n-type

N-type calcium channel blocker-1 is an orally active analgesic agent with a high affinity for functionally blocking N-type calcium channels.

D-(+)-Xylose (Wood sugar) is an aldopentose - a monosaccharide containing five carbon atoms and an aldehyde functional group. It has chemical formula C5H10O5 and is 40% as sweet as sucrose. Xylose is also found in mucopolysaccharides of connective tissue and sometimes in the urine. Xylose is the first sugar added to serine or threonine residues during proteoglycan type O-glycosylation. Therefore xylose is involved in the biosythetic pathways of most anionic polysaccharides such as heparan sulphate and chondroitin sulphate. In medicine, xylose is used to test for malabsorption by administering a xylose solution to the patient after fasting. If xylose is detected in the blood and/or urine within the next few hours, it has been absorbed by the intestines. Xylose is said to be one of eight sugars which are essential for human nutrition, the others being galactose, glucose, mannose, N-acetylglucosamine, N-acetylgalactosamine, fucose, and sialic acid. . Xylose in the urine is a biomarker for the consumption of apples and other fruits.

Pyrrole-2-carboxylic acid (Minaline) was first identified as a degradation product of sialic acids, then as a derivative of the oxidation of the D-hydroxyproline isomers by mammalian D-amino acid oxidase. The latter relationship results from the lability of the direct oxidation product, A'-pyrroline-4-hydroxy-2-carboxylic acid, which loses water spontaneously to form the pyrrole. A similar reaction is catalyzed by the more specific allohydroxy-D-proline oxidase of Pseudomonas. In whole animal observations, pyrrole-2-carboxylate (PCA) ' was identified in rat or human urine after administration of the D-isomers of hydroxyproline, a finding ascribable to the action of D-amino acid oxidase. Urinary excretion of N-(pyrrole-2-carboxyl) glycine has been reported in a 5-year-old affected with type II hyperprolinemia; The child has mild developmental delay, recurrent seizures of the grand mal type and EEG alterations.

Cilnidipine (FRC-8653)(FRC8653) is a dual L- and N-type calcium channel blocker and displays antihypertensive, sympatholytic and neuroprotective activity.

Sarcosine (Methylglycine) is a competitive inhibitor of the type I glycine transporter (GlyT1) and an N-methyl-D-aspartate receptor (NMDAR) co-agonist.

N-Acetyl-L-glutamic acid (Ac-L-Glu-OH) (NAcGlu) is an acetylated amino acid. NAcGlu is biosynthesized from glutamic acid and acetyl-CoA by the enzyme N-acetyl glutamate synthase (NAGS). NAcGlu activates carbamoyl phosphate synthetase in the urea cycle. A deficiency in N-acetyl glutamate synthase or a genetic mutation in the gene coding for the enzyme will lead to urea cycle failure in which ammonia is not converted to urea, but rather accumulated in the blood leading to the condition called Type I hyperammonemia.

N-Desmethyl Sildenafil is the major metabolite of Sildenafil, a potent phosphodiesterase type 5 (PDE5) inhibitor.

N,N'-Diacetyl-L-cystine (DiNAC) is the disulphide dimer of N-acetylcysteine with immunomodulating properties. N,N'-diacetyl-L-cystine also has antiatherosclerotic effects in Watanabe-heritable hyperlipidemic rabbit (WHHL) rabbits. N,N'-diacetyl-L-cystine is also an effective and orally active modulator of contact sensitivity delayed-type hypersensitivity reactions in rodents.

Roflumilast (APTA 2217) is an orally available, long-acting inhibitor of phosphodiesterase (PDE) type 4 (PDE4), with anti-inflammatory and potential antineoplastic activities. Upon administration, roflumilast and its active metabolite roflumilast N-oxide selectively and competitively bind to and inhibit PDE4, which leads to an increase of both intracellular levels of cyclic-3', 5'-adenosine monophosphate (cAMP) and cAMP-mediated signaling.

HIV-1 inhibitor-54 is a potent inhibitor of WT HIV-1 (strain IIIB) in MT-4 cells, demonstrating anti-HIV activity with an EC50 of 32 nM. [HIV-1 inhibitor-54 can be used to study viral infections.]

