PD 168368 | CAS#204066-82-0| NMB Receptor Antagonist

MedKoo Cat#: 532455 | Name: PD 168368

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Description:

WARNING: This product is for research use only, not for human or veterinary use.

PD 168368 is a competitive antagonist of neuromedin B (NMB) receptors (Kis = 15-45 nM for rat and human receptors expressed in various cell lines). It blocks the elevation of intracellular calcium and release of inositol phosphate induced by NMB in cells expressing NMB receptors.

Chemical Structure

PD 168368

CAS#204066-82-0

Theoretical Analysis

MedKoo Cat#: 532455

Name: PD 168368

CAS#: 204066-82-0

Chemical Formula: C31H34N6O4

Exact Mass: 554.2642

Molecular Weight: 554.65

Elemental Analysis: C, 67.13; H, 6.18; N, 15.15; O, 11.54

Price and Availability

Size	Price	Availability	Quantity
5mg	USD 600.00
10mg	USD 850.00

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Synonym

PD 168368; PD168368; PD-168368.

IUPAC/Chemical Name

(2S)-3-(1H-indol-3-yl)-2-methyl-2-[(4-nitrophenyl)carbamoylamino]-N-[(1-pyridin-2-ylcyclohexyl)methyl]propanamide

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

SMILES Code

O=C(NCC1(C2=NC=CC=C2)CCCCC1)[C@](NC(NC3=CC=C([N+]([O-])=O)C=C3)=O)(C)CC4=CNC5=C4C=CC=C5

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Instruction

View handling instruction

Biological target:

PD 168368 is a potent, competitive, and selective neuromedin B receptor (NMB-R) antagonist with the Ki of 15–45 nM.

In vitro activity:

The present study found that NMB and its receptor NMBR are aberrantly expressed in cervical cancer. NMB activates ERK1/2 and NF-κB signaling pathways, which promote the proliferation of cervical cancer cells and increase the expression of tumor necrosis factor α (TNF-α). The downregulation of NMBR by the specific inhibitor, PD168368, abrogates proliferation and promotes apoptosis of cervical cancer cells. Reference: Pathol Res Pract. 2022 Sep 6;238:154104. https://pubmed.ncbi.nlm.nih.gov/36095918/

In vivo activity:

As shown in Fig. 4D, the aortas of CKD rats had extensive calcification as compared with those from the sham rats. This was significantly alleviated in the aortas of the animals from PD168368-treated CKD group, resulting in reduced deposition of calcium as well as a small ratio of calcified area. The serum level of NMB was also increased in CKD rats compared with sham rats, which was restored to normal levels by PD 168368 treatment (Fig. 4E). Finally, western blotting demonstrated that PD168368 treatment blocked the osteogenic conversion and apoptosis in the aorta of CKD rats (Fig. 4F). Reference: BMB Rep. 2021 Nov;54(11):569-574. https://pubmed.ncbi.nlm.nih.gov/34674793/

	Solvent	mg/mL	mM
Solubility
	DMF	10.0	18.03
	DMSO	30.0	54.09
	DMSO:PBS (pH 7.2) (1:2)	0.3	0.54

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 554.65 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Zeng R, Xiong X. Effect of NMB-regulated ERK1/2 and p65 signaling pathway on proliferation and apoptosis of cervical cancer. Pathol Res Pract. 2022 Sep 6;238:154104. doi: 10.1016/j.prp.2022.154104. Epub ahead of print. PMID: 36095918. 2. Park HJ, Kim MK, Choi KS, Jeong JW, Bae SK, Kim HJ, Bae MK. Neuromedin B receptor antagonism inhibits migration, invasion, and epithelial-mesenchymal transition of breast cancer cells. Int J Oncol. 2016 Sep;49(3):934-42. doi: 10.3892/ijo.2016.3590. Epub 2016 Jun 30. PMID: 27571778. 3. Park HJ, Kim MK, Kim Y, Kim HJ, Bae SK, Bae MK. Neuromedin B modulates phosphate-induced vascular calcification. BMB Rep. 2021 Nov;54(11):569-574. doi: 10.5483/BMBRep.2021.54.11.089. PMID: 34674793; PMCID: PMC8633520. 4. Moody TW, Jensen RT, Garcia L, Leyton J. Nonpeptide neuromedin B receptor antagonists inhibit the proliferation of C6 cells. Eur J Pharmacol. 2000 Dec 8;409(2):133-42. doi: 10.1016/s0014-2999(00)00828-1. PMID: 11104826.

In vitro protocol:

In vivo protocol:

1. Park HJ, Kim MK, Kim Y, Kim HJ, Bae SK, Bae MK. Neuromedin B modulates phosphate-induced vascular calcification. BMB Rep. 2021 Nov;54(11):569-574. doi: 10.5483/BMBRep.2021.54.11.089. PMID: 34674793; PMCID: PMC8633520. 2. Moody TW, Jensen RT, Garcia L, Leyton J. Nonpeptide neuromedin B receptor antagonists inhibit the proliferation of C6 cells. Eur J Pharmacol. 2000 Dec 8;409(2):133-42. doi: 10.1016/s0014-2999(00)00828-1. PMID: 11104826.

