[CAS NO. 204066-82-0] PD168368
PRODUCTS SPECIFICATIONS [204066-82-0]
DESCRIPTION [204066-82-0]
Overview
| MDL | MFCD09971100 |
|---|---|
| Molecular Weight | 554.64 |
| Molecular Formula | C31H34N6O4 |
| SMILES | O=C([C@](C)(CC1=CNC2=C1C=CC=C2)NC(NC3=CC=C(C=C3)[N+]([O-])=O)=O)NCC4(CCCCC4)C5=NC=CC=C5 |
Summary
PD 168368 is a potent, competitive, and selective neuromedin B receptor ( NMB-R ) antagonist with the K i of 15–45 nM [1] . PD 168368 is neuromedin B receptor ( NMBR ; IC 50 =96 nM) / gastrin-releasing peptide receptor ( GRPR IC 50 =3500 nM) antagonist [2] . PD 168368 also is a mixed FPR1/FPR2/FPR3 agonist with EC 50 s of 0.57, 0.24, and 2.7 nM, respectively [3] .
In Vitro
PD 168368 (PD168368) is highly active and stimulated [Ca
2+
]
I
release in human neutrophils with EC
50
values in the nanomolar range
[3]
.
PD 168368 (PD168368) suppresses migration and invasion of the human breast cancer cell line MDA-MB-231. PD 168368 reduces epithelial-mesenchymal transition (EMT) of breast cancer cells by E-cadherin upregulation and vimentin downregulation. PD 168368 (5 μM) inhibits migration and invasiveness in breast cancer cells
[4]
.
PD 168368 (10 μM) suppresses the activation of mTOR/p70S6K/4EBP1 and AKT/GSK-3β pathways in breast cancer cells
[4]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Viability Assay [4]
| Cell Line: | Human breast cancer cell line MDA-MB-231 |
| Concentration: | 5 μM |
| Incubation Time: | 24 hours |
| Result: | Clearly decreased the migratory ability of MDA-MB-231 cells in a Boyden chamber migration assay. |
Cell Viability Assay [4]
| Cell Line: | MDA-MB-231 cells |
| Concentration: | 10 μM |
| Incubation Time: | 0, 0.5, 1, 2, 4, 8, and 16 hours |
| Result: | Decreased phosphorylation levels of mTOR, p70S6K, 4EBP1, AKT and GSK-3β in a time-dependent manner. |
In Vivo
PD 168368 (PD168368) potently inhibits in vivo metastasis of breast cancer. PD 168368 (1.2 mg/kg; intraperitoneal injection for 30 days) inhibits metastasis of breast cancer in mice [4] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
| Animal Model: | Female BALB/c-nude mice (age 8-10 weeks) bearing MDA-MB-231 xenograft model [4] |
| Dosage: | 1.2 mg/kg |
| Administration: | Intraperitoneal injection for 30 days |
| Result: | No metastatic tumor nodules were observed in lungs of PD 168368-treated mice compared to PEG-injected mice. |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Powder | -20°C | 3 years |
|---|---|---|
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
DMSO : 30 mg/mL ( 54.09 mM ; Need ultrasonic and warming)
DMF : 10 mg/mL ( 18.03 mM ; Need ultrasonic and warming)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 1.8030 mL | 9.0149 mL | 18.0297 mL |
| 5 mM | 0.3606 mL | 1.8030 mL | 3.6059 mL |
| 10 mM | 0.1803 mL | 0.9015 mL | 1.8030 mL |
References
- [1] R R Ryan, et al. Comparative pharmacology of the nonpeptide neuromedin B receptor antagonist PD 168368. J Pharmacol Exp Ther. 1999 Sep;290(3):1202-11.
- [2] K Tokita, et al. Tyrosine 220 in the 5th transmembrane domain of the neuromedin B receptor is critical for the high selectivity of the peptoid antagonist PD168368. J Biol Chem. 2001 Jan 5;276(1):495-504.
- [3] Igor A Schepetkin, et al. Gastrin-releasing peptide/neuromedin B receptor antagonists PD176252, PD168368, and related analogs are potent agonists of human formyl-peptide receptors. Mol Pharmacol. 2011 Jan;79(1):77-90.
- [4] Hyun-Joo Park, et al. Neuromedin B receptor antagonism inhibits migration, invasion, and epithelial-mesenchymal transition of breast cancer cells. Int J Oncol. 2016 Sep;49(3):934-42.