Apoptosis

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

<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>

<p>MA242 is a nuclear factor of activated T cells 1 (NFAT1) for Pancreatic Cancer Therapy and dual inhibitor of murine double minute 2 (MDM2).</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>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>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>AZD0424: oral Src/Abl kinase inhibitor; potential anticancer; induces apoptosis, cell cycle arrest in lymphoma.</p>

<p>Compound 5f, a potent tubulin polymerization inhibitor (IC50 = 1.09 μM), blocks cell migration, tube formation, and has anti-angiogenic effects.</p>

<p>Tubulin inhibitor 41 (Compd D19) is a promising lead compound for glioblastoma treatment, known for its ability to penetrate the blood-brain barrier (BBB). It functions as a tubulin inhibitor, inducing G2/M phase arrest, leading to cell apoptosis, and inhibiting the migration of U87 cells [1].</p>

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

<p>YK5 is an allosteric inhibitor pocket of Hsp70 and represents a previously unknown chemical tool to investigate cellular mechanisms associated with Hsp70.</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>Etalocib (LY293111) sodium is an orally active leukotriene B4 (LTB4) receptor antagonist with a Ki value of 25 nM for inhibiting [3H]LTB4 binding. It exhibits an IC50 of 20 nM against LTB4-induced calcium mobilization. Additionally, Etalocib sodium can induce apoptosis.</p>

<p>Soquelitinib (CPI-818) is a selective ITK inhibitor， inhibits tumor growth,T-cell, up-regulatCXCR3, IFNγ, TNFα, and CD107a expression in normal CD8 cells.</p>

<p>Microtubule stabilizer; halts cancer cell growth (IC50: 3-30 nM); arrests cells in prometaphase; prevents bipolar spindle formation.</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>TNF-α-IN-12, a TNF-α inhibitor with an IC50 of 0.1 μM, can reduce TNF-α blood levels [1].</p>

<p>TBC-1 is a chlorophyll-a derivative that acts as a photosensitizer for photodynamic therapy (PDT). It efficiently generates type I ROS and targets the endoplasmic reticulum. TBC-1 demonstrates in vitro biocompatibility and PDT effectiveness under both normoxic and hypoxic conditions.</p>

<p>p53 Activator 14 (Compound 7A) is a derivative of Neratinib that can induce DNA damage and activate p53, thereby inhibiting the proliferation of various cancer cells, with an IC50 of 7.21 μM for HCT116 cells. This compound hinders adhesion, migration, and invasion of HCT116 cells, disrupts the cell cycle, and triggers apoptosis. In addition, p53 Activator 14 exhibits anti-tumor properties and inhibits angiogenesis in the chick embryo chorioallantoic membrane (CAM) model.</p>

<p>MTDH-SND1 blocker 2 (compound C19) is an effective MTDH-SND1 inhibitor with an IC50 value of 487 nM. It binds to the SND1 protein with a Kd of 279 nM and can degrade the SND1 protein. Additionally, MTDH-SND1 blocker 2 exhibits antiproliferative activity and induces apoptosis, showing potential for breast cancer research.</p>

<p>GGTI298 is a potent GGTase I inhibitor; IC50 3μM for Rap1A, &gt;20μM for Ha-Ras.</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>Compound 3b inhibits tubulin polymerization, IC50 12.38 µM, with anticancer properties and promotes cell apoptosis.</p>

<p>WEHI-9625 is a tricyclic sulfone small molecule apoptosis inhibitor (EC50: 69 nM).</p>

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

<p>GRP78-IN-1 binds to GRP78 protein, inhibits cell growth, and triggers apoptosis in breast cancer; has -8.07 kcal/mol binding energy.</p>

<p>CP-31398 stabilizes the active conformation of p53 in cancer cells with either mutated or wild-type p53, enhancing its activity. Additionally, CP-31398 upregulates target genes of p53 such as p21WAF1/Cip1 and KILLER/DR5. This compound possesses tumor-suppressive properties.</p>

<p>WYJ-2, a selective agonist for toll-like receptor 2/1 (TLR2/1), demonstrates an EC50 of 18.57 nM in HEK 293T cells transiently co-transfected with human TLR2 and TLR1. It induces pyroptosis and has shown anticancer activity against non-small cell lung cancer (NSCLC) [1].</p>

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

<p>CB-184 is a selective ligand for sigma-2 (σ2) receptors, with Ki values of 7436 nM for sigma-1 (σ1) and 13.4 nM for sigma-2 (σ2), and it promotes apoptosis with antitumor activity.</p>

<p>BMS-751324: p38α MAPK inhibitor with carbamyl-methyl, esters, phosphate from HPA. Reduces rat arthritis swelling and TNFα.</p>

<p>3′-Hydroxyflavanone is a cyclized flavonoid with anti-tumor properties that induces apoptosis in HeLa cells.</p>

