PD-176252 | CAS#204067-01-6 | neuromedin B receptor Antagonist

MedKoo Cat#: 525902 | Name: PD-176252

Featured

Description:

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

PD-176252 is a non-peptide gastrin-releasing peptide receptor (GRP-R, BB2) and neuromedin B receptor (NMB-R, BB1) antagonist (Ki values are 0.17 and 1.0 nM for BB1 and BB2 respectively). It inhibits proliferation of rat C6 glioma cells (IC50 = 2 μM) and inhibits NCI-H1299 xenograft proliferation in nude mice (IC50 = 5 μM).

Chemical Structure

PD-176252

CAS#204067-01-6

Theoretical Analysis

MedKoo Cat#: 525902

Name: PD-176252

CAS#: 204067-01-6

Chemical Formula: C32H36N6O5

Exact Mass: 584.2747

Molecular Weight: 584.68

Elemental Analysis: C, 65.74; H, 6.21; N, 14.37; O, 13.68

Price and Availability

Size	Price	Availability	Quantity
10mg	USD 400.00

Bulk Inquiry

Buy Now

Add to Cart

Related CAS #

No Data

Synonym

PD-176252; PD 176252; PD176252.

IUPAC/Chemical Name

1H-Indole-3-propanamide, N-((1-(5-methoxy-2-pyridinyl)cyclohexyl)methyl)-alpha-methyl-alpha-((((4-nitrophenyl)amino)carbonyl)amino)-, (alphaS)-

InChi Key

NNFUWNLENRUDHR-HKBQPEDESA-N

InChi Code

InChI=1S/C32H36N6O5/c1-31(18-22-19-33-27-9-5-4-8-26(22)27,37-30(40)36-23-10-12-24(13-11-23)38(41)42)29(39)35-21-32(16-6-3-7-17-32)28-15-14-25(43-2)20-34-28/h4-5,8-15,19-20,33H,3,6-7,16-18,21H2,1-2H3,(H,35,39)(H2,36,37,40)/t31-/m0/s1

SMILES Code

O=C(NCC1(C2=NC=C(OC)C=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:

PD176252 is a potent antagonist of neuromedin-B preferring (BB1) and gastrin-releasing peptide-preferring (BB2) receptor with Kis of 0.17 nM and 1 nM for human BB1 and BB2 receptors, and 0.66 nM, 16 nM for Rat BB1 and BB2 receptors.

In vitro activity:

This paper describes the development of a novel series of non-peptide, "balanced" neuromedin-B preferring (BB1)/gastrin-releasing peptide preferring (BB2) receptor ligands as exemplified by PD 176252. PD 176252, which exhibits nanomolar affinity for both the BB1 (Ki = 0.15 nM) and BB2 (Ki = 1.0 nM) receptors, has been demonstrated to be a competitive antagonist at these bombesin receptor subtypes. Reference: Bioorg Med Chem Lett. 1998 Sep 22;8(18):2589-94. https://pubmed.ncbi.nlm.nih.gov/9873586/

In vivo activity:

The effects of PD 176252 [3-(1H-indol-3-yl)-N-[1-(5-methoxy-pyridin-2-yl)-cyclohexylmethyl]-2-methyl-2-[3-(nitro-phenyl)ureido]propionamide], a nonpeptide bombesin (BB) BB1/BB2 receptor antagonist, were assessed in rats using several ethologically relevant tests of anxiety. When administered directly to the dorsal raphé nucleus (DRN), PD 176252 (20-500 ng) increased social interaction under aversive conditions, as did the 5-HT1A receptor agonist 8-hydroxy-2(di-n-propylamino)tetralin (50 ng). Furthermore, intra-DRN microinfusion of the peptide antagonist (PD 176252) suppressed, whereas its agonist [neuromedin B (NMB)-30] promoted, the in vivo release of 5-HT in the ventral hippocampus. Reference: J Neurosci. 2006 Oct 11;26(41):10387-96. https://pubmed.ncbi.nlm.nih.gov/17035523/

	Solvent	mg/mL	mM
Solubility
	DMSO	86.7	148.35

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 584.68 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. 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. 2. Ashwood V, Brownhill V, Higginbottom M, Horwell DC, Hughes J, Lewthwaite RA, McKnight AT, Pinnock RD, Pritchard MC, Suman-Chauhan N, Webb C, Williams SC. PD 176252--the first high affinity non-peptide gastrin-releasing peptide (BB2) receptor antagonist. Bioorg Med Chem Lett. 1998 Sep 22;8(18):2589-94. doi: 10.1016/s0960-894x(98)00462-4. PMID: 9873586. 3. Merali Z, Bédard T, Andrews N, Davis B, McKnight AT, Gonzalez MI, Pritchard M, Kent P, Anisman H. Bombesin receptors as a novel anti-anxiety therapeutic target: BB1 receptor actions on anxiety through alterations of serotonin activity. J Neurosci. 2006 Oct 11;26(41):10387-96. doi: 10.1523/JNEUROSCI.1219-06.2006. PMID: 17035523; PMCID: PMC6674684.

In vitro protocol:

In vivo protocol:

1. Merali Z, Bédard T, Andrews N, Davis B, McKnight AT, Gonzalez MI, Pritchard M, Kent P, Anisman H. Bombesin receptors as a novel anti-anxiety therapeutic target: BB1 receptor actions on anxiety through alterations of serotonin activity. J Neurosci. 2006 Oct 11;26(41):10387-96. doi: 10.1523/JNEUROSCI.1219-06.2006. PMID: 17035523; PMCID: PMC6674684. 2. 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.

