neonatal

Bumetanide (PF 1593) is a potent sulfamoylanthranilic acid derivative belonging to the class of loop diuretics. In the brain, bumetanide may prevent seizures in neonates by blocking the bumetanide-sensitive sodium-potassium-chloride cotransporter (NKCC1), thereby inhibiting chloride uptake thus, decreasing the internal chloride concentration in neurons and may block the excitatory effect of GABA in neonates.

L-Albizziin (2-Methoxyidazoxan monohydrochloride) is a highly potent selective antagonist of the alpha 2r adrenergic receptor, with little or no antagonistic effect on imidazoline. It has a significantly higher affinity for the alpha 2D adrenergic receptor (pKd9.7) in guinea pigs than for the alpha 2A adrenergic receptor (pKd8.2) in rabbits.

FUREGRELATE, a thromboxane A2 (TxA2) synthase inhibitor, blunts the development of pulmonary arterial hypertension in neonatal piglets.

(R)-3,4-DCPG HCl is a potent and selective mGlu8a receptor agonist that activates metabotropic glutamate receptors on primary afferent terminals in the neonatal rat spinal cord.

Rocepafant (LAU8080) is a platelet-activating factor (PAF) antagonist that attenuates hypoxic-ischemic brain damage in neonatal rats.Rocepafant inhibits tumor necrosis factor-Afa-mediated cytotoxicity in mouse L929 tumor cells.

Oxodipine, a dihydropyridine-type calcium antagonist, inhibited KCl-induced aortic contraction in rabbits and reduced cardiac force in less potent rat ventricular test-paper contractions. In rat cultured neonatal ventricular myocytes, Oxodipine reduced L-type Ca currents (I) with an IC of 0.24 μM, and against T-type Ca currents (I) with an IC of 0.41 μM. Oxodipine causes constipation in mice and gingival hyperplasia in dogs.

L-Pipecolic acid (L-Homoproline) is a breakdown product of lysine, accumulates in body fluids of infants with generalized genetic peroxisomal disorders, such as Zellweger syndrome, neonatal adrenoleukodystrophy.

Tridecanedioic acid (Brassilic acid) is an unusual odd-numbered dicarboxylic acid that appears in the urines of children with neonatal adrenoleukodystrophy and Zellweger syndrome, as an additional marker of these peroxisomal disorders.

Reverse T3 (3,3',5'-triiodo-L-thyronine) inhibits the increase of sodium current generated by other thyroid hormone analogs in neonatal rat myocytes.

Temocapril is an inhibitor of tyrosine kinase.

Galactose is a monosaccharide and hexose sugar widely present in most living cells, primarily absorbed into the bloodstream via SGLT1 and GLUT2 transporters and metabolised through the Leloir pathway. It inhibits alglucerase activity in monkey kidney CoS-1 cells, is a key component of cellular glycosylation, and plays a crucial role in neonatal neural development.

BMS-470539 dihydrochloride is a selective and highly potent melanocortin 1 receptor (MC-1 R) agonist with anti-inflammatory activity. BMS-470539 attenuates oxidative stress and neuronal apoptosis via the MC1R/cAMP/PKA/Nurr1 signaling pathway in a neonatal hypoxia-ischemia rat model.

ZP3022 is a dual agonist targeting the glucagon-like peptide 1 receptor (GLP-1R) and cholecystokinin 2 (CCK2) receptor. It selectively enhances cAMP accumulation or ERK phosphorylation in HEK293 cells with GLP-1R or CCK2 receptor expression, compared to ERK phosphorylation in cells with the CCK1 receptor (EC50s: 0.02, 10.3, and >1,000 nM for human receptors, respectively). At 40 nM, ZP3022 promotes proliferation of rat neonatal β-cells in vitro. It also boosts glucose-induced insulin secretion (GSIS) in rat pancreatic islets at 10 and 100 nM concentrations and decreases body weight in rats at 40 nmol/kg doses twice daily. Administered at 100 nmol/kg daily, ZP3022 enhances β-cell and total pancreatic mass and improves glucose tolerance in db/db mice, while reducing food intake but not body weight in these mice.

