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Chemical Structure| 1446321-46-5 Chemical Structure| 1446321-46-5

Structure of Voxelotor
CAS No.: 1446321-46-5

Chemical Structure| 1446321-46-5

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GBT 440 is a modulator of sickle hemoglobin (HbS), which can be used in treating disorders mediated by hemoglobin and disorders that would benefit from tissue and/or cellular oxygenation.

Synonyms: GBT 440

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Product Details of Voxelotor

CAS No. :1446321-46-5
Formula : C19H19N3O3
M.W : 337.37
SMILES Code : O=CC1=C(OCC2=CC=CN=C2C3=CC=NN3C(C)C)C=CC=C1O
Synonyms :
GBT 440
MDL No. :MFCD29053764
InChI Key :FWCVZAQENIZVMY-UHFFFAOYSA-N
Pubchem ID :71602803

Safety of Voxelotor

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Isoform Comparison

Biological Activity

Description
Voxelotor, also known as GBT 440, is identified as a powerful inhibitor of the polymerization of haemoglobin S (HbS), showing promise for the treatment of sickle cell disease (SCD)[1].

In Vitro:

Cell Line
Concentration Treated Time Description References
Caco-2 cells 0.9 mg/mL 2 hours To evaluate the safety of Voxelotor SNEDDS in Caco-2 cells, results showed safety at 0.9 mg/mL. Pharmaceutics. 2021 Sep 2;13(9):1388
Sickle hemoglobin (HbS) 29.7 g/dL 3 hours To verify the effect of Voxelotor on HbS polymerization, results showed that Voxelotor does not affect the nucleation rate of HbS Biophys J. 2023 Jul 11;122(13):2782-2790
Sickle red blood cells 30 μM 1 hour Evaluate the ability of SNS-314M to inhibit sickling of red blood cells; results showed SNS-314M effectively prevented sickling under hypoxic conditions ACS Omega. 2022 Apr 15;7(16):14009-14016.

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Human Patients with sickle cell disease Oral 1500 mg Once daily for up to 72 weeks To evaluate the pharmacokinetics of Voxelotor in patients with sickle cell disease, supporting dose selection for optimal target engagement. Results showed that Voxelotor PK in plasma and whole blood is linear and comparable for adults and adolescents. CPT Pharmacometrics Syst Pharmacol. 2022 Jun;11(6):687-697
Human (sickle cell disease patients) Sickle cell disease (SCD) patient model Oral 900 mg or 1500 mg Once daily for 72 weeks To evaluate the efficacy and safety of Voxelotor in sickle cell disease and confirm 1500 mg once daily as the therapeutic dose. Results showed that the 1500 mg dose significantly increased hemoglobin levels, improved hemolysis markers, and had a favorable safety profile. CPT Pharmacometrics Syst Pharmacol. 2022 Jun;11(6):698-710

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.96mL

0.59mL

0.30mL

14.82mL

2.96mL

1.48mL

29.64mL

5.93mL

2.96mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2

References

 

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