Apoptose

<p>GLI1-IN-1 (CBC-1), a GLI-1 inhibitor, exhibits superior water solubility and anticancer properties. It effectively induces apoptosis and inhibits colorectal cancer growth by targeting the Hedgehog (HH) pathway (IC 50 = 1.3 μM) [1].</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>YCW-E11 is an antiapoptotic Bcl-2 family proteins inhibitor.</p>

<p>Elocalcitol is a calcitriol analog for inhibition of prostate cell growth.</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>Microtubule stabilizer; halts cancer cell growth (IC50: 3-30 nM); arrests cells in prometaphase; prevents bipolar spindle formation.</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>Tubulin inhibitor 13 (E27), IC50 16.1 μM, blocks tubulin polymerization, cancer cell migration, and invasion, induces apoptosis.</p>

<p>Pan-KRAS-IN-5 (compound 15a) is a pan-KRAS translation inhibitor targeting 5′-UTR RNA G-quadruplexes (rG4s). It induces cell cycle arrest and promotes apoptosis in KRAS-driven cancer cells [1].</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>Top/HDAC-IN-2 (45b) is a dual inhibitor of Top and HDAC that induces apoptosis and exhibits significant anti-tumour effects.</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>MDK-3345 is a reversible covalent inhibitor for Mcl-1.</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>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>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>2-Deoxy-L-ribose is the stereoisomer of 2-Deoxy-D-ribose and can inhibit the anti-apoptotic effects of 2-Deoxy-D-ribose. Additionally, 2-Deoxy-L-ribose is capable of suppressing tumor cell metastasis by downregulating thymidine phosphorylase overexpression.</p>

<p>RET-IN-11 selectively inhibits RET (IC50: 6.20 nM), promotes apoptosis, and hinders cell proliferation and migration.</p>

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

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

<p>ER covalent antagonist-1 (Compound 39D) acts as an antagonist of the estrogen receptor α (ERα). This compound inhibits the proliferation of ERα-positive MCF-7 cells with an IC50 of 0.98 μM, induces cell cycle arrest at the G0/G1 phase, and triggers apoptosis. Additionally, ER covalent antagonist-1 demonstrates antitumor activity in mouse models.</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>BMS 310705, an Epothilone B analog, targets ovarian/renal/bladder/lung cancer, inducing apoptosis via mitochondria.</p>

<p>(R)-SL18 is a degrader of ANXA3 that facilitates its breakdown via ubiquitination. This compound can inhibit the proliferation, migration, invasion, and colony formation of breast cancer cells, while also inducing apoptosis. (R)-SL18 is applicable for research in triple-negative breast cancer.</p>

<p>Belotecan (CKD-602) inhibits DNA topoisomerase I, blocks cell cycle, induces apoptosis, and is a camptothecin-derived anticancer agent.</p>

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

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

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

<p>Ferroptosis-IN-6 is an efficient ferroptosis inhibitor, protecting cells from cell death induced by ferroptosis inducers, and inhibiting STY-BODIPY oxidation.</p>

<p>Compound 3 (DOR agonist 2) acts as a Delta Opioid Receptor agonist. It inhibits the expression of TNF-α, obstructs NF-κB transportation to the nucleus, and activates the G protein-mediated ERK1/2 pathway. This compound is useful for research into neurodegenerative diseases.</p>

<p>Anticancer agent 69 targets PC3 cells (IC50=26 nM), raises ROS, lowers EGFR, and induces apoptosis.</p>

<p>APD-94 is a dual inhibitor targeting tubulin and Bmi-1. It disrupts the normal polymerization of tubulin and suppresses the expression of Bmi-1. This compound induces cell cycle arrest at the G2/M phase and triggers apoptosis, thereby inhibiting cancer cell proliferation. Additionally, APD-94 inhibits the growth of HT29 cell xenograft tumors in NOD/SCID mice and is applicable to colorectal cancer research.</p>

<p>Antitumor agent-42 inhibits microtubule multimerisation and NO release, exhibiting anti-angiogenic, colony-forming and apoptosis-inducing effects.</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>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>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>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>Antiangiogenic agent 7 (Compound 1) induces apoptosis, elevates Reactive Oxygen Species (Reactive Oxygen Species), and inhibits the intracellular enzyme thioredoxin reductase. It exhibits anticancer activity with IC50 values ranging from 0.08 to 3.5 μM against cervical cancer cells (HeLa), prostate cancer cells (PC-3), and non-small cell lung cancer cells (A549). Additionally, Antiangiogenic agent 7 suppresses tumor growth in a mouse xenograft model.</p>

