NPS-2143 HCl | CAS#324523-20-8 | CaSR antagonist

MedKoo Cat#: 526760 | Name: NPS-2143 HCl

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Description:

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

NPS-2143, also known as SB-262470 and SB-262470A, is a Calcium-sensing receptor antagonist (calcilytic). NPS-2143 stimulates release of parathyroid hormone. Calcilytic drugs have been researched as potential treatments for osteoporosis, and as the first such compound developed, NPS-2143 is still widely used in research into the CaSR receptor as well as design of newer calcilytic agents.

Chemical Structure

NPS-2143 HCl

CAS#324523-20-8 (HCl).

Theoretical Analysis

MedKoo Cat#: 526760

Name: NPS-2143 HCl

CAS#: 324523-20-8 (HCl).

Chemical Formula: C24H26Cl2N2O2

Exact Mass: 408.1605

Molecular Weight: 445.38

Elemental Analysis: C, 64.72; H, 5.88; Cl, 15.92; N, 6.29; O, 7.18

Price and Availability

Size	Price	Availability
5mg	USD 285.00	2 Weeks
10mg	USD 465.00	2 Weeks
25mg	USD 850.00	2 Weeks

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Related CAS #

284035-33-2 (free base) 324523-20-8 (HCl)

Synonym

NPS-2143; NPS 2143; NPS2143; SB-262470; SB 262470; SB262470; SB-262470A.

IUPAC/Chemical Name

(R)-2-chloro-6-(2-hydroxy-3-((2-methyl-1-(naphthalen-2-yl)propan-2-yl)amino)propoxy)benzonitrile hydrochloride

InChi Key

ZEBNDUQLNGYBNL-VEIFNGETSA-N

InChi Code

InChI=1S/C24H25ClN2O2.ClH/c1-24(2,13-17-10-11-18-6-3-4-7-19(18)12-17)27-15-20(28)16-29-23-9-5-8-22(25)21(23)14-26;/h3-12,20,27-28H,13,15-16H2,1-2H3;1H/t20-;/m1./s1

SMILES Code

N#CC1=C(OC[C@H](O)CNC(C)(C)CC2=CC=C3C=CC=CC3=C2)C=CC=C1Cl.[H]Cl

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:

NPS-2143 hydrochloride (SB-262470A hydrochloride) is a selective and potent calcium ion-sensing receptor (CaSR) antagonist.

In vitro activity:

The purpose of the present study was to investigate the protective role of NPS2143, a selective CaSR antagonist on cigarette smoke extract (CSE)-stimulated NCI-H292 mucoepidermoid human lung cells. Treatment of NPS2143 significantly inhibited the expression of MUC5AC in CSE-stimulated H292 cells. NPS2143 reduced the expression of MMP-9 in CSE-stimulated H292 cells. NPS2143 also decreased the release of proinflammatory cytokines such as IL-6 and TNF-α in CSE-stimulated H292 cells. Reference: Inflammation. 2017 Feb;40(1):184-194. https://pubmed.ncbi.nlm.nih.gov/27866297/

In vivo activity:

The present study aimed to investigate the effects of NPS2143-mediated inhibition of CaSR on VSMC proliferation and apoptosis in spontaneously hypertensive rat (SHR) VSMCs and to assess whether these effects were mediated by alterations to RAS signaling. Primary VSMCs were isolated from the aortas of SHRs and Wistar-Kyoto rats. SHR VSMCs were treated with CaSR antagonist NPS2143 and cell proliferation and CaSR and RAS-related protein expression levels were measured to assess the effect. The results indicated that NPS2143 treatment promoted SHR VSMC proliferation, lower CaSR expression levels and higher RAS-related proteins levels when compared with control treatment. Reference: Exp Ther Med. 2020 Aug;20(2):818-829. https://pubmed.ncbi.nlm.nih.gov/32742325/

	Solvent	mg/mL	mM
Solubility
	DMF	30.0	67.36
	DMSO	58.2	130.63
	DMSO:PBS (pH 7.2) (1:3)	0.3	0.56
	Ethanol	3.2	7.24
	Water	1.9	4.15

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 445.38 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. Lee JW, Park JW, Kwon OK, Lee HJ, Jeong HG, Kim JH, Oh SR, Ahn KS. NPS2143 Inhibits MUC5AC and Proinflammatory Mediators in Cigarette Smoke Extract (CSE)-Stimulated Human Airway Epithelial Cells. Inflammation. 2017 Feb;40(1):184-194. doi: 10.1007/s10753-016-0468-2. PMID: 27866297. 2. Nemeth EF, Delmar EG, Heaton WL, Miller MA, Lambert LD, Conklin RL, Gowen M, Gleason JG, Bhatnagar PK, Fox J. Calcilytic compounds: potent and selective Ca2+ receptor antagonists that stimulate secretion of parathyroid hormone. J Pharmacol Exp Ther. 2001 Oct;299(1):323-31. PMID: 11561095. 3. Xiang ZY, Tao DD. The role of calcium-sensitive receptor in ovalbumin-induced airway inflammation and hyperresponsiveness in juvenile mice with asthma. Kaohsiung J Med Sci. 2022 Dec;38(12):1203-1212. doi: 10.1002/kjm2.12601. Epub 2022 Sep 28. PMID: 36169192. 4. Zhao Y, Tang N, Xi D, Huang Z, Zhang T, Liu Y, Wang L, Tang Y, Zhong H, He F. Calcilytic NPS2143 promotes proliferation and inhibits apoptosis of spontaneously hypertensive rat vascular smooth muscle cells via activation of the renin-angiotensin system. Exp Ther Med. 2020 Aug;20(2):818-829. doi: 10.3892/etm.2020.8759. Epub 2020 May 15. PMID: 32742325; PMCID: PMC7388331.

