JNJ-54175446 | CAS#1627902-21-9 | P2X7 Receptor Antagonist

MedKoo Cat#: 530648 | Name: JNJ-54175446

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Description:

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

JNJ-54175446 is a potent and selective P2X7 Receptor Antagonist. JNJ-54175446 is potent, stable in liver microsomes and has an acceptable protein binding profile. JNJ-54175446 is highly permeable and has no evidence of efflux as measured by a Caco-2 cell line. JNJ-54175446 efficiently binds to recombinant rat and human P2X7 and to native tissues in both human and rat. JNJ-54175446 also inhibited P2X7 activity in human, rat, dog, mouse, and macaque Ca2+ flux assays and inhibited IL1-β release in human peripheral blood monocytes (pIC50 of 7.7 ± 0.1) and in human whole blood (pIC50 of 8.1 ± 0.1).

Chemical Structure

JNJ-54175446

CAS#1627902-21-9

Theoretical Analysis

MedKoo Cat#: 530648

Name: JNJ-54175446

CAS#: 1627902-21-9

Chemical Formula: C18H13ClF4N6O

Exact Mass: 440.0775

Molecular Weight: 440.79

Elemental Analysis: C, 49.05; H, 2.97; Cl, 8.04; F, 17.24; N, 19.07; O, 3.63

Price and Availability

Size	Price	Availability	Quantity
1mg	USD 750.00	2 Weeks
5mg	USD 1,550.00	2 Weeks

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Synonym

JNJ-54175446; JNJ 54175446; JNJ54175446

IUPAC/Chemical Name

(R)-(2-chloro-3-(trifluoromethyl)phenyl)(1-(5-fluoropyrimidin-2-yl)-4-methyl-1,4,6,7-tetrahydro-5H-[1,2,3]triazolo[4,5-c]pyridin-5-yl)methanone

InChi Key

CWFVVQFVGMFTBD-SECBINFHSA-N

InChi Code

InChI=1S/C18H13ClF4N6O/c1-9-15-13(29(27-26-15)17-24-7-10(20)8-25-17)5-6-28(9)16(30)11-3-2-4-12(14(11)19)18(21,22)23/h2-4,7-9H,5-6H2,1H3/t9-/m1/s1

SMILES Code

ClC1=C(C(F)(F)F)C=CC=C1C(N(CC2)[C@H](C)C(N=N3)=C2N3C4=NC=C(C=N4)F)=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

Inhibition of P2X7 and P2X7 mediated IL-1β release might therefore represent a novel approach to the treatment of mood disorders. JNJ-54175446 had excellent PK in multiple species, a very low predicted human efficacious dose, and an excellent preclinical safety profile, the compound was nominated for clinical development and has since been dosed in healthy volunteers at single doses from 0.5 mg to 600 mg.

Product Data

Product Data

Instruction

View handling instruction

Biological target:

JNJ-54175446 is a potent and selective brain penetrant P2X7 receptor antagonist, with pIC50s of 8.46 and 8.81 for hP2X7 receptor and rP2X7 receptor, respectively.

In vitro activity:

TBD

In vivo activity:

In nonhuman primate PET imaging studies, dose-dependent receptor occupancy of JNJ-54175446 was observed in 2 rhesus monkeys. At a 0.1 mg/kg dose (intravenous) of JNJ-54175446, the receptor occupancy was calculated to be 17% by Logan graphical analysis, whereas a dose of 2.5 mg/kg yielded a receptor occupancy of 60%. Reference: J Nucl Med. 2019 Aug;60(8):1154-1159. https://pubmed.ncbi.nlm.nih.gov/30733317/

	Solvent	mg/mL	mM
Solubility
	DMSO	62.5	141.79

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 440.79 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. Kolb HC, Barret O, Bhattacharya A, Chen G, Constantinescu C, Huang C, Letavic M, Tamagnan G, Xia CA, Zhang W, Szardenings AK. Preclinical Evaluation and Nonhuman Primate Receptor Occupancy Study of 18F-JNJ-64413739, a PET Radioligand for P2X7 Receptors. J Nucl Med. 2019 Aug;60(8):1154-1159. doi: 10.2967/jnumed.118.212696. Epub 2019 Feb 7. PMID: 30733317.

In vitro protocol:

TBD

In vivo protocol:

1: Letavic MA, Savall BM, Allison BD, Aliusio L, Andrés JI, De Angelis M, Ao H, Beauchamp DA, Bonaventure P, Bryant S, Carruthers NI, Ceusters M, Coe KJ, Dvorak CA, Fraser I, Gelin CF, Koudriakova T, Liang J, Lord B, Lovenberg TW, Otieno M, Schoetens F, Swanson DM, Wang Q, Wickenden AD, Bhattacharya A. 4-Methyl-6,7-dihydro-4H-triazolo[4,5-c]pyridine-based P2X7 Receptor Antagonists: Optimization of Pharmacokinetic Properties Leading to the Identification of a Clinical Candidate. J Med Chem. 2017 May 11. doi: 10.1021/acs.jmedchem.7b00408. [Epub ahead of print] PubMed PMID: 28493698.