Gefapixant | AF-219 | CAS#1015787-98-0 | P2X3 antagonist

MedKoo Cat#: 561852 | Name: Gefapixant

Description:

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

Gefapixant, also known as AF-219 or MK-7264, is a P2X3 receptor antagonist. Gefapixant is currently under clinical trials for chronic cough. It is believed that excessive activation of P2X3 receptors is associated with hyper-sensitization of sensory neurons. Neuronal hyper-sensitization in the airways and lungs, triggered by injury or infection, can cause an exaggerated, persistent and frequent urge to cough, so called chronic cough. P2X3 receptors seem to have a key role in mediation of cough neuronal hypersensitivity. Antagonists of P2X3 receptors such as AF-219 are a promising new group of antitussives.

Chemical Structure

Gefapixant

CAS#1015787-98-0 (free base)

Theoretical Analysis

MedKoo Cat#: 561852

Name: Gefapixant

CAS#: 1015787-98-0 (free base)

Chemical Formula: C14H19N5O4S

Exact Mass: 353.1158

Molecular Weight: 353.40

Elemental Analysis: C, 47.58; H, 5.42; N, 19.82; O, 18.11; S, 9.07

Price and Availability

Size	Price	Availability
25mg	USD 450.00	2 Weeks
50mg	USD 750.00	2 Weeks
100mg	USD 1,250.00	2 Weeks
200mg	USD 2,050.00	2 Weeks
500mg	USD 3,250.00	2 Weeks
1g	USD 4,650.00	2 Weeks

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Related CAS #

2310299-91-1 (citrate) 1015787-98-0 (free base)

Synonym

Gefapixant; AF-219; AF219; AF 219; RO4926219; RO-4926219; RO 4926219; RG-1646; RG1646; RG 1646; MK-7264; MK7264; MK 7264

IUPAC/Chemical Name

5-[(2,4-diaminopyrimidin-5-yl)oxy]-2-methoxy-4-(propan-2-yl)benzene-1-sulfonamide

InChi Key

HLWURFKMDLAKOD-UHFFFAOYSA-N

InChi Code

InChI=1S/C14H19N5O4S/c1-7(2)8-4-10(22-3)12(24(17,20)21)5-9(8)23-11-6-18-14(16)19-13(11)15/h4-7H,1-3H3,(H2,17,20,21)(H4,15,16,18,19)

SMILES Code

O=S(C1=CC(OC2=CN=C(N)N=C2N)=C(C(C)C)C=C1OC)(N)=O

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:

Gefapixant is an orally active and potent purinergic P2X3 receptor (P2X3R) antagonist, with IC50 values of ~30 nM versus recombinant hP2X3 homotrimers and 100-250 nM at hP2X2/3 heterotrimeric receptors.

In vitro activity:

Antagonism of human P2X3 receptors using a submaximal MK‐7264 concentration (300 nM; approximate IC70) was not surmounted by increasing the concentration of α,β‐meATP agonist (Figure 1e), indicating that MK‐7264 acts independently of agonist concentration to block P2X3. In addition to suppression of response maxima, MK‐7264 also significantly reduced α,β‐meATP potency (EC50 1.0 ± 0.1 μM vehicle vs. 6.0 ± 1.5 μM with 300‐nM MK‐7264; N = 5, paired sample t test P < .05). These data suggest that MK‐7264 is a negative allosteric modulator of the human P2X3 receptor. Reference: Br J Pharmacol. 2019 Jul;176(13):2279-2291. https://pubmed.ncbi.nlm.nih.gov/30927255/

In vivo activity:

Withdrawal threshold was 13.3 ± 0.2 g (N = 20) in naïve control rats. MK‐7264 was also efficacious in reducing weight‐bearing discomfort at 1 and 3 hr after dosing (Figure 4b). The maximum effect of MK‐7264 (30 mg·kg−1) was observed at 3 hr and similar to that of naproxen (20 mg·kg−1), where difference in weight bearing between contralateral and ipsilateral limbs was 55 ± 6 g, 35 ± 4 g, and 34 ± 4 g for vehicle control, MK‐7264, and naproxen (N = 10; P < .05 for all treatments vs. vehicle control), respectively. Reference: Br J Pharmacol. 2019 Jul;176(13):2279-2291. https://pubmed.ncbi.nlm.nih.gov/30927255/

	Solvent	mg/mL	mM
Solubility
	DMSO	38.0	107.53

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 353.40 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. Richards D, Gever JR, Ford AP, Fountain SJ. Action of MK-7264 (gefapixant) at human P2X3 and P2X2/3 receptors and in vivo efficacy in models of sensitisation. Br J Pharmacol. 2019 Jul;176(13):2279-2291. doi: 10.1111/bph.14677. Epub 2019 May 11. PMID: 30927255; PMCID: PMC6555852.

In vitro protocol:

In vivo protocol:

1: Wang J, Wang Y, Cui WW, Huang Y, Yang Y, Liu Y, Zhao WS, Cheng XY, Sun WS, Cao P, Zhu MX, Wang R, Hattori M, Yu Y. Druggable negative allosteric site of P2X3 receptors. Proc Natl Acad Sci U S A. 2018 May 8;115(19):4939-4944. doi: 10.1073/pnas.1800907115. Epub 2018 Apr 19. PubMed PMID: 29674445; PubMed Central PMCID: PMC5948998. 2: Burnstock G. The therapeutic potential of purinergic signalling. Biochem Pharmacol. 2018 May;151:157-165. doi: 10.1016/j.bcp.2017.07.016. Epub 2017 Jul 21. Review. PubMed PMID: 28735873. 3: Sheridan C. Merck stakes out 'irritable' neuron territory with $1.25 billion. Nat Biotechnol. 2016 Sep 8;34(9):900. doi: 10.1038/nbt0916-900. PubMed PMID: 27606448. 4: Abdulqawi R, Dockry R, Holt K, Layton G, McCarthy BG, Ford AP, Smith JA. P2X3 receptor antagonist (AF-219) in refractory chronic cough: a randomised, double-blind, placebo-controlled phase 2 study. Lancet. 2015 Mar 28;385(9974):1198-205. doi: 10.1016/S0140-6736(14)61255-1. Epub 2014 Nov 25. PubMed PMID: 25467586. 5: Morice AH. Developing antitussives the clinician's pipeline-what do we need? J Thorac Dis. 2014 Oct;6(Suppl 7):S735-8. doi: 10.3978/j.issn.2072-1439.2014.08.40. Review. PubMed PMID: 25383208; PubMed Central PMCID: PMC4222922. 6: Ochoa-Cortes F, Liñán-Rico A, Jacobson KA, Christofi FL. Potential for developing purinergic drugs for gastrointestinal diseases. Inflamm Bowel Dis. 2014 Jul;20(7):1259-87. doi: 10.1097/MIB.0000000000000047. Review. PubMed PMID: 24859298; PubMed Central PMCID: PMC4340257. 7: Ford AP, Undem BJ. The therapeutic promise of ATP antagonism at P2X3 receptors in respiratory and urological disorders. Front Cell Neurosci. 2013 Dec 19;7:267. doi: 10.3389/fncel.2013.00267. Review. PubMed PMID: 24391544; PubMed Central PMCID: PMC3867694.