degradation product

Orlistat degradation product is a degradation product of the digestive lipase inhibitor orlistat . It is formed via hydrolytic and thermal degradation as well as digestion by human carboxyl ester lipase.

Bis(p-chlorophenyl)acetic acid is a standard for pesticide residue analysis.

N4-Acetylcytidine (N-Acetylcytidine) is a modified nucleoside. N4-acetylcytidine is an endogenous urinary nucleoside product of the degradation of transfer ribonucleic acid (tRNA); urinary nucleosides are biological markers for patients with colorectal cancer.

3-hydroxybutyric acid is involved in the synthesis and degradation of ketone bodies. Like the other ketone bodies (acetoacetate and acetone), levels of beta-hydroxybutyrate are raised in the blood and urine in ketosis. Beta-hydroxybutyrate is a typical pa

Indole has a bicyclic structure, consisting of a six-membered benzene ring fused to a five-membered nitrogen-containing pyrrole ring. It can be produced by bacteria as a degradation product of the amino acid tryptophan. It occurs naturally in human feces and has an intense fecal smell. At very low concentrations, however, it has a flowery smell, and is a constituent of many flower scents (such as orange blossoms) and perfumes.

Penicillamine (Artamine), possessing antineoplastic properties, induces apoptosis by a p53-mediated mechanism and inhibits angiogenesis by chelating with copper, a cofactor for angiogenesis. Artamine is a beta dimethyl analog of the amino acid cysteine. As a degradation product of penicillin antibiotics, Artamine chelates with heavy metals and increases their urinary excretion.

DP-1 hydrochloride is a degradation product of SDC-TRAP-0063, a fragment of Ganetespib, a heat shock protein 90 (HSP90) inhibitor with antitumor activity.

Erythromycin A enol ether is a degradation product of Erythromycin A which is a macrolide antibiotic.

Xanthine (Isoxanthine) is a product on the pathway of purine degradation. Xanthine is subsequently converted to uric acid by the action of the Xanthine oxidase enzyme. Xanthine is found in most body tissues and fluids in various organisms. Biologically Xanthine is produced from guanine by cypin (guanine deaminase). Furthermore, Xanthines act as antagonists for adenosine receptors, with selectivity depending on whether there are substitution of alkyl groups.

N6-Methyladenosine is a methylated adenine residue, glycoside is an endogenous uridine product of transfer RNA degradation. It is the most prevalent internal modification of messenger RNA present in all higher eukaryotes and can modify viral RNA with antiviral activity.

Lysyllysine is a dipeptide composed of two lysine residues. It is an incomplete breakdown product of protein digestion or protein catabolism. Some dipeptides are known to have physiological or cell-signaling effects although most are simply short-lived in

Dihydroxy melphalan is an inactive degradation product of melphalan . It is formed by the hydrolysis of melphalan via the intermediate monohydroxy melphalan in aqueous solutions, including cell culture medium and human plasma.

Ketoisophorone (2,6,6-Trimethyl-2-cyclohexene-1,4-dione) is the major ingredients of saffron spice. It is a cyclic olefin and was reported as a product of the thermal degradation of β-carotene in aqueous suspension.

p,p'-DDE (p,p'-dichlorodiphenyldichloroethylene) is a metabolite and degradation product of the organochlorine pesticide DDT

Olanzapine lactam impurity is a potential impurity found in commercial preparations of olanzapine.1It is a degradation product formed by exposure to thermal or oxidative stress. 1.Baertschi, S.W., Brunner, H., Bunnell, C.A., et al.Isolation, identification, and synthesis of two oxidative degradation products of olanzapine (LY170053) in solid oral formulationsJ. Pharm. Sci.97(2)883-892(2008)

Palonosetron N-oxide is a metabolite of the serotonin (5-HT) receptor subtype 5-HT3antagonist palonosetron .1It is also a potential impurity in palonosetron preparations.2Palonosetron N-oxide is a degradation product formed by exposure to oxidative stress. 1.Stoltz, R.A., Cyong, J.-C., Shah, A., et al.Pharmacokinetic and safety evaluation of palonosetron, a 5-hydroxytryptamine-3 receptor antagonist, in U.S. and Japanese healthy subjectsJ. Clin. Pharmacol.44(5)520-531(2004) 2.Vishnu Murthy, M., Srinivas, K., Kumar, R., et al.Development and validation of a stability-indicating LC method for determining palonosetron hydrochloride, its related compounds and degradation products using naphthalethyl stationary phaseJ. Pharm. Biomed. Anal.56(2)429-435(2011)

Doramectin aglycone is an acid degradation product of doramectin , a disaccharide-containing anthelmintic that potentiates glutamate- and GABA-gated chloride channel opening in nematodes, and its acid-catalyzed hydrolysis product doramectin monosaccharide . Doramectin undergoes one round of acid-catalyzed hydrolysis to form doramectin monosaccharide which is then hydrolyzed again to remove the remaining saccharide unit and form doramectin aglycone.

