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].

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).

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.

ECDD-S18 (compound ECDD-S18) induces apoptosis in a dose-dependent manner, effectively targeting the vacuolar ATPase (V-ATPase) and impairing lysosomal acidification.

KF-52 is an inhibitor of phosphofructokinase-1 (PFK1), possessing an IC50 value of 2.1 μM. It significantly enhances the ratio of oxygen consumption rate (OCR) to extracellular acidification rate (ECAR).

Saliphenylhalamide (Saliphe) is an inhibitor of the influenza A virus (IAV). It targets the host cell's vacuolar ATPase, preventing endosomal acidification.

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.

AP232 is a selective inhibitor of U2AF1-UHM with an IC50 value of 7.96 μM. It shows 2.8 to 24 times selectivity over other UHM-containing proteins. AP232 exhibits anti-leukemia activity and demonstrates heightened effectiveness in cell lines with splicing factor mutations. It can induce G2/M and G1 phase arrest in leukemia cells, impair lysosomal acidification, and inhibit autophagy (autophagy). AP232 is applicable in cancer research, particularly for leukemia studies.

PRP020 is a potent and specific inhibitor of mycobacterial ATP synthase, which does not inhibit succinate-driven acidification. It exhibits a MIC95 of 2 μM against M. tuberculosis and remains effective against most resistant mutant strains. PRP020 is highly safe and suitable for use in tuberculosis research.

Nrf2-IN-4 (Compound PhcY) hydrobromide is an Nrf2 inhibitor that promotes ferroptosis by inhibiting NRF2. It disrupts cellular iron homeostasis, leading to ferritin degradation and ultimately triggering ferroptosis. Additionally, Nrf2-IN-4 hydrobromide induces lysosomal activation by enhancing iron-dependent reactive oxygen species (ROS) production and lysosomal acidification. This compound shows significant antitumor effects and is applicable in breast cancer research.

AP232 dihydrochloride is a selective U2AF1-UHM inhibitor with an IC50 value of 7.96 μM. It exhibits 2.8-24 times selectivity over other UHM-containing proteins and demonstrates anti-leukemic activity, showing heightened effectiveness in cell lines with splice factor mutations. AP232 dihydrochloride can induce G2/M and G1 phase arrest in leukemia cells, impair lysosomal acidification, and inhibit autophagy (autophagy). This compound is applicable in cancer research, specifically for leukemia.

BX 513 hydrochloride (VUF 2274 HCl) is a selective CCR1 antagonist (Ki=0.04 µM) that concentration-dependently inhibits CCL18-induced acidification in THP-1 monocytes and suppresses RANTES- and CCL18-induced chemotaxis in peripheral blood mononuclear cells (PBMCs).

NHI-2 is a lactate dehydrogenase A (LDHA) inhibitor with an IC50 value of 14.7 µM, demonstrating high selectivity for LDHA over LDHB, for which the IC50 is 55.8 µM. NHI-2 functions as an efficient anti-glycolytic agent, enhancing apoptosis, inducing cell cycle arrest at the S and G2 phases, and exerting broad-spectrum antiproliferative effects in cancer cells. NHI-2 additionally affects extracellular acidification rates and ATP production and has demonstrated tumor growth suppression in murine B78 melanoma models, highlighting its role in cancer metabolism research.

Concanamycin B is a macrolide antibiotic that selectively inhibits vacuolar type H+-ATPases (IC50 = 5 nM), thereby blocking vacuolar organelle acidification and early to late endosomal transport. It interferes with bone resorption, maturation of CD8 T lymphocytes, and prevents processing of major histocompatibility complex (MHC) class II precursors in human B cells, inhibiting MHC class II molecule expression on the cell surface.

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

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

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.

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

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].

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.

Concanamycin E is an inhibitor of lysosomal acidification with an IC50 value of 0.085 nM.

Concanamycin D is an inhibitor of lysosomal acidification with an IC50 value of 0.085 nM.

H-Ala-Ala-OH (L-Alanyl-L-alanine) is a dipeptide compound that can be absorbed by Caco-2 cells and induce cytoplasmic acidification, serving as a model for studying peptide conformational changes.

P9R is an antiviral peptide with broad-spectrum activity against coronaviruses (SARS-CoV-2, MERS-CoV, and SARS-CoV), influenza A H1N1 virus (A(H1N1)pdm09), influenza A H7N9 virus (A(H7N9) virus), and rhinovirus. It binds directly to viruses and inhibits virus-host endosomal acidification. P9R significantly protects mice from infection by influenza A H1N1 virus (A(H1N1)pdm09) without leading to resistant viruses. P9R is applicable in studying pH-dependent respiratory viruses.