In vitro protocol:

In vivo protocol:

1. Xiang ZY, Tao DD. The role of calcium-sensitive receptor in ovalbumin-induced airway inflammation and hyperresponsiveness in juvenile mice with asthma. Kaohsiung J Med Sci. 2022 Dec;38(12):1203-1212. doi: 10.1002/kjm2.12601. Epub 2022 Sep 28. PMID: 36169192. 2. Zhao Y, Tang N, Xi D, Huang Z, Zhang T, Liu Y, Wang L, Tang Y, Zhong H, He F. Calcilytic NPS2143 promotes proliferation and inhibits apoptosis of spontaneously hypertensive rat vascular smooth muscle cells via activation of the renin-angiotensin system. Exp Ther Med. 2020 Aug;20(2):818-829. doi: 10.3892/etm.2020.8759. Epub 2020 May 15. PMID: 32742325; PMCID: PMC7388331.

1: Hannan FM, Walls GV, Babinsky VN, Nesbit MA, Kallay E, Hough TA, Fraser WD, Cox RD, Hu J, Spiegel AM, Thakker RV. The Calcilytic Agent NPS 2143 Rectifies Hypocalcemia in a Mouse Model With an Activating Calcium-Sensing Receptor (CaSR) Mutation: Relevance to Autosomal Dominant Hypocalcemia Type 1 (ADH1). Endocrinology. 2015 Sep;156(9):3114-21. doi: 10.1210/en.2015-1269. Epub 2015 Jun 8. PubMed PMID: 26052899; PubMed Central PMCID: PMC4541614. 2: Letz S, Haag C, Schulze E, Frank-Raue K, Raue F, Hofner B, Mayr B, Schöfl C. Amino alcohol- (NPS-2143) and quinazolinone-derived calcilytics (ATF936 and AXT914) differentially mitigate excessive signalling of calcium-sensing receptor mutants causing Bartter syndrome Type 5 and autosomal dominant hypocalcemia. PLoS One. 2014 Dec 15;9(12):e115178. doi: 10.1371/journal.pone.0115178. eCollection 2014. PubMed PMID: 25506941; PubMed Central PMCID: PMC4266668. 3: Nakamura A, Hotsubo T, Kobayashi K, Mochizuki H, Ishizu K, Tajima T. Loss-of-function and gain-of-function mutations of calcium-sensing receptor: functional analysis and the effect of allosteric modulators NPS R-568 and NPS 2143. J Clin Endocrinol Metab. 2013 Oct;98(10):E1692-701. doi: 10.1210/jc.2013-1974. Epub 2013 Aug 21. PubMed PMID: 23966241. 4: Johansson H, Cailly T, Rojas Bie Thomsen A, Bräuner-Osborne H, Sejer Pedersen D. Synthesis of the calcilytic ligand NPS 2143. Beilstein J Org Chem. 2013 Jul 9;9:1383-7. doi: 10.3762/bjoc.9.154. eCollection 2013. PubMed PMID: 23946832; PubMed Central PMCID: PMC3740522. 5: Armato U, Chiarini A, Chakravarthy B, Chioffi F, Pacchiana R, Colarusso E, Whitfield JF, Dal Prà I. Calcium-sensing receptor antagonist (calcilytic) NPS 2143 specifically blocks the increased secretion of endogenous Aβ42 prompted by exogenous fibrillary or soluble Aβ25-35 in human cortical astrocytes and neurons-therapeutic relevance to Alzheimer's disease. Biochim Biophys Acta. 2013 Oct;1832(10):1634-52. doi: 10.1016/j.bbadis.2013.04.020. Epub 2013 Apr 26. PubMed PMID: 23628734. 6: Letz S, Rus R, Haag C, Dörr HG, Schnabel D, Möhlig M, Schulze E, Frank-Raue K, Raue F, Mayr B, Schöfl C. Novel activating mutations of the calcium-sensing receptor: the calcilytic NPS-2143 mitigates excessive signal transduction of mutant receptors. J Clin Endocrinol Metab. 2010 Oct;95(10):E229-33. doi: 10.1210/jc.2010-0651. Epub 2010 Jul 28. PubMed PMID: 20668040. 7: Rybczynska A, Jurska-Jasko A, Boblewski K, Lehmann A, Orlewska C. Blockade of calcium channels and AT1 receptor prevents the hypertensive effect of calcilytic NPS 2143 in rats. J Physiol Pharmacol. 2010 Apr;61(2):163-70. PubMed PMID: 20436216. 8: Rybczynska A, Lehmann A, Jurska-Jasko A, Boblewski K, Orlewska C, Foks H, Drewnowska K. Hypertensive effect of calcilytic NPS 2143 administration in rats. J Endocrinol. 2006 Oct;191(1):189-95. PubMed PMID: 17065402.