Phenylalanylglutamate is a dipeptide composed of phenylalanine and glutamate. It is an incomplete breakdown product of protein digestion or protein catabolism. Some dipeptides are known to have physiological or cell-signaling effects although most are sim

Lactenocin is a active degradation product.

β-Apooxytetracycline is a potential impurity found in commercial preparations of oxytetracycline. β-Apooxytetracycline is a degradation product formed from oxytetracycline via acid hydrolysis. It has a relative potency of 0.1 compared with oxytetracycline for inhibiting the growth of aerobic sludge bacteria, an MIC50 value of 32 mg/L for tetracycline-sensitive strains of Pseudomonas, and MIC50 values of greater than 32 mg/L for tetracycline-sensitive strains of Agrobacterium, Moraxella, and Bacillus, as well as tetracycline-resistant strains of E. coli. β-Apooxytetracycline (10 mg/kg) is toxic to rats, decreasing body weight, disrupting blood cell counts, and inducing hepatocyte necrosis.

O-Demethyl apremilast is an active metabolite of the phosphodiesterase 4 (PDE4) inhibitor apremilast .1It inhibits the activity of PDE4 isolated from U937 cells and LPS-induced TNF-α production in isolated human peripheral blood mononuclear cells (PBMCs; IC50s = 8.3 and 5.6 μM, respectively). O-Demethyl apremilast is also an oxidative degradation product of apremilast.2,3 1.Hoffmann, M., Kumar, G., Schafer, P., et al.Disposition, metabolism and mass balance of [14C]apremilast following oral administrationXenobiotica41(12)1063-1075(2011) 2.Lu, Y., Shen, X., Hang, T., et al.Identification and characterization of process-related substances and degradation products in apremilast: Process optimization and degradation pathway elucidationJ. Pharm. Biomed. Anal.14170-78(2017) 3.Bhole, R.P., Naksakhare, S.R., and Bonde, C.G.A stability indicating HPTLC method for apremilast and identification of degradation products using MS/MSJ. Pharm. Sci. & Res.11(5)1861-1869(2019)

Lysylcysteine is a dipeptide composed of lysine and cysteine. It is an incomplete breakdown product of protein digestion or protein catabolism. Some dipeptides are known to have physiological or cell-signaling effects although most are simply short-lived

Epianhydrotetracycline (EATC) is a degradation product of the antibiotic tetracycline .1 EATC is active against Pseudomonas, Agrobacterium, Moraxella, Bacillus, and E. coli (MIC50s = 0.75-16 mg/L).

Desethylene ciprofloxacin is a major metabolite of ciprofloxacin . It is also a degradation product of ciprofloxacin that can be created through advanced oxygenation processes as a potential way to remove ciprofloxacin from wastewater. It is also created during degradation of ciprofloxacin by chlorination.

(S)-nitro-Blebbistatin is a more stable form of (-)-blebbistatin , which is a selective cell-permeable inhibitor of non-muscle myosin II ATPases. (-)-Blebbistatin rapidly and reversibly inhibits Mg-ATPase activity and in vitro motility of non-muscle myosin IIA and IIB for several species (IC50s = 0.5-5 μM), while poorly inhibiting smooth muscle myosin (IC50 = 80 μM). Through these effects, it blocks apoptosis-related bleb formation, directed cell migration, and cytokinesis in vertebrate cells. However, prolonged exposure to blue light (450-490 nm) results in degradation of blebbistatin to an inactive product via cytotoxic intermediates, which may be problematic for its use in fluorescent live cell imaging applications. The addition of a nitro group stabilizes the molecule to circumvent its degradation by prolonged blue light exposure. (S)-nitro-Blebbistatin has the same stereochemistry as the active (-)-blebbistatin enantiomer.

Levofloxacin N-oxide is an inactive metabolite of the antibiotic levofloxacin . Levofloxacin N-oxide is also a degradation product of levofloxacin that is formed through exposure to daylight or hydrogen peroxide.

