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Drug-Target Interaction

Drug

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PubChem ID:1533
Structure:
Synonyms:
123080_ALDRICH
135995-51-6
2-amino-4-methyl pyridine
2-Amino-4-methylpyridine
2-AMINO-4-PICOLINE
2-Pyridinamine, 4-methyl-
4-Methyl-2-aminopyridine
4-Methyl-2-pyridinamine
4-Methyl-2-pyridylamine
4-Methyl-pyridin-2-ylamine
4-METHYLPYRIDIN-2-AMINE
4-methylpyridin-2-ylamine
4-Picoline, 2-amino-
4-Picolylamine
4M2AP
5-22-09-00325 (Beilstein Handbook Reference)
695-34-1
A0402
A183
AC-2481
AC-907/25014131
AC1L1BOC
AC1Q2IS5
AG-G-70819
AG-H-07330
AI3-23984
AIDS-167145
AIDS167145
AKOS000119085
alpha-Amino-gamma-picoline
Aminton
Ascensil
BBL002943
BRD-K74039237-001-01-7
BRN 0107066
BVF
C6H8N2
CHEBI:159752
CHEBI:41210
CHEMBL40833
EINECS 211-780-9
FT-0084405
HSCI1_000374
LS-109611
Methyl-4 amino-2-pyridine
MolPort-000-145-997
NCGC00024943-01
nchembio.115-comp6
NSC 1490
NSC 6972
NSC1490
NSC6972
Pyridine, 2-amino-4-methyl-
RA 1226
SBB004354
STK385035
TL806166
Tocris-1020
VMI 20-4
W 45
W 45 Raschig
WLN: T6NJ BZ D1

Target

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Uniprot ID:NOS3_MOUSE
Synonyms:
cNOS
Constitutive NOS
EC-NOS
Endothelial NOS
eNOS
Nitric oxide synthase, endothelial
NOS type III
NOSIII
EC-Numbers:1.14.13.39
Organism:Mouse
Mus musculus
PDB IDs:-

Binding Affinities:

Ki: Kd:Ic 50:Ec50/Ic50:
----

References:

8937711
2-Amino-4-methylpyridine as a potent inhibitor of inducible NO synthase activity in vitro and in vivo.. W S Faraci; A A Nagel; K A Verdries; L A Vincent; H Xu; L E Nichols; J M Labasi; E D Salter; E R Pettipher (1996) British journal of pharmacology display abstract
1. The ability of 2-amino-4-methylpyridine to inhibit the catalytic activity of the inducible NO synthase (NOS II) enzyme was characterized in vitro and in vivo. 2. In vitro, 2-amino-4-methylpyridine inhibited NOS II activity derived from mouse RAW 264.7 cells with an IC50 of 6 nM. Enzyme kinetic studies indicated that inhibition is competitive with respect to arginine. 2-Amino-4-methylpyridine was less potent on human recombinant NOS II (IC50 = 40 nM) and was still less potent on human recombinant NOS I and NOS III (IC50 = 100 nM). NG-monomethyl-L-arginine (L-NMMA), N6-iminoethyl-L-lysine (L-NIL) and aminoguanidine were much weaker inhibitors of murine NOS II than 2-amino-4-methylpyridine but, unlike 2-amino-4-methylpyridine, retained similar activity on human recombinant NOS II. L-NMMA inhibited all three NOS isoforms with similar potency (IC50S 3-7 microM). In contrast, compared to activity on human recombinant NOS III, L-NIL displayed 10 x selectivity for murine NOS II and 11 x selectivity for human recombinant NOS II while aminoguanidine displayed 7.3 x selectivity for murine NOS II and 3.7 x selectivity for human recombinant NOS II. 3. Mouse RAW 264.7 macrophages produced high levels of nitrite when cultured overnight in the presence of lipopolysaccharide (LPS) and interferon-gamma. Addition of 2-amino-4-methylpyridine at the same time as the LPS and IFN-gamma, dose-dependently reduced the levels of nitrite (IC50 = 1.5 microM) without affecting the induction of NOS II protein. Increasing the extracellular concentration of arginine decreased the potency of 2-amino-4-methylpyridine but at concentrations up to 10 microM, 2-amino-4-methylpyridine did not inhibit the uptake of [3H]-arginine into the cell. Addition of 2-amino-4-methylpyridine after the enzyme was induced also dose-dependently inhibited nitrite production. Together, these data suggest that 2-amino-4-methylpyridine reduces cellular production of NO by competitive inhibition of the catalytic activity of NOS II, in agreement with results obtained from in vitro enzyme kinetic studies. 4. When infused i.v. in conscious unrestrained rats, 2-amino-4-methylpyridine inhibited the rise in plasma nitrate produced in response to intraperitoneal injection of LPS (ID50 = 0.009 mg kg-1 min-1). Larger doses of 2-amino-4-methylpyridine were required to raise mean arterial pressure in untreated conscious rats (ED50 = 0.060 mg kg-1 min-1) indicating 6.9 x selectivity for NOS II over NOS III in vivo. Under the same conditions, L-NMMA was nonselective while L-NIL and aminoguanidine displayed 5.2 x and 8.6 x selectivity respectively. All of these compounds caused significant increases in mean arterial pressure at doses above the ID50 for inhibition of NOS II activity in vivo. 5. 2-Amino-4-methylpyridine also inhibited LPS-induced elevation in plasma nitrate after either subcutaneous (ID50 = 0.3 mg kg-1) or oral (ID50 = 20.8 mg kg-1) administration. 6. These data indicate that 2-amino-4-methylpyridine is a potent inhibitor of NOS II activity in vitro and in vivo with a similar degree of isozyme selectivity to that of L-NIL and aminoguanidine in rodents.