lysosomal autophagy

Lys05, or Lys01 trihydrochloride, is a potent, water soluble lysosomal autophagy inhibitor. Lys05 is a previously undescribed dimeric chloroquine which more potently accumulates in the lysosome and blocks autophagy compared with HCQ. Lys05 produced more p

Siramesine hydrochloride (Lu 28-179 hydrochloride) is a selective sigma-2 receptor agonist, which has been shown to trigger cell death of Y cells and to exhibit a potent anticancer activity in vivo.

Ezurpimtrostat hydrochloride (GNS561 hydrochloride) is an orally available palmitoyl protein thioesterase-1 inhibitor with antifibrotic, antiviral, and anticancer effects that blocks cancer cell proliferation by interacting with palmitoyl protein thioesterase to inhibit late autophagy and dose-dependently increase lysosomal accumulation.

DC661 is a palmitoyl-protein thioesterase 1 (PPT1) inhibitor that acts as an anti-lysosomal agent by inhibiting autophagy, demonstrating anti-cancer activity.

ML-SA1 (Mucolipin synthetic agonist 1) is a selective TRPML agonist, inhibits Dengue virus 2 (DENV2) and Zika virus (ZIKV) by promoting lysosomal acidification and protease activity. The IC50 value of ML-SA1 against DENV2 RNA and ZIKV RNA is 8.3 μM and 52.99 μM, respectively[1].

VPS34 inhibitor 1 (Compound 19, PIK-III analogue) (PIK-III analogue) is a potent and selective inhibitor of VPS34( IC50 : 15 nM)

Vacuolin-1 is a cell-permeable inhibitor of Ca2+ dependent fusion of lysosomes to the cell membrane. It acts by inhibiting release of lysosomal content.vacuolin‐1 is a potent and selective PIKfyve inhibitor and inhibits late‐stage autophagy by impairing lysosomal maturation

WX8 (Ro 91-4714) is an ATP-competitive inhibitor of PIKFYVE, displaying Kd values of 0.9 nM for PIKFYVE and 340 nM for PIP4K2C. This compound inhibits lysosomal fission without affecting homotypic lysosome fusion. WX8 (Ro 91-4714) is applicable in research on autophagy-dependent cancers.

LYS01 free base is a new lysosomal autophagy inhibitor.

YT 6-2 is an autophagy-targeting ligand (ATL) aimed at p62 SQSTM1, used in the synthesis of AUTOTAC degrader ATC-324. ATC-324 induces the formation of AR p62 complexes, leading to the autophagic-lysosomal degradation of AR. It reduces nuclear AR levels, downregulates the expression of AR and AR-v7 target genes, and also degrades common AR mutants in PCa.

Gossypetin, a hexahydroxylated flavonoid extractable from Rhodiola rosea Linn. is a potent MKK3 and MKK6 inhibitor that strongly attenuates the MKK3 6-p38 signaling pathway.Gossypetin exhibits antimutagenic, antiatherosclerotic, antioxidant, as well as cytoprotective and antimicrobial effects.It inhibits bone resorption by downregulating lysosomal caspase K activity and inducing autophagy-associated proteins in actin ring osteoclasts. Gossypetin has anti-mutagenic, anti-atherosclerotic, anti-oxidant, cytoprotective and antibacterial effects, and it inhibits bone resorption by down-regulating lysosomal caspase K activity and by inducing autophagy-associated protein in actin ring osteoblasts.

Autophagy-IN-6 (compound 1u) is an inhibitor of lysosomal autophagy that induces the accumulation of the LC3-II protein. Additionally, it exhibits antiproliferative activity.

ARN5187 is a lysosomal compound, REV-ERB β Ligand. ARN5187 inhibits REV-ERB-mediated transcriptional regulation and autophagy. ARN5187 shows lysosomal efficacy and cytotoxicity, and can induce apoptosis.

EN6-mediated ATP6V1A modification decouples the v-ATPase from the Rags, leading to inhibition of mTORC1 signaling, increased lysosomal acidification and activation of autophagy. EN6 clears TDP-43 aggregates, a causative agent in frontotemporal dementia, in a lysosome-dependent manner. EN6 is a small-molecule in vivo activator of autophagy that covalently targets cysteine 277 in the ATP6V1A subunit of the lysosomal the vacuolar H+ ATPase (v-ATPase).

ARN5187 trihydrochloride is a lysosomal REV-ERBβ ligand that inhibits REV-ERB-mediated transcriptional regulation and autophagy. ARN5187 trihydrochloride has lysosomal potency and cytotoxicity and induces apoptosis.

NAMPT Degrader-1 (Compound A3), a nicotinamide phosphoribosyltransferase (NAMPT) degrader, exhibits potent antitumor activity in cells by specifically inducing the degradation of NAMPT via the autophagy-lysosomal pathway, with an inhibitory concentration (IC50) of 0.023 μM [1].

MPM-1, a mimic of marine Eusynstyelamides, serves as an effective anticancer agent. It swiftly induces a necrosis-like death in cancer cells in vitro, facilitates immunogenic cell death, and disrupts autophagy, leading to lysosomal swelling in cancer cells.

YT 6-2-PEG3-C2-NH2 is a conjugate of the autophagy-targeting ligand (ATL) targeting p62 SQSTM1 and an AUTOTAC linker. It is used in the synthesis of the AUTOTAC degrader ATC-324 for the androgen receptor (AR). ATC-324 induces the formation of the AR p62 complex, leading to autophagy-lysosomal degradation of AR. This action reduces nuclear AR levels and downregulates target gene expression of AR and AR-v7, effectively degrading common AR mutants found in prostate cancer (PCa).

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.

KRAS degrader-1 (compound 1) is a potent agent that selectively targets KRAS proteins for degradation via the autophagy-lysosomal pathway [1].

YT 6-2 analog-1 (compound 2-3) serves as an autophagy-targeting ligand (ATL) aimed at p62 SQSTM1, useful in synthesizing the AUTOTAC degrader ATC-324 for the Androgen Receptor (AR). ATC-324 promotes the formation of AR p62 complexes, leading to the autophagic-lysosomal degradation of AR. It effectively reduces nuclear AR levels, downregulates the expression of AR and AR-v7 target genes, and can degrade common AR mutants found in prostate cancer (PCa).

MMRi62 (7-[(2,3-dichlorophenyl)-(pyridin-2-ylamino)methyl]quinolin-8-ol), a ferroptosis inducer targeting MDM2-MDM4 (negative regulators of tumor suppressor p53). MMRi62 shows a P53-independent pro-apoptotic activity against pancreatic ductal adenocarcinoma (PDAC) cells and induce autophagy. MMRi62 inducesferroptosis, resulting in a increase of reactive oxygen and lysosomal degradation of ferritin heavy chain (FTH1). MMRi62 also leads to proteasomal degradation of mutant p53, also inhibits orthotopic xenograft PDAC mouse model in vivo with high frequency mutation characteristics of KRAS and TP53.12.

Anle138b-F105 is an autophagy-targeting chimera (AUTOTAC) with a DC50 value of 3 nM. It targets tauP301L for lysosomal degradation.

20-DEOXYINGENOL is a natual product.