<p>TAI-95 is an inhibitor of highly expressed cancer protein 1 (Hec1).</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>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>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>HDAC/PSMD14-IN-1 is a derivative of gambogic acid. It serves as an orally active dual inhibitor targeting PSMD14 and HDAC1, with IC50 values of 238.7 nM and 141.2 nM, respectively. The compound exhibits significant cytotoxicity against ESCC cell lines (IC50: 30-250 nM) and effectively reverses epithelial-mesenchymal transition (EMT). Additionally, HDAC/PSMD14-IN-1 can induce apoptosis. In KYSE30 cell xenograft models in mice, it displays antitumor activity. HDAC/PSMD14-IN-1 is useful for researching esophageal cancer treatment.</p>

<p>Fosizensertib is an inhibitor of RIP-1 kinase and is used in research related to ulcerative colitis.</p>

<p>Bcl-2-IN-6 suppresses Bcl-2, upregulates p53/Bax/caspase-7, arrests cell cycle, and induces MCF-7 apoptosis; IC50s: MCF-7 20.91 μM, others &lt;48 μM.</p>

<p>EGFR-IN-45: Strong EGFR/CDK2 inhibitor (IC50s: 0.4 &amp; 1.6 μM), halts cancer cell cycle pre-G1, prompts apoptosis, also targets Topo I/II.</p>

<p>HDAC1-IN-5 inhibits HDAC1 (IC50=15 nM) &amp; HDAC6 (IC50=20 nM), promotes apoptosis, damages chromatin, and reduces tumor growth in mice.</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>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>Metamizole (Dipyrone) hemimagnesium is an anti-inflammatory and antioxidant compound known for its ability to reduce fever. It decreases levels of C-reactive protein (CRP) and interleukin 6 (IL-6). Additionally, Metamizole hemimagnesium acts as an orally active cyclooxygenase (COX) inhibitor, suppressing cell proliferation and promoting apoptosis. It is utilized in the study of inflammation and fever.</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>HL001 is an orally active small molecule inhibitor of cyclophilin A (CypA) and a receptor antagonist of lysophosphatidic acid 1 (LPA1). It induces cell cycle arrest and apoptosis in tumor cells via p53. By downregulating G3BP1, HL001 promotes reactive oxygen species production and DNA damage to stabilize p53. It disrupts the interaction between MDM2 and p53-72R in a CypA-dependent manner. HL001 exhibits antitumor activity and can also be used in research on pulmonary fibrosis.</p>

<p>IMB5046 is a microtubule inhibitor that induces apoptosis (cell death) by obstructing the G2/M phase of the cell cycle. It possesses antitumor properties.</p>

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

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

<p>NA-17 is a naphthalimide compound with antitumor activity and exhibits lower toxicity to normal cells such as HL-7702 and WI-38. It demonstrates p53-dependent inhibition selectivity in various NSCLC cells, inducing the accumulation of active p53 in the mitochondria and nuclei of these cells. NA-17 causes cell cycle arrest in the G1 phase and promotes apoptosis and cell death.</p>

<p>PARP10/15-IN-2 (Compound 8h) blocks PARP10/15, has IC50s: 0.15μM/0.37μM, cell-permeable, prevents apoptosis.</p>

<p>Autophagy-IN-1 blocks autophagy in cancer cells, hinders tumor growth in mice, and aids in studying colorectal cancer.</p>

<p>Nitrovin is an antimicrobial growth promoter that induces ROS-mediated non-apoptotic and quasi-apoptotic cell death by targeting TrxR1. It exhibits anticancer activity with IC50 values ranging from 1.31 to 6.60 μM for both tumor and normal cells.</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>GLS1 Inhibitor-6: IC50=68nM, 220x more selective for GLS2, has anti-tumor and pro-apoptosis effects.</p>

<p>BRD1991 is a chemical compound that specifically disrupts the interaction between Beclin 1 and Bcl-2, thereby inducing autophagy.</p>

