Anemia is defined as a low number of red blood cells. In a routine blood test, anemia is reported as a low hemoglobin or hematocrit. Hemoglobin is the main protein in your red blood cells. It carries oxygen, and delivers it throughout your body. If you have anemia, your hemoglobin level will be low too. If it is low enough, your tissues or organs may not get enough oxygen. Symptoms of anemia -- like fatigue or pain -- happen because your organs aren't getting what they need to work the way they should.
Anemia has three main causes: blood loss, lack of red blood cell production, and high rates of red blood cell destruction.
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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.
Enarodustat is a novel potent, orally active HIF prolyl hydroxylase (PHD) inhibitor with IC50 of 0.22 uM for PHD2; increases EPO release from Hep3B cells with EC50 of 5.7 uM, increases hemoglobin levels in rats.
Rivipansel sodium (GMI-1070, PF-06460031) is a novel small molecule glycomimetic pan-Selectin antagonist with IC50 of 4.3 uM, 423 uM and 337 uM for E-selectin, P-selectin and L-selectin, respectively; predominantly inhibits E-selectin-mediated adhesion and dramatically inhibits sRBC-leukocyte interactions, leading to improved microcirculatory blood flow and improved survival; a valuable novel therapeutic intervention for acute sickle cell crises.
Molidustat (BAY 85-3934) is an orally active small molecule inhibitor of hypoxia inducible factor prolyl hydroxylase (HIF-PH) with IC50 of 480 nM, 280 nM and 450 nM for PHD1, PHD2, and PHD3, respectively; causes dose-dependent production of erythropoietin (EPO) in healthy Wistar rats and cynomolgus monkeys, increases hemoglobin levels and shows effectivity in the treatment of renal anemia in rats with impaired kidney function, resultsin normalization of hypertensive blood pressure in rat model of CKD.
GMI-1070 (Rivipansel, PF-06460031) is a novel small molecule glycomimetic pan-Selectin antagonist with IC50 of 4.3 uM, 423 uM and 337 uM for E-selectin, P-selectin and L-selectin, respectively; predominantly inhibits E-selectin-mediated adhesion and dramatically inhibits sRBC-leukocyte interactions, leading to improved microcirculatory blood flow and improved survival; a valuable novel therapeutic intervention for acute sickle cell crises.
Roxadustat (FG4592, FG-4592) is a potent, orally available HIF prolyl hydroxylase (HIF-PHD) with IC50 of 591.4 nM; FG-4592 stimulates erythropoiesis, regulates iron metabolism, and reduces hepcidin, demonstrates potential for treatment of anemia.
Vadadustat (PG-1016548, AKB-6548) is a novel, potent, orally active HIF-PH inhibitor in development for the treatment of anemia in both nondialysis-dependent (NDD) and dialysis-dependent CKD; induces endogenous erythropoietin synthesis and enhances iron mobilization.
JTZ-951 hydrochloride(JTZ 951;JTZ951;Enarodustat) is a potent and orally active HIF prolyl hydroxylase (PHD) inhibitor with IC50 of 0.22 uM (PHD2); significantly increases plasma EPO levels in mice without anorectic effects, dose-dependently increases hemoglobin levels in rats, demonstrates potential for treatment of renal anemia.
Daprodustat (GSK-1278863;GSK 1278863) is a nove, orally active HIF-prolyl hydroxylase (PHD) inhibitor that stimulate endogenous EPO synthesis and induces effective erythropoiesis by non-EPO effects; shows potential for the treatment of anemia associated with chronic kidney disease.
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