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Setipiprant (ACT-129968 and KYTH-105) is a novel, potent, orally bioavailable and selective CRTH2 antagonist. It has been demonstrated to be more specific for DP2 (prostaglandin D2 receptor 2-CRTH2) than for DP1. The G protein-coupled receptor for PGD2 is called CRTH2. When taken orally in multiple doses, setipiprant was well tolerated and in allergic asthmatics it decreased the allergen-induced lung inflammation as well as the related airway hyperresponsiveness. Treating allergic disorders may benefit from targeting CRTH2.
Physicochemical Properties
| Molecular Formula | C24H19FN2O3 |
| Molecular Weight | 402.41767 |
| Exact Mass | 402.137 |
| Elemental Analysis | C, 71.63; H, 4.76; F, 4.72; N, 6.96; O, 11.93 |
| CAS # | 866460-33-5 |
| Appearance | Light yellow to yellow solid powder |
| Density | 1.4±0.1 g/cm3 |
| Boiling Point | 690.4±55.0 °C at 760 mmHg |
| Flash Point | 371.4±31.5 °C |
| Vapour Pressure | 0.0±2.3 mmHg at 25°C |
| Index of Refraction | 1.682 |
| LogP | 3.39 |
| SMILES | O=C(CN1C2CCN(CC=2C2C1=CC=C(C=2)F)C(C1C2C(=CC=CC=2)C=CC=1)=O)O |
| InChi Key | IHAXLPDVOWLUOS-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C24H19FN2O3/c25-16-8-9-21-19(12-16)20-13-26(11-10-22(20)27(21)14-23(28)29)24(30)18-7-3-5-15-4-1-2-6-17(15)18/h1-9,12H,10-11,13-14H2,(H,28,29) |
| Chemical Name | 2-[8-fluoro-2-(naphthalene-1-carbonyl)-3,4-dihydro-1H-pyrido[4,3-b]indol-5-yl]acetic acid |
| Synonyms | Setipiprant; ACT-129968; ACT 129968; ACT129968; KYTH-105; KYTH105; KYTH 105 |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets | hCRTH2 ( IC50 = 6 nM ); hDP1 ( IC50 = 1290 nM ); EP2 ( IC50 = 2600 nM ) |
| ln Vitro |
Setipiprant (0-10 μM; 90 min) interacts with the hCRTH2 receptor in the assay buffer both with and without human serum albumin (HSA) with IC50 values of 6 and 340 nM, respectively[1]. Setipiprant (0-10 μM; 5-20 min) inhibits human eosinophil shape change, intracellular cAMP release mediated by the hCRTH2 receptor, and IC50 values of 30, 80, and 235 nM, respectively[1]. Setipiprant (0-10 μM) inhibits the prostanoid receptors hDP1, hEP2, and hEP4 with IC50 values of 1290, 2600, and <10000 nM, respectively[1]. |
| ln Vivo | 1.19 Pharmacokinetic properties of Setipiprant in rats and dogs [1]. AUC0-last (ng·h/mL) CL (mL/min/kg) T1/2 (hr) F (%) Rat IV 2 mg/kg 58500 1.3 6 44 Dog PO 10 mg/kg 91100 55 |
| References |
[1]. 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) Antagonis. 2013. |
Solubility Data
| Solubility (In Vitro) | DMSO: ~80 mg/mL (~198.8 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.21 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 + to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4850 mL | 12.4248 mL | 24.8497 mL | |
| 5 mM | 0.4970 mL | 2.4850 mL | 4.9699 mL | |
| 10 mM | 0.2485 mL | 1.2425 mL | 2.4850 mL |