Description

Efaproxiral is an allosteric hemoglobin (Hb) modifier that reduces the affinity of Hb for oxygen, increasing the diffusion of oxygen from blood to tissue. In isolated human whole blood, efaproxiral (1.75 mM) increases the partial pressure of oxygen at which Hb is 50% saturated (p50) from 26.75 to 38.63 mm Hg and decreases the percent oxyhemoglobin (Hb-O₂) saturation from 48 to 33.8% at a partial oxygen pressure (pO₂) of 26 mm Hg. Efaproxiral (150 mg/kg) increases tumor pO₂ from 5.2 to 13.1 mm Hg 30 minutes after administration in a RIF-1 mouse fibrosarcoma flank tumor model. Efaproxiral (100 μM) enhances radiation-induced cytotoxicity in EMT6 mouse breast cancer cells grown under hypoxic conditions and increases radiosensitization and inhibits tumor growth in a hypoxic Lewis lung tumor mouse model when administered at a dose of 100 mg/kg. It also increases the running capacity of normal mice and mice with left coronary artery (LCA) ligation-induced myocardial infarction (MI) when administered at a dose of 150 mg/kg.

Chemical Properties

Off-White to Tan Solid

Uses

Allosteric modifier of hemoglobin (HB). Binds in the central water cavity of the Hb molecule causing a conformational change such that bound oxygen is released more readily. Antineoplastic adjunct (radiosensitizer).

in vivo

References

[1] STEFFEN R P. Effect of RSR13 on temperature-dependent changes in hemoglobin oxygen affinity of human whole blood.[J]. Advances in experimental medicine and biology, 1998, 454: 653-661. DOI: 10.1007/978-1-4615-4863-8_77
[2] HUAGANG HOU M.D. , PH.D. Effect of RSR13, an allosteric hemoglobin modifier, on oxygenation in murine tumors: an in vivo electron paramagnetic resonance oximetry and bold MRI study[J]. International Journal of Radiation Oncology Biology Physics, 2004, 59 3: Pages 834-843. DOI: 10.1016/j.ijrobp.2004.02.039
[3] B A TEICHER. Allosteric effectors of hemoglobin as modulators of chemotherapy and radiation therapy in vitro and in vivo.[J]. Cancer Chemotherapy and Pharmacology, 1998, 42 1: 24-30. DOI: 10.1007/s002800050780
[4] MD T W, PHD  Toshihiro T M, PHD  Shungo H M  Shigemiki Omiya MD, et al. Reduction in Hemoglobin–Oxygen Affinity Results in the Improvement of Exercise Capacity in Mice With Chronic Heart Failure[J]. Journal of the American College of Cardiology, 2008, 52 9: Pages 779-786. DOI: 10.1016/j.jacc.2008.06.003