1: de Paula GSM, Wilieman M, Silva KR, Baptista LS, Boudina S, de Souza LL, Bento-Bernardes T, Asensi KD, Goldenberg RCDS, Pazos-Moura CC. Neuromedin B receptor disruption impairs adipogenesis in mice and 3T3-L1 cells. J Mol Endocrinol. 2019 Jul;63(1):93-102. doi: 10.1530/JME-19-0032. PMID: 31067509; PMCID: PMC9931200. 2: Ehling S, Fukuyama T, Ko MC, Olivry T, Bäumer W. Neuromedin B Induces Acute Itch in Mice via the Activation of Peripheral Sensory Neurons. Acta Derm Venereol. 2019 May 1;99(6):587-893. doi: 10.2340/00015555-3143. PMID: 30734045; PMCID: PMC9083373. 3: Park HJ, Kim MK, Choi KS, Jeong JW, Bae SK, Kim HJ, Bae MK. Neuromedin B receptor antagonism inhibits migration, invasion, and epithelial-mesenchymal transition of breast cancer cells. Int J Oncol. 2016 Sep;49(3):934-42. doi: 10.3892/ijo.2016.3590. Epub 2016 Jun 30. PMID: 27571778. 4: Sukhtankar DD, Ko MC. Physiological function of gastrin-releasing peptide and neuromedin B receptors in regulating itch scratching behavior in the spinal cord of mice. PLoS One. 2013 Jun 24;8(6):e67422. doi: 10.1371/journal.pone.0067422. PMID: 23826298; PMCID: PMC3691251. 5: Schepetkin IA, Kirpotina LN, Khlebnikov AI, Leopoldo M, Lucente E, Lacivita E, De Giorgio P, Quinn MT. 3-(1H-indol-3-yl)-2-[3-(4-nitrophenyl)ureido]propanamide enantiomers with human formyl-peptide receptor agonist activity: molecular modeling of chiral recognition by FPR2. Biochem Pharmacol. 2013 Feb 1;85(3):404-16. doi: 10.1016/j.bcp.2012.11.015. Epub 2012 Dec 3. PMID: 23219934; PMCID: PMC3553303. 6: Park HJ, Kim SR, Kim MK, Choi KS, Jang HO, Yun I, Bae SK, Bae MK. Neuromedin B receptor antagonist suppresses tumor angiogenesis and tumor growth in vitro and in vivo. Cancer Lett. 2011 Dec 15;312(1):117-27. doi: 10.1016/j.canlet.2011.08.014. Epub 2011 Aug 22. PMID: 21908103. 7: Su PY, Ko MC. The role of central gastrin-releasing peptide and neuromedin B receptors in the modulation of scratching behavior in rats. J Pharmacol Exp Ther. 2011 Jun;337(3):822-9. doi: 10.1124/jpet.111.178970. Epub 2011 Mar 18. PMID: 21421741; PMCID: PMC3101014. 8: Schepetkin IA, Kirpotina LN, Khlebnikov AI, Jutila MA, Quinn MT. 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. doi: 10.1124/mol.110.068288. Epub 2010 Oct 13. PMID: 20943772; PMCID: PMC3014281. 9: Giraud AS, Dumesny C, Whitley JC, Parker LM, Jennings I, Kemp B, Moody TW, Sancho V, Jensen RT, Shulkes A. Isolation, identification and biological activity of gastrin-releasing peptide 1-46 (oGRP 1-46), the primary GRP gene- derived peptide product of the pregnant ovine endometrium. Peptides. 2010 Feb;31(2):284-90. doi: 10.1016/j.peptides.2009.11.013. Epub 2009 Nov 26. PMID: 19944725; PMCID: PMC2818757. 10: Moody TW, Leyton J, Garcia-Marin L, Jensen RT. Nonpeptide gastrin releasing peptide receptor antagonists inhibit the proliferation of lung cancer cells. Eur J Pharmacol. 2003 Aug 1;474(1):21-9. doi: 10.1016/s0014-2999(03)01996-4. PMID: 12909192. 11: Moody TW, Jensen RT, Garcia L, Leyton J. Nonpeptide neuromedin B receptor antagonists inhibit the proliferation of C6 cells. Eur J Pharmacol. 2000 Dec 8;409(2):133-42. doi: 10.1016/s0014-2999(00)00828-1. PMID: 11104826. 12: Tokita K, Hocart SJ, Katsuno T, Mantey SA, Coy DH, Jensen RT. 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. doi: 10.1074/jbc.M006059200. PMID: 11013243. 13: Ryan RR, Katsuno T, Mantey SA, Pradhan TK, Weber HC, Coy DH, Battey JF, Jensen RT. Comparative pharmacology of the nonpeptide neuromedin B receptor antagonist PD 168368. J Pharmacol Exp Ther. 1999 Sep;290(3):1202-11. PMID: 10454496.