Apoptosis

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).

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

<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>

MDK-3345 is a reversible covalent inhibitor for Mcl-1.

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.

Bomedemstat (IMG-7289) hydrochloride, an oral LSD1 inhibitor, has anticancer properties, blocking cell growth and triggering apoptosis.

NiCur is an effective and selective inhibitor of CBP histone acetyltransferase (HAT), with an IC50 of 0.35 μM.

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

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

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.

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.

PD-L1/HDAC6-IN-1 (Compound HP29) is an inhibitor targeting both PD-L1 and HDAC6, effectively disrupting the PD-L1/PD-1 interaction and inhibiting HDAC6 activity, with IC50 values of 26.8 nM and 69 nM, respectively. This compound enhances the cytotoxicity of Jurkat T cells against HepG2 cells, exhibiting an IC50 of 3.4 μM. In rats, PD-L1/HDAC6-IN-1 demonstrates favorable pharmacokinetics, showing a drug exposure level of 871.62 ng·h/mL, and displays antitumor activity in a B16-F10 xenograft mouse model.

VEGFR-2-IN-52 (compound 14d) serves as a powerful inhibitor of VEGFR-2, exhibiting an IC 50 of 191.1 nM. It effectively reduces the protein expression levels of p-VEGFR-2, MMP9, p-ERK1/2, and p-MEK1. In addition, VEGFR-2-IN-52 demonstrates cytotoxic properties by inducing apoptosis and arresting the cell cycle at the G0/G1 phase, and it enhances the levels of ROS.

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

<p>Apoptosisinducer 36 (Compound 42) exhibits anti-leukemic activity by reducing leukemia stem cells (LSC) and inducing differentiation. It inhibits proliferation of AML cells by causing cell cycle arrest in the G1 phase, and induces PANoptosis, which includes apoptosis, pyroptosis, and necrosis.</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>

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.

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.

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.

HDAC-IN-34 inhibits HDAC1 (IC50: 0.022 μM) & HDAC6 (IC50: 0.45 μM), binds DNA causing damage, and halts HCT-116 cell growth (IC50: 1.41 μM).