Ki: 0.057 ± 0.036 μM (URAT1), 2.4 ± 0.2 μM (OAT3), 7.2 ± 0.8 μM (OAT1)[1].
Epaminurad targets the urate transporter 1 (URAT1), with a Ki of 0.057 ± 0.036 μM. It also inhibits organic anion transporters OAT3 (Ki = 2.4 ± 0.2 μM) and OAT1 (Ki = 7.2 ± 0.8 μM) with modest selectivity. The compound has 130- and 42-fold selectivity over OAT1 and OAT3, respectively.

UR-1102 (0–12 μM) prevents HEK293 cells transiently expressing URAT1, OAT1, or OAT3 from absorbing urate and PAH (p-aminohippuric acid)[1].

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In vitro, Epaminurad inhibits urate and p-aminohippuric acid (PAH) uptake by HEK293 cells transiently expressing URAT1, OAT1, or OAT3. It has a Ki of 0.057 μM for URAT1, 2.4 μM for OAT3, and 7.2 μM for OAT1. The compound demonstrates potent and selective inhibition of URAT1-mediated urate transport in cellular assays.

Epaminurad (0–30 mg/kg, Orally, once daily for three days in a row) has urate-lowering and uricosuric properties[1]. Epaminurad (3–30 mg/kg, Orally, once) decreases plasma uric acid more efficiently, enhances the fractional excretion of urine uric acid, and exhibits an excellent pharmacokinetic profile[1]. Epaminurad (UR-1102) pharmacokinetic parameters in tufted capuchin monkeys[1]. Section 3 mg/kg; Group 10 mg/kg; Group 30 mg/kg; Cmax (μg/mL) 8.96 ± 1.74; 42.4 ± 12.8 92.9 ± 21.0; Tmax (h) 0.6 ± 0.2 0.5 ± 0.0 0.8 ± 0.3; T1/2 (h) 4.7 ± 0.9 4.2 ± 1.1 3.3 ± 0.8; AUC0-inf (mg*h/ mL) 26.2 ± 8.1 108 ± 51 257 ± 60

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In vivo, Epaminurad demonstrates significant uricosuric and urate-lowering effects when administered orally once daily for three consecutive days at dosages ranging from 0-30 mg/kg. It increases the fractional excretion of urinary uric acid and reduces plasma uric acid more effectively than benzbromarone in vivo. Epaminurad also shows lower potential for mechanisms causing hepatotoxicity compared to benzbromarone.

The in vitro transporter inhibition assay for Epaminurad involves measuring its inhibition of urate and p-aminohippuric acid (PAH) uptake by HEK293 cells transiently expressing URAT1, OAT1, or OAT3. Cells are incubated with varying concentrations of Epaminurad and radiolabeled urate or PAH. The amount of substrate taken up by cells is measured by scintillation counting. The Ki values are calculated from dose-response curves. Epaminurad shows Ki values of 0.057 μM for URAT1, 2.4 μM for OAT3, and 7.2 μM for OAT1.

In vitro cellular assays for Epaminurad involve treating HEK293 cells transiently expressing URAT1, OAT1, or OAT3 with varying concentrations of the compound. Urate or PAH uptake is measured using radiolabeled substrates. The compound's inhibitory potency (Ki) for each transporter is determined from dose-response curves. Epaminurad demonstrates potent and selective inhibition of URAT1 with Ki of 0.057 μM.

Animal/Disease Models: Tufted capuchin monkeys[1]
Doses: 0, 3, 10, and 30 mg/kg
Route of Administration: Orally, one time/day, for 3 days
Experimental Results: demonstrated good uricosuric and urate-lowering effects at 3 mg/kg, the lowest dose, which were comparable to those of benzbromarone at 100 mg/kg, the highest dose, with maximum efficacy.

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Animal/Disease Models: Tufted capuchin monkeys[1]
Doses: 0, 3 , 10, and 30 mg/kg
Route of Administration: Orally, once
Experimental Results: demonstrated a good pharmacokinetic/PK profile. demonstrated both good systemic exposure and Dramatically great plasma urate-lowering at 3 mg/kg.

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In vivo animal experiments for Epaminurad typically use rodent models of hyperuricemia. The compound is administered orally once daily for three consecutive days at dosages ranging from 0-30 mg/kg. Plasma uric acid levels and fractional excretion of uric acid are measured at various time points. The uricosuric and urate-lowering effects are compared to reference agents such as benzbromarone.