<p>EGFR-IN-134 (compound 3f) is a triazolo[3,4-a]quinoline derivative and functions as a potent EGFR inhibitor with an IC50 of 0.023 µM. It induces apoptosis and necrosis in cells, and causes cell cycle arrest in the G2/M and pre-G1 phases. EGFR-IN-134 modulates the expression of apoptosis-regulating proteins by downregulating anti-apoptotic protein Bcl2 and upregulating pro-apoptotic proteins p53, Bax, and caspases 3, 8, and 9, demonstrating significant antiproliferative and anticancer activities.</p>

<p>GPD-1116 is an orally active inhibitor of phosphodiesterase (PDE)4 and PDE1. The compound effectively reduces smoke-induced apoptosis in lung cells. Additionally, GPD-1116 has shown efficacy in various animal disease models, including emphysema, acute lung injury, chronic obstructive pulmonary disease (COPD), asthma, and pulmonary arterial hypertension.</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>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>DC-U4106: USP8 inhibitor, Kd 4.7μM, IC50 1.2μM, degrades Erα, low-toxicity tumor suppressor for breast cancer research.</p>

<p>RIPK1-IN-28 (compound 13) is an orally active inhibitor of RIPK1. It exhibits inhibitory effects on human I2.1 and Hepa1-6 cells, with IC50 values of 0.4 and 1.2 nM, respectively.</p>

<p>ABL-L is able to induce apoptosis in human laryngeal cancer cells using a p53-dependent pathway.</p>

<p>Pim-1 Kinase Inhibitor 10 (compound 13a) acts as both a competitive and non-competitive inhibitor of PIM-1/2 kinase, promoting cell apoptosis and displaying anticancer properties. Additionally, this compound triggers the activation of caspase 3/7 [1].</p>

<p>SM-433 hydrochloride, a Smac mimetic &amp; IAP inhibitor, binds XIAP BIR3; potent IC50 &lt;1 μM. (Patent WO2008128171A2)</p>

<p>LSD1-IN-21: potent LSD1 inhibitor, crosses blood-brain barrier, IC50 of 0.956 μM; lowers TNF-α, anti-cancer, anti-inflammatory.</p>

<p>TFCP2L1-IN-1 is a TFCP2L1 transcription factor inhibitor that regulates cell proliferation and promotes antitumor effect of Sorafenib by STAT3/NANOG pathway.</p>

<p>Minnelide is a prodrug of triptolide,and shows potent antitumor activity in a number of tumor types.</p>

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

<p>Tubulin inhibitor 14 blocks NQO2 and microtubule formation, disrupts blood vessels, and may target tumors; IC50 of 1.0 μM.</p>

<p>PROTAC FKBP Degrader-3, with FKBP and VHL binding groups linked, is a potent FKBP degrader.</p>

<p>HAC-Y6 exerts its anticancer effects by inducing cell cycle arrest. It prompts apoptosis in COLO 205 cells with an IC50 of 0.52 µM.</p>

<p>Claturafenib is a brain-permeable, selective, all-mutant BRAF inhibitor.PF-07799933 has shown antitumor activity, used in combination with MEK inhibitors.</p>

<p>Triphen diol, a phenol diol, fights pancreatic cancer &amp; cholangiocarcinoma, inducing apoptosis via caspase-dependent &amp; -independent paths.</p>

<p>EGFR/HER2-IN-6 is a dual inhibitor of EGFR, HER2, and DHFR with IC50s: 0.122, 0.078, and 0.585 μM, showing anticancer potential and selectivity.</p>

<p>NLRP3-IN-78 (compound 21) is an NLRP3 inhibitor with a 46.72% inhibition rate of GSDMD-induced pyroptosis at 5 μM. It binds to the NLRP3 protein and prevents GSDMD-NT oligomerization. Additionally, NLRP3-IN-78 inhibits GSDMD cleavage and upstream NF-κB signaling, demonstrating anti-inflammatory activity.</p>

<p>N-ω-chloroacetyl-L-ornithine (NCAO) serves as a powerful reversible competitive inhibitor of ornithine decarboxylase (ODC), displaying cytotoxic and antiproliferative properties against various tumor cell lines, with EC50 values spanning from 1 to 50.6 µM. In vitro studies reveal that NCAO promotes Apoptosis and restricts tumor cell migration. Additionally, it demonstrates significant antitumor efficacy in a mouse model, targeting both solid and ascitic tumors using the myeloma (Ag8) cell line. NCAO holds promise in the development of antitumor agents.</p>

<p>FKBP12 PROTAC dTAG-13 is a PROTAC and selective degrader for target validation by splicing FKBP12 F36V with CRBN and thereby degrading FKBP12 F36V.</p>

