acidification

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].

2F-Peracetyl-Fucose (1,3,4-Tri-O-acetyl-2-deoxy-2-fluoro-L-fucopyranos) is a potent fucosyltransferase (FUT) inhibitor that inhibits salivary acidification and fucosylation in an in vitro inflammatory model.

Angiopeptin TFA, a cyclic octapeptide analogue of somatostatin, acts as a partial agonist at sst 2/sst 5 receptors, exhibiting IC50 values of 0.26 nM and 6.92 nM, respectively. This compound effectively inhibits the release of growth hormone and the production of insulin-like growth factor-1 (IGF-1). Additionally, it either inhibits adenylate cyclase activity or promotes extracellular acidification. Notably, Angiopeptin TFA shows promise for use in coronary atherosclerosis research [1] [2].

Concanamycin B is a macrolide antibiotic that selectively inhibits vacuolar type H+-ATPases, also known as V-ATPases (IC50 = 5 nM). In this way, it blocks the acidification of vacuolar organelles as well as early to late endosomal transport. Concanamycin B interferes with bone resorption and maturation of CD8 T lymphocytes. It also prevents processing of major histocompatibility complex (MHC) class II precursors in human B cells, inhibiting the expression of MHC class II molecules on the cell surface.

C-02, a proteolysis-targeting chimera (PROTAC) that combines the hexokinase inhibitor lonidamine with the cereblon ligand thalidomide, effectively induces the degradation of hexokinase 2 in 786-O and PANC-1 cells at a concentration of 20 µM. This compound exhibits cytotoxicity to a range of cancer cells, including 786-O, 4T1, PANC-1, HGC-27, and MCF-7, with IC50 values of 34.07 µM, 5.08 µM, 31.53 µM, 6.11 µM, and 21.65 µM, respectively. Additionally, at 20 µM, C-02 diminishes both the extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) in 4T1 cells, suggesting a suppression of glycolysis and mitochondrial damage. In vivo studies reveal that at a dosage of 50 mg/kg, C-02 not only reduces tumor volume but also promotes intratumoral cytokine accumulation and triggers pyroptosis in a 4T1 murine mammary carcinoma model.

N-Despropyl ropinirole is an active metabolite of the dopamine D2 receptor agonist ropinirole. It increases extracellular acidification rates in CHO cells expressing human dopamine D2, D3, and D4 receptors (EC50s = 0.63, 0.063, and 1.23 µM, respectively). N-Despropyl ropinirole is also a potential impurity found in commercial preparations of ropinirole.

Concanamycin A (Folimycin), a polycyclic lactone antibiotic, is a selective inhibitor of vacuolar H+-ATPase (V-ATPase) and lysosomal acidification, and can be used to study inflammation.Concanamycin A enhances the immune clearance of infected progenitor cells by cytotoxic T lymphocytes, and inhibits Nef et al. from different branches of HIV and simian immunodeficiency virus. Concanamycin A enhances immune clearance of cytotoxic T lymphocytes from infected progenitor cells, inhibits the Nef allele from different branches of HIV and simian immunodeficiency virus, and can be used to study HIV infection.

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).

Human GALP (3-32) (Galanin-like peptide (3-32)) serves as a high-affinity agonist for galanin receptors GalR1 (IC50 = 33 nM) and GalR2 (IC50 = 15 nM), as evidenced by competitive binding studies. It demonstrates significant potency in modifying the extracellular acidification rate in SH-SY5Y cells expressing GalR2 (EC50 = 360 nM) [1].

NS-3736 is a chloride channel inhibitor that has been shown to prevent osteoclastic acidification and resorption.