N-Oleoyl valine is an endogenous N-acyl amine that acts as an antagonist at the transient receptor potential vanilloid type 3 (TRPV3) receptor, which is involved in thermoregulation. N-Oleoyl valine is increased in mice following cold exposure for up to at least 16 days. Acute lung injury in mice increases the concentration of N-Oleoyl valine in lung tissue. N-acyl amines also promote mitochondrial uncoupling.

PD0176078 () is a newly blocker of N-type Calcium channel.

N-5984, a β3-adrenergic receptor agonist, is used potentially for the treatment of obesity, overactive bladder and type 2 diabetes.

NSC-697923 (2-[(4-methylphenyl)sulfonyl]-5-nitrofuran), a potent inhibitor of UBE2N (ubiquitin-conjugating enzyme E2 N, Ubc13), exhibits its role in inducing cell death in neuroblastoma (NB) cells through two distinct mechanisms. In p53 wild-type NB cells, NSC-697923 promotes the nuclear importation of p53, thereby triggering cell death. Meanwhile, in p53 mutant NB cells, NSC-697923 activates the JNK-mediated apoptotic pathway, leading to cell death. Additionally, NSC-697923 inhibits DNA damage and NF-κB signaling, further contributing to its antitumor activity.

Ziconotide Acetate (107452-89-1 free base) (Prialt) is an analgesic agent and has been used to treat neuropathic and non-neuropathic pain. Ziconotide Acetate (107452-89-1 free base) acts by binding to N-type calcium channels situated on the terminal part of primary afferent neurons of the nociceptive pathway therefore reducing synaptic transmission with potent antinociceptive effects.

OMDM-1 ((Z)-N-[(2S)-1-hydroxy-3-(4-hydroxyphenyl)propan-2-yl]octadec-9-enamide) is a selective and metabolically stable anandamide cellular uptake (ACU)inhibitor with a Ki of 2.4 μM.

MY-5445 (N-(3-chlorophenyl)-4-phenylphthalazin-1-amine) is a specific inhibitor of phosphodiesterase type 5 (PDE5). MY-5445 selectively inhibits cGMP PDE (Ki:1.3 μM).

ML-336 is an inhibitor of of the Venezuelan equine encephalitis virus (VEEV) strain TC-83.

N-Formylcytisine ((-)-N-Formylcytisine) is a natural product isolated from the stem bark of Maackia amurensis.

Cav 2.2 blocker 1 is an N-type calcium channel (Cav 2.2; IC50: 1 nM) blocker for the treatment of pain.

Norverapamil hydrochloride (D591 hydrochloride) ((±)-Norverapamil hydrochloride) is an N-demethylated metabolite of Verapamil and it is an L-type calcium channel blocker and a P-glycoprotein (P-gp) function inhibitor.

Physalin F is a natural blocker of CaV2.3 (R-type) and CaV2.2 (N-type) voltage-gated calcium channels.It is a secosteroid with potent anti-inflammatory and immunomodulatory activities. Physalin F induces apoptosis of PBMC, decreasing the spontaneous proliferation and cytokine production caused by Human T-lymphotropic virus type 1 (HTLV-1) infection

Ca2+ channel agonist 1 is an agonist of N-type Ca2+ channel and an inhibitor of Cdk2 (EC50s: 14.23 μM and 3.34 μM) and is used as a potential treatment for motor nerve terminal dysfunction.

GV-58 is a selective N- and P/Q-type Ca2+ channels agonist (EC50: 7.21/8.81 uM for N-type/P-Q-type Ca2+ channel). The inhibitory of GV-58 is 20-fold fewer for CDK kinases activity.

NS13001 (N-(4-Chlorophenyl)-2-(3,5-dimethyl-1H-pyrazol-1-yl)-9-methyl-9H-purin-6-amine) is a potent, selective, orally active allosteric positive modulator of SK channels (small conductance calcium-activated potassium channels). The EC50s are 1.8 and 0.14 μM for SK2 and SK3, respectively. NS13001 holds promise as a potential therapeutic agent for treatment of spinocerebellar ataxia type 2 (SCA2) and possibly other cerebellar ataxias.

