Home Transmembrane Transporters OAT inhibitor Verinurad (RDEA3170) For research use only.

Verinurad (RDEA3170)

Verinurad (RDEA3170) is a high-affinity inhibitor of the URAT1 transporter with an IC50 of 25 nM for inhibiting transport activity of human URAT1. It inhibits the related URAT1 homologs OAT4 and OAT1 with approximately 200-fold lower affinity compared to URAT1 with IC50 values of 5.9 µM and 4.6 µM, respectively.

Verinurad (RDEA3170) Chemical Structure

Verinurad (RDEA3170) Chemical Structure

CAS No. 1352792-74-5

Purity & Quality Control

Batch: S873601 DMSO]70 mg/mL]false]Water]Insoluble]false]Ethanol]Insoluble]false Purity: 99.35%
99.35

Verinurad (RDEA3170) Related Products

Biological Activity

Description Verinurad (RDEA3170) is a high-affinity inhibitor of the URAT1 transporter with an IC50 of 25 nM for inhibiting transport activity of human URAT1. It inhibits the related URAT1 homologs OAT4 and OAT1 with approximately 200-fold lower affinity compared to URAT1 with IC50 values of 5.9 µM and 4.6 µM, respectively.
Targets
URAT1 transporter [1]
(Cell-free assay)
25 nM
In vitro
In vitro

Verinurad inhibited the transport activity of human URAT1 in a dose-dependent manner, at high potency with an IC50 of 25 nM. Verinurad inhibited the related URAT1 homologs OAT4 and OAT1 with approximately 200-fold lower affinity compared to URAT1 with IC50 values of 5.9 μM and 4.6 μM, respectively. Human URAT1 (IC50=0.025 μM) has a 1,640-fold higher affinity for verinurad compared to rat URAT1(IC50 = 41 μM). Verinurad has a high potency for human URAT1, and residues 35, 365 and 481 all contribute to verinurad affinity. Human URAT1 carrying a chimeric point mutation at position 365, in which human Phe-365 is replaced by rat Tyr-365 (human URAT1-F365Y or h-F365Y) has an IC50 of 4.0 μM, a significant 160-fold lower affinity relative to human URAT1. Meanwhile, rat URAT1 carrying the opposite point mutation (rat URAT1-Y365F or r-Y365F), had an IC50 of 2.9 μM, a significant 14-fold higher affinity compared to rat URAT1[1].
Cell Research Cell lines HEK-293T cells
Concentrations 0.1 nM-1 mM
Incubation Time 5 min
Method

URAT1 and OAT4 activity assays were performed in assay buffer con- sisting of 25 mM MES pH 5.5 (from a 1 M MES solution adjusted to pH 5.5 with sodium hydroxide), 125 mM sodium gluconate, 4.8 mM potassium gluconate, 1.2 mM monobasic potassium phosphate, 1.2 mM magnesium sulfate, 1.3 mM calcium gluconate and 5.6 mM glucose. URAT1 inhibitors were serially diluted into assay buffer and added to the cells for 5 minutes prior to addition of substrate. URAT1-expressing cells were incubated with 100 μM 14C-uric acid for 10 minutes and OAT4-expressing cells were incubated with 20 μM carboxyfluorescein for 5 minutes. Cells were then washed three times in 25 mM MES pH 5.5/125 mM sodium gluconate, and solubilized in Ultima Gold prior to liquid scintillation counting. Each treatment is measured in triplicate.
In Vivo
In vivo

In human, absorption of a single dose is rapid, and exposure (Cmax and AUC) increases with dose up to the maximum dose tested. Cmax is at 0.5-0.75 hours post dose in the fasted state, and is slightly delayed to 1.25 hours post dose in the fed state. The t1/2 is approximately 10-15 hours across doses. Verinurad was well tolerated at the doses studied. In the systemic circulation, verinurad appeared to be a high clearance drug (CL/F ranged ~30-50 L/h) with extensive extravascular distribution. Renal excretion of verinurad is limited to only ~2%–3% in the urine, suggesting that the majority of verinurad is likely cleared in the liver via biotransformation to metabolites[2].
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT04256629 Completed
Healthy Volunteers (Intended Indication: Chronic Kidney Disease)
AstraZeneca|Parexel
 March 3 2020 Phase 1
NCT02498652 Completed
Gout
Ardea Biosciences Inc.
 July 28 2015 Phase 2
NCT02336594 Completed
Gout
Ardea Biosciences Inc.
 November 2014 Phase 1

Chemical Information & Solubility

Molecular Weight 348.42 Formula

C20H16N2O2S
CAS No. 1352792-74-5 SDF --
Smiles CC(C)(C(=O)O)SC1=C(C=NC=C1)C2=CC=C(C3=CC=CC=C32)C#N
Storage (From the date of receipt) 3 years -20°C powder

In vitro
Batch:

DMSO : 70 mg/mL ( (200.9 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble


Molecular Weight Calculator

In vivo
Batch:

Add solvents to the product individually and in order.


In vivo Formulation Calculator

Preparing Stock Solutions

Molarity Calculator

Mass Concentration Volume Molecular Weight

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

mg/kg g μL

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

Tel: +1-832-582-8158 Ext:3
If you have any other enquiries, please leave a message.

* Indicates a Required Field

Please enter your name.
Please enter your email. Please enter a valid email address.
Please write something to us.
Tags: buy Verinurad (RDEA3170) | Verinurad (RDEA3170) supplier | purchase Verinurad (RDEA3170) | Verinurad (RDEA3170) cost | Verinurad (RDEA3170) manufacturer | order Verinurad (RDEA3170) | Verinurad (RDEA3170) distributor