Apoptosis

<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>Evo312 is an inhibitor of protein kinase C beta I (PKCβI) with an IC50 of 117.34 nM and exhibits dose-dependent characteristics. It acts by inhibiting the expression of the PKCβI protein, which leads to cell cycle arrest and apoptosis in PANC-GR (gemcitabine-resistant pancreatic cancer cells). Evo312 also demonstrates antiproliferative effects in pancreatic cancer cells PANC-1 and PANC-GR, with IC50 values of 0.08 μM and 0.07 μM respectively, while presenting an IC50 of 2.95 μM in normal human pancreatic ductal epithelial cells HPDE6-c7. Additionally, Evo312 has shown antitumor activity in a mouse xenograft model using PANC-GR 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>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>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>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>

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

<p>NF-κB-IN-4 (compound 17) is a potent inhibitor of NF-κB pathway which can cross blood brain barrier (BBB).</p>

<p>OICR12694 (JNJ-65234637) is an orally active inhibitor of B cell lymphoma 6 (BCL6) .</p>

<p>YLL545 is an inhibitor of Vascular Endothelial Growth Factor Receptor 2 (VEGFR2). It inhibits VEGF-induced phosphorylation of VEGFR2 and the activation of downstream signaling mediators (such as phosphorylated STAT3 and phosphorylated ERK1/2) in human umbilical vein endothelial cells (HUVEC). Additionally, YLL545 suppresses HUVEC proliferation, migration, invasion, and angiogenesis. It also induces apoptosis and inhibits tumor growth in a mouse model of breast cancer.</p>

<p>XPO1-IN-1: an oral MM.1S cell inhibitor (IC50: 24 nM), induces apoptosis, stable metabolism, good pharmacokinetics.</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>Rezatapopt (PC14586) is a p53 reactivator with antitumor activity for the study of locally advanced or metastatic solid tumors.</p>

<p>GA001 is a potent G9a antagonist with an IC50 of 1.32 μM. It can induce autophagy and apoptosis, and is applicable in the treatment of breast cancer.</p>

<p>RIP1 kinase inhibitor 1 is an orally available and brain-penetrating inhibitor of RIP1 kinase with pKi of 9.04.</p>

XJTU-L453, a PI3Kα inhibitor, exhibits an IC50 of 0.4 nM. It inhibits the proliferation of breast cancer cell lines T47D and MCF7, with IC50 values of 0.2 μM and 0.5 μM respectively. Additionally, XJTU-L453 disrupts the PI3K pathway, leading to cell cycle arrest and cell apoptosis (apoptosis). It also demonstrates antitumor activity in MCF7 xenograft mice.

<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>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>NLRP3-IN-26 (compound 15Z), with an IC50 of 0.13 μM, functions as an inhibitor of NLRP3. It is applicable in studies involving the DSS-induced colitis model [1].</p>

<p>GPX4-IN-13 (compound 16), a GPX4 inhibitor, exhibits anticancer properties by diminishing the expression of GPX4, thereby reducing thyroid cell proliferation and inducing ferroptosis. Additionally, this compound effectively inhibits the growth of three distinct thyroid cancer cell lines: N-thy-ori-3-1 (IC 50 =8.39 μM), MDA-T32 (IC 50 =10.28 μM), and MDA-T41 (IC 50 =8.18 μM).</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>TfR-1-IN-1 is a TfR-1 inhibitor, also a Fe(III) salivary phenol complex, inducing apoptosis and inhibiting tumor and normal cell growth.</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>PSF-IN-2 (Compound (C)-30) is a PSF inhibitor with an IC50 value of 0.005 pM. It exhibits anticancer properties, inhibiting the proliferation of 22Rv1 cells with an IC50 value of 0.5 μM. PSF-IN-2 activates the p53 signaling pathway by disrupting PSF-RNA binding, inducing expression of related genes, promoting apoptosis, and inhibiting the cell cycle. This compound is applicable in cancer research.</p>

<p>FLT3/TrKA-IN-1: Potent dual kinase inhibitor for FLT3 &amp; TrKA, promising for AML research.</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>

