WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 530648
Description: 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).
MedKoo Cat#: 530648
Chemical Formula: C18H13ClF4N6O
Exact Mass: 440.0775
Molecular Weight: 440.7866
Elemental Analysis: C, 49.05; H, 2.97; Cl, 8.04; F, 17.24; N, 19.07; O, 3.63
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
The following data is based on the product molecular weight 440.7866 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|
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.
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.