autophagic

ML-SA5 is an MCOLN1 agonist and arrests autophagic flux by perturbing fusion between autophagosomes and lysosomes.

MPP+ iodide, the metabolite of a neurotoxin MPTP, causes symptom of Parkinson's disease (PD) in animal models by selectively destroying dopaminergic neurons in substantia nigra. MPP+ induces dopamine transporter (DAT) externalization in dopaminergic (DA)

Clarithromycin (A-56268) is a Macrolide Antimicrobial. The mechanism of action of clarithromycin is as a Cytochrome P450 3A4 Inhibitor, and Cytochrome P450 3A Inhibitor, and P-Glycoprotein Inhibitor. The chemical classification of clarithromycin is Macrolides.

Indomethacin farnesil (Infree) is a prodrug of indomethacin. It acts as a nonsteroidal anti-inflammatory drug (NSAID) and disease-modifying anti-rheumatic drug (DMARD).

HJ-PI01 (HJ-PI01) is a Pim-2 inhibitor. HJ-PI01 (HJ-PI01) induces apoptosis and autophagic cell death in triple-negative human breast cancer.

EACC, a reversible autophagy inhibitor, selectively impedes Stx17, an autophagosome-specific SNARE, from translocating, hence obstructing the fusion between autophagosomes and lysosomes. This compound effectively halts autophagic flux.

MHY1485 is a mTOR activator. It inhibits the autophagic process by inhibition of fusion between autophagosomes and lysosomes, leading to the accumulation of LC3II protein and enlarged autophagosomes.

1. Oleandrin (Folinerin), the principal cardiac glycoside component of PBI-524, can quantitatively account for regulation of BDNF at both the protein and transcriptional levels. 2. Oleandrin are known to inhibit the Na, K-ATPase pump, resulting in a consequent increase in calcium influx in heart muscle. 3. Oleandrin has stronger anti-proliferative activity in undifferentiated CaCO-2 cells (IC50, 8.25 nM) , causes an autophagic cell death and altered ERK phosphorylation in undifferentiated.

CTB (Cholera Toxin B subunit) is an activator of p300 histone acetyltransferase and induces apoptosis in MCF-7 cells.

BL-918 is a potent activator of UNC-51-like kinase 1 (ULK1) with an EC50 of 24.14 nM.

NSC 185058, an inhibitor of ATG4B (a major cysteine protease), can also attenuate autophagic activity.

Monascuspiloin is a fungal metabolite that has been found inM. pilosusM93-fermented rice.1It induces endoplasmic reticulum stress and autophagy in PC3 prostate cancer cells. Monascuspiloin (15-45 μM) decreases viability of PC3 cells and has an additive effect on the reduction in viability of PC3 cells induced by irradiation when used at a concentration of 25 μM. It induces intratumor apoptosis and autophagy and reduces tumor growth in a PC3 mouse xenograft model when administered at doses of 40 and 120 mg/kg.2 1.Chiu, H.-W., Fang, W.-H., Chen, Y.-L., et al.Monascuspiloin enhances the radiation sensitivity of human prostate cancer cells by stimulating endoplasmic reticulum stress and inducing autophagyPLoS One7(7)e40462(2012) 2.Chen, R.-J., Hung, C.-M., Chen, Y.-L., et al.Monascuspiloin induces apoptosis and autophagic cell death in human prostate cancer cells via the Akt and AMPK signaling pathwaysJ. Agric. Food Chem.60(29)7185-7193(2012)

OAB-14 is a Bexarotene derivative that improves Alzheimer's disease-related pathologies and cognitive impairments by increasing β-amyloid clearance in APP/PS1 mice. OAB-14 effectively ameliorates the dysfunction of the endosomal-autophagic-lysosomal(EAL) pathway in APP/PS1 transgenic mice [1] [2].

KRA-533, a potent KRAS agonist, directly targets the GTP/GDP binding pocket within the KRAS protein, inhibiting GTP cleavage. This inhibition leads to the buildup of constitutively active GTP-bound KRAS, which subsequently activates both apoptotic and autophagic cell death pathways specifically in cancer cells.

1. Liensinine, a kind of isoquinoline alkaloid, can antagonize the ventricular arrhythmias.

Autophagy Inducer 3 is a chemical compound that exhibits autophagy-induced activity, specifically inducing robust autophagic cell death in various cancer cells while sparing normal cells. This compound induces lethal autophagy through the formation of distinct autophagic vacuoles, LC3 puncta formation, and upregulation of signature autophagy markers such as Beclin and Atg family proteins [1].

Lup-20(29)-en-28-oic acid exhibits anticancer activities in various cancer types by inhibiting autophagic flux and synergistically enhancing the effectiveness of chemotherapeutic agents against HeLa cells. Pulsatilla saponin D demonstrates strong haemolytic activity.

