JNJ-31020028 | CAS#1094873-14-9 | Y2R antagonist

MedKoo Cat#: 510336 | Name: JNJ-31020028

Description:

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

JNJ-31020028 is a selective brain penetrant small molecule antagonist of the neuropeptide Y Y(2) receptor. JNJ-31020028 bound with high affinity (pIC(50) = 8.07 +/- 0.05, human, and pIC(50) = 8.22 +/- 0.06, rat) and was >100-fold selective versus human Y(1), Y(4), and Y(5) receptors. JNJ-31020028 was demonstrated to be an antagonist (pK(B) = 8.04 +/- 0.13) in functional assays. JNJ-31020028 occupied Y(2) receptor binding sites (approximately 90% at 10 mg/kg) after subcutaneous administration in rats. JNJ-31020028 increased norepinephrine release in the hypothalamus, consistent with the colocalization of norepinephrine and neuropeptide Y. In a variety of anxiety models, JNJ-31020028 was found to be ineffective, although it did block stress-induced elevations in plasma corticosterone, without altering basal levels, and normalized food intake in stressed animals without affecting basal food intake.

Chemical Structure

JNJ-31020028

CAS#1094873-14-9 (recemate)

Theoretical Analysis

MedKoo Cat#: 510336

Name: JNJ-31020028

CAS#: 1094873-14-9 (recemate)

Chemical Formula: C34H36FN5O2

Exact Mass: 565.2853

Molecular Weight: 565.60

Elemental Analysis: C, 72.19; H, 6.41; F, 3.36; N, 12.38; O, 5.66

Price and Availability

Size	Price	Availability
10mg	USD 150.00	Ready to ship
25mg	USD 250.00	Ready to ship
50mg	USD 450.00	Ready to ship
100mg	USD 750.00	Ready to ship
200mg	USD 1,250.00	Ready to ship
500mg	USD 2,650.00	Ready to ship
1g	USD 4,250.00	Ready to ship
2g	USD 6,450.00	Ready to ship

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Related CAS #

1094873-17-2 (R-isomer) 1094873-16-1 (S-isomer) 1094873-14-9 (recemate)

Synonym

JNJ31020028; JNJ 31020028; JNJ-31020028.

IUPAC/Chemical Name

N-(4-(4-(2-(diethylamino)-2-oxo-1-phenylethyl)piperazin-1-yl)-3-fluorophenyl)-2-(pyridin-3-yl)benzamide

InChi Key

OVUNRYUVDVWTTE-UHFFFAOYSA-N

InChi Code

InChI=1S/C34H36FN5O2/c1-3-38(4-2)34(42)32(25-11-6-5-7-12-25)40-21-19-39(20-22-40)31-17-16-27(23-30(31)35)37-33(41)29-15-9-8-14-28(29)26-13-10-18-36-24-26/h5-18,23-24,32H,3-4,19-22H2,1-2H3,(H,37,41)

SMILES Code

O=C(NC1=CC=C(N2CCN(C(C3=CC=CC=C3)C(N(CC)CC)=O)CC2)C(F)=C1)C4=CC=CC=C4C5=CC=CN=C5

Appearance

White to off-white 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, not in water

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

Certificate of Analysis

View CoA: current batch, Lot#C7R06B19

View CoA: current batch, Lot#CRB50810

QC Data

View QC data: current batch, Lot#CRB50810

View QC data: current batch, Lot#C7R06B19

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

JNJ-31020028 is a selective brain penetrant antagonist of neuropeptide Y2 receptor with high affinity (pIC50=8.07, human; pIC50=8.22 rat); >100-fold selective versus human Y1/Y4/Y5 receptors.

In vitro activity:

In this study, JNJ-47965567, a centrally permeable, high-affinity, selective P2X7 antagonist was characterized. A combination of in vitro assays (calcium flux, radioligand binding, electrophysiology, IL-1β release) were used in both recombinant and native systems. JNJ-47965567 is potent high affinity (pKi 7.9 ± 0.07), selective human P2X7 antagonist, with no significant observed speciation. In native systems, the potency of the compound to attenuate IL-1β release was 6.7 ± 0.07 (human blood), 7.5 ± 0.07 (human monocytes) and 7.1 ± 0.1 (rat microglia). JNJ-47965567 exhibited target engagement in rat brain, with a brain EC50 of 78 ± 19 ng·mL(-1) (P2X7 receptor autoradiography) and functional block of Bz-ATP induced IL-1β release. Reference: Br J Pharmacol. 2013 Oct;170(3):624-40. https://pubmed.ncbi.nlm.nih.gov/23889535/

In vivo activity:

