lysosomes

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.

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.

Siramesine (Lu 28-179)(Lu 28-179) is a selective sigma-2 receptor agonist, which has been shown to trigger cell death of cancer cells and to exhibit a potent anticancer activity in vivo.lysosome-destabilizing agent siramesine can induce rapid cell death in a number of cell lines at concentrations above 20 μM. In HaCaT cells, cell death was accompanied by caspase activation, rapid loss of mitochondrial membrane potential (MMP), cytochrome c release, cardiolipin peroxidation and typical apoptotic morphology, whereas in U-87MG cells most apoptotic hallmarks were not notable, although MMP was rapidly lost

Leupeptin hemisulfate is a protease inhibitor with cell membrane-permeable, reversible, competitive, and oral activities. Leupeptin hemisulfate inhibits the activity of Cathepsin B, Cathepsin H, and Cathepsin L, and blocks fusion of amphipathic lysosomes. Leupeptin hemisulfate also has anti-inflammatory activity.

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.

1-Dodecylimidazole (N-Dodecylimidazole) is a chemical compound that acts as a cytotoxic agent and lysosomotropic detergent, inducing cell death through acid-dependent lysosomal accumulation, disrupting the lysosomal membrane, and releasing cysteine proteases into the cytoplasm. It also exhibits hypocholesterolemic and broad-spectrum antifungal activities.

TriGalNAc CBz is a GalNAc derivative. As an ASGPR ligand, tri-GalNAc targets lysosomes in mRNA drug delivery and LYTAC studies.L-DABA hydrobromide.

Ferrostatin-1 diyne (Fer-1 diyne) (compound 2) serves as an inhibitor of ferroptosis, accumulating in cellular lysosomes, mitochondria, and the endoplasmic reticulum. It notably inhibits ferroptosis independently of lysosomal and mitochondrial activity.

LYMTAC-2 is a lysosome-targeting chimera (LYMTAC) developed to degrade membrane-associated proteins through lysosomal membrane proteins (LMP) such as RNF152, LAPTM4a, and LAPTM5. It forms a ternary complex with target proteins like KRASG12D, facilitating their relocation to lysosomes and resulting in ubiquitin-dependent degradation. This compound has potential for studying membrane protein regulation and devising strategies to counter resistance in KRAS-driven signaling pathways.

Lysosomal P-gp targeted agent 1 (Compound 14) is an antitumor drug that targets lysosomal P-glycoprotein (Pgp). It is selectively transported to lysosomes via overexpressed Pgp, releasing nitric oxide that generates reactive oxygen species (ROS), causing lysosomal membrane permeabilization (LMP) and inducing apoptosis. This compound can overcome resistance mediated by P-glycoprotein, leading to cell cycle arrest while maintaining relatively low toxicity to normal cells. It exhibits antitumor activity by significantly inhibiting tumor growth.

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.

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

NIM-7 is a fluorescent probe, allowing lipid droplets and lysosomes to be labelled simultaneously and with high specificity, being visualized readily through yellow and red fluorescence, using different excitation and detection channels.

Ganglioside GM2 is a glycosphingolipid component of cellular membranes, primarily the plasma membrane. Levels of ganglioside GM2 are elevated in the brain of patients with Sandhoff disease, as well as feline and mouse models of the disease. Ganglioside GM2 accumulates in the lysosomes of individuals with Tay-Sachs disease and GM2-activator deficiency, as well as in the CNS of patients with and animal models of mucopolysaccharide storage disorders and Niemann-Pick disease types A, C1, and C2. Ganglioside GM2 mixture contains ganglioside GM2 molecular species with C18:1 and C20:1 sphingoid backbones.

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

Acid phosphatase (ACP) is an enzyme that releases attached phosphate groups from other molecules during digestion, is stored in lysosomes, has an optimal acidic pH, and serves as a medical marker and target for cancer immunotherapy.

Clervonafusp alfa (VAL-1221) is a fusion protein targeting both cytosolic and lysosomal glycogen, addressing the mechanisms of Pompe disease. It combines the Fab segment of a cell-penetrating antibody with recombinant human acid alpha-glucosidase (rhGAA). The Fab portion utilizes the nucleoside transporter ENT-2 for cytosolic entry, while rhGAA accesses lysosomes via mannose-6-phosphate receptors (M6PRs). This dual-targeting approach suggests Clervonafusp alfa as a potential therapeutic research candidate for late-onset Pompe disease [1].

Zilovertamab vedotin (VLS-101) is a novel antibody-drug conjugate composed of the humanized monoclonal antibody zilovertamab linked to the anti-microtubule cytotoxin monomethyl auristatin E (MMAE). Upon binding to ROR1 on tumor cells, it is rapidly internalized and directed to lysosomes for cleavage, releasing MMAE and inducing apoptosis in targeted cells. Zilovertamab vedotin has potential applications in cancer research [1].

NDBM, a tumor-specific probe that targets Pim-1 kinase, exhibits heightened fluorescence upon binding and induces cytotoxicity, facilitating both cell screening and killing. It possesses targeted action on lysosomes and a sensitive pH response, enabling the monitoring of intracellular pH variations associated with autophagy and external stimuli [1].

3β,5α,6β-Trihydroxycholanic acid, a metabolite derived from 5α,6β-dihydroxycholestanol, exhibits elevated levels in dried blood spots of patients diagnosed with Niemann-Pick disease type C, a neurodegenerative disorder characterized by the accumulation of cholesterol and sphingolipids in lysosomes.

RPS6-IN-1 (Compound 22o) inhibits cell migration and induces apoptosis (increasing the expression of Bax, p53, cleaved-caspase 3, and cleaved-PARP). It reduces mitochondrial membrane potential and activates autophagy (Autophagy) through the PI3K-Akt-mTOR signaling pathway, damaging mitochondria and lysosomes within the cell and causing endoplasmic reticulum stress. RPS6-IN-1 also inhibits the phosphorylation of RPS6. Notably, RPS6-IN-1 is a low systemic toxicity anticancer agent.

HDAC3-IN-4 is a selective and orally active inhibitor of HDAC3, boasting an IC50 of 89 nM. It induces the degradation of PD-L1 by modulating cathepsin B (CTSB) in lysosomes, with a DC50 of 5.7 μM. Compared to HDAC1, HDAC6, HDAC7, and HDAC8, HDAC3-IN-4 demonstrates superior selectivity for HDAC3.