| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 50mg |
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Purity: ≥98%
Olodanrigan (EMA-401; PD-126055; EMA401) is a novel, orally bioavailable, peripherally restricted and highly selective AT2R (angiotensin II type 2 receptor) antagonist that can be potentially used for treatment of postherpetic neuralgia (PHN). Decreased hyperexcitability and DRG neuron sprouting are prevented by inhibiting augmented AngII/AT2R-induced p38 and p42/p44 MAPK activation. As a treatment for neuropathic pain, it is currently under development.
| Targets |
AT2R
Angiotensin II type 2 receptor (AT2R) antagonist (Selective AT2R antagonist with >1000-fold selectivity over AT1R). [1] |
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| ln Vitro |
EMA401 may work through intracrine or paracrine processes at peripheral nerve terminals to lessen the signaling of neuropathic pain in AngII/NGF/TRPV1-convergent pathways.[1]
EMA401 (100 nM) reversed the AngII-mediated increase in phosphorylated p38 (pp38) and p42/44 MAPK (pp42/44) signal intensity in cultured rat dorsal root ganglion (rDRG) neurons. The increase caused by AngII was similar to that induced by NGF. [1] In cultured human (hDRG) and rat (rDRG) neurons, EMA401 inhibited AngII-mediated sensitization of capsaicin responses (measured by calcium imaging), which was dependent on MAPK and TrkA pathways. [1] EMA401 inhibited neurite outgrowth promoted by AngII and neurotrophic factors (NTFs) in cultured DRG neurons, as shown in a previous study cited within this work. [1] |
| ln Vivo |
EMA401, at day 14, rats treated with a selective small molecule AT2R antagonist exhibit a significant reduction in theta power and an increase in paw withdrawal latencies (PWL) following chronic constriction injury (CCI).[2]
The clinical efficacy of orally administered EMA401 was referenced from a separate randomized, double-blind, placebo-controlled trial in patients with post-herpetic neuralgia, where it produced significant pain relief over 4 weeks and was well-tolerated. [1] |
| Cell Assay |
Duplicate plates were plated for 48 hours, and then treated for 30 minutes at 37 °C with AngII (10 nM), AngII + EMA401 (10 and 100 nM, respectively), 100 nM EMA401, NGF (100 ng/ml), or the vehicle treatment (control 0). After that, the dishes were fixed for 30 minutes with 4% PFA in preparation for immunostaining.
Calcium Imaging in DRG Neurons: Human or rat DRG neurons were cultured and loaded with Fura2 AM. Capsaicin-sensitive neurons were identified with an initial 200 nM capsaicin stimulus. After a 40-minute rest, a second capsaicin stimulus (1 µM) was applied with or without test compounds (e.g., AngII, EMA401). The effect of EMA401 (and other kinase inhibitors like PD98059, staurosporine, GW441756) on AngII-mediated sensitization was tested by pre-incubating with the inhibitor for 10 minutes before adding AngII, followed by the second capsaicin stimulus 10 minutes later. Responses were normalized to the first capsaicin response. [1] Neurite Outgrowth Assay: Rat DRG neurons were cultured in medium without NTFs for 48 hours. Duplicate dishes were then treated with AngII (10 nM), NTFs, or vehicle for another 48 hours. Cultures were fixed, immunostained for Gap43, and the longest neurite lengths from approximately 50 neurons per group were measured and normalized to controls. EMA401 was tested for its ability to inhibit AngII-promoted neurite outgrowth. [1] Immunofluorescence for Phospho-MAPK: Rat DRG neurons were cultured for 48 hours and then treated with AngII (10 nM), AngII + EMA401 (10 nM and 100 nM, respectively), EMA401 alone (100 nM), NGF (100 ng/ml), or vehicle for 30 minutes. Cells were fixed, permeabilized, and immunostained with antibodies against phospho-p38 MAPK or phospho-p44/42 MAPK (ERK1/2). Fluorescence images were acquired with consistent settings, and signal intensity was measured from at least 120 neurons per group after background subtraction using ImageJ software. [1] |
| Animal Protocol |
Adult male Sprague-Dawley (SD) rats with a unilateral chronic constriction injury (CCI) of the sciatic nerve
1 mg/kg (i.v.); 10 mg/kg (p.o.) i.v.; p.o. |
| ADME/Pharmacokinetics |
EMA401 is described as a peripherally restricted analgesic, indicating that it does not penetrate the central nervous system (CNS). [1]
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| Toxicity/Toxicokinetics |
In the aforementioned clinical trials, oral administration of EMA401 for 4 weeks was well tolerated. [1]
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| References | |
| Additional Infomation |
Olodanigans is being investigated in the clinical trial NCT03297294 (Safety and efficacy of EMA401 in patients with diabetic neuropathic pain (PDN). EMA401 is a novel, orally effective, highly selective AT2 receptor antagonist for the treatment of neuropathic pain. [1] Its mechanism of action is believed to be the blocking of enhanced angiotensin II/AT2 receptor signaling in dorsal root ganglion (DRG) neurons, thereby inhibiting the activation of p38 and p42/p44 MAPK, neuronal hyperexcitability, and aberrant neurogenesis. It may exert its effects through paracrine/autocrine or endocrine mechanisms. [1] The clinical efficacy of this drug in the treatment of postherpetic neuralgia and its limiting effect on peripheral nerves suggest that it represents a new class of analgesics for the treatment of neuropathic pain, with potentially improved side effects due to the lack of central nervous system activity. [1]
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| Molecular Formula |
C32H29NO5
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|---|---|
| Molecular Weight |
507.5764
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| Exact Mass |
507.204
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| Elemental Analysis |
C, 75.72; H, 5.76; N, 2.76; O, 15.76
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| CAS # |
1316755-16-4
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| Related CAS # |
Olodanrigan sodium; 1316755-17-5; 1348410-84-3 (potasium)
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| PubChem CID |
9937291
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| Appearance |
White to off-white solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
745.3±60.0 °C at 760 mmHg
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| Flash Point |
404.5±32.9 °C
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| Vapour Pressure |
0.0±2.6 mmHg at 25°C
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| Index of Refraction |
1.631
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| LogP |
5.98
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
38
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| Complexity |
752
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| Defined Atom Stereocenter Count |
1
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| SMILES |
O(C([H])([H])C1C([H])=C([H])C([H])=C([H])C=1[H])C1=C(C([H])=C([H])C2=C1C([H])([H])[C@@]([H])(C(=O)O[H])N(C(C([H])(C1C([H])=C([H])C([H])=C([H])C=1[H])C1C([H])=C([H])C([H])=C([H])C=1[H])=O)C2([H])[H])OC([H])([H])[H]
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| InChi Key |
GHBCIXGRCZIPNQ-MHZLTWQESA-N
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| 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
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| Chemical Name |
(3S)-2-(2,2-diphenylacetyl)-6-methoxy-5-phenylmethoxy-3,4-dihydro-1H-isoquinoline-3-carboxylic acid
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| Synonyms |
EMA 401; PD-126055; EMA401; PD 126055; EMA-401; EMA-401 potasium; PD126055 potasium
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: ~100 mg/mL (~197.0 mM)
Ethanol: ~100 mg/mL |
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9701 mL | 9.8507 mL | 19.7013 mL | |
| 5 mM | 0.3940 mL | 1.9701 mL | 3.9403 mL | |
| 10 mM | 0.1970 mL | 0.9851 mL | 1.9701 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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