SB-649868

Research use only, not for human use.

A potent, selective, orally bioavailable, dual orexin OX1/OX2R antagonist with pKi of 9.4 and 9.5 respectively.

A potent, selective, orally bioavailable, dual orexin OX1/OX2R antagonist with pKi of 9.4 and 9.5 respectively; displays >1,000-fold selectivity for the orexin target receptors in a broad panel of GPCRs, ion channels and enzymes; demonstrates high effectivity in pre-clinical model of sleep disorders.Sleep Disorder Phase 2 Discontinued(In Vitro):SB-649868 is identified as one the most in vitro potent dual OX1 and OX2 receptor antagonist known at that time (pKi=9.4 and 9.5 at the OX1 and OX2 receptor, respectively) . SB-649868 antagonizes orexin-A-induced inositol 1 phosphate (IP1) accumulation with the following pKB value (OX1=9.67; OX2=9.64). SB-649868 displaces the [3H]ACT-078573 receptor binding with the following pKi values: OX1=9.27; OX2=8.91. Increasing concentrations of SB-649868 (0.3 nM-30 nM) induces a rightward shift of the orexin-A CRCs with a depression of the agonist efficacy suggesting a clear non-surmountable behavior. The calculated apparent pKb values are 9.67±0.03 and 9.64±0.07 for OX1 and OX2.

SB-649868 is identified as one the most in vitro potent dual OX1 and OX2 receptor antagonist known at that time (pKi=9.4 and 9.5 at the OX1 and OX2 receptor, respectively) . SB-649868 antagonizes orexin-A-induced inositol 1 phosphate (IP1) accumulation with the following pKB value (OX1=9.67; OX2=9.64). SB-649868 displaces the [3H]ACT-078573 receptor binding with the following pKi values: OX1=9.27; OX2=8.91. Increasing concentrations of SB-649868 (0.3 nM-30 nM) induces a rightward shift of the orexin-A CRCs with a depression of the agonist efficacy suggesting a clear non-surmountable behavior. The calculated apparent pKb values are 9.67±0.03 and 9.64±0.07 for OX1 and OX2.

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SB 649868 | SB649868

GPCR/G Protein

Orexin Receptor

Orexin Receptor

Neurological Disease

Sleep Disorder

380899-24-1

477.554

C26H24FN3O3S

>98% (HPLC)

In Vitro:?DMSO : 100 mg/mL (209.40 mM)

O=C(C1=C2C=COC2=CC=C1)NC[C@H]3N(C(C4=C(C5=CC=C(F)C=C5)SC(C)=N4)=O)CCCC3

(S)-N-((1-(5-(4-fluorophenyl)-2-methylthiazole-4-carbonyl)piperidin-2-yl)methyl)benzofuran-4-carboxamide

(-20℃)

With Ice Pack

≥ 2 years