Voxelotor

Biological Activity

Voxelotor (GBT440) is a hemoglobin S allosteric modulator. Voxelotor (GBT440) increases haemoglobin oxygen affinity, reduces sickling and prolongs RBC half-life in a murine model of sickle cell disease.

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

Species	Mouse	Rat	Rabbit	Guinea pig	Hamster	Dog
Weight (kg)	0.02	0.15	1.8	0.4	0.08	10
Body Surface Area (m2)	0.007	0.025	0.15	0.05	0.02	0.5
Km factor	3	6	12	8	5	20

Animal A (mg/kg) = Animal B (mg/kg) multiplied by	Animal B Km
	Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the K_m factor for a mouse and then divide by the K_m factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Chemical Information

References

Impact of voxelotor (GBT440) on unconjugated bilirubin and jaundice in sickle cell disease
Paul Telfer, et al. Hematol Rep. 2018 May 22;10(2):7643. PMID: 30046415.

Voxelotor (GBT440), a first-in-class hemoglobin oxygen-affinity modulator, has promising and reassuring preclinical and clinical data
Jeremie H Estepp. Am J Hematol. 2018 Mar;93(3):326-329. PMID: 29352729.

GBT440 increases haemoglobin oxygen affinity, reduces sickling and prolongs RBC half-life in a murine model of sickle cell disease
Donna Oksenberg, et al. Br J Haematol. 2016 Oct;175(1):141-53. PMID: 27378309.