CGP 35348 is a selective antagonist of GABAB receptor (EC50 = 34 μM). CGP 35348 can be used in studies of neuromuscular coordination and spatial learning after neonatal brain damage in albino mice.

ADR-925, an active chelated iron metabolite of dexrazoxane, has the ability to protect neonatal rat cardiomyocytes from doxorubicin-induced injury.

Biliatresone, an environmental toxin isolated from the coccolithophores Dysphania glomulifera and D. littoralis, induced C57BL/6J neonatal cholangiopathy, induced a decrease in glutathione (GSH) levels, induced a significant decrease in SOX17 cholangiocyte levels, and induced extrahepatic cholangiocyte damage and fibrosis in mice.

Nitisinone-13C6is intended for use as an internal standard for the quantification of nitisinone by GC- or LC-MS. Nitisinone is an inhibitor of 4-hydroxyphenylpyruvate dioxygenase (HPPD), which converts 4-hydroxyphenylpyruvate (HPPA) to homogentisate in the tyrosine catabolic pathway.1Nitisinone increases urinary levels of HPPA and 4-hydroxyphenyllactate (HPLA) in rats when administered at a dose of 10 mg/kg. Nitisinone (3 mg/kg) prevents the neonatal lethality of fumarylacetoacetate hydrolase (FAH) deficiency in mice when administered to pregnant dams.2It exhibits hepatoprotective effects inFAH-/-mice, such as prevention of increases in plasma levels of aspartate serine aminotransferase (AST) and conjugated bilirubin, when administration is continued following birth at a dose of 1 mg/kg. Nitisinone (100 μg) decreases urinary excretion of homogentisate and increases urinary excretion of HPPA, HPLA, and 4-hydroxyphenylacetate in a mouse model of alkaptonuria induced by ethylnitrosourea.3Formulations containing nitisinone have been used in the treatment of hereditary tyrosinemia type 1 (HT-1). 1.Ellis, M.K., Whitfield, A.C., Gowans, L.A., et al.Inhibition of 4-hydroxyphenylpyruvate dioxygenase by 2-(2-nitro-4-trifluoromethylbenzoyl)-cyclohexane-1,3-dione and 2-(2-chloro-4-methanesulfonylbenzoyl)-cyclohexane-1,3-dioneToxicol. Appl. Pharmacol.133(1)12-19(1995) 2.Grompe, M., Lindstedt, S., al-Dhalimy, M., et al.Pharmacological correction of neonatal lethal hepatic dysfunction in a murine model of hereditary tyrosinaemia type INat. Genet.10(4)453-460(1995) 3.Suzuki, Y., Oda, K., Yoshikawa, Y., et al.A novel therapeutic trial of homogentisic aciduria in a murine model of alkaptonuriaJ. Hum. Genet.44(2)79-84(1999)

17R(18S)-EpETE is an oxylipin and a cytochrome P450 metabolite of eicosapentaenoic acid .1,217R(18S)-EpETE is an activator of large-conductance calcium-activated potassium (BKCa) channels, increasing the potassium current amplitude by 15-fold in isolated rat cerebral artery vascular smooth muscle cells (VSMCs) at +60 mV when used at a concentration of 50 nM.2It has negative chronotropic effects in isolated neonatal rat cardiomyocytes (NRCMs; EC50= ~1-2 nM) and prevents calcium-induced increases in the spontaneous beating of NRCMs.3,4 1.Schwarz, D., Kisselev, P., Ericksen, S.S., et al.Arachidonic and eicosapentaenoic acid metabolism by human CYP1A1: Highly steroselective formation of 17(R), 18(S)-epoxyeicosatetraenoic acidBiochem. Pharmacol.67(8)1445-1457(2004) 2.Lauterbach, B., Barbosa-Sicard, E., Wang, M.H., et al.Cytochrome P450-dependent eicosapentaenoic acid metabolites are novel BK channel activatorsHypertension39(2 Pt. 2)609-613(2002) 3.Falck, J.R., Wallukat, G., Puli, N., et al.17(R),18(S)-Epoxyeicosatetraenoic acid, a potent eicosapentaenoic acid (EPA) derived regulator of cardiomyocyte contraction: Structure-activity relationships and stable analoguesJ. Med. Chem.54(12)4109-4118(2011) 4.Arnold, C., Markovic, M., Blossey, K., et al.Arachidonic acid-metabolizing cytochrome P450 enzymes are targets of omega-3 fatty acidsJ. Biol. Chem.285(43)32720-32733(2010)

