WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 526854
CAS#: 1254977-87-1
Description: JNJ-42153605 is a potent and selective mGlu2 receptor PAM with an acceptable pharmacokinetic profile in rodent and nonrodent species. JNJ-42153605 showed centrally mediated in vivo effectivity in models sensitive to mGlu2 receptor modulation such as sleep−wake electroencephalogram (sw-EEG) in rats,34 showing suppressed REM sleep during the first 4 h after oral administration of a 3 mg/kg dose.
MedKoo Cat#: 526854
Name: JNJ-42153605
CAS#: 1254977-87-1
Chemical Formula: C22H23F3N4
Exact Mass: 400.1875
Molecular Weight: 400.4492
Elemental Analysis: C, 65.99; H, 5.79; F, 14.23; N, 13.99
Synonym: JNJ-42153605; JNJ 42153605; JNJ42153605.
IUPAC/Chemical Name: 3-(Cyclopropylmethyl)-7-(4-phenyl-1-piperidinyl)-8-(trifluoromethyl)[1,2,4]triazolo[4,3-a]pyridine
InChi Key: BQAVZGJJQFJSMW-UHFFFAOYSA-N
InChi Code: InChI=1S/C22H23F3N4/c23-22(24,25)20-18(10-13-29-19(14-15-6-7-15)26-27-21(20)29)28-11-8-17(9-12-28)16-4-2-1-3-5-16/h1-5,10,13,15,17H,6-9,11-12,14H2
SMILES Code: FC(C1=C(N2CCC(C3=CC=CC=C3)CC2)C=CN4C1=NN=C4CC5CC5)(F)F
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
| Biological target: | JNJ-42153605 is a positive allosteric modulator of the metabotropic glutamate 2 (mGlu2) receptor with an EC50 of 17 nM. |
| In vitro activity: | Consistent with the effects of an allosteric potentiator, JNJ-42153605 shifts the concentration-response curve of glutamate to the left (Fig 1C left panel), increasing the potency of glutamate up to ∼25-fold. At the human mGluR2, the EC50 of glutamate decreases from ∼10 to 0.5 μM with the addition of 3 μM JNJ-42153605. Reference: PLoS One. 2015 Dec 11;10(12):e0144017. https://pubmed.ncbi.nlm.nih.gov/26658273/ |
| In vivo activity: | JNJ-40411813, JNJ-42153605, and LY404039 dose dependently inhibited spontaneous locomotion and PCP- and scopolamine-induced hyperlocomotion but not d-amphetamine-induced hyperlocomotion (Fig. 2; Table 2) in mice. Reference: Pharmacol Res Perspect. 2015 Mar;3(2):e00097. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4324682/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMF | 30.0 | 74.92 | |
| DMF:PBS (pH 7.2) (1:3) | 0.25 | 0.62 | |
| DMSO | 10.34 | 25.81 | |
| Ethanol | 10.0 | 24.97 |
The following data is based on the product molecular weight 400.4492 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. Ahnaou A, Lavreysen H, Tresadern G, Cid JM, Drinkenburg WH. mGlu2 Receptor Agonism, but Not Positive Allosteric Modulation, Elicits Rapid Tolerance towards Their Primary Efficacy on Sleep Measures in Rats. PLoS One. 2015 Dec 11;10(12):e0144017. doi: 10.1371/journal.pone.0144017. PMID: 26658273; PMCID: PMC4684355. 2. Lavreysen H, Langlois X, Donck LV, Nuñez JM, Pype S, Lütjens R, Megens A. Preclinical evaluation of the antipsychotic potential of the mGlu2-positive allosteric modulator JNJ-40411813. Pharmacol Res Perspect. 2015 Mar;3(2):e00097. doi: 10.1002/prp2.97. Epub 2015 Jan 30. PMID: 25692027; PMCID: PMC4324682. 3. Cid JM, Tresadern G, Vega JA, de Lucas AI, Matesanz E, Iturrino L, Linares ML, Garcia A, Andrés JI, Macdonald GJ, Oehlrich D, Lavreysen H, Megens A, Ahnaou A, Drinkenburg W, Mackie C, Pype S, Gallacher D, Trabanco AA. Discovery of 3-cyclopropylmethyl-7-(4-phenylpiperidin-1-yl)-8-trifluoromethyl[1,2,4]triazolo[4,3-a]pyridine (JNJ-42153605): a positive allosteric modulator of the metabotropic glutamate 2 receptor. J Med Chem. 2012 Oct 25;55(20):8770-89. doi: 10.1021/jm3010724. Epub 2012 Oct 16. PMID: 23072213. |
