IC50 values of 37.89 nM for RSK2, 30.78 nM for RSK1, 20.51 nM for RSK3, and 91.28 nM for RSK4. It suppresses tumor cell proliferation, induces apoptosis, and causes cell cycle arrest at the G2/M phase.</p>

<p>TopoisomeraseI/II inhibitor 8 (Compound Ru7) is a dual catalytic inhibitor of TopoisomeraseI/II that induces DNA damage and activates PARP-1, leading to the activation of RIPK1, RIPK3, and MLKL, ultimately causing necroptosis. It shows significant anticancer activity by effectively targeting cancer cell nuclei and inducing cell death through necroptosis, offering substantial clinical potential in overcoming resistance in cancer treatment.</p>

<p>S100A2-p53-IN-1 inhibits S100A2-p53 in pancreatic cancer, stunting MiaPaCa-2 cell growth at 1.2-3.4 μM.</p>

<p>Casein kinase1δ-IN-29 (Compound 18) is an inhibitor that targets p38α and casein kinase 1 (CK1), exhibiting inhibitory effects on p38α, CK1δ, and CK1ε with IC50 values of 0.041 µM, 0.005 µM, and 0.447 µM, respectively. This compound causes cell cycle arrest at the subG1 phase and induces apoptosis in AC1-M88 cells.</p>

<p>Top/HDAC-IN-2 (45b) is a dual inhibitor of Top and HDAC that induces apoptosis and exhibits significant anti-tumour effects.</p>

<p>RIPK1-IN-24 is an inhibitor of receptor-interacting protein kinase 1 (RIPK1) with an IC50 of 1.3 μM. It is utilized in research on inflammatory diseases.</p>

<p>Anticancer agent 14: a potent breast cancer inhibitor; induces cell death, disrupts mito. membrane potential (IC50: 0.20-0.65 μM).</p>

<p>SLCB050 is a compound with anticancer activity that inhibits the interaction between DX2 and p14/ARF. It decreases the viability of human lung cancer cells, particularly small cell lung cancer cells, in a p14/ARF-dependent manner, and induces cell apoptosis (apoptosis) and senescence.</p>

<p>BMS 310705, an Epothilone B analog, targets ovarian/renal/bladder/lung cancer, inducing apoptosis via mitochondria.</p>

<p>WEHI-539 is a selective Bcl-XL inhibitor (IC50: 1.1 nM).</p>

<p>TNF-α-IN-14, a potent TNFα inhibitor, exhibits a selective inhibition profile with an IC50 of 1.1 µM and demonstrates antiinflammatory properties (WO2001072735A2; compound 12) [1].</p>

<p>VEGFR-2-IN-13 (Compound 19a) is a potent VEGFR-2 inhibitor (IC50: 3.4 nM). vEGFR-2-IN-13 arrests the HepG2 cell cycle in G2/M phase and induces apoptosis.</p>

<p>Flonoltinib maleate is an orally active dual inhibitor of JAK2/FLT3, with IC50 values of 0.7 nM for JAK2, 4 nM for FLT3, 26 nM for JAK1, and 39 nM for JAK3. It exhibits anticancer properties.</p>

<p>TrxR/EGFR-IN-1 (Compound L1Au2) is a TrxR/EGFR inhibitor with activity against both gefitinib-sensitive and -resistant lung cancer, effectively suppressing tumor proliferation and promoting apoptosis. It enhances GPX4 degradation through autophagosome-lysosome and proteasome pathways, leading to ferroptosis. Additionally, it induces endoplasmic reticulum stress and triggers immunogenic cell death, making it applicable for studies on gefitinib-resistant lung cancer.</p>

<p>ASP9831 is an orally active PDE4 inhibitor. It suppresses LPS-induced TNF-α production and exhibits anti-inflammatory properties. ASP9831 is useful in the study of steatohepatitis.</p>

<p>Sampangine, an alkaloid, induces apoptosis by causing cell cycle arrest at the G0/G1 phase and inhibits the biosynthesis of heme.</p>

Z-VA-DL-D-FMK (Z-VA-DL-D(OH)-FMK) acts as an inhibitor of caspases. It irreversibly binds to caspases, enhancing the sensitivity to TNF-α and stimulating HIV replication in infected T cells ACH-2.

<p>PAK4-IN-5 (Compound 12i) is a potent inhibitor of PAK4 (IC50: PAK4 at 7.68 nM, PAK1 at 1872.01 nM) that forms stable interactions with the PAK4 enzyme. This compound effectively inhibits the proliferation and migration potential of MDA-MB-231 cells by hindering the phosphorylation of PAK4 and LIMK1. Additionally, PAK4-IN-5 arrests the cell cycle in the G0/G1 phase, induces apoptosis, and prompts the production of reactive oxygen species. The LD50 in mice is greater than 500 mg/kg (oral).</p>

<p>ZB-R-55 is an oral and highly potent bimodal RIPK1 inhibitor with excellent kinase selectivity in lps-induced sepsis models for the study of SIRS and sepsis.</p>

<p>MLKL-IN-6 (compound P28) is a mixed lineage kinase inhibitor that specifically targets the Mixed Lineage Kinase domain-like (MLKL) protein.</p>