Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C24H16F3N5 |
Molecular Weight | 431.4125 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 1 / 1 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
NC1=N[C@](C2=C1C(F)=CC=C2)(C3=CC(=NC=C3)C(F)F)C4=CC=CC(=C4)C5=CN=CN=C5
InChI
InChIKey=MRXBCEQZNKUUIP-DEOSSOPVSA-N
InChI=1S/C24H16F3N5/c25-19-6-2-5-18-21(19)23(28)32-24(18,17-7-8-31-20(10-17)22(26)27)16-4-1-3-14(9-16)15-11-29-13-30-12-15/h1-13,22H,(H2,28,32)/t24-/m0/s1
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/27129013Curator's Comment: The description was created based on several sources, including
https://clinicaltrials.gov/ct2/show/NCT01348737 | https://www.ncbi.nlm.nih.gov/pubmed/22924815 | https://www.drugbank.ca/drugs/DB12368
Sources: https://www.ncbi.nlm.nih.gov/pubmed/27129013
Curator's Comment: The description was created based on several sources, including
https://clinicaltrials.gov/ct2/show/NCT01348737 | https://www.ncbi.nlm.nih.gov/pubmed/22924815 | https://www.drugbank.ca/drugs/DB12368
AZD3839 is a potent and selective BACE1 inhibitor with about 14-fold selectivity over BACE2. In SH-SY5Y cells, AZD3839 efficiently decreases the Aβ40 levels and decreases the formation of sAPPβ. AZD3839 also decreases the Aβ40 levels secreted from C57BL/6 mouse primary cortical neurons, N2A cells, and Dunkin-Hartley guinea pig primary cortical neurons. AZD3839 causes in vitro BACE1 inhibition in the cell assay with the IC50 value of 16.7 nM. In C57BL/6 mice, AZD3839 (69 mg/kg, p.o.) causes a dose- and time-dependent reduction of plasma and brain Aβ. In guinea pig and non-human primates, AZD3839 also inhibits Aβ generation. AZD3839 has been used in phase I clinical trials studying the basic science of Safety and Tolerability. However future development has been discontinued.
CNS Activity
Originator
Sources: https://encrypted.google.com/patents/WO2010056196A1
Curator's Comment: # AstraZeneca AB
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL4593 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22924815 |
51.0 nM [IC50] | ||
Target ID: CHEMBL2525 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22924815 |
370.0 nM [Ki] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Unknown Approved UseUnknown |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
3400 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24917547 |
300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered: |
AZD-3839 plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
3807 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27129013 |
300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered: |
AZD-3839 plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
3.6% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27129013 |
300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered: |
AZD-3839 plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
Sample Use Guides
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/27129013
In phase I clinical trials single oral ascending doses (1–300 mg) of AZD3839 were administered to 54 young healthy volunteer.
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/22924815
SH-SY5Y cells (human neuroblastoma cell line) were cultured in DMEM/F-12 with Glutamax, 10% FCS, and 1% nonessential amino acids. The test compound (AZD3839) was incubated with cells for 16 h at 37 °C, 5% CO2. Meso Scale Discovery (MSD) plates were used for the detection of sAPPβ release; MSD sAPPβ plates were blocked in 3% BSA in Tris wash buffer for 1 h at rt and washed four times in Tris buffer. After incubation, 20 μL of medium was transferred to the preblocked and washed 384-well MSD sAPPβ microplate and incubated with shaking at rt for 2 h followed by washing four times in Tris buffer. A 10 μL volume of detection antibody was added (1 nM) followed by incubation with shaking at rt for 2 h followed by washing four times in Tris buffer. A 40 μL volume of read buffer was added per well, and the plates were read in a SECTOR imager. In addition, the cells incubated with test compound were further lysed and analyzed for any cytotoxic effects of the compounds using the ViaLight Plus cell proliferation/cytotoxicity kit
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46202416
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DB12368
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I8ID590133
Created by
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1227163-84-9
Created by
admin on Sat Dec 16 10:14:06 GMT 2023 , Edited by admin on Sat Dec 16 10:14:06 GMT 2023
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ACTIVE MOIETY