Synonym
JNJ-40418677; JNJ 40418677; JNJ40418677;
IUPAC/Chemical Name
(S)-2-(4,4''-bis(trifluoromethyl)-[1,1':3',1''-terphenyl]-5'-yl)-4-methylpentanoic acid
InChi Key
RQOWDDLKGBMJFX-QHCPKHFHSA-N
InChi Code
InChI=1S/C26H22F6O2/c1-15(2)11-23(24(33)34)20-13-18(16-3-7-21(8-4-16)25(27,28)29)12-19(14-20)17-5-9-22(10-6-17)26(30,31)32/h3-10,12-15,23H,11H2,1-2H3,(H,33,34)/t23-/m0/s1
SMILES Code
O=C(O)[C@@H](CC(C)C)C1=CC(C2=CC=C(C(F)(F)F)C=C2)=CC(C3=CC=C(C(F)(F)F)C=C3)=C1
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-40418677 inhibits Aβ42 and NS2B-NS3 protease, with IC50s of 200 nM and 3.9 μM, respectively.
In vitro activity:
JNJ-40418677 selectively inhibited Aβ42 secretion in cell culture supernatants of WT APP SKNBE-2 cells (mean IC50= 200 nM; n = 10) (Figure 2A) and primary rat cortical neuronal cultures (mean IC50= 185 nM; n = 37) (Figure 2B).
Reference: Br J Pharmacol. 2011 May;163(2):375-89. https://pubmed.ncbi.nlm.nih.gov/21232036/
In vivo activity:
Four hours after oral treatment of mice with various doses of JNJ-40418677, there was a significant effect of treatment on Aβ42 levels [F(4,22) = 8.58, P < 0.001] (Figure 5A). Aβ42 brain levels were reduced in a dose-dependent manner 4 h after JNJ-40418677 treatment to 82 ± 10%, 64 ± 4%, 39 ± 3% and 31 ± 4% of the levels in vehicle-treated mice for doses of 10, 30, 100 and 300 mg·kg−1 respectively (Figure 5A).
Reference: Br J Pharmacol. 2011 May;163(2):375-89. https://pubmed.ncbi.nlm.nih.gov/21232036/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMF |
25.0 |
52.03 |
| DMSO |
10.0 |
20.81 |
| Ethanol |
10.0 |
20.81 |
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
480.45
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. Van Broeck B, Chen JM, Tréton G, Desmidt M, Hopf C, Ramsden N, Karran E, Mercken M, Rowley A. Chronic treatment with a novel γ-secretase modulator, JNJ-40418677, inhibits amyloid plaque formation in a mouse model of Alzheimer's disease. Br J Pharmacol. 2011 May;163(2):375-89. doi: 10.1111/j.1476-5381.2011.01207.x. PMID: 21232036; PMCID: PMC3087138.
In vitro protocol:
1. Van Broeck B, Chen JM, Tréton G, Desmidt M, Hopf C, Ramsden N, Karran E, Mercken M, Rowley A. Chronic treatment with a novel γ-secretase modulator, JNJ-40418677, inhibits amyloid plaque formation in a mouse model of Alzheimer's disease. Br J Pharmacol. 2011 May;163(2):375-89. doi: 10.1111/j.1476-5381.2011.01207.x. PMID: 21232036; PMCID: PMC3087138.
In vivo protocol:
1. Van Broeck B, Chen JM, Tréton G, Desmidt M, Hopf C, Ramsden N, Karran E, Mercken M, Rowley A. Chronic treatment with a novel γ-secretase modulator, JNJ-40418677, inhibits amyloid plaque formation in a mouse model of Alzheimer's disease. Br J Pharmacol. 2011 May;163(2):375-89. doi: 10.1111/j.1476-5381.2011.01207.x. PMID: 21232036; PMCID: PMC3087138.
1: Hamilton JY, Sarlah D, Carreira EM. Iridium-catalyzed enantioselective allyl-alkene coupling. J Am Chem Soc. 2014 Feb 26;136(8):3006-9. doi: 10.1021/ja412962w. Epub 2014 Feb 12. PubMed PMID: 24521052.
2: Mikulca JA, Nguyen V, Gajdosik DA, Teklu SG, Giunta EA, Lessa EA, Tran CH, Terak EC, Raffa RB. Potential novel targets for Alzheimer pharmacotherapy: II. Update on secretase inhibitors and related approaches. J Clin Pharm Ther. 2014 Feb;39(1):25-37. doi: 10.1111/jcpt.12112. Epub 2013 Dec 8. Review. PubMed PMID: 24313554.
3: Van Broeck B, Chen JM, Tréton G, Desmidt M, Hopf C, Ramsden N, Karran E, Mercken M, Rowley A. Chronic treatment with a novel γ-secretase modulator, JNJ-40418677, inhibits amyloid plaque formation in a mouse model of Alzheimer's disease. Br J Pharmacol. 2011 May;163(2):375-89. doi: 10.1111/j.1476-5381.2011.01207.x. PubMed PMID: 21232036; PubMed Central PMCID: PMC3087138.