<p>HDAC6/HSP90-IN-2, a cancer research chemical, inhibits HDAC6 &amp; Hsp90 with IC50s of 105.7 &amp; 61 nM.</p>

<p>[D-Leu-4]-OB3 suppresses the expression of genes associated with inflammation, proliferation, and metastasis, as well as the expression of PD-L1.</p>

<p>EGFR-IN-47: strong oral EGFRL858R/T790M/C797S blocker, induces cell death; promising for NSCLC research. IC50: 0.01 μM.</p>

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

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

<p>HDAC-IN-9, a dual tubulin/HDAC inhibitor, impedes A549 cell invasion/migration and shows strong anti-tumor/angiogenic effects.</p>

<p>Anticancer agent 64 (5m) induces apoptosis, has IC50 2.4μM in CCRF-CEM, activates caspases, cleaves PARP, affects mitochondria.</p>

<p>GGTI298 is a potent GGTase I inhibitor; IC50 3μM for Rap1A, &gt;20μM for Ha-Ras.</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>RIPK1-IN-14 inhibits RIPK1 with 92 nM IC50 and reduces necrotic apoptosis in U937 cells.</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>Multi-kinase-IN-1, a powerful kinase inhibitor, exhibits antitumor properties by inducing cell apoptosis.</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>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>Tubulin inhibitor 14 blocks NQO2 and microtubule formation, disrupts blood vessels, and may target tumors; IC50 of 1.0 μM.</p>

<p>HBV/HDV-IN-2 (Compd 143) functions as an inhibitor for HBV, HDV, and PD-1/PD-L1, demonstrating an EC 50 of 35 nM in T cell activation.</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>Anticancer agent 14: a potent breast cancer inhibitor; induces cell death, disrupts mito. membrane potential (IC50: 0.20-0.65 μM).</p>

<p>QTX125 TFA: Potent, selective HDAC6 inhibitor with antitumor effects.</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>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>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>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>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>Pan-Trk-IN-3: potent Trk inhibitor (IC50: 2-26 nM), effective against drug-resistant mutants, induces apoptosis, anti-tumor effects.</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>TP-030-2 is a RIPK1 inhibitor (human K i =0.43 nM ; mouse IC 50 =100 nM) .</p>

<p>SM-433 hydrochloride, a Smac mimetic &amp; IAP inhibitor, binds XIAP BIR3; potent IC50 &lt;1 μM. (Patent WO2008128171A2)</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>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>Antitumor agent-43 (Compound 4B) is a potent antitumor agent that induces cell cycle arrest at G2/M phase.</p>

<p>Sinulatumolin E, a terpenoid, inhibits TNF-α (IC 50: 3.6 μM); has anti-inflammatory properties.</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>Compound 12, an anticancer agent, halts G2/M phase, triggers cell death, and activates p53 &amp; PTEN for tumor suppression.</p>

<p>RMS5: hambanine analogue, inhibits P-gp, anti-cancer with cytotoxic, anti-proliferative effects, reduces Bcl-2 proteins, cleaves PARP.</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>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>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>Antitumor agent-78 blocks GPx-4, raises COX2, triggers apoptosis, halts EMT, and stifles cancer cell growth and migration.</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>Thalidomide-NH-amido-C4-NH2 is a synthetic E3 ligase ligand-linker conjugate composed of a Thalidomide-based cereblon ligand and a linker, which is utilized in the synthesis of PROTAC.</p>

<p>N-a-Tosyl-L-lysinyl-chloromethylketone hydrochloride (TLCK hydrochloride) is an irreversible serine protease inhibitor that functions by alkylating the histidine residue at the active site, thus inhibiting trypsin and trypsin-like proteases. It effectively inhibits caspase-3, caspase-6, and caspase-7 with IC50 values of 12.0, 54.5, and 19.3 μM, respectively. Additionally, N-a-Tosyl-L-lysinyl-chloromethylketone hydrochloride induces apoptosis in HL-60 cells and prevents the reduction of mitochondrial transmembrane potential during the apoptosis process.</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>TFCP2L1-IN-1 is a TFCP2L1 transcription factor inhibitor that regulates cell proliferation and promotes antitumor effect of Sorafenib by STAT3/NANOG pathway.</p>