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.

NAADP tetrasodium is a second messenger that releases Ca2+ from acidic endosomes and lysosomes. It is used in the study of cancer, such as oral squamous cell carcinoma and malignant melanoma, as well as in research related to angiogenesis-associated diseases.

Nrf2-IN-4 is an Nrf2 inhibitor that induces ferroptosis by disrupting cellular iron homeostasis, promoting ferritin degradation, and ultimately triggering ferroptosis. It activates lysosomes through iron-dependent reactive oxygen species (ROS) production and lysosomal acidification. Nrf2-IN-4 demonstrates significant antitumor effects and is applicable in breast cancer research.

CDN prodrug-1 (Compound 2) acts as a STING ligand. It is composed of a cyclic dinucleotide (CDN) linked by a diproline peptide. Once CDN prodrug-1 is internalized into lysosomes by cathepsins, it can be cleaved to release the parent CDN. Additionally, CDN prodrug-1 can be synthesized into nanoparticles for drug delivery research.

NM-001 is a theranostic prodrug that targets ανβ3 integrin. It consists of cRGD peptides, GFLG peptides, a dichloromethane fluorophore, and Chlorambucil. The compound enters tumor cell lysosomes through cRGD peptides, where overexpressed cathepsin B (CTSB) facilitates intracellular cleavage of GFLG peptides, generating NM-002 and Chlorambucil. Under physiological conditions, NM-001 exhibits green fluorescence, which switches to near-infrared fluorescence upon CTSB activation. In a HeLa cell xenograft mouse model, NM-001 demonstrates significant antitumor activity with reduced toxicity and is suitable for real-time drug release monitoring studies.

DMBP is a VPS41 inhibitor that induces methuosis, a vacuolar form of cell death, in cancer cells and inhibits autophagy. It prevents the fusion of late lysosomes and autophagosomes with lysosomes. DMBP effectively suppresses metastasis in a metastatic melanoma mouse model and is applicable for melanoma research.

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].