19R(20S)-EpDPA is an oxylipin and a metabolite of docosahexaenoic acid .1,2It is formed from DHA by various cytochrome P450 (CYP) isoforms in a stereoselective manner.219R(20S)-EpDPA (30 nM) prevents calcium-induced increases in the spontaneous beating of isolated neonatal rat cardiomyocytes (NRCMs).3 1.Cinelli, M.A., Yang, J., Scharmen, A., et al.Enzymatic synthesis and chemical inversion provide both enantiomers of bioactive epoxydocosapentaenoic acidsJ. Lipid Res.59(11)2237-2252(2018) 2.Lucas, D., Goulitquer, S., Marienhagen, J., et al.Stereoselective epoxidation of the last double bond of polyunsaturated fatty acids by human cytochromes P450J. Lipid Res.51(5)1125-1133(2010) 3.Burke, J.E., and Dennis, E.A.Phospholipase A2 structure/function, mechanism, and signalingJ. Lipid Res.50(Suppl)S237-S242(2009)

Burnettramic acid A is a fungal metabolite originally isolated fromA. burnettiithat has diverse biological activities.1It is active againstB. subtilis,S. aureus,C. albicans, andS. cerevisiae(IC50s = 2.3, 5.9, 0.5, and 0.2 μg ml, respectively). Burnettramic acid A is cytotoxic to NS-1 murine myeloma cells but not neonatal foreskin fibroblasts (IC50s = 13.8 and >100 μg ml, respectively). 1.Li, H., Gilchrist, C.L.M., Lacey, H.J., et al.Discovery and heterologous biosynthesis of the burnettramic acids: Rare PKS-NRPS-derived bolaamphiphilic pyrrolizidinediones from an Australian fungus, Aspergillus burnettiiOrg. Lett.21(5)1287-1291(2019)

Burnettramic acid A aglycone is a fungal metabolite and an aglycone form of burnettramic acid A, originally isolated from [A. burnettii], that exhibits anticancer activity. It is cytotoxic to NS-1 murine myeloma cells (IC50 = 8.4 μg ml) but not to neonatal foreskin fibroblasts (IC50 > 100 μg ml).

O-Desmethyl-N-deschlorobenzoyl indomethacin is a metabolite of the non-steroidal anti-inflammatory drug (NSAID) and COX inhibitor indomethacin, formed from indomethacin in isolated rabbit hepatocytes. O-Desmethyl-N-deschlorobenzoyl indomethacin (600 μM) decreases the viability of HL-60 leukemia cells when cultured with glucose oxidase. It has also been used in the synthesis of prostaglandin D2 receptor antagonists.

5-hydroxy Indomethacin is a metabolite of indomethacin .1It is formed from indomethacin in rabbit hepatic microsomes. 1.Evans, M.A., Papazafiratou, C., Bhat, R., et al.Indomethacin metabolism in isolated neonatal and fetal rabbit hepatocytesPediatr. Res.15(11)1406-1410(1981)

DPC-AJ1951 is a peptide agonist of the parathyroid hormone (PTH)/PTH-related peptide receptor (PPR; EC50 = 0.15 nM in HEK293 cells expressing human PPR). It induces cAMP production in SAOS-2 and UMR106 cells that endogenously express human and rat PPR, respectively (EC50s = 2.2 and 1.1 nM, respectively). DPC-AJ1915 stimulates osteoclast-mediated bone resorption in fetal rat long-bone explant cultures and increases collagen synthesis and cell proliferation in neonatal mouse parietal bone explants. In vivo, DPC-AJ1951 normalizes serum calcium levels in thyroidparathyroidectomized rats.