Details
Stereochemistry | ACHIRAL |
Molecular Formula | C16H11Cl2FO2 |
Molecular Weight | 325.162 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
OC(=O)C1(CC1)C2=CC=C(C(F)=C2)C3=CC=C(Cl)C(Cl)=C3
InChI
InChIKey=LIYLTQQDABRNRX-UHFFFAOYSA-N
InChI=1S/C16H11Cl2FO2/c17-12-4-1-9(7-13(12)18)11-3-2-10(8-14(11)19)16(5-6-16)15(20)21/h1-4,7-8H,5-6H2,(H,20,21)
Molecular Formula | C16H11Cl2FO2 |
Molecular Weight | 325.162 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
DescriptionCurator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/23968157
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/23968157
CHF-5074 is a small molecule with a unique microglial modulating mechanism of action capable of selectively reducing pro-inflammatory activities of microglial cells while increasing their ability to remove neurotoxic amyloid beta (“Aβ”) aggregates in the brain by phagocytosis. CHF-5074 reduces Aβ42 and Aβ40 secretion, with an IC50 of 3.6 and 18.4 μM, respectively. Microglia are small cells that migrate through the brain to remove waste products, such as amyloid aggregates that cause inflammation and irreversible damage to nerve cells. Chronic dysfunction of microglia is increasingly believed to play an important role at the very beginnings of Alzheimer’s disease. The results from Chiesi’s human clinical studies corroborate the large body of data from published preclinical studies. In Alzheimer’s disease transgenic mouse models, CHF-5074 was shown to reduce neuroinflammation, inhibit brain amyloid β plaque deposits, reduce tau pathology, and reverse associated memory deficits. These findings indicate CHF-5074 acts simultaneously on several important therapeutic targets, and this neuroprotective multi-target approach may translate into preventing the memory loss that is the hallmark of Alzheimer’s disease.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL2487 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17895400 |
3.6 nM [IC50] | ||
Target ID: CHEMBL2094135 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Unknown Approved UseUnknown |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
151 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22922591/ |
600 mg 1 times / day steady-state, oral dose: 600 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
CHF-5074 plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
|
56.3 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22922591/ |
200 mg 1 times / day steady-state, oral dose: 200 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
CHF-5074 plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
|
88.7 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22922591/ |
400 mg 1 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
CHF-5074 plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
1530 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22922591/ |
600 mg 1 times / day steady-state, oral dose: 600 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
CHF-5074 plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
|
621 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22922591/ |
200 mg 1 times / day steady-state, oral dose: 200 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
CHF-5074 plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
|
948 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22922591/ |
400 mg 1 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
CHF-5074 plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
25.3 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22922591/ |
600 mg 1 times / day steady-state, oral dose: 600 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
CHF-5074 plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
|
31.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22922591/ |
200 mg 1 times / day steady-state, oral dose: 200 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
CHF-5074 plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
|
31.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22922591/ |
400 mg 1 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
CHF-5074 plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
Sample Use Guides
In Vivo Use Guide
Sources: https://clinicaltrials.gov/ct2/show/NCT01421056
oral tablet, 1x, once a day in the morning for 24 weeks
oral tablet, 1x, once a day in the morning for 4 weeks, followed by oral tablet, 2x, once a day in the morning for 20 weeks
oral tablet, 1x, once a day in the morning for 4 weeks, followed by oral tablet, 2x, once a day in the morning for 4 weeks, followed by oral tablet, 3x, once a day in the morning for 16 weeks
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/20930267
CHF5074 (10-30 uM) caused a concentration-dependent stellation of rat astrocytes in primary cultures, associated with the reorganization of GFAP and actin filaments.
Substance Class |
Chemical
Created
by
admin
on
Edited
Sat Dec 16 05:09:30 GMT 2023
by
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on
Sat Dec 16 05:09:30 GMT 2023
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Record UNII |
C35RF1MWQZ
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Record Status |
Validated (UNII)
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Record Version |
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