NTP42 is a novel thromboxane A2 (TXA2) receptor antagonist with an IC50 of 3.278 nM for antagonizing T prostanoid receptor (TP)- mediated [Ca2+] mobilization following stimulation of cells with the alternative TP agonist U46609. The pulmonary arterial hypertension (PAH) condition can be treated with NTP42. Treatment for pulmonary arterial hypertension (PAH) is presently being developed with NTP42. Excessive pulmonary vasoconstriction, vascular remodeling, inflammation, fibrosis, in situ thrombosis, and right ventricular hypertrophy are just a few of the pathophysiological features of PAH, a devastating disease.
Physicochemical Properties
| Molecular Formula | C25H23F2N3O5S |
| Molecular Weight | 515.529031991959 |
| Exact Mass | 515.13 |
| Elemental Analysis | C, 58.25 H, 4.50 F, 7.37 N, 8.15 O, 15.52 S, 6.22 |
| CAS # | 2055599-51-2 |
| PubChem CID | 124147085 |
| Appearance | White to off-white solid powder |
| LogP | 5.3 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 8 |
| Rotatable Bond Count | 8 |
| Heavy Atom Count | 36 |
| Complexity | 888 |
| Defined Atom Stereocenter Count | 0 |
| InChi Key | RIIKDGPBTPECSW-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C25H23F2N3O5S/c1-25(2,3)29-24(31)30-36(32,33)22-13-16(15-28)7-12-21(22)34-20-6-4-5-18(14-20)17-8-10-19(11-9-17)35-23(26)27/h4-14,23H,1-3H3,(H2,29,30,31) |
| Chemical Name | 1-tert-butyl-3-[5-cyano-2-[3-[4-(difluoromethoxy)phenyl]phenoxy]phenyl]sulfonylurea |
| Synonyms | NTP-42; NTP 42; NTP42 |
| 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 | TXA2 |
| ln Vivo | NTP42 (0.25 mg/kg BID) was successful in the hemodynamic evaluation of the PAH trajectory model induced by monocrotaline (MCT) (a 28-day medication regimen initiated within 24 hours of MCT). NTP42 lowers right systolic blood pressure (RSVP) and mean pulmonary artery pressure (mPAP), two measures of PAH brought on by MCT. Moreover, NTP42 was linked to a significant reduction in pulmonary vascular proliferation, activation of inflammatory mast cells, and fibrosis in animals treated with MCT when combined with sildenafil and Selelexipag[2]. |
| Animal Protocol |
Male Wistar-Kyoto rats 0.25 mg/kg BID 28-day drug treatment was initiated within 24 h post-MCT (60 mg/kg) |
| References |
[1]. Thromboxane receptor antagonists. WO2016203314A1. [2]. NTP42, a novel antagonist of the thromboxane receptor, attenuates experimentally induced pulmonary arterial hypertension. |
Solubility Data
| Solubility (In Vitro) | DMSO: ~31.3 mg/mL (~60.6 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.03 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 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 20.8 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. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.03 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9398 mL | 9.6988 mL | 19.3975 mL | |
| 5 mM | 0.3880 mL | 1.9398 mL | 3.8795 mL | |
| 10 mM | 0.1940 mL | 0.9699 mL | 1.9398 mL |