1: Zhu Y, Wang H, Yu M, Li C, Meng X, He M, Yao R. Design, Synthesis and Biological Evaluation of Novel 1, 3, 4-Oxadiazole PD176252 Analogues as Potential GRPR Inhibitors. Anticancer Agents Med Chem. 2022;22(17):3009-3024. doi: 10.2174/1871520622666220501162813. PMID: 35490428. 2: Yu MJ, Yao S, Li TT, Yang R, Yao RS. Dual Anti-cancer and Anti-Itch Activity of PD176252 Analogues: Design, Synthesis and Biological Evaluation. Anticancer Agents Med Chem. 2019;19(8):992-1001. doi: 10.2174/1871520619666190408133141. PMID: 30961511. 3: Lacivita E, Lucente E, Kwizera C, Antunes IF, Niso M, De Giorgio P, Perrone R, Colabufo NA, Elsinga PH, Leopoldo M. Structure-activity relationship study towards non-peptidic positron emission tomography (PET) radiotracer for gastrin releasing peptide receptors: Development of [18F] (S)-3-(1H-indol-3-y l)-N-[1-[5-(2-fluoroethoxy)pyridin-2-yl]cyclohexylmethyl]-2-methyl-2-[3-(4-nitro phenyl)ureido]propionamide. Bioorg Med Chem. 2017 Jan 1;25(1):277-292. doi: 10.1016/j.bmc.2016.10.031. Epub 2016 Oct 29. PMID: 27863916. 4: Carrieri A, Lacivita E, Belviso BD, Caliandro R, Mastrorilli P, Gallo V, Niso M, Leopoldo M. Structural Determinants in the Binding of BB2 Receptor Ligands: In Silico, X-Ray and NMR Studies in PD176252 Analogues. Curr Top Med Chem. 2017;17(14):1599-1610. doi: 10.2174/1568026617666161104102459. PMID: 27823569. 5: Pereira PJ, Machado GD, Danesi GM, Canevese FF, Reddy VB, Pereira TC, Bogo MR, Cheng YC, Laedermann C, Talbot S, Lerner EA, Campos MM. GRPR/PI3Kγ: Partners in Central Transmission of Itch. J Neurosci. 2015 Dec 9;35(49):16272-81. doi: 10.1523/JNEUROSCI.2310-15.2015. PMID: 26658875; PMCID: PMC4682789. 6: Laukkanen MO, Castellone MD. Gastrin-Releasing Peptide Receptor Targeting in Cancer Treatment: Emerging Signaling Networks and Therapeutic Applications. Curr Drug Targets. 2016;17(5):508-14. doi: 10.2174/1389450116666151001112130. PMID: 26424393. 7: 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. 8: Tattersall M, Cordeaux Y, Charnock-Jones DS, Smith GC. Expression of gastrin- releasing peptide is increased by prolonged stretch of human myometrium, and antagonists of its receptor inhibit contractility. J Physiol. 2012 May 1;590(9):2081-93. doi: 10.1113/jphysiol.2012.228239. Epub 2012 Mar 12. PMID: 22411014; PMCID: PMC3447152. 9: 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. 10: Li X, Lv Y, Yuan A, Yi S, Ma Y, Li Z. Gastrin-releasing peptide promotes the growth of HepG2 cells via EGFR-independent ERK1/2 activation. Oncol Rep. 2010 Aug;24(2):441-8. doi: 10.3892/or_00000877. PMID: 20596631. 11: Zhang Q, Bhola NE, Lui VW, Siwak DR, Thomas SM, Gubish CT, Siegfried JM, Mills GB, Shin D, Grandis JR. Antitumor mechanisms of combined gastrin-releasing peptide receptor and epidermal growth factor receptor targeting in head and neck cancer. Mol Cancer Ther. 2007 Apr;6(4):1414-24. doi: 10.1158/1535-7163.MCT-06-0678. PMID: 17431120. 12: Bédard T, Mountney C, Kent P, Anisman H, Merali Z. Role of gastrin-releasing peptide and neuromedin B in anxiety and fear-related behavior. Behav Brain Res. 2007 Apr 16;179(1):133-40. doi: 10.1016/j.bbr.2007.01.021. Epub 2007 Jan 31. PMID: 17335915. 13: Merali Z, Bédard T, Andrews N, Davis B, McKnight AT, Gonzalez MI, Pritchard M, Kent P, Anisman H. Bombesin receptors as a novel anti-anxiety therapeutic target: BB1 receptor actions on anxiety through alterations of serotonin activity. J Neurosci. 2006 Oct 11;26(41):10387-96. doi: 10.1523/JNEUROSCI.1219-06.2006. PMID: 17035523; PMCID: PMC6674684. 14: Moody TW, Nakagawa T, Kang Y, Jakowlew S, Chan D, Jensen RT. Bombesin/gastrin-releasing peptide receptor antagonists increase the ability of histone deacetylase inhibitors to reduce lung cancer proliferation. J Mol Neurosci. 2006;28(3):231-8. doi: 10.1385/JMN:28:3:231. PMID: 16691010. 15: 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. 16: 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. 17: Ashwood V, Brownhill V, Higginbottom M, Horwell DC, Hughes J, Lewthwaite RA, McKnight AT, Pinnock RD, Pritchard MC, Suman-Chauhan N, Webb C, Williams SC. PD 176252--the first high affinity non-peptide gastrin-releasing peptide (BB2) receptor antagonist. Bioorg Med Chem Lett. 1998 Sep 22;8(18):2589-94. doi: 10.1016/s0960-894x(98)00462-4. PMID: 9873586.