Date: 2017-02-14
Type of information: Publication of results in a medical journal
phase: preclinical
Announcement: publication of resultsi n ACS Medicinal Chemistry Letters
Company: Global Blood Therapeutics (USA - CA)
Product: GBT440
Action
mechanism: hemoglobin modifier. GBT440 is being developed as an oral, once-daily therapy for patients with sickle cell disease. GBT440 works by increasing hemoglobin's affinity for oxygen. Since oxygenated sickle hemoglobin does not polymerize, GBT believes GBT440 blocks polymerization and the resultant sickling of red blood cells (RBCs). With the potential to restore normal hemoglobin function and improve oxygen delivery, GBT440 may be capable of modifying the progression of sickle cell disease. The FDA has granted GBT440 both Fast Track and Orphan Drug designation for the treatment of patients with sickle cell disease in recognition of the critical need for new treatments.
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news: * On February 14, 2017, Global Blood Therapeutics announced that a paper describing the discovery of GBT440 and its ability to bind to hemoglobin and prevent red blood cells from sickling was published online in ACS Medicinal Chemistry Letters, a peer-reviewed publication of the American Chemical Society. GBT440 is in phase 3 development as a potentially disease-modifying therapy for sickle cell disease. The published paper describes the process by which scientists discovered GBT440. The researchers first developed a series of compounds that increased the oxygen affinity of sickle hemoglobin (HbS) -- both on the isolated hemoglobin protein and in whole blood from sickle cell patients. They then selected compounds that demonstrated the best time to onset of polymerization of HbS. One compound in particular, now known as GBT440, demonstrated favorable pharmacokinetics in several animal species, showing that it could be given orally. Additionally, GBT440 was found to accumulate highly and favorably into red blood cells, suggesting that potentially therapeutic concentrations of GBT440 can be achieved in red blood cells at comparatively low plasma concentrations.
