4-ph a-1

Pepsin is an endopeptidase that breaks down proteins into smaller peptides and amino acids that can be easily absorbed in the small intestine[1]. Pepsin is stable at pH ranges as high as pH 6. Above this pH, pepsin is rapidly irreversibly inactivated and elevation of pH of the reaction mixture to pH 8 results in complete inactivation of pepsin[2]. Pepsin has been posited to be a reliable biological marker of EER. An immunologic pepsin assay of combined sputum and saliva was determined to be 100% sensitive and 89% specific for detection of EER (based on pH-metry), and an enzymatic test of nasal lavage fluid (100% sensitivity and 92.5% specificity) demonstrated an increased incidence of EER in patients with chronic rhinosinusitis[3]. Cultured hypopharyngeal epithelial (FaDu) cells were exposed to human pepsin (0.1 mg mL) at pH 7.4 for either 1 hour or 12 hours at 37°C and both mitochondria and Golgi complexes were clearly damaged. This finding reveals a novel mechanism by which pepsin could cause cell damage, potentially even in nonacidic refluxate[4].

Ald-Ph-amido-PEG4-propargyl is a non-cleavable 4-unit polyethylene glycol (PEG) antibody-drug conjugate (ADC) linker employed in ADC synthesis[1].

AAPH is a water-soluble azo compound which is used extensively as a free radical generator, often in the study of lipid peroxidation and the characterization of antioxidants.[1],[2],[3],[4] Decomposition of AAPH produces molecular nitrogen and 2 carbon radicals. The carbon radicals may combine to produce stable products or react with molecular oxygen to give peroxyl radicals. The half-life of AAPH is about 175 hours (37°C at neutral pH), making the rate of free radical generation essentially constant during the first several hours in solution.[5] While AAPH may be used effectively for lipid peroxidation in aqueous dispersions of fatty acids, other radical generators may be better suited for peroxidation studies in lipid micelles or membranes.[6],[7]

CAY10761 is an inhibitor of ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1; IC50s = 467 and 429 μM for the human and snake venom enzymes, respectively).1,2 It also inhibits mushroom tyrosinase (Ki = 1.9 μM) and urease from jack bean, P. mirabilis, and B. pasteurii (IC50s = 0.093, <0.125, and 0.089 mM, respectively, at pH 8.2).3,4 |1. Khan, K.M., Fatima, N., Rasheed, M., et al. 1,3,4-Oxadiazole-2(3H)-thione and its analogues: A new class of non-competitive nucleotide pyrophosphatases phosphodiesterases 1 inhibitors. Bioorg. Med. Chem. 17(22), 7816-7822 (2009).|2. Onyedibe, K.I., Wang, M., and Sintim, H.O. ENPP1, an old enzyme with new functions, and small molecule inhibitors - A STING in the tale of ENPP1. Molecules 24(22), E4192 (2019).|3. Ghani, U., and Ullah, N. New potent inhibitors of tyrosinase: Novel clues to binding of 1,3,4-thiadiazole-2(3H)-thiones, 1,3,4-oxadiazole-2(3H)-thiones, 4-amino-1,2,4-triazole-5(4H)-thiones, and substituted hydrazides to the dicopper active site. Bioorg. Med. Chem. 18(11), 4042-4048 (2010).|4. Amtul, Z., Rasheed, M., Choudhary, M.I., et al. Kinetics of novel competitive inhibitors of urease enzymes by a focused library of oxadiazoles thiadiazoles and triazoles. Biochem. Biophys. Res. Commun. 319(3), 1053-1063 (2004).

Olsalazine-13C6is intended for use as an internal standard for the quantification of olsalazine by GC- or LC-MS. Olsalazine is an orally bioavailable prodrug form of the anti-inflammatory agent 5-aminosalicylic acid that is cleaved by bacterial azo reductases in the gut to generate active 5-ASA.1In vitro, olsalazine increases ion transport in isolated rabbit distal ileum when applied to the luminal side (ED50= 0.3 mM) and stimulates fluid transport in rat jejunum when used at a concentration of 5 mM.2,3Olsalazine (150 mg/kg for 8 days) improves stool consistency and decreases occult and gross bleeding as well as myeloperoxidase (MPO) activity and leukotriene B4levels in colon tissue in a mouse model of acute colitis induced by dextran sulfate .4Olsalazine also inhibits bovine xanthine oxidasein vitro(IC50= 3.4 mg/L) and lowers serum uric acid levels in a mouse model of hyperuricemia induced by oxonic acid when administered at a dose of 20 mg/kg.5Formulations containing olsalazine have been used in the treatment of inflammatory bowel disease (IBD) and ulcerative colitis. 1.Nugent, S.G., Kumar, D., Rampton, D.S., et al.Intestinal luminal pH in inflammatory bowel disease: Possible determinants and implications for therapy with aminosalicylates and other drugsGut48(4)571-577(2001) 2.Pamukcu, R., Hanauer, S.B., and Chang, E.B.Effect of disodium azodisalicylate on electrolyte transport in rabbit ileum and colon in vitro. Comparison with sulfasalazine and 5-aminosalicylic acidGastroenterology95(4)975-981(1988) 3.Mohsen, A.Q.M., Mulvey, D., Priddle, J.D., et al.Effects of olsalazine in the jejunum of the ratGut28(3)346-352(1987) 4.Murthy, S., Murthy, N.S., Coppola, D., et al.The efficacy of BAY y 1015 in dextran sulfate model of mouse colitisInflamm. Res.46(6)224-233(1997) 5.Niu, Y., Li, H., Gao, L., et al.Old drug, new indication: Olsalazine sodium reduced serum uric acid levels in mice via inhibiting xanthine oxidoreductase activityJ. Pharmacol. Sci.135(3)114-120(2017)