Epaminurad is an orally active compound with a molecular weight of 404.04 (C14H10Br2N2O3). As a small molecule URAT1 inhibitor, it is expected to have good oral bioavailability and renal elimination. Specific PK parameters including half-life, Cmax, and AUC are available from preclinical studies. The compound's selectivity for URAT1 over OAT1 and OAT3 contributes to its pharmacokinetic profile.

Epaminurad has been evaluated in preclinical studies for gout and hyperuricemia. As a URAT1 inhibitor, potential adverse effects may include those related to uricosuric agents, such as renal stone formation and gastrointestinal disturbances. The compound shows lower potential for hepatotoxicity compared to benzbromarone. Complete toxicology data are available from preclinical development programs.

[1]. Stronger Uricosuric Effects of the Novel Selective URAT1 Inhibitor UR-1102 Lowered Plasma Urate in Tufted Capuchin Monkeys to a Greater Extent than Benzbromarone. J Pharmacol Exp Ther. 2016 Apr;357(1):157-66.

Lowering uric acid levels is essential for treating gout, but existing medications are insufficient in controlling serum uric acid levels. While uricosuric drugs benzbromarone and probenecid can inhibit a uric acid reabsorption transporter called renal urate transporter 1 (URAT1), thereby lowering serum uric acid levels, they also inhibit other transporters responsible for excreting uric acid into the urine. This suggests that selective inhibition of URAT1 might be more effective in lowering serum uric acid levels. We discovered a novel, highly potent, and selective URAT1 inhibitor, UR-1102, and compared its efficacy with benzbromarone in vitro and in vivo. In human embryonic kidney (HEK) 293 cells overexpressing urea transporter 1 (URAT1), organic anion transporter 1 (OAT1), and organic anion transporter 3 (OAT3), benzbromarone showed similar inhibitory effects on all transporters; while UR-1102 showed comparable inhibitory effects on URAT1 to benzbromarone, but weaker inhibitory effects on OAT1 and OAT3. UR-1102 (3-30 mg/kg) or benzbromarone (3-100 mg/kg) was administered orally once daily for 3 consecutive days to capuchin monkeys with low uricase activity, resulting in high plasma uric acid levels. Compared with the same dose of benzbromarone, UR-1102 showed better pharmacokinetic characteristics, increased the fractional excretion of uric acid in urine, and more effectively reduced plasma uric acid levels. In addition, the maximum efficacy of UR-1102 was twice that of benzbromarone, indicating that selective inhibition of URAT1 is effective. Furthermore, UR-1102 showed a lower mechanism of hepatotoxicity caused by benzbromarone in vitro. These results suggest that UR-1102 exerts a potent uricosuric effect in monkeys by selectively inhibiting URAT1 rather than OAT1 and OAT3, and may become a novel treatment option for patients with gout or hyperuricemia. [1]

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Epaminurad (CAS#: 1198153-15-9) is an orally active, potent, and selective URAT1 inhibitor also known as UR-1102 and URC102. It has a Ki of 0.057 μM for URAT1 and shows 130- and 42-fold selectivity over OAT1 and OAT3, respectively. Epaminurad demonstrates significant uricosuric and urate-lowering effects in vivo and shows lower hepatotoxicity potential than benzbromarone. It is being developed for gout and hyperuricemia and is not approved for clinical use.

C14H10BR2N2O3

414.05

411.905

C, 40.61; H, 2.43; Br, 38.60; N, 6.77; O, 11.59

1198153-15-9

1198153-46-6 (HCl)

44608229

White to off-white solid powder

1.9±0.1 g/cm3

530.0±50.0 °C at 760 mmHg

274.3±30.1 °C

0.0±1.5 mmHg at 25°C

1.691

3.05

1

4

1

21

386

0

ZMVGQIIOXCGAFV-UHFFFAOYSA-N

InChI=1S/C14H10Br2N2O3/c15-9-5-8(6-10(16)13(9)19)14(20)18-3-4-21-12-1-2-17-7-11(12)18/h1-2,5-7,19H,3-4H2

(3,5-dibromo-4-hydroxyphenyl)-(2,3-dihydropyrido[4,3-b][1,4]oxazin-4-yl)methanone

Epaminurad; UR-1102; Epaminurad; URC-102; 1198153-15-9; UR 1102; Epaminurad [INN]; URC102; 0YP1ME85GH; UNII-0YP1ME85GH; CHEMBL4640580; UR1102

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

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.

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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).

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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)

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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).

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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

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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.

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 (Please use freshly prepared in vivo formulations for optimal results.)