| Identification | Back Directory | [Name]
PD-126055 sodium salt | [CAS]
1316755-17-5 | [Synonyms]
EMA401 sodium
Olodanrigan sodium
PD-126055 sodium salt
Olodanrigan sodium (PD126055
(S)-PD-126055 Sodium (EMA401 Sodium)
3-Isoquinolinecarboxylic acid, 2-(2,2-diphenylacetyl)-1,2,3,4-tetrahydro-6-methoxy-5-(phenylmethoxy)-, sodium salt (1:1), (3S)- | [Molecular Formula]
C32H28NNaO5 | [MDL Number]
MFCD30502664 | [MOL File]
1316755-17-5.mol | [Molecular Weight]
529.558 |
| Hazard Information | Back Directory | [Uses]
Olodanrigan (EMA401) sodium is a highly selective, orally active, peripherally restricted angiotensin II type 2 receptor (AT2R) antagonist. Olodanrigan sodium is under development as a neuropathic pain therapeutic agent. Olodanrigan sodium analgesic action appears to involve inhibition of augmented AngII/AT2R induced p38 and p42/p44 MAPK activation, and hence inhibition of DRG neuron hyperexcitability and sprouting of DRG neurons[1][2][3][4]. | [Biological Activity]
Orally availableselectivehigh-affinity type-2 angiotensin II receptor (AT2R) antagonist with in vivo pain relief efficacy.
EMA401the (3S)-enantiomer of EMA400 (PD-126,055)is a selectivehigh-affinity type-2 angiotensin II receptor (AT2R) antagonist (IC50 = 39.5 nM/>39 μM against 50 pM CGP 42112A for binding human AT2R/AT1R; IC50 = 39.5 nM/408 μM against 40 nM Ang II for binding r at AT2R/AT1R). EMA401but not the AT1R antagonist losartanis shown to inhibit capsaicin (200 nM) responses in cultured neurons of human and r at DRG (IC50 = 10 nM). EMA401 is orally available (F = 33.2%t1/2 = 5.7 hCmax = 885 ng/mL post 10 mg/kg oral dosage in rats) and exhibits in vivo pain relief efficacy among adult male SD rats with a unilateral chronic constriction injury (CCI) of the sciatic nerve (ED50 = 10 μg/kg via i.p. using the racemate EMA400). | [in vivo]
EMA401 sodium (10?mg/kg; p.o.) results in a significant attenuation of theta power and increase in paw withdrawal latencies (PWL) in rats at day 14 after chronic constriction injury (CCI)[4]. | [IC 50]
AT2 Receptor | [References]
[1] Rice AS et al. EMA401, an orally administered highly selective angiotensin II type 2 receptor antagonist, as a novel treatment for postherpetic neuralgia: a randomised, double-blind, placebo-controlled phase 2 clinical trial.
Lancet. 2014 May 10;383(9929):1637-47. DOI:10.1016/S0140-6736(13)62337-5
[2] Anand U et al. Mechanisms underlying clinical efficacy of Angiotensin II type 2 receptor (AT2R) antagonist EMA401 in neuropathic pain: clinical tissue and in vitro studies. Mol Pain. 2015 Jun 26;11:38. DOI:10.1186/s12990-015-0038-x
[3] Suguru Koyama,et al. An Electroencephalography Bioassay for Preclinical Testing of Analgesic Efficacy. |
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