Apoptose

<p>MI-888 (TFA) is an orally active inhibitor of the MDM2-p53 interaction with a Ki of 0.44 nM. It can induce rapid, complete, and durable tumor regression in xenograft mouse models.</p>

<p>DC-U4106: USP8 inhibitor, Kd 4.7μM, IC50 1.2μM, degrades Erα, low-toxicity tumor suppressor for breast cancer research.</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>Antitumor agent-43 (Compound 4B) is a potent antitumor agent that induces cell cycle arrest at G2/M phase.</p>

<p>Anticancer agent 44 induces apoptosis, is selective, cytotoxic to cancer cells, and minimally toxic to human lymphocytes.</p>

<p>Compound 14 is a peptidomimetic that significantly lowers TNFα, NO, CD40, and CD86, showcasing strong anti-inflammatory effects.</p>

<p>Tofacitinib Prodrug-1: an oral prodrug reducing Tofacitinib's side effects, treats ulcerative colitis in mice effectively with low toxicity.</p>

<p>Topoisomerase I/II inhibitor 4 halts cell growth and spread, induces apoptosis, and is used in liver cancer research.</p>

<p>SphK1-IN-2: SphK1 inhibitor, IC50: 19.81 nM; less effective on SphK2. Induces apoptosis, hinders cancer cell growth.</p>

<p>QTX125 TFA: Potent, selective HDAC6 inhibitor with antitumor 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>Microtubulin-IN-1 (Compound 8g) is an inhibitor of microtubulin, targeting the colchicine-binding site to disrupt tubulin integrity and induce upregulation of p53 protein expression. It exhibits antiproliferative activity across various cancer cell lines, including NCI-H460, BxPC-3, and HT-29, with IC50 values of 2.4, 1.6, and 2.07 nM, respectively. Additionally, Microtubulin-IN-1 induces cell cycle arrest at the G2/M phase and apoptosis in NCI-H460 cells.</p>

<p>PD-1/PD-L1-IN-17 (Compound P20) is a potent PD-1/PD-L1 inhibitor (IC50: 26.8 nM).</p>

<p>CRI9 effectively inhibits the c-MET/PI3K/Akt/mTOR axis, suppressing the proliferation of hepatocellular carcinoma (HCC) cells. This compound exhibits potent cytotoxicity against HCC cells and induces 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>(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>JAK-2-/3-IN-3 (ST4j) is a potent JAK2/3 inhibitor for leukemia research, with IC50s: JAK2, 13 nM; JAK3, 14.86 nM; induces apoptosis.</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>Topo I/COX-2-IN-1: potent dual inhibitor; IC50 0.24μM (COX-2), 4.42μM (Topo I); anti-cancer; induces apoptosis, halts migration.</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>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>EGFR-IN-47: strong oral EGFRL858R/T790M/C797S blocker, induces cell death; promising for NSCLC research. IC50: 0.01 μM.</p>

<p>SL-176, a WIP1 inhibitor, when combined with GSK-J4, can induce cell cycle arrest and apoptosis (apoptosis), thereby inhibiting tumor growth both in vitro and in vivo.</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>Topoisomerase IIα-IN-4 (F2) is a non-intercalative ATP-competitive inhibitor of human DNA topoisomerase II, specifically inhibiting TopoIIα with an IC50 value</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>Sampangine, an alkaloid, induces apoptosis by causing cell cycle arrest at the G0/G1 phase and inhibits the biosynthesis of heme.</p>

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

<p>Lometrexol disodium: Inhibits hSHMT1/2 and GARFT, anticancer by blocking purine synthesis, induces apoptosis and cell cycle arrest.</p>

<p>PD-1/PD-L1-IN-23: potent, oral PD-1/PD-L1 inhibitor; L7's ester prodrug; exhibits strong antitumor effects.</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>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>GPX4-IN-3 (26a) is a potent GPX4 inhibitor, inducing selective ferroptosis with 71.7% inhibition at 1 μM.</p>

<p>FAK-IN-2: potent oral FAK inhibitor, IC50 35 nM, reduces tumor growth, migration, and induces cell death.</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>MRK003, a γ-secretase inhibitor, induces apoptosis, halts cell growth in myeloma/NHL, and affects notch signaling and PI3K/Akt pathway.</p>

<p>DWP-05195 is a TRPV1 antagonist capable of inhibiting pain signal transduction. Additionally, it induces ER stress-dependent apoptosis in human ovarian cancer cells via the ROS-p38-CHOP pathway.</p>