GW406108X (GW108X) is a Kif15 inhibitor with an IC50 of 0.82 uM in ATPase assays. GW406108X is also an ULK1 kinase inhibitor with pIC50 values of 6.37 (427 nM) and block autophagic flux.

Autophagy-IN-2 (Compound 7h) is an autophagic flux inhibitor that induces cancer cell apoptosis, making it a valuable agent for triple-negative breast cancer research [1].

Cathepsin B, a cysteine protease, plays a role in various forms of programmed cell death, such as apoptosis, pyroptosis, ferroptosis, necroptosis, and autophagic cell death [1].

Gypenoside L inhibits autophagic flux and induces cell death in human esophageal cancer cells through endoplasm reticulum stress-mediated Ca2+ release. It also inhibit non-small cell lung carcinoma A549 cell inhibitory activity.

Dendrogenin A (DDA) is a compound acting as a selective liver X receptor (LXR) modulator, cholesterol epoxide hydrolase inhibitor (Ki = 120 nM), and a metabolic product of cholesterol, originating from 5,6α-epoxy cholesterol through histamine conjugation via DDA synthase. This compound is present in non-cancerous human mammary epithelial cells and melanocytes, but absent or minimally present in various breast carcinoma, melanoma cells, and isolated human breast tumor tissues. DDA impedes the activation of LXRβ and LXRα induced by 22(R)-hydroxy cholesterol (IC50s = 76 and 362 nM, respectively), yet it also functions as a partial LXR agonist, boosting the protein levels of Nur77, NOR-1, LC3-I, and LC3-II in B16/F10 murine melanoma cells. It shows a preference for LXRα and LXRβ modulation while displaying selectivity over other receptors including pregnane X receptor (PXR), and various others at a concentration of 2.5 µM. Moreover, DDA enhances LC3-II protein levels in cancer cells and prompts autophagic cell death at specific concentrations. Notably, DDA (0.37 µg/kg) has been shown to diminish tumor growth in melanoma and mammary cancer murine models and promotes cancer cell differentiation both in vitro and in vivo.

DHA-37 is an inducer of autophagic cell death through upregulation of HMGB1 in A549 cells.

CAY17c is an inhibitor of bromodomain-containing protein 4 (BRD4; IC50= 0.71 μM), as well as class I histone deacetylases (HDACs; IC50s = 0.046, 0.058, 0.075, and 0.167 μM for HDAC1, -2, -3, and -8, respectively) and class IIb HDACs (IC50s = 0.073 and 0.923 μM for HDAC6 and HDAC10, respectively).1It is selective for these enzymes over BRD2, -3, and -T (IC50s = >20 μM for all), as well as over HDAC4, -5, -7, -9, and -11 (IC50s = >10 μM for all). CAY17c inhibits the proliferation of HCT116, SW620, and DLD-1 colorectal cancer cells (IC50s = 0.45, 1.78, and 2.11 μM, respectively), as well as induces apoptosis and autophagy in HCT116 cells. It reduces tumor growth in an HCT116 mouse xenograft model when administered at doses of 15 and 30 mg/kg. 1.Pan, Z., Li, X., Wang, Y., et al.Discovery of thieno[2,3-d]pyrimidine-based hydroxamic acid derivatives as bromodomain-containing protein 4/histone deacetylase dual inhibitors induce autophagic cell death in colorectal carcinoma cellsJ. Med. Chem.63(7)3678-3700(2020)

Alisol A (Alisol-A) may be an autophagic inducer, it has anti-cancer activity, it presents inhibitory effects on cancer cell lines tested(HepG2, MDA-MB-231, and MCF-7 cells).

LV-320 is a potent, uncompetitive ATG4B inhibitor with an IC50 of 24.5 μM and a Kd of 16 μM. LV-320 inhibits ATG4B enzymatic activity, blocks autophagic flux in cells, and is stable, non-toxic, and active in vivo. These findings suggest that LV-320 will serve as a relevant chemical tool to study the various roles of ATG4B in cancer and other contexts [1].

PIK5-12d, a potent PROTAC PIKfyve degrader (DC50: 1.48 nM), effectively induces cytoplasmic vacuolization and inhibits autophagic flux in various prostate cancer cell lines, concurrently halting their proliferation. This compound has demonstrated significant anti-tumor activity [1].

DCAP, a broad-spectrum antibiotic, disrupts the membranes of both Gram-positive and Gram-negative bacteria. Additionally, it inhibits late-stage autophagy by blocking autophagolysosome maturation and interrupting autophagic flux [1].

Autophagy-IN-1 is a potent inhibitor of autophagy mitophagy that blocks autophagosomal-lysosomal fusion in cancer cells while selectively increasing autophagic flux. It significantly inhibits tumor growth in the HCT116 mouse xenograft tumour model with low toxicity and can be used to study colorectal cancer.

