SB-222200 is a novel, potent, selective, reversible, brain penetrant and competitive antagonist of human NK-3 receptor with Ki of 4.4 nM. SB-222200 counteracted NKB-induced Ca(2+) mobilization in HEK 293 cells that were stably expressing the hNK-3 receptor (HEK 293-hNK-3R) with an IC(50) = 18.4 nM.It also inhibited (125)I-[MePhe(7)]neurokinin B (NKB) binding to Chinese hamster ovary (CHO) cell membranes stably expressing the hNK-3 receptor (CHO-hNK-3R) with a K(i) = 4.4 nM. Comparing hNK-3 receptors to hNK-1 (K(i) > 100,000 nM) and hNK-2 (K(i) = 250 nM) receptors, SB-222200 was more selective for your target.
Physicochemical Properties
| Molecular Formula | C26H24N2O |
| Molecular Weight | 380.4816 |
| Exact Mass | 380.189 |
| Elemental Analysis | C, 82.07; H, 6.36; N, 7.36; O, 4.20 |
| CAS # | 174635-69-9 |
| PubChem CID | 6604009 |
| Appearance | White to off-white solid powder |
| Density | 1.142g/cm3 |
| Boiling Point | 553.5ºC at 760 mmHg |
| Flash Point | 288.6ºC |
| Vapour Pressure | 2.7E-12mmHg at 25°C |
| Index of Refraction | 1.633 |
| LogP | 6.482 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 2 |
| Rotatable Bond Count | 5 |
| Heavy Atom Count | 29 |
| Complexity | 523 |
| Defined Atom Stereocenter Count | 1 |
| SMILES | O=C(C1C2=C([H])C([H])=C([H])C([H])=C2N=C(C2C([H])=C([H])C([H])=C([H])C=2[H])C=1C([H])([H])[H])N([H])[C@]([H])(C1C([H])=C([H])C([H])=C([H])C=1[H])C([H])([H])C([H])([H])[H] |
| InChi Key | MQNYRKWJSMQECI-QFIPXVFZSA-N |
| InChi Code | InChI=1S/C26H24N2O/c1-3-22(19-12-6-4-7-13-19)28-26(29)24-18(2)25(20-14-8-5-9-15-20)27-23-17-11-10-16-21(23)24/h4-17,22H,3H2,1-2H3,(H,28,29)/t22-/m0/s1 |
| Chemical Name | 3-methyl-2-phenyl-N-[(1S)-1-phenylpropyl]quinoline-4-carboxamide |
| Synonyms | SB222200; SB-222200; SB 222200 |
| 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 | NK3 |
| ln Vitro |
SB-222200 prevents CHO cell membranes from being bound by 125I-[MePhe7]neurokinin B (NKB), which is necessary for the stable expression of the hNK-3 receptor (CHO-hNK-3R) at a Ki of 4.4 nM[1]. SB-222200 stably expresses the hNK-3 receptor (HEK 293-hNK-3R), inhibiting NKB-induced Ca2+ mobilization in these cells with an IC50 of 18.4 nM[1]. SB-222200 is hNK-3 receptor selective as opposed to hNK-1 (Ki>100,000 nM) and hNK-2 (Ki=250 nM) receptors[1]. SB-222200 (10 nM-1 μM) inhibits NKB-induced Ca2+ mobilization in a concentration-dependent and surmountable manner in HEK 293-hNK-3R cells[1]. |
| ln Vivo |
SB-222200 (5 mg/kg; 30 min pretreatment) produces inhibition of behavioral responses in mice induced by senktide (HY-P0187), a selective agonist of the NK-3 receptor[1]. SB-2222006 indicates that after oral administration of 10 mg/kg, the rat has a moderate oral bioavailability (46%) and a Cmax of 427 ng/mL[1]. SB-2222006 displays a terminal elimination half-life of 1.9 hours in rats as a result of a high plasma clearance of 56 mL/min/kg after intravenous administration of 2.5 mg/kg.[1]. |
| Animal Protocol |
Male BALB/c mice (19-21 g) 5 mg/kg Oral administration |
| References |
[1]. Nonpeptide tachykinin receptor antagonists. II. Pharmacological and pharmacokinetic profile of SB-222200, a central nervous system penetrant, potent and selective NK-3 receptor antagonist. J Pharmacol Exp Ther. 2000 Oct;295(1):373-81. |
| Additional Infomation | 3-methyl-2-phenyl-N-[(1S)-1-phenylpropyl]-4-quinolinecarboxamide is a member of quinolines. |
Solubility Data
| Solubility (In Vitro) | DMSO: ≥ 100 mg/mL (~262.8 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.57 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 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. Solubility in Formulation 2: ≥ 2.5 mg/mL (6.57 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 25.0 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 | 2.6283 mL | 13.1413 mL | 26.2826 mL | |
| 5 mM | 0.5257 mL | 2.6283 mL | 5.2565 mL | |
| 10 mM | 0.2628 mL | 1.3141 mL | 2.6283 mL |