<p>ERK-MYD88 Interaction Inhibitor 1, an agent that disrupts the interaction between ERK and MYD88, has demonstrated the ability to trigger an HRI-mediated integrated stress response (ISR) that specifically promotes immunogenic cell apoptosis (apoptosis) in cancer cells. Additionally, in models using Lewis lung cancer mice, this compound has been shown to stimulate anti-tumor T cell responses, thereby exhibiting significant anti-tumor activity.</p>

<p>Rezatapopt (PC14586) is a p53 reactivator with antitumor activity for the study of locally advanced or metastatic solid tumors.</p>

<p>Samuraciclib (CT7001) is an oral CDK7 inhibitor with 41 nM IC50, notable for its high selectivity and potency against breast cancer cells.</p>

<p>JND4135, a type II TRK inhibitor, exhibits IC50 values targeting TRKA, TRKB, and TRKC at 2.79, 3.19, and 3.01 nM, respectively. It can overcome resistance due to TRKxDFG and other mutations in the BaF3 stable model, inhibiting the phosphorylation of TRKs WT, xDFG mutations, and their downstream signaling molecules. Additionally, JND4135 induces G0/G1 phase arrest and cell apoptosis (apoptosis) in BaF3–CD74-TRKA-G667C cells. This compound also demonstrates antitumor activity in a BaF3-CD74-TRKA-G667C mouse xenograft model by suppressing tumor growth.</p>

<p>Triphen diol, a phenol diol, fights pancreatic cancer &amp; cholangiocarcinoma, inducing apoptosis via caspase-dependent &amp; -independent paths.</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>FLT3-ITD-IN-3 (13v) is an orally active inhibitor of FLT3-ITD (internal tandem duplication of FLT3), which works by blocking FLT3 signaling. This inhibition leads to cell cycle arrest in the G0/G1 phase and induces apoptosis. The compound is currently employed in studies related to acute myeloid leukemia (AML).</p>

<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>

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

<p>TP-030-1, RIPK1 inhibitor: K(i) hRIPK1 at 3.9nM, IC50 mRIPK1 at 4.2μM; targets inflammation, neurodegeneration research.</p>

<p>Potent dual c-Met/HDAC inhibitor, IC50: HDAC1 5.4 nM, c-Met 18.49 nM; anti-cancer, induces apoptosis, G2/M arrest in HCT-116.</p>

<p>DHU-Se1: potent anti-inflammatory, releases reactive selenium from macrophages, inhibits iNOS/TNF-α, blocks M0 to M1 polarization.</p>

<p>Tubulin inhibitor 43 exhibits significant antitumor activity by impeding the proliferation and growth of cancer cells through the inhibition of β-microtubulin activity, ultimately inducing apoptosis [1].</p>

<p>VDX-111, an analog of vitamin D, exhibits cytotoxicity in ovarian cancer cells by upregulating the RIPK1/RIPK3 pathway and inducing necroptosis. It also promotes the expression of cytokines and demonstrates antitumor activity in a mouse model [1].</p>

<p>SMO-IN-5 (Compound 25(B31)) is an effective inhibitor of smoothened (SMO), which suppresses the Hedgehog (Hh) signaling pathway. This compound inhibits cellular proliferation and induces apoptosis, demonstrating antitumor activity.</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>Compound 3b inhibits tubulin polymerization, IC50 12.38 µM, with anticancer properties and promotes cell apoptosis.</p>

<p>Tubulin polymerization-IN-61 (Compound 9a), a tubulin polymerization inhibitor, disrupts the microtubule skeleton, arrests the cell cycle at the G2/M phase, induces Apoptosis, and impedes cancer cell migration and colony formation. This compound demonstrates antitumor efficacy in vivo within the 4T1 xenograft model [1].</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>LSD1-IN-21: potent LSD1 inhibitor, crosses blood-brain barrier, IC50 of 0.956 μM; lowers TNF-α, anti-cancer, anti-inflammatory.</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>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>TLBC, a borane-chalcone derivative, exhibits dose-dependent inhibitory effects across various glioma cell lines with IC50 values ranging from 5.5 to 25.5 μM. TLBC induces apoptosis independently of alterations in the tumor suppressor factor p53.</p>

<p>Ferroptosis-IN-15 (compound 12) serves as an effective inhibitor of ferroptosis, exhibiting EC50 values of 0.76 μM and 0.67 μM in A375 cells and 786-O cells, respectively. It acts as a potential iron chelator and radical-scavenging antioxidant.</p>

<p>Antiproliferative agent-63 (compound 4d) is a cyclic analog of cannabidiol that acts as an anticancer agent. It demonstrates favorable activity against breast and colorectal cancer. Moreover, this compound can arrest the cell cycle in the G1 phase and induce apoptosis through the mitochondrial pathway in breast cancer cell lines.</p>