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

<p>Compound 3b inhibits tubulin polymerization, IC50 12.38 µM, with anticancer properties and promotes cell apoptosis.</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>TNF-α-IN-12, a TNF-α inhibitor with an IC50 of 0.1 μM, can reduce TNF-α blood levels [1].</p>

<p>Tubulin/NRP1-IN-1 (compound TN-2) serves as a dual inhibitor targeting both Tubulin and NRP1, exhibiting IC50 values of 0.71 μM and 0.85 μM, respectively. This compound notably reduces the viability of prostate tumor cell lines and triggers apoptosis [1].</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>Microtubule stabilizer; halts cancer cell growth (IC50: 3-30 nM); arrests cells in prometaphase; prevents bipolar spindle formation.</p>

<p>PI3K/AKT-IN-1 is a dual inhibitor of PI3K and AKT with anti-cancer activity, inhibiting the PI3K/AKT pathway and inducing caspase 3-dependent apoptosis.</p>

<p>Ivaltinostat (CG-200745) is an oral panHDAC inhibitor, inducing apoptosis and enhancing cancer drug sensitivity.</p>

<p>Top/HDAC-IN-1: Dual Top/HDAC inhibitor, potent against HDAC1-3,6,8 and HCT116 cells; blocks G2 phase, induces apoptosis.</p>

XSJ05, a derivative of camptothecin (CPT), exhibits anti-cancer activity by inhibiting topoisomerase I (Topo I). This compound induces DNA double-strand breaks, leading to DNA damage. Furthermore, XSJ05 stifles the growth of colorectal cancer (CRC), halts the cell cycle in the G2/M phase, and induces apoptosis.

SPI-001 is a selective inhibitor of PPM1D (IC50=0.48 µM) that exhibits anticancer activity. The compound inhibits the phosphatase activity of PPM1D in human breast cancer cells overexpressing PPM1D and enhances the phosphorylation of p53. Additionally, SPI-001 suppresses cell proliferation by inducing apoptosis.

<p>Gallium 8-Hydroxyquinolinate is an inducer of apoptosis that initiates both p53-dependent and independent cell death in cancer cells through the induction of Ca2+ signaling transduction. In addition to its apoptotic properties, this compound's nanostructures exhibit excellent optical performance, making it suitable for use in tumor research.</p>

<p>MB710 is an amino-benzothiazole derivative that tightly binds to the Y220C pocket and stabilizes p53-Y220C in vitro.</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>Mcl-1 inhibitor21 (Example 1-36) is an Mcl-1 inhibitor with an IC50 of 328 nM. It exhibits pro-apoptotic and anti-proliferative activity against SUDHL5 and SUDHL10 cell lines, making it applicable for cancer research.</p>

<p>CK156 inhibits DAPK with high selectivity; IC50: 182 nM (DRAK1), 34 μM (CK2a1), 39 μM (CK2a2); key in autoimmune/inflammation research.</p>

<p>RET-IN-7 exhibits strong inhibitory effects against RET kinase in vitro and shows significant efficacy in treating RET-driven tumor xenografts in mice through</p>

<p>FTO-IN-13 (compound 8t) is a potent FTO inhibitor with antiproliferative properties. It induces apoptosis (cell apoptosis) and reduces the expression of Bcl-2 and Caspase 3 active proteins. Additionally, FTO-IN-13 lowers the expression of MYC and CEBPA genes and demonstrates anticancer activity.</p>

<p>MC3629, an inhibitor of the histone methyltransferase (EZH2), exhibits antitumor activity. This compound effectively inhibits the proliferation and self-renewal of SHH MB cancer cells while inducing cell apoptosis (apoptosis). MC3629 is also useful in research on tumor aggressiveness and resistance.</p>

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

<p>PF-7006, an Mps1 kinase inhibitor, exhibits a Ki value of 0.27 nM and an IC50 value of 2.5 nM. It disrupts cell cycle checkpoints by inhibiting the catalytic activity of Mps1, reduces histone H3 levels, and shortens the duration of mitosis, thereby inducing apoptosis (Apoptosis) in cancer cells. When used in combination with Palbociclib, the tolerance of cancer cells to PF-7006 is enhanced. PF-7006 is applicable for research on breast cancer.</p>

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