Osivelotor (also known as GBT 021601, GBT 601, or PF-07940367) is an investigational next-generation hemoglobin S (HbS) polymerization inhibitor being developed for the treatment of sickle cell disease (SCD). It is designed to increase hemoglobin’s oxygen affinity, thereby reducing HbS polymerization and red blood cell sickling. Preclinical data and early-phase clinical studies suggest that Osivelotor has higher potency and improved pharmacokinetics compared to voxelotor (Oxbryta).
MedKoo Cat#: 130043
Name: Osivelotor
CAS#: 2417955-18-9
Chemical Formula: C20H22N2O6
Exact Mass: 386.1478
Molecular Weight: 386.40
Elemental Analysis: C, 62.17; H, 5.74; N, 7.25; O, 24.84
HbS polymerization only happens when hemoglobin is deoxygenated, meaning it is not fully bound to oxygen molecules. Osivelotor binds directly to hemoglobin and works to increase its affinity for oxygen and stabilize it in its oxygenated state. The idea is that if HbS is fully oxygenated, it won’t polymerize, thereby preventing red blood cell sickling and easing SCD symptoms.
In a Phase 1 study (NCT04983264), healthy volunteers receiving single ascending doses showed dose-dependent increases in hemoglobin oxygen affinity and well-tolerated safety profiles; pharmacokinetic data indicated a half-life supportive of once-daily oral dosing. Compared to voxelotor, Osivelotor achieves similar or greater Hb occupancy at lower doses, potentially enabling improved target engagement and efficacy in patients with SCD.
The following data is based on the product molecular weight 386.40 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