Tat-CBD3 is a chemical compound inhibiting the interaction between the N-type voltage-gated calcium channel Cav2.2 and collapsin response mediator protein 2 (CRMP2), as well as the interaction between CRMP2 and the NMDA receptor NR2B subunit. At a concentration of 10 µM, Tat-CBD3 reduces the Cav2.2-CRMP2 interaction by 43% in cell-free assays and impedes the NMDA receptor NR2B subunit-CRMP2 interaction in immunoprecipitation assays. It lowers voltage-induced calcium currents by about 60% in primary rat dorsal root ganglion (DRG) neurons and decreases glutamate-induced cytosolic calcium level rises in primary rat hippocampal neurons. When administered at 20 mg/kg, Tat-CBD3 lessens infarct volume in a rat model of cerebral ischemia following middle cerebral artery occlusion (MCAO). Additionally, intrathecal delivery of Tat-CBD3 at a dose of 20 µg/5 µl mitigates carrageenan-induced thermal hypersensitivity in rats.

Azelnidipine, (S)-, is an L-type calcium channel blocker (CCB). Studies have shown that in patients with hypertension (HT) and heart failure preserved ejection fraction (HFpEF), azelnidipine improved the severity of HF and cardiac sympathetic nerve activity compared with cilnidipine, an N-type CCB (Cat#326734).

SP-187, also known as N-9-DNJ and UV-4B, is an alpha-Glucosidase inhibitor potentially for the treatment of dengue fever and influenza infection. Proline-producing strains of Serratia marcescens were more osmotolerant than wild-type strains. Growth inhibition by proline analogs was significantly enhanced by increasing the osmotic stress of the medium.

Gepotidacin hydrochloride, also known as GSK-2140944 hydrochloride, is a potent Type II DNA topoisomerase inhibitor. Gepotidacin hydrochloride is a novel antibacterial drug candidate. Gepotidacin hydrochloride Demonstrates Absence of Fluoroquinolone-Like Arthropathy in Juvenile Rats. Gepotidacin hydrochloride is efficacious in a nonhuman primate model of pneumonic plague. When tested against Gram-negative (n = 333) and Gram-positive (n = 225) anaerobes by agar dilution, Gepotidacin hydrochloride inhibited 90% of isolates at concentrations of 4 and 2 μg/mL, respectively.

Norverapamil-d7 HCl is a deuterated compound of Norverapamil HCl. Norverapamil HCl has a CAS number of 67812-42-4. Norverapamil hydrochloride ((±)-Norverapamil hydrochloride) is an N-demethylated metabolite of Verapamil and it is an L-type calcium channel blocker and a P-glycoprotein (P-gp) function inhibitor.

N-Acetylhexosamine kinase (NahK) acts as an anomeric kinase, primarily catalyzing the phosphorylation of GlcNAc or GalNAc at their anomeric C1 positions using ATP. This process results in the formation of N-acetylhexosamine 1-phosphate (GlcNAc-1P/GalNAc-1P), operating on glucose-type substrates [1] [2].

Huwentoxin I (HWTX-I) is a peptide toxin that inhibits voltage-gated sodium channels and N-type calcium channels. It effectively blocks sodium channels in rat hippocampus and cockroach dorsal unpaired median (DUM) neurons, with IC50 values of 66.1 nM and 4.80 nM, respectively [1].

D-Glucosyl-β-1,1′-N-palmitoylsphingosine (C16 Glucosyl(β) Ceramide (d18:1 16:0)) is an endogenous ligand for the Macrophage-Inducible C-type Lectin (Mincle) with immunostimulatory properties [1].

IQ-1S free acid (IQ-1S) is an effective and specific c-Jun N-Terminal Kinase Inhibitor. IQ-1S inhibits murine delayed-type hypersensitivity. IQ-1S can reduce inflammation and cartilage loss associated with CIA and can serve as a small-molecule modulator for mechanistic studies of JNK function in rheumatoid arthritis. IQ-1S is highly specific for JNK and that its neutral form is the most abundant species at physiologic pH.

