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.

Physicochemical Properties

Molecular Formula	C32H29NO5
Molecular Weight	507.5764
Exact Mass	507.204
Elemental Analysis	C, 75.72; H, 5.76; N, 2.76; O, 15.76
CAS #	1316755-16-4
Related CAS #	Olodanrigan sodium; 1316755-17-5; 1348410-84-3 (potasium)
PubChem CID	9937291
Appearance	White to off-white solid powder
Density	1.3±0.1 g/cm3
Boiling Point	745.3±60.0 °C at 760 mmHg
Flash Point	404.5±32.9 °C
Vapour Pressure	0.0±2.6 mmHg at 25°C
Index of Refraction	1.631
LogP	5.98
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	8
Heavy Atom Count	38
Complexity	752
Defined Atom Stereocenter Count	1
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]
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
Chemical Name	(3S)-2-(2,2-diphenylacetyl)-6-methoxy-5-phenylmethoxy-3,4-dihydro-1H-isoquinoline-3-carboxylic acid
Synonyms	EMA 401; PD-126055; EMA401; PD 126055; EMA-401; EMA-401 potasium; PD126055 potasium
HS Tariff Code	2934.99.9001
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)

Biological Activity

Targets	AT2R
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]
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]
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.
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.
References	[1]. Mol Pain . 2015 Jun 26:11:38. [2]. Pain Med . 2013 May;14(5):692-705.
Additional Infomation	Olodanrigan is under investigation in clinical trial NCT03297294 (Safety and Efficacy of EMA401 in Patients With Painful Diabetic Neuropathy (PDN)).

Solubility Data

Solubility (In Vitro)

DMSO: ~100 mg/mL (~197.0 mM) Ethanol: ~100 mg/mL

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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (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.