PD 168368 is a potent, competitive and selective neuregulin B receptor (NMB-R) antagonist (inhibitor) with Ki of 15-45 nM. PD 168368 is a dual antagonist of the neuregulin B receptor (NMBR; IC50=96 nM) and gastrin-releasing peptide receptor (GRPR; IC50=3500 nM). PD 168368 is also a mixed agonist of FPR1/FPR2/FPR3 with EC50 of 0.57, 0.24 and 2.7 nM respectively.

Physicochemical Properties

Molecular Formula	C31H34N6O4
Molecular Weight	554.65
Exact Mass	554.264
CAS #	204066-82-0
PubChem CID	9937534
Appearance	White to off-white solid powder
LogP	6.99
Hydrogen Bond Donor Count	4
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	8
Heavy Atom Count	41
Complexity	913
Defined Atom Stereocenter Count	1
SMILES	C[C@](CC1=CNC2=CC=CC=C21)(C(=O)NCC3(CCCCC3)C4=CC=CC=N4)NC(=O)NC5=CC=C(C=C5)[N+](=O)[O-]
InChi Key	AFDXUTWMFMAQJO-PMERELPUSA-N
InChi Code	InChI=1S/C31H34N6O4/c1-30(19-22-20-33-26-10-4-3-9-25(22)26,36-29(39)35-23-12-14-24(15-13-23)37(40)41)28(38)34-21-31(16-6-2-7-17-31)27-11-5-8-18-32-27/h3-5,8-15,18,20,33H,2,6-7,16-17,19,21H2,1H3,(H,34,38)(H2,35,36,39)/t30-/m0/s1
Chemical Name	(2S)-3-(1H-indol-3-yl)-2-methyl-2-[(4-nitrophenyl)carbamoylamino]-N-[(1-pyridin-2-ylcyclohexyl)methyl]propanamide
Synonyms	PD-168368; PD168368; PD 168368
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

ln Vitro	With EC50 values in the nanomolar range, PD 168368 (PD168368) is a highly active compound that stimulates the release of [Ca2+]I from human neutrophils [3]. Inhibiting the migration and invasion of the human breast cancer cell line MDA-MB-231 is PD 168368 (PD168368). In breast cancer cells, PD 168368 inhibits the epithelial-mesenchymal transition (EMT) by up-regulating E-cadherin and down-regulating vimentin. The migration and invasion of breast cancer cells is inhibited by PD 168368 (5 μM) [4]. In breast cancer cells, PD 168368 (10 μM) inhibits the activation of the mTOR/p70S6K/4EBP1 and AKT/GSK-3β pathways [4].
ln Vivo	Effectively preventing breast cancer metastases in vivo is PD 168368 (PD168368). Mice treated intraperitoneally with PD 168368 (1.2 mg/kg for 30 days) are less likely to develop breast cancer [4].
Cell Assay	Cell viability assay [4] Cell Types: Human breast cancer cell line MDA-MB-231 Tested Concentrations: 5 μM Incubation Duration: 24 hrs (hours) Experimental Results: The migration ability of MDA-MB-231 cells was Dramatically diminished in the Boyden chamber migration assay. Cell viability assay[4] Cell Types: MDA-MB-231 Cell Tested Concentrations: 10 μM Incubation Duration: 0, 0.5, 1, 2, 4, 8 and 16 hrs (hours) Experimental Results: diminished mTOR, p70S6K, 4EBP1, AKT phosphorylation levels and GSK-3β in a time-dependent manner.
Animal Protocol	Animal/Disease Models: Female BALB/c-nude mice (8-10 weeks) carrying MDA-MB-231 xenograft model [4] Doses: 1.2 mg/kg Route of Administration: intraperitoneal (ip) injection for 30 days Experimental Results: No metastatic tumors were observed Nodules in the lungs of PD 168368-treated mice compared with PEG-injected mice.
References	[1]. Comparative pharmacology of the nonpeptide neuromedin B receptor antagonist PD 168368. J Pharmacol Exp Ther. 1999 Sep;290(3):1202-11. [2]. 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]. 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]. Neuromedin B receptor antagonism inhibits migration, invasion, and epithelial-mesenchymal transition of breast cancer cells. Int J Oncol. 2016 Sep;49(3):934-42.

Solubility Data

Solubility (In Vitro)

DMSO : ~30 mg/mL (~54.09 mM) DMF : 10 mg/mL (~18.03 mM)

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.8029 mL	9.0147 mL	18.0294 mL
	5 mM	0.3606 mL	1.8029 mL	3.6059 mL
	10 mM	0.1803 mL	0.9015 mL	1.8029 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.