Apoptose

HDAC1-IN-5 inhibits HDAC1 (IC50=15 nM) & HDAC6 (IC50=20 nM), promotes apoptosis, damages chromatin, and reduces tumor growth in mice.

<p>ASP9831 is an orally active PDE4 inhibitor. It suppresses LPS-induced TNF-α production and exhibits anti-inflammatory properties. ASP9831 is useful in the study of steatohepatitis.</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>

Compound C11 inhibits 14-3-3η protein (KD: 35 μM), targets liver cancer cells, blocks G1-S phase, and induces apoptosis.

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

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>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>

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>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>

(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.

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>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>

VNPP433-3β acts as a molecular glue degrader, targeting the androgen receptor (AR) and its splice variants (AR-Vs) as well as MAP kinase-interacting serine/threonine protein kinase Mnk1/2. It effectively inhibits the proliferation of cancer cells LNCaP, C4-2B, and CWR22Rv1, with GI50 values of 0.2, 0.3, and 0.31 μM, respectively. Additionally, VNPP433-3β shows favorable pharmacokinetics in CD-1 mice and suppresses tumor growth in the CWR22Rv1 xenograft mouse model.

<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>

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.

Antitumor agent-76 is a water-soluble, orally active, rapid-release prodrug of Triptolide that exhibits anticancer effects.

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

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

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.

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

MG-B-28, a BTLA-HVEM inhibitor, demonstrates an IC50 value of 906 nM. It promotes T cell activation dose-dependently by inhibiting the interaction between BTLA and HVEM.

NDs-IN-1 (Compound 3g) is a novel non-covalent multi-target inhibitor that inhibits the activities of key enzymes such as hBACE-1, hAChE, and hMAO-B, and is primarily used in the study of neurodegenerative diseases [1].

<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>

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

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

Aeroplysinin I is an antibacterial compound from the sponge. It has cytotoxic activity against colon cancer cells by promoting β-catenin degradation.

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

Apoptosis inducer42 is an apoptosis inducer that triggers late-stage apoptosis and inhibits the secretion of IL-6. It exhibits high cytotoxicity toward cancer cells and is applicable in cancer research, including studies on colon cancer.

<p>Topo II/HDAC-IN-2 (8d) demonstrates remarkable dual inhibitory effects on Topo II and HDAC, and also induces apoptosis [1].</p>

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

<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>

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

4-Bromo A23187 is a halogenated analog of the calcium ionophore A-23187. 4-Bromo A23187 is a calcium modulator and induces apoptosis in different cells.

DeFer-2 is a ferritin PROTAC degrader (Kd= 17.1 μM). It triggers the degradation of ferritin leading to the accumulation of free iron ions and an increase in ROS, which subsequently initiates caspase 3-GSDME mediated pyroptosis in cancer cells. DeFer-2 significantly inhibits tumor growth and extends the survival of mice with subcutaneous B16F10 tumors, and it is useful for melanoma research.

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

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

t9,t11,c15-CLNA is an isomer of conjugated linolenic acid (CLNA) produced by Lactobacillus plantarum ZS2058. It exhibits key activities including anti-inflammatory and antioxidant effects, as well as enhancement of intestinal barrier function. The regulatory mechanisms of t9,t11,c15-CLNA involve the upregulation of tight junction proteins, the inhibition of pro-inflammatory cytokines (such as TNF-α, IL-6), and the activation of antioxidant enzymes (such as SOD, CAT). t9,t11,c15-CLNA can be utilized in research on inflammatory bowel disease (like colitis).

Spicamycin can be used as a potent inducer of differentiation of human myeloid leukemia cells (HL-60) and murine myeloid leukemia cells (M1).

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

Compound B6, also known as TOPOI/PARP-1-IN-1, is a dual inhibitor targeting TOPOI and PARP, exhibiting low cytotoxicity and oral activity with a PARP1 IC 50 of 0.09 μM. This compound effectively inhibits cancer cell proliferation and migration, induces cell cycle arrest at the G0/G1 phase, and triggers apoptosis. In murine models, TOPOI/PARP-1-IN-1 demonstrated a tumor growth inhibition rate (TGI) of 75.4% [1].

<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>

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

NPB-1575 is a potent, orally active anti-inflammatory agent capable of crossing the blood-brain barrier. It mitigates neuroinflammation and resists ferroptosis by activating IRS2/Nrf2/NF-κB. NPB-1575 protects against cerebral ischemic injury and improves neurological function outcomes, making it suitable for research in focal ischemic stroke.

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

AKT-IN-3: potent oral Akt inhibitor with low hERG blockage. IC50: 1.4-1.7 nM for Akt1-3. Inhibits AGC kinases like PKA, PKC.

VEGFR-2-IN-18 is a potent VEGFR-2 inhibitor with a 60 nM IC50, promoting cell apoptosis and anticancer effects.