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Voxelotor

Name: Voxelotor
Brand: Selleck Chemicals
SKU: S8540
Rating: 5 (1 reviews)

Synonyms: GBT440, GTx011

Catalog No.S8540 Purity: 99.96%

Voxelotor is a novel small molecule hemoglobin modifier which increases hemoglobin oxygen affinity.

Voxelotor Chemical Structure

CAS: 1446321-46-5

Purity & Quality Control

Batch: Purity: 99.96%

99.96

Voxelotor Related Products

Biological Activity

Description	Voxelotor is a novel small molecule hemoglobin modifier which increases hemoglobin oxygen affinity.

In vitro
In vitro	GBT440 is a new potent allosteric effector of sickle cell hemoglobin that increases the affinity of hemoglobin for oxygen and consequently inhibits its polymerization when subjected to hypoxic conditions. GBT440 inhibits these isozymes(CYP 1A2, 2C8, 2C9, 2C19, 2D6, and 3A4) with IC50 ranging from 7.9 to 148 μM. It is not a substrate for either P-gp or BCRP transporters^[1]. It binds to the N-terminal a chain of Hb^[2].
Cell Research	Cell lines	sickle RBCs
	Concentrations	0, 300, 600, 1000 μM
	Incubation Time	1 h
	Method	whole blood (20% Hct) from SCD patients who has been transfusion free for 2 to 3 months (HbS > 70%) is incubated with various concentrations of GBT440 for 1 h at 37°C, diluted 100-fold in TES/saline buffer and deoxygenated in a Hemox Analyser

In Vivo
In vivo	GBT440 has favorable oral bioavailability of 60, 37, and 36% in rats, dogs, and monkeys, respectively, with similar blood and plasma half-lives of approximately 20 h each. T1/2 value of GBT440 in all animal species is significantly shorter than the T1/2 of red blood cells (∼20 days), which supports that binding of GBT440 to hemoglobin is a reversible process. GBT440 is currently in Phase 3 clinical trials (NCT03036813) in SCD patients^[1]. GBT440 increases haemoglobin oxygen affinity, reduces sickling and prolongs RBC half-life in a murine model of sickle cell disease. In a murine model of SCD, GBT440 extends the half-life of RBCs, reduces reticulocyte counts and prevents ex vivo RBC sickling. Importantly, oral dosing of GBT440 in animals demonstrates suitability for once daily dosing in humans and a highly selective partitioning into RBCs, which is a key therapeutic safety attribute. GBT440 shows dose proportional PK, a terminal half-life of 1.5-3 d^[2].
Animal Research	Animal Models	Sprague-Dawley rats
	Dosages	7.2 to 120 mg/kg
	Administration	oral administration

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
Clinical Trial Information (data from https://clinicaltrials.gov, updated on 2024-01-11)
NCT06023199	Recruiting	Sickle Cell Disease	Inova Health Care Services\|Pfizer	October 23 2023	--
NCT05561140	Active not recruiting	Sickle Cell Disease\|Leg Ulcers	Pfizer	June 8 2022	Phase 3
NCT05289570	Suspended	Acute Lung Injury\|End Stage Lung Disease	Duke University	May 3 2022	Phase 2
NCT05018728	Recruiting	Sickle Cell Anemia in Children	Amy Tang\|Pfizer\|Emory University	March 28 2022	Phase 2
NCT05494541	Completed	Sickle Cell Disease	Novartis Pharmaceuticals\|Novartis	August 30 2021	--

References

Chemical Information & Solubility

Molecular Weight	337.37	Formula	C₁₉H₁₉N₃O₃
CAS No.	1446321-46-5	SDF	Download Voxelotor SDF
Smiles	CC(C)N1C(=CC=N1)C2=C(C=CC=N2)COC3=CC=CC(=C3C=O)O
Storage (From the date of receipt)	3 years-20°Cpowder	Storage of Stock Solutions Aliquot the stock solutions to avoid repeated freeze-thaw cycles	1 year-80°Cin solvent
Storage (From the date of receipt)	3 years-20°Cpowder		1 month-20°Cin solvent

In vitro
Batch:

DMSO : 67 mg/mL ( (198.59 mM)； Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 5 mg/mL

Water : 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

Dilution Calculator Molecular Weight Calculator

In vivo Formulation Calculator (Clear solution)

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

Dosage: mg/kg Average weight of animals: g Dosing volume per animal:μL Number of animals:

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

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