<p>ZSH-512 is a potent inhibitor of RARγ with antiproliferative properties. It induces apoptosis and reduces the expression of CD133, NANOG, SOX2, and EPCAM proteins. ZSH-512 exhibits anticancer activity and shows potential for colorectal cancer research.</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>Tubulin polymerization-IN-4: inhibits tubulin (IC50=4.6 μM), blocks G2/M phase, induces apoptosis, hinders cell cloning/migration, damages vasculature.</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>HER2-IN-10 is a psoralen derivative that induces apoptosis. HER2-IN-10 shows anti-breast cancer activity and light-activated cytotoxicity [1].</p>

<p>06:0 PE (PE(6:0/6:0)) is a water-soluble phospholipid characterized by its short acyl chains. It possesses notable antitumor activity and can inhibit tumor progression in the body. Additionally, it exhibits antiproliferative and pro-apoptotic properties, and serves as a precursor for phosphatidylcholine and phosphatidylethanolamine.</p>

<p>ZLWT-37: Oral CDK inhibitor, CDK9 IC50=0.002 µM, CDK2 IC50=0.054 µM; halts HCT116 cells at G2/M, induces apoptosis.</p>

<p>JH-XVII-10: potent, oral DYRK1A/B inhibitor (IC50: 3/5 nM), shows antitumor activity in HNSCC.</p>

<p>Anticancer agent 46, potent and selective, induces apoptosis, is cytotoxic to cancer cells, with low toxicity to human lymphocytes.</p>

<p>MB710 is an amino-benzothiazole derivative that tightly binds to the Y220C pocket and stabilizes p53-Y220C in vitro.</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>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>inhibitor of Akt, protein kinase C, PDK1 and cyclin-dependent kinases</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>EGFR-IN-3 is an EGFR inhibitor with antitumor activity.EGFR-IN-3 inhibits EGFRwt-TK, induces apoptosis (cell death), and can block cells in the G2/M phase.</p>

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

<p>MLS-0053105, a chloromaleimide, functions as a selective inhibitor of BFL-1, exhibiting an IC50 of 0.4 µM against Bfl-1/F-Bid. Its inhibitory potency is over tenfold lower for Bcl-W, Bcl-2, and Bcl-XL, and it shows no activity against Bcl-B and Mcl-1.</p>

<p>Ph-Ph+ is a dimerized phenanthroline derivative with antitumor, antibacterial, and antifungal effects.</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>RET-IN-11 selectively inhibits RET (IC50: 6.20 nM), promotes apoptosis, and hinders cell proliferation and migration.</p>

<p>CCT369260 (compound 1), an orally active inhibitor targeting B-cell lymphoma 6 (BCL6), demonstrates anti-tumor efficacy with an IC50 value of 520 nM [1].</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>MLKL-IN-6 (compound P28) is a mixed lineage kinase inhibitor that specifically targets the Mixed Lineage Kinase domain-like (MLKL) protein.</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>GGTI-2154 hydrochloride: selective GGTase I inhibitor, IC50 21 nM, used in cancer research.</p>

<p>ZLHQ-5f inhibits CDK2/Topo I, with IC50 of 0.145μM for CDK2/CycA2, and promotes apoptosis by arresting HCT116 cells in S phase.</p>

<p>Thalidomide-O-PEG4-amine TFA is a synthetic E3 ligase ligand-linker conjugate, composed of a cereblon ligand derived from Thalidomide and a single linker.</p>

<p>Z-VAD is an irreversible pan-caspase inhibitor, suppressing multiple caspases including caspase-3, -6, -7, -8, and -9. Z-VAD induces autophagy in tumour cells.</p>

<p>Autophagy-IN-1 blocks autophagy in cancer cells, hinders tumor growth in mice, and aids in studying colorectal cancer.</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>Topo II/HDAC-IN-2 (8d) demonstrates remarkable dual inhibitory effects on Topo II and HDAC, and also induces apoptosis [1].</p>

<p>Lometrexol hydrate, an antipurine antifolate, inhibits GARFT and purine synthesis, leading to cancer cell apoptosis without causing DNA breaks.</p>

<p>Mcl-1 Inhibitor 9 (Example 2) is a potent inhibitor of myeloid cell leukemia 1 (Mcl-1), demonstrating anti-tumor activity with an IC50 value of 0.21889 nM.</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>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>Elocalcitol is a calcitriol analog for inhibition of prostate cell growth.</p>