| In vitro protocol: | 1. Ahnaou A, Lavreysen H, Tresadern G, Cid JM, Drinkenburg WH. mGlu2 Receptor Agonism, but Not Positive Allosteric Modulation, Elicits Rapid Tolerance towards Their Primary Efficacy on Sleep Measures in Rats. PLoS One. 2015 Dec 11;10(12):e0144017. doi: 10.1371/journal.pone.0144017. PMID: 26658273; PMCID: PMC4684355. |
| In vivo protocol: | 1. Lavreysen H, Langlois X, Donck LV, Nuñez JM, Pype S, Lütjens R, Megens A. Preclinical evaluation of the antipsychotic potential of the mGlu2-positive allosteric modulator JNJ-40411813. Pharmacol Res Perspect. 2015 Mar;3(2):e00097. doi: 10.1002/prp2.97. Epub 2015 Jan 30. PMID: 25692027; PMCID: PMC4324682. 2. Cid JM, Tresadern G, Vega JA, de Lucas AI, Matesanz E, Iturrino L, Linares ML, Garcia A, Andrés JI, Macdonald GJ, Oehlrich D, Lavreysen H, Megens A, Ahnaou A, Drinkenburg W, Mackie C, Pype S, Gallacher D, Trabanco AA. Discovery of 3-cyclopropylmethyl-7-(4-phenylpiperidin-1-yl)-8-trifluoromethyl[1,2,4]triazolo[4,3-a]pyridine (JNJ-42153605): a positive allosteric modulator of the metabotropic glutamate 2 receptor. J Med Chem. 2012 Oct 25;55(20):8770-89. doi: 10.1021/jm3010724. Epub 2012 Oct 16. PMID: 23072213. |
1: Ahnaou A, Lavreysen H, Tresadern G, Cid JM, Drinkenburg WH. mGlu2 Receptor
Agonism, but Not Positive Allosteric Modulation, Elicits Rapid Tolerance towards
Their Primary Efficacy on Sleep Measures in Rats. PLoS One. 2015 Dec
11;10(12):e0144017. doi: 10.1371/journal.pone.0144017. eCollection 2015. PubMed
PMID: 26658273; PubMed Central PMCID: PMC4684355.
2: Lavreysen H, Langlois X, Donck LV, Nuñez JM, Pype S, Lütjens R, Megens A.
Preclinical evaluation of the antipsychotic potential of the mGlu2-positive
allosteric modulator JNJ-40411813. Pharmacol Res Perspect. 2015 Mar;3(2):e00097.
doi: 10.1002/prp2.97. Epub 2015 Jan 30. PubMed PMID: 25692027; PubMed Central
PMCID: PMC4324682.
3: Wyckhuys T, Wyffels L, Langlois X, Schmidt M, Stroobants S, Staelens S. The
[18F]FDG μPET readout of a brain activation model to evaluate the metabotropic
glutamate receptor 2 positive allosteric modulator JNJ-42153605. J Pharmacol Exp
Ther. 2014 Aug;350(2):375-86. doi: 10.1124/jpet.114.213959. Epub 2014 Jun 4.
PubMed PMID: 24898267.
4: Megens AA, Hendrickx HM, Hens KA, Talloen WJ, Lavreysen H. mGlu(2)
receptor-mediated modulation of conditioned avoidance behavior in rats. Eur J
Pharmacol. 2014 Mar 15;727:130-9. doi: 10.1016/j.ejphar.2014.01.044. Epub 2014
Jan 30. PubMed PMID: 24486391.
5: Cid JM, Tresadern G, Vega JA, de Lucas AI, Matesanz E, Iturrino L, Linares ML,
Garcia A, Andrés JI, Macdonald GJ, Oehlrich D, Lavreysen H, Megens A, Ahnaou A,
Drinkenburg W, Mackie C, Pype S, Gallacher D, Trabanco AA. Discovery of
3-cyclopropylmethyl-7-(4-phenylpiperidin-1-yl)-8-trifluoromethyl[1,2,4]triazolo[4
,3-a]pyridine (JNJ-42153605): a positive allosteric modulator of the metabotropic
glutamate 2 receptor. J Med Chem. 2012 Oct 25;55(20):8770-89. doi:
10.1021/jm3010724. Epub 2012 Oct 16. PubMed PMID: 23072213.
