WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H526889
CAS#: 1316755-16-4 (free acid)
Description: Olodanrigan, also known as EMA-401 and PD-126055, is an angiotensin AT2 antagonist potentially for treatment of postherpetic neuralgia (PHN). EMA401 targets angiotensin II type 2 receptors, which may have importance for painful sensitization. EMA401 may alleviate pain and provides relief by blocking the AngII induced potentiation which is thought to be coupled to protein kinase A.
Hodoodo Cat#: H526889
Name: Olodanrigan free acid
CAS#: 1316755-16-4 (free acid)
Chemical Formula: C32H29NO5
Exact Mass: 507.20
Molecular Weight: 507.590
Elemental Analysis: C, 75.72; H, 5.76; N, 2.76; O, 15.76
Related CAS #: 1316755-16-4 (free acid) 1348410-84-3 (potasium) 1316755-17-5 (sodium)
Synonym: EMA-401; EMA401; EMA 401; EMA-401 potasium, PD-126055; PD 126055; PD126055 potasium Olodanrigan.
IUPAC/Chemical Name: (S)-5-(benzyloxy)-2-(2,2-diphenylacetyl)-6-methoxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid
InChi Key: GHBCIXGRCZIPNQ-MHZLTWQESA-N
InChi Code: InChI=1S/C32H29NO5/c1-37-28-18-17-25-20-33(31(34)29(23-13-7-3-8-14-23)24-15-9-4-10-16-24)27(32(35)36)19-26(25)30(28)38-21-22-11-5-2-6-12-22/h2-18,27,29H,19-21H2,1H3,(H,35,36)/t27-/m0/s1
SMILES Code: O=C([C@H]1N(C(C(C2=CC=CC=C2)C3=CC=CC=C3)=O)CC4=C(C(OCC5=CC=CC=C5)=C(OC)C=C4)C1)O
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
More Info: Angiotensin II (AngII) is an octapeptide that regulates blood pressure, controls water fluid balance, and pain perception. It activates two G protein-coupled receptors: angiotensin II type 1 receptors (AT1R) and angiotensin II type 2 receptors (AT2R). AngII co-localized in neurons that express substance P and calcitonin gene-related peptide suggesting its presence in nociceptors (noxious-stimuli sensing neurons). EMA401 may alleviate pain and provides relief by blocking the AngII induced potentiation which is thought to be coupled to protein kinase A.
| Biological target: | Olodanrigan (EMA401) is a highly selective, peripherally restricted angiotensin II type 2 receptor (AT2R) antagonist. |
| In vitro activity: | Pre-incubation with EMA401 reduced the subsequent capsaicin response shown in a different hDRG neuron (response to capsaicin first stimulus, Fig. 2D; inhibitory effect of EMA401, Fig. 2E). In a rDRG neuron, sample traces demonstrate the response to the first capsaicin stimulus (Fig. 2F), lack of response on addition of 100 nmol/L AngII (Fig. 2G) and enhanced response to second capsaicin stimulus (Fig. 2H). In Fig. 2J, dose-related inhibition of capsaicin responses is shown in hDRG neurons (0 EMA401, n = 4 neurons; 1 nmol/L EMA401, n = 3 neurons; 10 nmol/L EMA401, n = 4 neurons; 100 nmol/L EMA401, n = 5 neurons; 1000 nmol/L EMA401, n = 3 neurons; IC50 = 10 nmol/L). In rDRG neurons treated with EMA401 (Fig. 3H), there was a tendency for mean neurite density to be reduced compared with untreated controls, but this was not statistically significant. Reference: Eur J Pain. 2013 Aug;17(7):1012-26. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23255326/ |
| In vivo activity: | The study demonstrates the rapid absorption and distribution of drug-related material mainly to the tissues associated with absorption and elimination (GI tract, liver, and kidney). EMA401was then readily eliminated metabolically via the bile (95% of dose) predominantly in the form of the direct acylglucuronide (40% of dose), which was further hydrolysed by the intestinal flora to the active parent drug. Other metabolic pathways such as dealkylations and hydroxylation were also involved in the elimination of EMA401 to a lesser extent. Reference: Biopharm Drug Dispos. 2020 Apr;41(4-5):166-183. https://doi.org/10.1002/bdd.2226 |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 20.0 | 39.40 |
The following data is based on the product molecular weight 507.59 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. Anand U, Facer P, Yiangou Y, Sinisi M, Fox M, McCarthy T, Bountra C, Korchev YE, Anand P. Angiotensin II type 2 receptor (AT2 R) localization and antagonist-mediated inhibition of capsaicin responses and neurite outgrowth in human and rat sensory neurons. Eur J Pain. 2013 Aug;17(7):1012-26. doi: 10.1002/j.1532-2149.2012.00269.x. Epub 2012 Dec 17. PMID: 23255326; PMCID: PMC3748799. 2. Murgasova R, Carreras ET, Suetterlin-Hachmann M, da Silva Torrao LR, Kittelmann M, Alexandra V, Fredenhagen A. Non-clinical characterization of the disposition of EMA401, a novel small molecule angiotensin II type 2 receptor (AT2R) antagonist. Biopharm Drug Dispos. 2020 Apr;41(4-5):166-183. doi: 10.1002/bdd.2226. Epub 2020 Apr 7. PMID: 32190910. |
| In vitro protocol: | 1. Anand U, Facer P, Yiangou Y, Sinisi M, Fox M, McCarthy T, Bountra C, Korchev YE, Anand P. Angiotensin II type 2 receptor (AT2 R) localization and antagonist-mediated inhibition of capsaicin responses and neurite outgrowth in human and rat sensory neurons. Eur J Pain. 2013 Aug;17(7):1012-26. doi: 10.1002/j.1532-2149.2012.00269.x. Epub 2012 Dec 17. PMID: 23255326; PMCID: PMC3748799. |
| In vivo protocol: | 1. Murgasova R, Carreras ET, Suetterlin-Hachmann M, da Silva Torrao LR, Kittelmann M, Alexandra V, Fredenhagen A. Non-clinical characterization of the disposition of EMA401, a novel small molecule angiotensin II type 2 receptor (AT2R) antagonist. Biopharm Drug Dispos. 2020 Apr;41(4-5):166-183. doi: 10.1002/bdd.2226. Epub 2020 Apr 7. PMID: 32190910. |
1: Nascimento OJ, Pessoa BL, Orsini M, Ribeiro P, Davidovich E, Pupe C, Filho PM, Dornas RM, Masiero L, Bittencourt J, Bastos VH. Neuropathic Pain Treatment: Still a Challenge. Neurol Int. 2016 Jun 29;8(2):6322. doi: 10.4081/ni.2016.6322. eCollection 2016 Jun 15. PubMed PMID: 27441065; PubMed Central PMCID: PMC4935814.
2: Pessoa BL, Escudeiro G, Nascimento OJ. Emerging Treatments for Neuropathic Pain. Curr Pain Headache Rep. 2015 Dec;19(12):56. doi: 10.1007/s11916-015-0530-z. Review. PubMed PMID: 26530058.
3: Sałat K, Kowalczyk P, Gryzło B, Jakubowska A, Kulig K. New investigational drugs for the treatment of neuropathic pain. Expert Opin Investig Drugs. 2014 Aug;23(8):1093-104. doi: 10.1517/13543784.2014.916688. Epub 2014 Jun 4. Review. PubMed PMID: 24896842.
