GBT1118

• CAT Number: I041177
• CAS Number: 1628799-51-8
• Molecular Formula: C19H20N2O4
• Molecular Weight: 340.37
• Purity: ≥95%
• Synonyms: 2-hydroxy-6-[[(2S)-1-(pyridine-3-carbonyl)piperidin-2-yl]methoxy]benzaldehyde
• InChI: InChI=1S/C19H20N2O4/c22-12-16-17(23)7-3-8-18(16)25-13-15-6-1-2-10-21(15)19(24)14-5-4-9-20-11-14/h3-5,7-9,11-12,15,23H,1-2,6,10,13H2/t15-/m0/s1
• InChIKey: DIXJEEIWNGTEBR-HNNXBMFYSA-N
• SMILES: C1CCN(C(C1)COC2=CC=CC(=C2C=O)O)C(=O)C3=CN=CC=C3

GBT1118 is a potent and orally active allosteric modifier of hemoglobin oxygen affinity. GBT1118 increases tolerance to severe hypoxia[1].
GBT1118 binds covalently and reversibly via an imine intermediate to the N-terminal valine of hemoglobin α chain, and allosterically increases intracellular hemoglobin affinity for O2[1].
GBT1118 (25% of sample hemoglobin concentration) protects red blood cells from damage during severe hypoxia[2].
GBT1118 (70 or 140 mg/kg; oral; once) increases tolerance to severe hypoxia in mice[1].
Blood and plasma pharmacokinetic parameters of GBT1118 in male mice following 10 mg/kg IV Administration of GBT1118[1]

Matrix
T1/2 (h)
AUC0-∞ (μg⋅h/mL)
Vss (L/kg)
CLs (mL/min/kg)
Blood/Plasma Ratio

Blood
13.9
2929
0.07
0.06
51.4

Plasma
11.3
60
2.95
3.21

Blood and plasma pharmacokinetic parameters of GBT1118 in male mice following 100 mg/kg PO Administration of GBT1118[1]

Matrix
Tmax (h)
Cmax (μg/mL)
AUC0-∞ (μg•h/mL)
F (%)
Blood/Plasma Ratio

Blood
2
318
13428
45.8
34.1

Plasma
8
12
224
33.5

Reference

[1]. Dufu K, et al. GBT1118, a potent allosteric modifier of hemoglobin O2 affinity, increases tolerance to severe hypoxia in mice. Am J Physiol Heart Circ Physiol. 2017 Aug 1;313(2):H381-H391.
 [Content Brief]

[2]. Tarasev M, et al. GBT1118, a voxelotor analog, protects red blood cells from damage during severe hypoxia. Am J Transl Res. 2022 Jan 15;14(1):240-251.
 [Content Brief]