RHC-80267

Names

[ Name ]:
RHC-80267

[Synonym ]:
1,6-Bis-cyclohexylidenaminooxycarbonylamino-hexan
(Hexane-1,6-diyldiimino)bis{[(cyclohexylideneamino)oxy]methanone}
Cyclohexanone, O,O'-[1,6-hexanediylbis(iminocarbonyl)]oxime
(1,6-Hexanediyldiimino)bis{[(cyclohexylideneamino)oxy]methanone}
1,6-bis-cyclohexylidenaminooxycarbonylamino-hexane

Biological Activity

[Description]:

RHC 80267 (U-57908) is a potent and selective inhibitor of diacylglycerol lipase (DAGL) (with IC50 of 4 μM in canine platelets). RHC-80267 inhibits cholinesterase activity with an IC50 of 4 μM, thereby enhancing the relaxation evoked by acetylcholine. RHC 80267 also inhibits COX and the hydrolysis of phosphatidylcholine (PC)[1][2][3][4].

[Related Catalog]:

Signaling Pathways >> Neuronal Signaling >> mAChR

Signaling Pathways >> Metabolic Enzyme/Protease >> Phospholipase

Signaling Pathways >> GPCR/G Protein >> mAChR

Signaling Pathways >> Immunology/Inflammation >> COX

Research Areas >> Metabolic Disease

Research Areas >> Neurological Disease

[Target]

IC50: 4 μM (Canine diacylglycerol lipase), 4 μM (Cholinesterase); COX; Phosphatidylcholine[1][3][4]

[In Vitro]

The potentiation by RHC 80267 of the relaxation to acetylcholine could be caused by the inhibition of cholinesterase: (1) RHC 80267 does not affect the responses to carbachol, the carbamyl derivative of acetylcholine which only differs from acetylcholine by its resistance to hydrolysis by cholinesterase, and (2) the effect of RHC 80267 is mimicked by the inhibitor of cholinesterase neostigmine, RHC 80267 showing no additional effect in the presence of a maximally effective concentration of neostigmine. The determination of the effect of RHC 80267 on the cholinesterase activity of brain homogenate confirmed that RHC 80267 inhibits this enzyme in the same range of concentrations increasing the relaxation to acetylcholine, namely at 1-10 μM[2].

[In Vivo]

RHC 80267 (40 μM) enhances contractions induced by U46619 (a thromboxane A2 analog) in human and rat pulmonary arteries (hPAs and rPAs, respectively) and by angiotensin II (ANG II) in rPAs in an endothelium-dependent manner[3].

[References]

[1]. Sutherland CA, et al. Relative activities of rat and dog platelet phospholipase A2 and diglyceride lipase. Selective inhibition of diglyceride lipase by RHC 80267. J Biol Chem. 1982 Dec 10;257(23):14006-10.

[2]. Ghisdal P, et al. The diacylglycerol lipase inhibitor RHC-80267 potentiates the relaxation to acetylcholine in rat mesenteric artery by anti-cholinesterase action. Eur J Pharmacol. 2005 Jul 4;517(1-2):97-102.

[3]. Karpińska O, et al. Activation of CB1 receptors by 2-arachidonoylglycerol attenuates vasoconstriction induced by U46619 and angiotensin II in human and rat pulmonary arteries. Am J Physiol Regul Integr Comp Physiol. 2017 Jun 1;312(6):R883-R893.

[4]. Oglesby TD, et al. The inhibition of arachidonic acid metabolism in human platelets by RHC 80267, a diacylglycerol lipase inhibitor. Biochim Biophys Acta. 1984 Apr 18;793(2):269-77.

Chemical & Physical Properties

[ Density]:
1.2±0.1 g/cm3

[ Molecular Formula ]:
C₂₀H₃₄N₄O₄

[ Molecular Weight ]:
394.508

[ Exact Mass ]:
394.257996

[ PSA ]:
101.38000

[ LogP ]:
3.12

[ Index of Refraction ]:
1.571

MSDS

Click to get detail MSDS

Safety Information

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

[ Hazard Codes ]:
Xi

[ Safety Phrases ]:
22-24/25

[ RIDADR ]:
NONH for all modes of transport

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Articles

Capsazepine, a vanilloid antagonist, abolishes tonic responses induced by 20-HETE on guinea pig airway smooth muscle.

Am. J. Physiol. Lung Cell. Mol. Physiol. 288(3) , L460-70, (2005)

The aim of this study was to delineate the mode of action of 20-hydroxy-eicosatetraenoic acid (20-HETE) in airway smooth muscle (ASM) cells. ASM metabolizes arachidonic acid by various enzymatic pathw...

L- and N-current but not M-current inhibition by M1 muscarinic receptors requires DAG lipase activity.

J. Cell Physiol. 216(1) , 91-100, (2008)

Stimulation of postsynaptic M(1) muscarinic receptors (M(1)Rs) increases firing rates of both sympathetic and central neurons that underlie increases in vasomotor tone, heart rate, and cognitive memor...

Brain phospholipase C-diacylglycerol lipase pathway is involved in vasopressin-induced release of noradrenaline and adrenaline from adrenal medulla in rats.

Eur. J. Pharmacol. 499(1-2) , 99-105, (2004)

Recently, we reported that intracerebroventricularly (i.c.v.) administered arginine-vasopressin evokes the release of noradrenaline and adrenaline from adrenal medulla by brain thromboxane A2-mediated...