<p>HDAC-IN-27 dihydrochloride (Compound 11h) is a potent, orally active, HDACI class-selective inhibitor, with IC50 values ranging from 0.43 to 3.01 nM for HDAC1-3. This compound exhibits both in vivo and in vitro anticancer activity. HDAC-IN-27 shows significant antiproliferative effects against acute myeloid leukemia (AML) cell lines by inducing apoptosis and histone acetylation (AcHH3 and AcHH4). It is useful for research on acute myeloid leukemia (AML).</p>

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

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

<p>AMG 397 is an oral MCL1 inhibitor .</p>

<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>

<p>Spliceostatin A is an anticancer agent and splicing inhibitor that induces apoptosis by inducing cell cycle arrest in the G1 and G2/M phases.</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>TH-6, a potent HDAC inhibitor (IC50: HDAC1-0.115, 2-0.135, 3-0.242, 6-0.138, 8-2.120 μM), blocks cell migration, invasion, and has anti-tumor properties.</p>

<p>HER2-IN-11 is a psoralen derivative that induces apoptosis. HER2-IN-11 shows light-activated cytotoxicity and also exhibits anti-breast cancer activity [1].</p>

<p>eIF4E-IN-4 (Compound 33) is a selective inhibitor of the eukaryotic initiation factor 4E (eIF4E) with a biochemical activity value of 95 nM. It inhibits cap-dependent mRNA translation with an IC50 of 2.5 μM and is applicable in research on breast cancer, colon cancer, and head and neck cancer.</p>

<p>LSD1/ER-IN-1 inhibits ER &amp; LSD1 (IC50: 1.55 μM), and fights MCF-7 breast cancer (IC50: 8.79 μM).</p>

<p>RET-IN-10: Potent RET inhibitor, may treat congenital megacolon and tumors (Patent WO2021135938A1, compound 18).</p>

<p>VEGFR-2-IN-15 (Compound 14b) is a potent inhibitor of VEGFR-2. VEGFR-2-IN-15 inhibits the growth of HepG2 cells in the Pre-G1 phase and induces apoptosis.</p>

<p>PI4KIII beta inhibitor 4 (Compound 16) is a selective inhibitor of PI4KIIIβ with an IC50 of 0.005 μM. By inhibiting the PI3K/AKT pathway, PI4KIII beta inhibitor 4 induces apoptosis, causes cell cycle arrest, and triggers autophagy in tumor cells. This compound is applicable for tumor research.</p>

<p>Compound 2c is a potent p38α MAPK inhibitor with antitumor effects, enhancing apoptosis and ROS.</p>

<p>PD-1/PD-L1-IN-16 is a potent inhibitor of PD-1/PD-L1 (IC50: 53.2 nM) and has shown research potential for tumour immunotherapy.</p>

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

<p>GGTI-2154 hydrochloride: selective GGTase I inhibitor, IC50 21 nM, used in cancer research.</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>L5-DA, a G-quadruplex ligand, stabilizes G4s in HeLa cells, induces apoptosis, and is cytotoxic with an IC50 of 4.3 μM.</p>

<p>Necrosis Inhibitor 3 (compound B3) effectively inhibits necrosis, demonstrating an IC50 of 0.29 nM in HT29 cells [1].</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>MD102, with an IC50 value of 0.35 μM, is a potent TG2 inhibitor that stabilizes p53 by inhibiting TG2. This results in a decrease in p-AKT and p-mTOR downstream signaling, ultimately inducing tumor cell apoptosis [1].</p>

<p>Antitumor agent-58 suppresses tumor growth, colony formation, cell migration, and induces mitochondrial dysfunction in MGC-803 cells.</p>

<p>Fluvastatin (XU 62-320) sodium monohydrate, a fully synthetic competitive HMG-CoA reductase inhibitor, features an IC 50 of 8 nM. This compound also safeguards vascular smooth muscle cells from oxidative stress via the Nrf2-dependent antioxidant pathway [1] [2].</p>

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

<p>KDM1/CDK1-IN-1 inhibits KDM1 (IC50: 0.096 μM) &amp; CDK1 (IC50: 0.078 μM), blocks HOP-92 G2/M phase, induces apoptosis, toxic to cancer cells.</p>

<p>JAK2/FLT3-IN-1 (TFA), an oral JAK2/FLT3 inhibitor, shows anticancer properties; IC50: JAK2 (0.7 nM), FLT3 (4 nM), JAK1 (26 nM), JAK3 (39 nM).</p>

<p>PD-1/PD-L1-IN-15 is a potent inhibitor of PD-1/PD-L1 (IC50: 60.1 nM) and has shown investigational potential for tumor immunotherapy.</p>

<p>Antitumor agent-43 (Compound 4B) is a potent antitumor agent that induces cell cycle arrest at G2/M phase.</p>