Doramectin monosaccharide is an acid degradation product of doramectin , a disaccharide-containing anthelmintic that potentiates glutamate- and GABA-gated chloride channel opening in nematodes. Doramectin undergoes acid-catalyzed hydrolysis to form doramectin monosaccharide.

Ivermectin B1a aglycone is an acid degradation product produced by hydrolysis of the disaccharide unit of ivermectin. It can inhibit nematode larval development, but does not cause paralytic activity.

para-amino-Blebbistatin is a more water-soluble form of (S)-4'-nitro-blebbistatin , which is a more stable and less phototoxic form of (-)-blebbistatin .1,2,3 (-)-Blebbistatin is a selective cell-permeable inhibitor of non-muscle myosin II ATPases that rapidly and reversibly inhibits Mg-ATPase activity and in vitro motility of non-muscle myosin IIA and IIB for several species (IC50s = 0.5-5 μM), while poorly inhibiting smooth muscle myosin (IC50 = 80 μM).2,3,4 Through these effects, it blocks apoptosis-related bleb formation, directed cell migration, and cytokinesis in vertebrate cells. However, prolonged exposure to blue light (450-490 nm) results in degradation of blebbistatin to an inactive product via cytotoxic intermediates, which may be problematic for its use in fluorescent live cell imaging applications.5,6 The addition of a 4'-amino group increases its water solubility, decreases the inherent fluorescence, stabilizes the molecule to circumvent its degradation by prolonged blue light exposure, and decreases its phototoxicity while retaining the in vitro and in vivo activity of blebbistatin.7 para-amino-Blebbistatin has the same stereochemistry as the active (-)-blebbistatin enantiomer. |1. Várkuti, B.H., Képiró, M., Horváth, I.á., et al. A highly soluble, non-phototoxic, non-fluorescent blebbistatin derivative. Sci. Rep. 6:26141, (2016).|2. Straight, A.F., Cheung, A., Limouze, J., et al. Dissecting temporal and spatial control of cytokinesis with a myosin II inhibitor. Science 299(5613), 1743-1747 (2003).|3. Kovács, M., Tóth, J., Hetényi, C., et al. Mechanism of blebbistatin inhibition of myosin II. J. Biol. Chem. 279(34), 35557-35563 (2004).|4. Limouze, J., Straight, A.F., Mitchison, T., et al. Specificity of blebbistatin, an inhibitor of myosin II. J. Muscle Res. Cell Motil. 25(4-5), 337-341 (2004).|5. Kolega, J. Phototoxicity and photoinactivation of blebbistatin in UV and visible light. Biochem. Biophys. Res. Commun. 320(3), 1020-1025 (2004).|6. Sakamoto, T., Limouze, J., Combs, C.A., et al. Blebbistatin, a myosin II inhibitor, is photoinactivated by blue light. Biochemistry 44(2), 584-588 (2005).|7. Verhasselt, S., Roman, B.I., Bracke, M.E., et al. Improved synthesis and comparative analysis of the tool properties of new and existing D-ring modified (S)-blebbistatin analogs. Eur. J. Med. Chem. 136, 85-103 (2017).

N-Methylhydantoin (1-Methyl-hydantoin) is a small molecular weight polar substance, the product of degradation of creatinine by bacteria. In mammals, the Metabolism of N-Methylhydantoin occurs via 5-hydroxy-1-methylhydantoin. In a reported human case,N-Methylhydantoin was found as an unexpected metabolite of the intelligence-affecting substance dupracetam.

(3R,5R)-Rosuvastatin, a potential impurity detected in bulk rosuvastatin formulations, arises as a degradation product through various stresses including acid or base hydrolysis, thermal, photolytic, hydrolytic, oxidative stress, or during storage. This compound is associated with the HMG-CoA reductase inhibitor class to which rosuvastatin belongs.

Desvaleryl valsartan is a potential impurity found in commercial preparations of the angiotensin II type 1 (AT1) receptor antagonist valsartan. It is a degradation product formed under acidic conditions.

Karacolinem is a natural product, reduces degradation of the extracellular matrix (ECM) in intervertebral disc degeneration (IDD) via the NF-κB signaling pathway.

Monohydroxy melphalan is a DNA alkylating agent and a degradation product of melphalan . Monohydroxy melphalan is formed by the hydrolysis of melphalan in aqueous solutions, including cell culture medium and human plasma. It increases the level of DNA adducts in ML-1 myeloblastic leukemia cells in a concentration-dependent manner and induces cytotoxicity with an IC50 value of 28.1 μg/ml.