NG 25 is a type II kinase inhibitor that inhibits MAP4K2 and TAK1 (IC50s = 21.7 and 149 nM, respectively).1It also inhibits the Src family kinases Src and LYN (IC50s = 113 and 12.9 nM, respectively) and Abl family kinases (IC50s = 75.2 nM), as well as CSK, FER, and p38α (IC50s = 56.4, 82.3, and 102 nM, respectively). NG 25 (100 nM) prevents TNF-α-induced IKKα/β phosphorylation and IκB-α degradation in L929 cells. It inhibits secretion of IFN-α and IFN-β induced by CpG type B and CL097, respectively, in Gen2.2 cells in a concentration-dependent manner.2NG 25 decreases cell viability of HCT116KRASWT, and to a greater degree of HCT116KRASG13D, colorectal cancer cells in a concentration-dependent manner.3It also reduces tumor growth and increases the number of TUNEL-positive tumor cells in a CT26KRASG12Dmouse orthotopic model of colorectal cancer. 1.Tan, L., Nomanbhoy, T., Gurbani, D., et al.Discovery of type II inhibitors of TGFβ-activated kinase 1 (TAK1) and mitogen-activated protein kinase kinase kinase kinase 2 (MAP4K2)J. Med. Chem.58(1)183-196(2015) 2.Pauls, E., Shpiro, N., Peggie, M., et al.Essential role for IKKβ in production of type 1 interferons by plasmacytoid dendritic cellsJ. Biol. Chem. 287(23)19216-19228(2012) 3.Ma, Q., Gu, L., Liao, S., et al.NG25, a novel inhibitor of TAK1, suppresses KRAS-mutant colorectal cancer growth in vitro and in vivoApoptosis24(1-2)83-94(2019)

ONO-2921 is a Novel N-Type Ca Channel Blocker

Urocortin III is a neuropeptide hormone and member of the corticotropin-releasing factor (CRF) family which includes mammalian CRF , urocortin , urocortin II , frog sauvagine, and piscine urotensin I.1 Human urocortin III shares 90, 40, 37, and 21% identity to mouse urocortin III , mouse urocortin II , human urocortin , and mouse urocortin, respectively. Urocortin III selectively binds to type 2 CRF receptors (Kis = 21.7, 13.5, and >100 nM for rat CRF2α, rat CRF2β, and human CRF1, respectively). It stimulates cAMP production in CHO cells expressing rat CRF2α and mouse CRF2β (EC50s = 0.16 and 0.12 nM, respectively) as well as cultured anterior pituitary cells expressing endogenous CRF2β. Urocortin III is co-released with insulin to potentiate glucose-stimulated somatostatin release in vitro in human pancreatic β-cells.2 In vivo, urocortin III reduces food intake in a dose- and time-dependent manner in mice with a minimum effective dose (MED) of 0.3 nmol/animal.3 It increases swimming time in a forced swim test in mice, indicating antidepressant-like activity.4References1. Lewis, K., Li, C., Perrin, M.H., et al. Identification of urocortin III, an additional member of the corticotropin-releasing factor (CRF) family with high affinity for the CRF2 receptor. Proc. Natl. Acad. Sci. U.S.A. 98(13), 7570-7575 (2001).2. van der Meulen, T., Donaldson, C.J., Cáceres, E., et al. Urocortin3 mediates somatostatin-dependent negative feedback control of insulin secretion. Nat. Med. 21(7), 769-776 (2015).3. Pelleymounter, M.A., Joppa, M., Ling, N., et al. Behavioral and neuroendocrine effects of the selective CRF2 receptor agonists urocortin II and urocortin III. Peptides 25(4), 659-666 (2004).4. Tanaka, M., Kádár, K., Tóth, G., et al. Antidepressant-like effects of urocortin 3 fragments. Brain Res. Bull. 84(6), 414-418 (2011). Urocortin III is a neuropeptide hormone and member of the corticotropin-releasing factor (CRF) family which includes mammalian CRF , urocortin , urocortin II , frog sauvagine, and piscine urotensin I.1 Human urocortin III shares 90, 40, 37, and 21% identity to mouse urocortin III , mouse urocortin II , human urocortin , and mouse urocortin, respectively. Urocortin III selectively binds to type 2 CRF receptors (Kis = 21.7, 13.5, and >100 nM for rat CRF2α, rat CRF2β, and human CRF1, respectively). It stimulates cAMP production in CHO cells expressing rat CRF2α and mouse CRF2β (EC50s = 0.16 and 0.12 nM, respectively) as well as cultured anterior pituitary cells expressing endogenous CRF2β. Urocortin III is co-released with insulin to potentiate glucose-stimulated somatostatin release in vitro in human pancreatic β-cells.2 In vivo, urocortin III reduces food intake in a dose- and time-dependent manner in mice with a minimum effective dose (MED) of 0.3 nmol/animal.3 It increases swimming time in a forced swim test in mice, indicating antidepressant-like activity.4 References1. Lewis, K., Li, C., Perrin, M.H., et al. Identification of urocortin III, an additional member of the corticotropin-releasing factor (CRF) family with high affinity for the CRF2 receptor. Proc. Natl. Acad. Sci. U.S.A. 98(13), 7570-7575 (2001).2. van der Meulen, T., Donaldson, C.J., Cáceres, E., et al. Urocortin3 mediates somatostatin-dependent negative feedback control of insulin secretion. Nat. Med. 21(7), 769-776 (2015).3. Pelleymounter, M.A., Joppa, M., Ling, N., et al. Behavioral and neuroendocrine effects of the selective CRF2 receptor agonists urocortin II and urocortin III. Peptides 25(4), 659-666 (2004).4. Tanaka, M., Kádár, K., Tóth, G., et al. Antidepressant-like effects of urocortin 3 fragments. Brain Res. Bull. 84(6), 414-418 (2011).

