autophagosomes

ROC-325 is an effective and orally active inhibitor of autophagy with anticancer activity. ROC-325 induces renal cell carcinoma apoptosis and exhibits favorable selectivity.

MHY1485 is an mTOR activator that is cell-permeable. MHY1485 inhibits autophagosome and lysosome fusion, leading to accumulation of LC3II proteins and increased autophagosomes, thereby inhibiting cellular autophagy.

Bafilomycin A1 belongs to the macrolide class of antibiotics and is a V-ATPase inhibitor (IC50=0.44 nM) that is specific and reversible. Bafilomycin A1 is an inhibitor of the late phase of autophagy, blocking the fusion of autophagosomes with lysosomes. Bafilomycin A1 also induces apoptosis.

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.

ALLO-1 is a crucial autophagy receptor responsible for facilitating the formation of autophagosomes around paternal organelles. It directly interacts with the worm LC3 homologue, LGG-1, through its LC3-interacting region (LIR) motif.

Autophagyinducer 6 (Compound 3) inhibits the production of ROS and RNS by targeting COX-1 (IC50=15.3 µM) and COX-2 (IC50=4.58 µM). It facilitates the formation of autophagosomes and induces autophagy (autopagy) as a cellular protection mechanism. Additionally, Autophagyinducer 6 triggers mild apoptosis (apoptosis) and suppresses the proliferation of cancer cell lines MC38, HCT116, and HCT29 with IC50 values of 9.5, 11.5, and 17.6 µM, respectively.

YAP-IN-1 (Compound (+)-1) is an autophagy inhibitor specifically targeting YAP1. It binds to the Hippo pathway transcription factor YAP1 with a Kd of 9.13 μM, promoting its degradation through the chaperone-mediated autophagy (CMA) pathway. This process inhibits the Rab7-mediated fusion of autophagosomes with lysosomes and decreases autophagy levels without affecting lysosomal function. YAP-IN-1 shows potential for cancer research, including in hepatocellular carcinoma and breast cancer.

CDK9degrader-1 is a selective CDK9 degrader (DC50: 0.4073 µM). It recruits ATG101 to initiate the autophagy-lysosome pathway and forms autophagosomes by recruiting LC3, which then fuse with lysosomes to degrade CDK9 and its partner protein, Cyclin T1 (DC50: 1.215 µM). CDK9degrader-1 induces caspase 3-mediated apoptosis and exhibits antitumor activity in a mouse HCT116 xenograft model.

DK-1-49 is an autophagonizer. It causes accumulation of autophagy-associated LC3-II and enhanced levels of autophagosomes and acidic vacuoles.

MRT-68601 HCl, a potent TBK1 (TANK-binding kinase-1), inhibits the formation of autophagosomes in lung cancer cells.

Potent TBK1 (TANK-binding kinase-1) inhibitor (IC50 = 6 nM). Inhibits the formation of autophagosomes in lung cancer cells. Newman et al (2012) TBK1 kinase addiction in lung cancer cells is mediated via autophagy of Tax1bp1/Ndp52 and non-canonical NF-κB signalling. PLoS ONE 7 e50672 PMID:23209807 |McIver et al (2012) Synthesis and structure-activity relationships of a novel series of pyrimidines as potent inhibitors of TBK1/IKKe kinases. Bioorg.Med.Chem.Lett. 22 7169 PMID:23099093

ML-SA5 is a MCOLN1 agonist that blocks autophagic flux by disrupting fusion between autophagosomes and lysosomes.

TrxR-IN-3 (Compound 2c) is an effective TrxR inhibitor that exhibits strong antiproliferative activities against five human cancer cell lines, particularly breast tumor cells. It increases ROS levels, induces apoptosis by regulating apoptosis-related protein expression in breast cancer cells, and promotes autophagosome and autolysosome formation by enhancing LC3-II and Beclin-1 expression and reducing LC3-I and p62 protein expression [1].

MOPIPP is a novel indolebased chalcone that can cross the blood-brain barrier. MOPIPP inhibits the tumor progression agaisnt glioblastoma cells. MOPIPP induces cellular vacuolization as well as increases autophagosomes numbers. MOPIPP also triggers methuosis and distrupts glucose uptake and glycolytic metabolism [1] [2] [3].

LC3-mHTT-IN-AN1 is a mHTT-LC3 linker compound that interacts with both mutant huntingtin protein (mHTT) and LC3B. LC3-mHTT-IN-AN1 targeted mHTT to autophagosomes reduces the levels of mHTT in an allele-selective manner in cultured Huntington disease (HD) mouse neurons.

6-(1-Hydroxyethyl)-5,6-dihydrochelerythrine, an alkaloid, significantly alters the characteristics of early endosomes, mitochondria, and autophagosomes in Parkinson's Disease patient-derived olfactory cells [1].