1400W dihydrochloride

Names

[ Name ]:
1400W dihydrochloride

[Synonym ]:
(1E)-N'-[3-(Aminomethyl)benzyl]ethanimidamide dihydrochloride
1400 W dihydrochloride
MFCD03428622
Ethanimidamide, N'-[[3-(aminomethyl)phenyl]methyl]-, (1E)-, hydrochloride (1:2)
1400W dihydrochloride
1400W (Dihydrochloride)

Biological Activity

[Description]:

1400W dihydrochloride is a potent and selective inhibitor of human inducible NO synthase with Ki values of 7 nM.

[Related Catalog]:

Signaling Pathways >> Immunology/Inflammation >> NO Synthase

Research Areas >> Cardiovascular Disease

Research Areas >> Inflammation/Immunology

[Target]

Ki: 7 nM (iNOS), 2 µM (nNOS), 50 µM (eNOS)[1]

[In Vitro]

1400W is a slow, tight binding inhibitor of human inducible nitric- oxide synthase (iNOS). The slow onset of inhibition by 1400W shows saturation kinetics with a maximal rate constant of 0.028 s-1 and a binding constant of 2.0 μM. Inhibition is dependent on the cofactor NADPH. 1400W is at least 5000-fold selective for iNOS versus eNOS. In contrast, inhibition of human neuronal NOS and endothelial NOS (eNOS) is relatively weaker, rapidly reversible, and competitive with L-arginine, with Ki values of 2 μM and 50 μM, respectively[1]. 1400W treatment inhibits iNOS expression without affecting nNOS or eNOS. 1400W also reduces NO, 3-NT and MDA production, and prevents neuronal cell apoptosis in cerebral cortex[2].

[In Vivo]

1400W potently (ED50=0.3 mg/kg) reduces the delayed vascular injury in rats attributable to LPS-induced iNOS but fails to exacerbate acute vascular leakage when given concurrently with LPS[1]. Administration of 1400W lowers NOx levels in all the experimental groups. In addition, lipid peroxidation, the percentage of apoptotic cells, and nitrated protein expression fall in the late post-hypoxia period (48 h and 5 days)[3].

[Animal admin]

Rats: The effects of 1400W on plasma leakage are assessed in rats by determining the leakage of [125I]human serum albumin from plasma into organs. 1400W (0.1-10 mg/kg, subcutaneous) is dissolved in isotonic saline and administered either concurrently with endotoxin or 3 h following LPS administration (E. coli LPS, 3 mg/kg intravenously). Plasma leakage is then assessed 1 or 5 h after delivery of 1400W[1].

[References]

[1]. Garvey EP, et al. 1400W is a slow, tight binding, and highly selective inhibitor of inducible nitric-oxide synthase in vitro and in vivo. J Biol Chem. 1997 Feb 21;272(8):4959-63.

[2]. Shi Q, et al. 1400W ameliorates acute hypobaric hypoxia/reoxygenation-induced cognitive deficits by suppressing the induction of inducible nitric oxide synthase in rat cerebral cortex microglia. Behav Brain Res. 2017 Feb 15;319:188-199.

[3]. Rus A, et al. Inducible NOS inhibitor 1400W reduces hypoxia/re-oxygenation injury in rat lung. Redox Rep. 2010;15(4):169-78.

[Related Small Molecules]

Chemical & Physical Properties

[ Boiling Point ]:
329ºC at 760 mmHg

[ Molecular Formula ]:
C₁₀H₁₇Cl₂N₃

[ Molecular Weight ]:
250.168

[ Flash Point ]:
152.7ºC

[ Exact Mass ]:
249.079956

[ PSA ]:
61.90000

[ LogP ]:
4.02700

[ Vapour Pressure ]:
0.000183mmHg at 25°C

[ Storage condition ]:
-20℃

MSDS

Click to get detail MSDS

Safety Information

[ Personal Protective Equipment ]:
Eyeshields;Gloves;type N95 (US);type P1 (EN143) respirator filter

[ RIDADR ]:
NONH for all modes of transport

Articles

NOS1-dependent negative feedback regulation of the epithelial sodium channel in the collecting duct.

Am. J. Physiol. Renal Physiol. 308(3) , F244-51, (2015)

With an increase in urine flow there is a significant increase in shear stress against the renal epithelium including the inner medullary collecting duct, resulting in an increase in nitric oxide (NO)...

Gardenamide A Protects RGC-5 Cells from H₂O₂-Induced Oxidative Stress Insults by Activating PI3K/Akt/eNOS Signaling Pathway.

Int. J. Mol. Sci. 16 , 22350-67, (2015)

Gardenamide A (GA) protects the rat retinal ganglion (RGC-5) cells against cell apoptosis induced by H₂O₂. The protective effect of GA was completely abrogated by the specific phosphoinositide 3-kinas...

Selective inhibition of inducible nitric oxide synthase inhibits tumor growth in vivo: studies with 1400W, a novel inhibitor.

Cancer Res. 57 , 3300, (1997)

We have investigated the effect of N-(3-(aminomethyl)benzyl)acetamidine (1400W), a novel and highly selective inhibitor for inducible NOS (iNOS), on in vivo growth of solid tumors expressing iNOS. For...