16-epiLatrunculin B, a stereoisomer of the actin polymerization inhibitor latrunculin B, was initially isolated from the Red Sea sponge N. magnifica. At concentrations of 5-10 µg/ml, it disrupts microfilament activity in actin disruption assays and exhibits cytotoxic effects on mouse KA31T and NIH3T3 tumor cells, with GI50 values of 1 and 4 µg/ml, respectively. Furthermore, it shows antiviral activity against herpes simplex type 1 virus, with an ED50 of 1 µg/ml.

N-Desmethyl Sildenafil-d8 is a deuterated compound of N-Desmethyl Sildenafil. N-Desmethyl Sildenafil has a CAS number of 139755-82-1. N-Desmethyl Sildenafil (Desmethylsildenafil) is a prominent metabolite of Sildenafil, a potent inhibitor of phosphodiesterase type 5 (PDE5).

MONIRO-1 is a T- and N-type calcium channel blocker that acts on hCav2.2 (IC50: 34 μM), hCav3.1 (IC50: 3.3 μM), hCav3.2 (IC50: 1.7 μM) and hCav3.3 (IC50: 7.2 μM).

Nucleoside hydrolase (IAGNH), a type of glycosidase, facilitates the recycling of nucleobases and ribose by catalyzing the cleavage of the N-glycosidic bond in nucleosides.

Peptide neurotoxin; wide spectrum blocker of N, P and Q type calcium channels.

Kurtoxin is a selective Cav3 (T-type) voltage-gated Ca2+ channel gating inhibitor with a dissociation constant (Kd) of 15 nM for the Cav3.1 (α1G T-type) Ca2+ channel. It exhibits high-affinity interactions with native neuronal high-threshold L-type, N-type, and P-type Ca2+ channels in both central and peripheral neurons and displays cross-reactivity with the voltage-gated Na+ channel [1].

Ziconotide TFA (SNX-111 TFA), a peptide-based and potent selective N-type calcium channel antagonist, effectively reduces synaptic transmission and is utilized in chronic pain research [1].

Huwentoxin XVI TFA, a potent analgesic derived from the Chinese tarantula Ornithoctonus huwena, acts as a highly reversible and selective antagonist of mammalian N-type calcium channels (IC 50 of ~60 nM), with no impact on voltage-gated T-type calcium channels, potassium channels, or sodium channels [1].

ω-Conotoxin GVIA TFA is an inhibitor of the N-type Ca2+ channel [1].

ω-Agatoxin IVA TFA is a potent selective inhibitor of P Q type Ca2+ (Cav2.1) channels, with IC50 values of 2 nM for P-type and 90 nM for Q-type channels. It effectively inhibits glutamate exocytosis and calcium influx induced by high potassium, with IC50 values ranging from 30 to 225 nM. Additionally, it blocks high potassium-induced serotonin and norepinephrine release, without impacting L-type or N-type calcium channels [1][2].

N-desmethyl Rosiglitazone is a major metabolite of rosiglitazone , a potent and selective PPARγ ligand present in formulations that have been used to treat type 2 diabetes. Rosiglitazone is metabolized by the cytochrome P450 (CYP) isoform CYP2C8 to form N-desmethyl rosiglitazone.

NP118809 (39-1B4) is a potent N-type calcium channel blocker(IC50 : 0.11 μM).

PD 173212 is a blocker that blocks N-type voltage sensitive calcium channel (Cav2.2). PD173212 (0.0017-1.7 μmol kg, Intraperitoneal Injection.) dose-dependently reduced DNBS-induced visceral hypersensitivity in mice.