Maysin, a neuroprotective C-glycosyl-flavone isolated from corn silk, protects against Syn amyloid aggregates-oligomers and fibrils-induced damage by preventing oxidative stress and intracellular calcium imbalance through autophagic activation. It is utilized in Parkinson's disease (PD) research [1].

Z36 is a novel Bcl-xL inhibitor, upregulating the expression levels of FAM134B, LC3, and Atg9, inducing autophagy along with autophagic cell death, resulting in ER stress and the unfolded protein response (UPR).

DMGF, also known as 7,7-dimethoxyagastisfavone, is a biflavonoid isolated from Taxus × media cv. Hicksii. DMGF induces apoptotic and autophagic cell death. DMGF could effectively attenuate the motility of B16F10 cells, and the results of real-time PCR revealed that DMGF also suppressed the expressions of matrix metalloproteinase-2 (MMP-2). MGF can inhibit the metastasis of highly invasive melanoma cancer cells through the down-regulation of F-actin polymerization DMGF may be further developed to serve as a chemoprevention drug for patients with metastatic melanoma.

Aurantiamide has anti-cancer, anti-inflammatory and antinociceptive activities, it may suppress the growth of malignant gliomas by blocking autophagic flux.Aurantiamide has an anti-neuroinflammatory effect on LPS stimulation through its inhibition of the

Chromomycin A2 is an aureolic acid that has been found in several marine actinomycetes and has antibacterial and anticancer activities. Chromomycin A2 inhibits the growth of B. subtilis in an agar diffusion assay. It also inhibits the growth of human SGC7901 gastric cancer, HepG2 hepatocellular carcinoma, A549 lung epithelial adenocarcinoma, HCT116 colon cancer, and COC1 ovarian cancer cells, as well as human umbilical vein endothelial cells (HUVECs; IC50s = 4, 0.5, 3, 5, 5, and 8 nM, respectively). Chromomycin A2 (30 nM) halts the cell cycle in the G0/G1 phase and increases the protein levels of LC3A and LC3B in MALME-3M melanoma cells, indicating that it induces autophagy. It also increases the levels and promoter activity of the autophagic proteins ATG7 and ATG10 and reduces cell viability to 50% in human SCC-11 squamous cell carcinoma cells when used at a concentration of 30 nM.

Mitochondria Degrader-1 (example 5) is a potent agent for inducing the autophagic degradation of damaged mitochondria. It is applicable in the research of various conditions including neurodegenerative, cancer, inflammatory, age-related, metabolic, mitochondrial, and Down's diseases.

BRD4 Inhibitor-25, a chemical compound targeting the BD1 and BD2 domains of BRD4 with half-maximal inhibitory concentrations (IC50s) of 0.82 μM and 1.94 μM respectively, demonstrates efficacy in inducing apoptotic and autophagic cell death in ovarian cancer cells. This compound is utilized in researching cancers, cardiovascular, neuromuscular, and inflammatory disorders.

Lucanthone hydrochloride is a novel acridine derivative which supresses autophagic degradation and triggers apoptosis in colon cancer cells.

Thalidezine, a novel AMPK activator, eliminates apoptosis-resistant cancer cells through energy-mediated autophagic cell death, it can inhibit the growth of mouse L1210 cells in vitro. Thalidezine possesses antimicrobial activity against Mycobacterium sme

PLM-101 is an anticancer compound orally active against acute myeloid leukemia by targeting FLT3 and RET. It impedes RET function, promoting autophagic breakdown of FLT3, and suppresses the PI3K and Ras/ERK pathways, contributing to its anti-leukemic effects. The compound's antitumor efficacy is demonstrated in both a mouse MV4-11 flank xenograft model (doses of 3 and 10 mg/kg; po) and an allogeneic xenograft mouse model (dose of 40 mg/kg; po) [1].

CAA0225 is a selective inhibitor of cathepsin L. CAA0225 is a probe for autophagic proteolysis.

Cannabisin B possesses considerable antiproliferative activity and that it may be utilised as a promising chemopreventive agent against hepatoblastoma disease. It induces autophagic cell death by inhibiting the AKT/mTOR pathway and S phase cell cycle arre

N6-Isopentenyladenosine, an end product of the mevalonate pathway, is an autophagy inhibitor with anti-melanoma activity. N6-Isopentenyladenosine, an RNA modification found in cytokinins, regulates plant growth/differentiation and improves the efficiency

HMS607P03 is an activator of SIRT1 which induces autophagic cell death via the AMPK-mTOR-ULK complex and induces mitophagy by the SIRT1-PINK1-Parkin pathway. HMS607P03 downregulates 14-3-3γ, catalase, profilin-1, and HSP90α.

FTO-IN-10 (compound 7), a potent inhibitor of the human demethylase FTO (fat mass and obesity-associated protein), exhibits an IC50 of 4.5 μM. It interacts with the binding pocket of FTO's structural domain II via hydrophobic and hydrogen bonding interactions, and promotes DNA damage and autophagic cell death in A549 cells [1].