Tyroserleutide hydrochloride is a small molecule tripeptide isolated from the degradation product of pig spleen, which can inhibit tumor growth in vivo and in vitro.

N-Nitrosoglyphosate sodium, a nitrosamine degradation product and synthetic impurity of glyphosate herbicide [1], is a chemical compound resulting from the breakdown or contamination of glyphosate, a widely used herbicide.

LH-RH (7-10), a tetrapeptide, constitutes a principal degradation product of luteinizing-hormone releasing hormone (LHRH) through the action of the pituitary and hypothalamus. This compound is synthesized in macrophages, as well as type I-like and type II pneumocytes [3].

DL-Penicillamine (3-Sulfanylvaline) is a chelating agent recommended for the removal of excess copper in patients with Wilson's disease. DL-Penicillamine is only found in individuals that have used or taken this drug. It is the most characteristic degradation product of the penicillin antibiotics. It is used as an antirheumatic and as a chelating agent in Wilson's disease. From in vitro studies which indicate that one atom of copper combines with two molecules of DL-penicillamine. DL-Penicillamine also reduces excess cystine excretion in cystinuria. This is done, at least in part, by disulfide interchange between DL-penicillamine and cystine, resulting in the formation of penicillamine-cysteine disulfide, a substance that is much more soluble than cysteine and is excreted readily. DL-Penicillamine interferes with the formation of cross-links between tropocollagen molecules and cleaves them when newly formed. The mechanism of action of DL-penicillamine in rheumatoid arthritis is unknown although it appears to suppress disease activity. Unlike cytotoxic immunosuppressants, DL-penicillamine markedly lowers IgM rheumatoid factor but produces no significant depression in absolute levels of serum immunoglobulins. Also unlike cytotoxic immunosuppressants which act on both, DL-penicillamine in vitro depresses T-cell activity but not B-cell activity.

Isocyclosporin A is a rearranged degradation product. It is formed by acid treatment of cyclosporin A under aqueous and non-aqueous conditions.

5-aminovalerate (or 5-aminopentanoic acid) is a lysine degradation product. It can be produced both endogenously or through bacterial catabolism of lysine. 5-aminovalerate is formed via the following multi-step reaction: L-lysine leads to cadverine leads

Opc 15161 is a degradation product of OPC-15160 and superoxide inhibitor.

Rizatriptan N-oxide is a potential impurity found in commercial preparations of rizatriptan.1It is a degradation product formed under oxidative conditions.

Dehydro amlodipine is a potential impurity found in commercial preparations of amlodipine. It is a degradation product formed during storage or when amlodipine is subjected to oxidative or acidic conditions or undergoes photo or electrochemical degradation.

Ochratoxin α is a less toxic photolytic and thermal degradation product of Ochratoxin A.

4-Chlorocatechol, a significant degradation product of 4-chloro-2-aminophenol (4C2AP), serves as a substrate for both catechol 1,2-dioxygenases and chlorocatechol dioxygenase [1] [2].

(R)-nitro-Blebbistatin is a more stable form of (+)-blebbistatin , which is the inactive form of (-)-blebbistatin . Prolonged exposure to blue light (450-490 nm) results in degradation of blebbistatin to an inactive product via cytotoxic intermediates, which may be problematic for its use in fluorescent live cell imaging applications. The addition of a nitro group stabilizes the molecule to circumvent its degradation by prolonged blue light exposure. (R)-nitro-Blebbistatin has the same stereochemistry as the inactive (+)-blebbistatin enantiomer.

Descarbamoyl cefuroxime is also an intermediate in the synthesis of cephalosporin antibiotics. Decarbamyl cefuroxime is a degradation product of cefuroxime.

Lansoprazole N-oxide is a potential impurity in lansoprazole bulk preparations, identified as a degradation product under acidic or basic conditions. This compound is related to lansoprazole, a proton pump inhibitor.

Monohydroxy melphalan, a degradation product and DNA alkylating agent derived from melphalan, results from melphalan hydrolysis in aqueous solutions such as cell culture medium and human plasma. It enhances DNA adducts in ML-1 myeloblastic leukemia cells based on concentration and induces cytotoxicity with an IC50 value of 28.1 μg/ml.

3-Amino-2-methylpropanoic acid (α-Methyl-β-alanine) is the product from the conversion of N-carbamyl-beta-aminoisobutyric acid by the enzyme Beta-ureidopropionase (EC 3.5.1.6), the last step in pyrimidine degradation. Beta-ureidopropionase deficiency is an inborn error of pyrimidine degradation associated with neurological abnormalities.