L-161,982 - CAS 147776-06-5
Category: Inhibitor
Please be kindly noted products are not for therapeutic use. We do not sell to patients.
Molecular Formula:
C32H29F3N4O4S2
Molecular Weight:
654.72
COA:
Inquire
Targets:
Prostanoid Receptor
Description:
L-161,982 is a selective and potent EP4 receptor antagonist with Ki value of 0.024 µM. It is selective over all other members of the prostanoid receptor family with Ki values of 19, 23 and 1.90μM for human EP1, EP2 and EP3 receptors respectively. It suppresses PGE2-induced bone formation in young rats at 10 mg/kg/day and prevents the nociceptive response induced by misoprostol in formalin-injected mice. It reverses the anti-inflammatory action of PGE2 in LPS-activated human macrophages at 100 nM. It blocks PGE2-induced cell proliferation in HCA-7 colon cancer cells at 10 µM.
Purity:
≥99% by HPLC
Synonyms:
L-161,982; L 161,982; L161,982; N-[[4'-[[3-Butyl-1,5-dihydro-5-oxo-1-[2-(trifluoromethyl)phenyl]-4H-1,2,4-triazol-4-yl]methyl][1,1'-biphenyl]-2-yl]sulfonyl]-3-methyl-2-thiophenecarboxamide
MSDS:
Inquire
InChIKey:
MMDNKTXNUZFVKD-UHFFFAOYSA-N
InChI:
InChI=1S/C32H29F3N4O4S2/c1-3-4-13-28-36-39(26-11-7-6-10-25(26)32(33,34)35)31(41)38(28)20-22-14-16-23(17-15-22)24-9-5-8-12-27(24)45(42,43)37-30(40)29-21(2)18-19-44-29/h5-12,14-19H,3-4,13,20H2,1-2H3,(H,37,40)
Canonical SMILES:
CCCCC1=NN(C(=O)N1CC2=CC=C(C=C2)C3=CC=CC=C3S(=O)(=O)NC(=O)C4=C(C=CS4)C)C5=CC=CC=C5C(F)(F)F
1.The anti-inflammatory effects of PGE
Gill SK;Yao Y;Kay LJ;Bewley MA;Marriott HM;Peachell PT Br J Pharmacol. 2016 Nov;173(21):3099-3109. doi: 10.1111/bph.13565. Epub 2016 Sep 6.
BACKGROUND AND PURPOSE: ;PGE;2; inhibits cytokine generation from human lung macrophages. However, the EP receptor that mediates this beneficial anti-inflammatory effect of PGE;2; has not been defined. The aim of this study was to identify the EP receptor by which PGE;2; inhibits cytokine generation from human lung macrophages. This was determined by using recently developed EP receptor ligands.;EXPERIMENTAL APPROACH: ;The effects of PGE;2; and EP-selective agonists on LPS-induced generation of TNF-α and IL-6 from macrophages were evaluated. The effects of EP;2; -selective (PF-04852946, PF-04418948) and EP;4; -selective (L-161,982, CJ-042794) receptor antagonists on PGE;2; responses were studied. The expression of EP receptor subtypes by human lung macrophages was determined by RT-PCR.;KEY RESULTS: ;PGE;2; inhibited LPS-induced and Streptococcus pneumoniae-induced cytokine generation from human lung macrophages. Analysis of mRNA levels indicated that macrophages expressed EP;2; and EP;4; receptors. L-902,688 (EP;4; receptor-selective agonist) was considerably more potent than butaprost (EP;2; receptor-selective agonist) as an inhibitor of TNF-α generation from macrophages. EP;2; receptor-selective antagonists had marginal effects on the PGE;2; inhibition of TNF-α generation, whereas EP;4; receptor-selective antagonists caused rightward shifts in the PGE;2; concentration-response curves.
2.Activation of intestinal Cl- secretion by lubiprostone requires the cystic fibrosis transmembrane conductance regulator.
Bijvelds MJ;Bot AG;Escher JC;De Jonge HR Gastroenterology. 2009 Sep;137(3):976-85. doi: 10.1053/j.gastro.2009.05.037. Epub 2009 May 18.
BACKGROUND & AIMS: ;Lubiprostone alleviates constipation by stimulating intestinal fluid secretion, purportedly through activation of ClC-2-type Cl(-) channels. Intestinal obstruction is also a recurrent cause of distress in cystic fibrosis (CF) patients, caused by loss of CF transmembrane conductance regulator (CFTR) Cl(-) channel activity. Because ClC-2 recruitment might be beneficial to CF patients, we investigated lubiprostone's mode of action.;METHODS: ;Cl(-) transport was measured in an Ussing chamber, in 3 model systems: (1) T84 colonocytes, (2) intestinal epithelium of wild-type and CF mice, and (3) intestinal epithelium of CF patients and controls.;RESULTS: ;In T84 monolayers, lubiprostone induced a robust secretory response. Selective permeabilization of the basolateral plasma membrane revealed that lubiprostone activated an apical Cl(-) conductance. The lubiprostone response was attenuated by H89, an inhibitor of the cAMP-dependent protein kinase, and lubiprostone precluded responsiveness to the cAMP agonist forskolin. CFTR blockage by CFTRinh172, but not ClC-2 blockage by CdCl(2), inhibited the lubiprostone response. Lubiprostone induced a CdCl(2)-insensitive secretory response in mouse intestine, but failed to induce intestinal Cl(-) secretion in Cftr-null mice.
3.Prostaglandin potentiates 5-HT responses in stomach and ileum innervating visceral afferent sensory neurons.
Kim S;Jin Z;Lee G;Park YS;Park CS;Jin YH Biochem Biophys Res Commun. 2015 Jan 2;456(1):167-72. doi: 10.1016/j.bbrc.2014.11.053. Epub 2014 Nov 22.
Gastrointestinal disorder is a common symptom induced by diverse pathophysiological conditions that include food tolerance, chemotherapy, and irradiation for therapy. Prostaglandin E2 (PGE2) level increase was often reported during gastrointestinal disorder and prostaglandin synthetase inhibitors has been used for ameliorate the symptoms. Exogenous administration of PGE2 induces gastrointestinal disorder, however, the mechanism of action is not known. Therefore, we tested PGE2 effect on visceral afferent sensory neurons of the rat. Interestingly, PGE2 itself did not evoked any response but enhanced serotonin (5-HT)-evoked currents up to 167% of the control level. The augmented 5-HT responses were completely inhibited by a 5-HT type 3 receptor antagonist, ondansetron. The PGE2-induced potentiation were blocked by a selective E-prostanoid type 4 (EP4) receptors antagonist, L-161,982, but type 1 and 2 receptor antagonist AH6809 has no effect. A membrane permeable protein kinase A (PKA) inhibitor, KT5720 also inhibited PGE2 effects. PGE2 induced 5-HT current augmentation was observed on 15% and 21% of the stomach and ileum projecting neurons, respectively. Current results suggest a synergistic signaling in visceral afferent neurons underlying gastrointestinal disorder involving PGE2 potentiation of 5-HT currents.
Molecular Weight Calculator Molarity Calculator Solution Dilution Calculator