<p>BRD4/CK2-IN-1 is a small-molecule inhibitor targeting BRD4 and CK2, inducing apoptosis and autophagy-related cell death.</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>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>Tandutinib (MLN518) sulfate is an effective and selective inhibitor of FLT3, with an IC50 value of 0.22 μM. It also inhibits c-Kit and PDGFR, displaying IC50 values of 0.17 μM and 0.20 μM respectively. This compound can be utilized in the treatment of acute myeloid leukemia and has the capability to cross the blood-brain barrier.</p>

<p>MB710 is an amino-benzothiazole derivative that tightly binds to the Y220C pocket and stabilizes p53-Y220C in vitro.</p>

<p>eIF4A3-IN-4 is a novel inhibitor of eIF4A (IC50: 8.6 μM).</p>

<p>GPX4-IN-3 (26a) is a potent GPX4 inhibitor, inducing selective ferroptosis with 71.7% inhibition at 1 μM.</p>

<p>Z-3578 is a small molecule antagonist targeting the MrgX2 (Mas-related G protein-coupled receptor X2) with notable anti-pseudoallergic properties, exhibiting a KD value of 729 nM. It effectively inhibits mast cell degranulation induced by substance P (SP) and C48/80, with IC50 values of 4.90 µM and 6.18 µM, respectively, suppresses the release of β-hexosaminidase, and significantly reduces the release of histamine and TNF-α, as well as intracellular calcium flux. Additionally, in a mouse pseudoallergy model, Z-3578 significantly alleviates foot swelling, dye leakage, and reduces serum histamine levels, indicating a strong in vivo anti-allergic effect. Z-3578 presents as a promising lead compound in the field of anti-allergic treatments, particularly for pseudoallergic reactions.</p>

<p>GLUT-1-IN-4 (Compound 13) is an inhibitor of the GLUT-1 glucose transporter that depends on the p53 protein. It suppresses the proliferation of various cancer cells at submicromolar IC50 levels. Additionally, GLUT-1-IN-4 can halt the cell cycle, induce oxidative stress, and promote apoptosis (cell death).</p>

<p>Ferrostatin-1 diyne (Fer-1 diyne) (compound 2) serves as an inhibitor of ferroptosis, accumulating in cellular lysosomes, mitochondria, and the endoplasmic reticulum. It notably inhibits ferroptosis independently of lysosomal and mitochondrial activity.</p>

<p>CDK-IN-9: A potent CDK inhibitor, gels to enhance CDK12/DDB1 binding, targets CDK2/E (IC50: 4 nM), induces apoptosis via dephosphorylation.</p>

<p>D18: Dual agonist for TLR7/8, boosts PD-L1, aids tumor sensitivity to PD-1/PD-L1 inhibitors, and is a cytotoxin for ADC HE-S2.</p>

<p>HDAC-IN-37 inhibits HDACs 1, 3, 8, &amp; 6, induces histone acetylation, halts G1 to S phase, and triggers early apoptosis.</p>

<p>PLK1-IN-13 is a selective, orally active PLK1 inhibitor with an IC50 of 0.27 nM. It also inhibits PLK2 (IC50: 12.72 nM) and PLK3 (IC50: 4.12 nM). PLK1-IN-13 induces cell cycle arrest at the G2 phase, promotes apoptosis, and downregulates the transcription of the cancer-associated oncogene c-MYC. This compound inhibits tumor growth and is applicable for research in acute myeloid leukemia (AML).</p>

<p>ZLMT-12: tacrine derivative, inhibits CDK2/CDK9, weak on AChE/BuChE, anti-proliferative, low toxicity, blocks S/G2/M phase, induces apoptosis.</p>

<p>Compound 8a, a dual PARP10 &amp; PARP15 inhibitor, has IC50s: PARP10 at 0.14μM &amp; PARP15 at 0.40μM; it's cell-permeable &amp; anti-apoptotic.</p>

<p>ERK1/2 inhibitor 11 (compound L6) is a dual inhibitor of ERK1/2 that promotes the accumulation of DSBs and the degradation of ERK1/2 expression. This compound decreases BCL-2 levels and induces DNA damage by inhibiting PARP and ERK1/2. Additionally, ERK1/2 inhibitor 11 activates caspase 3 to induce apoptosis.</p>

<p>PARP1/BRD4-IN-2, a potent inhibitor of PARP1 and BRD4, halts cell cycle, triggers apoptosis, and has antitumor effects on TNBC.</p>

<p>Compound 5a, an anticancer agent, enhances P53 and has antiproliferative effects.</p>

<p>BTK-IN-7 is a potent inhibitor for BTK with 4.0 nM IC50, highly selective over ITK and EGFR, showing strong antitumor activity.</p>

<p>TP-030-2 is a RIPK1 inhibitor (human K i =0.43 nM ; mouse IC 50 =100 nM) .</p>