To explore skeletal impacts of JNJ-31020028 treatment, bone mineral density was assessed in OVX mice using dual energy X-ray absorptiometry (DEXA). Representative whole-body scans from JNJ-31020028-treated and vehicle mice and the regions of interest are shown in Figure 3A. Bone mineral density (BMD) was significantly higher in Y2 antagonist-treated mice compared to mice receiving the vehicle control (p=0.045; 2-tailed t-test) (Figure 3B and Table 1). The BMD values observed for vehicle- and JNJ31020028-treated OVX mice were within normal range (Delahunty et al., 2009). Correspondingly connectivity density (ConnD) and trabecular thickness (TB.Th) were also significantly greater in Y2 antagonist-treated mice compared to mice in the vehicle control group. Furthermore, treated mice exhibited lower structural model index (SMI), indicative of greater plate-like, as opposed to rod-like, composition within trabecular bone (Table 2). Analysis of femurs showed greater BV/TV within trabecular regions of Y2 antagonisttreated mice, which was associated with an increase in trabecular number and a reduction in trabecular separation (Figure 4, Table 2). Taken together, these data may indicate the Y2 antagonist slows bone metabolism in vivo. Reference: Neuropeptides. 2018 Feb; 67: 45–55. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5805636/

	Solvent	mg/mL	mM
Solubility
	DMSO	44.0	77.79

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 565.60 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. Shoblock JR, Welty N, Nepomuceno D, Lord B, Aluisio L, Fraser I, Motley ST, Sutton SW, Morton K, Galici R, Atack JR, Dvorak L, Swanson DM, Carruthers NI, Dvorak C, Lovenberg TW, Bonaventure P. In vitro and in vivo characterization of JNJ-31020028 (N(4-{4-[2-(diethylamino)-2-oxo-1-phenylethyl]piperazin-1-yl}-3-fluorophenyl)-2-pyridin-3-ylbenzamide), a selective brain penetrant small molecule antagonist of the neuropeptide Y Y(2) receptor. Psychopharmacology (Berl). 2010 Feb;208(2):265-77. doi: 10.1007/s00213-009-1726-x. Epub 2009 Dec 2. PMID: 19953226. 2. Morales-Medina JC, Dumont Y, Bonaventure P, Quirion R. Chronic administration of the Y2 receptor antagonist, JNJ-31020028, induced anti-depressant like-behaviors in olfactory bulbectomized rat. Neuropeptides. 2012 Dec;46(6):329-34. doi: 10.1016/j.npep.2012.09.009. Epub 2012 Oct 25. PMID: 23103057. 3. Seldeen KL, Halley PG, Volmar CH, Rodríguez MA, Hernandez M, Pang M, Carlsson SK, Suva LJ, Wahlestedt C, Troen BR, Brothers SP. Neuropeptide Y Y2 antagonist treated ovariectomized mice exhibit greater bone mineral density. Neuropeptides. 2018 Feb;67:45-55. doi: 10.1016/j.npep.2017.11.005. Epub 2017 Nov 7. PMID: 29129406; PMCID: PMC5805636.

In vitro protocol:

In vivo protocol:

1. Morales-Medina JC, Dumont Y, Bonaventure P, Quirion R. Chronic administration of the Y2 receptor antagonist, JNJ-31020028, induced anti-depressant like-behaviors in olfactory bulbectomized rat. Neuropeptides. 2012 Dec;46(6):329-34. doi: 10.1016/j.npep.2012.09.009. Epub 2012 Oct 25. PMID: 23103057. 2. Seldeen KL, Halley PG, Volmar CH, Rodríguez MA, Hernandez M, Pang M, Carlsson SK, Suva LJ, Wahlestedt C, Troen BR, Brothers SP. Neuropeptide Y Y2 antagonist treated ovariectomized mice exhibit greater bone mineral density. Neuropeptides. 2018 Feb;67:45-55. doi: 10.1016/j.npep.2017.11.005. Epub 2017 Nov 7. PMID: 29129406; PMCID: PMC5805636.

