For research use only.
Catalog No.S8540 Synonyms: GTx011
CAS No. 1446321-46-5
Voxelotor (GBT440, GTx011) is a novel small molecule hemoglobin modifier which increases hemoglobin oxygen affinity.
Purity & Quality Control
|Description||Voxelotor (GBT440, GTx011) is a novel small molecule hemoglobin modifier which increases hemoglobin oxygen affinity.|
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. It binds to the N-terminal a chain of Hb.
|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. 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.|
|In vitro||DMSO||67 mg/mL (198.59 mM)|
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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||ul||Number of animals|
|Step 2: Enter the in vivo formulation ()|
|% DMSO % % Tween 80 % ddH2O|
Working concentration： mg/ml；
Method for preparing DMSO master liquid: ： mg drug pre-dissolved in μL DMSO (Master liquid concentration mg/mL，)
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.
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Clinical Trial Information
|NCT Number||Recruitment||interventions||Conditions||Sponsor/Collaborators||Start Date||Phases|
|NCT04335721||Not yet recruiting||Drug: Voxelotor||Sickle Cell Disease|Sickle Cell Nephropathy||University of Illinois at Chicago|Global Blood Therapeutics||December 2020||Phase 1|Phase 2|
|NCT03114540||Completed||Drug: GBT440||Hepatic Impairment||Global Blood Therapeutics||March 17 2017||Phase 1|
|NCT03161015||Completed||Drug: GBT440||Renal Impairment||Global Blood Therapeutics||November 2016||Phase 1|
|NCT02989168||Terminated||Drug: GBT440||Idiopathic Pulmonary Fibrosis|Hypoxemia||Global Blood Therapeutics||November 2016||Phase 2|
|NCT03041909||Completed||Drug: GBT440||Sickle Cell Disease||Global Blood Therapeutics||August 2016||Phase 2|
|NCT02846324||Completed||Drug: GBT440|Drug: Placebo||Idiopathic Pulmonary Fibrosis|Hypoxemia||Global Blood Therapeutics||June 2016||Phase 2|
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.
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