Related Prostanoid Receptor Products


CAS 1164462-05-8 TG 4-155

TG 4-155
(CAS: 1164462-05-8)

TG 4-155 is a high affinity and selective EP2 receptor antagonist (KB = 2.4 and 34.5 nM for EP2 and DP1 receptors, respectively) displaying >500-fold selectivit...

CAS 33458-93-4 AH 6809

AH 6809
(CAS: 33458-93-4)

AH 6809 is an EP1 (pA2 = 6.8) and EP2 (Ki = 350 nM) receptor antagonist.

CAS 19395-87-0 SC 19220

SC 19220
(CAS: 19395-87-0)

SC 19220 is a selective EP1 receptor antagonist (IC50 = 6.7 μM for inhibition of [3H]-PGE2 binding to EP1 transfected COS cells). SC-19220 acts as a PGE2 antago...

CAS 475086-01-2 NS-304

NS-304
(CAS: 475086-01-2)

NS-304 is a selective prostacyclin IP1 receptor agonist as prodrug of the active form of MRE-269 with a Ki value of 20 nM.

CAS 363-24-6 Prostaglandin E2

Prostaglandin E2
(CAS: 363-24-6)

Binds with high affinity to EP1, EP2, EP3 and EP4 receptors (Kd values range between ~ 1 - 10 nM), Prostaglandin E2 is one of the primary COX products of arachi...

CAS 221529-58-4 RO1138452

RO1138452
(CAS: 221529-58-4)

RO1138452 is one of the most potent high-affinity ligands and functional antagonists for the human IP (prostacyclin) receptor. It exhibits no affinity at other ...

CAS 146032-79-3 SC 51322

SC 51322
(CAS: 146032-79-3)

SC 51322 is a potent EP1 prostanoid receptor antagonist (Ki = 13.8 nM) with analgesic properties in vivo. SC 51322 inhibits PGE2 signaling in a guinea pig ileum...

CAS 346673-06-1 TCS 2510

TCS 2510
(CAS: 346673-06-1)

TCS 2510 is a selective EP4 agonist (EC50 = 2.5 nM; Ki = 1.2 nM) that displays no significant binding at other prostaglandin receptors at concentrations up to 1...

Chemical Structure

CAS 147776-06-5 L-161,982

Quick Inquiry

Verification code

Featured Items