GBT-440

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

镰状细胞血红蛋白的一种新的有效变构效应物；增加血红蛋白对氧的亲和力，从而在缺氧条件下抑制其聚合。

A new potent allosteric effector of sickle cell hemoglobin; increases the affinity of hemoglobin for oxygen and consequently inhibits its polymerization when subjected to hypoxic conditions; orally bioavailable and partitions highly and favorably into the red blood cell with a RBC/plasma ratio of ～150.Anemia Phase 3 Clinical(In Vitro):Voxelotor (GBT440) binds to the N-terminal a chain of haemoglobin (Hb), increases haemoglobin S (HbS) affinity for oxygen, delays in vitro HbS polymerization and prevents sickling of red blood cells (RBCs).(In Vivo):Voxelotor (GBT440; 100-150 mg/kg; administered twice a day by oral gavage for 9-12 days) reduces ex vivo sickling and prolongs red blood cells (RBCs) half-life in a murine model of sickle cell disease (SCD).Voxelotor shows T1/2s of 11.7, 19.1±1.5, 66.0±11, 28.8±4.0 hours for mouse (70 mg/kg; i.v.), rat (1.6 mg/kg; i.v.), dog (1 mg/kg; i.v.), and momkey (1 mg/kg; i.v.), respectively.Voxelotor shows Cmaxs of 81.9, 71.2±6.0, 5.56±1.6, and 25.2±5.5 μg/mL for mouse (30 mg/kg; p.o.), rat (7.2 mg/kg; p.o.), dog (2.5 mg/kg; p.o.), and momkey (4.25 mg/kg; p.o.), respectively.

——

Animal Model:HbSS Townes knock-in sickle mice (SS mice)Dosage:100 and 150 mg/kg Administration:Oral administration; twice a day; for 9-12 days Result:Reduced haemolysis.Animal Model:C57BL/6J mice, Sprague-Dawley rats, Beagle dogs and Cynomolgus monkeys Dosage:70, 1.6, 1 and 1 mg/kg for mice, rats, dogs and monkeys, respectively.Oral (PO: 30, 7 2, 2 5 and 4 3 mg/kg, respectively) Result:T1/2s of 11.7, 19.1±1.5, 66.0±11, 28.8±4.0 hours for mouse (70 mg/kg; i.v.), rat (1.6 mg/kg; i.v.), dog (1 mg/kg; i.v.), and momkey (1 mg/kg; i.v.), respectively.Cmaxs of 81.9, 71.2±6.0,5.56±1.6, and 25.2±5.5 μg/mL for mouse (30 mg/kg; p.o.), rat (7.2 mg/kg; p.o.), dog (2.5 mg/kg; p.o.), and momkey (4.25 mg/kg; p.o.), respectively.

GBT 440 | GBT440 | Voxelotor

Others

Other Targets

Other Targets

Other Indications

Anemia

1446321-46-5

337.3725

C19H19N3O3

>98% (HPLC)

10 mM in DMSO

O=CC1=C(OCC2=CC=CN=C2C3=CC=NN3C(C)C)C=CC=C1O

Benzaldehyde, 2-hydroxy-6-[[2-[1-(1-methylethyl)-1H-pyrazol-5-yl]-3-pyridinyl]methoxy]-

(-20℃)

With Ice Pack

≥ 2 years