1: Andersen TL, Friis SD, Audrain H, Nordeman P, Antoni G, Skrydstrup T. Efficient (11)C-Carbonylation of Isolated Aryl Palladium Complexes for PET: Application to Challenging Radiopharmaceutical Synthesis. J Am Chem Soc. 2015 Feb 4;137(4):1548-55. doi: 10.1021/ja511441u. Epub 2015 Jan 26. PubMed PMID: 25569730. 2: Winterdahl M, Audrain H, Landau AM, Smith DF, Bonaventure P, Shoblock JR, Carruthers N, Swanson D, Bender D. PET brain imaging of neuropeptide Y2 receptors using N-11C-methyl-JNJ-31020028 in pigs. J Nucl Med. 2014 Apr;55(4):635-9. doi: 10.2967/jnumed.113.125351. Epub 2014 Mar 10. PubMed PMID: 24614224. 3: Kallupi M, Vendruscolo LF, Carmichael CY, George O, Koob GF, Gilpin NW. Neuropeptide YY(2)R blockade in the central amygdala reduces anxiety-like behavior but not alcohol drinking in alcohol-dependent rats. Addict Biol. 2014 Sep;19(5):755-7. doi: 10.1111/adb.12059. Epub 2013 May 3. PubMed PMID: 23639035; PubMed Central PMCID: PMC3872251. 4: Wu W, Bates MA, Bursian SJ, Flannery B, Zhou HR, Link JE, Zhang H, Pestka JJ. Peptide YY3-36 and 5-hydroxytryptamine mediate emesis induction by trichothecene deoxynivalenol (vomitoxin). Toxicol Sci. 2013 May;133(1):186-95. doi: 10.1093/toxsci/kft033. Epub 2013 Mar 1. PubMed PMID: 23457120; PubMed Central PMCID: PMC3627556. 5: Morales-Medina JC, Dumont Y, Bonaventure P, Quirion R. Chronic administration of the Y2 receptor antagonist, JNJ-31020028, induced anti-depressant like-behaviors in olfactory bulbectomized rat. Neuropeptides. 2012 Dec;46(6):329-34. doi: 10.1016/j.npep.2012.09.009. Epub 2012 Oct 25. PubMed PMID: 23103057. 6: Janssen P, Verschueren S, Rotondo A, Tack J. Role of Y(2) receptors in the regulation of gastric tone in rats. Am J Physiol Gastrointest Liver Physiol. 2012 Apr;302(7):G732-9. doi: 10.1152/ajpgi.00404.2011. Epub 2012 Jan 19. PubMed PMID: 22268097. 7: Swanson DM, Wong VD, Jablonowski JA, Shah C, Rudolph DA, Dvorak CA, Seierstad M, Dvorak LK, Morton K, Nepomuceno D, Atack JR, Bonaventure P, Lovenberg TW, Carruthers NI. The discovery and synthesis of JNJ 31020028, a small molecule antagonist of the Neuropeptide Y Y₂ receptor. Bioorg Med Chem Lett. 2011 Sep 15;21(18):5552-6. doi: 10.1016/j.bmcl.2011.06.136. Epub 2011 Jul 18. PubMed PMID: 21802951. 8: Aydin C, Oztan O, Isgor C. Effects of a selective Y2R antagonist, JNJ-31020028, on nicotine abstinence-related social anxiety-like behavior, neuropeptide Y and corticotropin releasing factor mRNA levels in the novelty-seeking phenotype. Behav Brain Res. 2011 Sep 23;222(2):332-41. doi: 10.1016/j.bbr.2011.03.067. Epub 2011 Apr 8. PubMed PMID: 21497168; PubMed Central PMCID: PMC3096753. 9: Cippitelli A, Rezvani AH, Robinson JE, Eisenberg L, Levin ED, Bonaventure P, Motley ST, Lovenberg TW, Heilig M, Thorsell A. The novel, selective, brain-penetrant neuropeptide Y Y2 receptor antagonist, JNJ-31020028, tested in animal models of alcohol consumption, relapse, and anxiety. Alcohol. 2011 Sep;45(6):567-76. doi: 10.1016/j.alcohol.2010.09.003. Epub 2010 Dec 10. PubMed PMID: 21145691. 10: Shoblock JR, Welty N, Nepomuceno D, Lord B, Aluisio L, Fraser I, Motley ST, Sutton SW, Morton K, Galici R, Atack JR, Dvorak L, Swanson DM, Carruthers NI, Dvorak C, Lovenberg TW, Bonaventure P. In vitro and in vivo characterization of JNJ-31020028 (N-(4-{4-[2-(diethylamino)-2-oxo-1-phenylethyl]piperazin-1-yl}-3-fluorophenyl)-2- pyridin-3-ylbenzamide), a selective brain penetrant small molecule antagonist of the neuropeptide Y Y(2) receptor. Psychopharmacology (Berl). 2010 Feb;208(2):265-77. doi: 10.1007/s00213-009-1726-x. Epub 2009 Dec 2. PubMed PMID: 19953226.

Tang T, Hartig C, Chen Q, Zhao W, Kaiser A, Zhang X, Zhang H, Qu H, Yi C, Ma L, Han S, Zhao Q, Beck-Sickinger AG, Wu B. Structural basis for ligand recognition of the neuropeptide Y Y2 receptor. Nat Commun. 2021 Feb 2;12(1):737. doi: 10.1038/s41467-021-21030-9. PMID: 33531491; PMCID: PMC7854658.