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Setipiprant (ACT-129968, KYTH-105)

Cat. No. M20536
Setipiprant (ACT-129968, KYTH-105) Structure
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Biological Activity

Setipiprant(ACT-129968, KYTH-105) is a selective, orally available antagonist of the prostaglandin D2 receptor 2 (DP2) that that has been shown to have greater specificity for DP2 (CRTH2) than for DP1.

Chemical Information
Molecular Weight 402.42
Formula C24H19FN2O3
CAS Number 866460-33-5
Solubility (25°C) DMSO 80 mg/mL
Storage Powder          -20°C   3 years ;  4°C   2 years
In solvent       -80°C   6 months ;  -20°C   1 month
Conversion of different model animals based on BSA (PMID: 27057123)
Species Mouse Rat Rabbit Guinea pig Hamster Dog
Weight (kg) 0.02 0.15 1.8 0.4 0.08 10
Body Surface Area (m2) 0.007 0.025 0.15 0.05 0.02 0.5
Km factor 3 6 12 8 5 20
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.

References

[1] Andreas Krause, et al. Clin Pharmacokinet. Pharmacokinetic/Pharmacodynamic Modelling of Receptor Internalization with CRTH2 Antagonists to Optimize Dose Selection

[2] Philippe Risch, et al. J Med Chem. Verification of the Major Metabolic Oxidation Path for the Naphthoyl Group in Chemoattractant Receptor-Homologous Molecule Expressed on Th2 Cells (CRTh2) Antagonist 2-(2-(1-Naphthoyl)-8-fluoro-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)acetic Acid (Setipi䲧皬Ỵ皭㧀皫羹癆

[3] Martine Gehin, et al. Eur J Clin Pharmacol. Pharmacokinetic interactions between simvastatin and setipiprant, a CRTH2 antagonist

[4] Z Diamant, et al. Clin Exp Allergy. Setipiprant, a selective CRTH2 antagonist, reduces allergen-induced airway responses in allergic asthmatics

[5] Heinz Fretz, et al. J Med Chem. Identification of 2-(2-(1-naphthoyl)-8-fluoro-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)acetic acid (setipiprant/ACT-129968), a potent, selective, and orally bioavailable chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) antagon䲧皬

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