Structure of Avagacestat
CAS No.: 1146699-66-2
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
Avagacestat is an inhibitor of γ-secretase Aβ40 and Aβ42 with IC50s of 0.3 nM and 0.27 nM, respectively.
Synonyms: BMS-708163
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CAS No. : | 1146699-66-2 |
Formula : | C20H17ClF4N4O4S |
M.W : | 520.89 |
SMILES Code : | O=C(N)[C@H](N(CC1=CC=C(C2=NOC=N2)C=C1F)S(=O)(C3=CC=C(Cl)C=C3)=O)CCC(F)(F)F |
Synonyms : |
BMS-708163
|
MDL No. : | MFCD13195458 |
InChI Key : | XEAOPVUAMONVLA-QGZVFWFLSA-N |
Pubchem ID : | 46883536 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
In Vitro:
Cell Line
|
Concentration | Treated Time | Description | References |
ANPP cells | 100 nM | 1 hour | Through a large-scale photolabeling experiment, the binding site of the BMS-708163 probe on PS1 was determined, showing that the probe labeled the L282 site of PS1. | PMC5516958 |
HeLa cells | 2 µM | 1 hour | E2012-BPyne specifically labels PS1-NTF, and the labeling is competed in the presence of E2012 | PMC3617273 |
H4-APP cells | 1 µM | 1 hour | E2012-BPyne specifically labels PS1-NTF, and the labeling is competed in the presence of E2012 | PMC3617273 |
ANP.24 cells | 1 µM | 1 hour | E2012-BPyne preferentially labels active PS1-NTF over inactive full-length PS1 | PMC3617273 |
PS1-G378E neurons | 10 nM | 20 days | To evaluate the effect of BMS-708163 on the expression levels of RAB3A and SV2B proteins in PS1-G378E neurons, finding that RAB3A and SV2B protein levels increased by 2-fold and 3-fold, respectively | PMC5027582 |
hepatic stellate cells | 1 μM and 10 μM | 24 hours | To investigate the effect of testosterone on hepatic stellate cell activation in a KDM5B/KDM5C-dependent manner, results showed that testosterone significantly increased the expression of HSC activation markers in KDM5B/KDM5C-deficient cells. | PMC11609386 |
LX2 cells | 5 μM and 10 μM | 24 hours | Inhibited TGFβ-induced HSC activation and contractility, significantly reduced collagen I, α-SMA, and vimentin expression | PMC4677309 |
RAW264.7 macrophages | 10 μM | 24 hours | Inhibited M1 macrophage polarization, significantly reduced Hes1 expression and NO release | PMC4677309 |
Mouse primary neurons | 2 μM | 4 days | To investigate the effect of Avagacestat on PS1 levels, results showed that Avagacestat increased PS1 protein levels. | PMC5948247 |
HeLa cells | 20 nM | To study the interaction of BMS-708163 probes with γ-secretase, the results showed that the labeling efficiency of PS1-NTF correlated with the IC50 values of the probes. | PMC5516958 | |
H4-8Sw cells | 0.30 nM | Inhibition of Aβ40 and Aβ42 formation | PMC4007960 |
In Vivo:
Species
|
Animal Model
|
Administration | Dosage | Frequency | Description | References |
Mice | alcohol-induced liver fibrosis model | Oral | 10 mg/kg | twice weekly for 4 weeks | To evaluate the role of Notch signaling in alcohol-induced liver fibrosis, results showed that inhibiting Notch signaling significantly reduced liver fibrosis and abolished the effect of Kdm5b/Kdm5c loss. | PMC11609386 |
Mice | Tg2576 transgenic mice | Oral | 1-10 mg/kg | Once daily for 8 days | To compare the effects of GSIs and GSM on cognitive function in Tg2576 mice. The results showed that GSIs ameliorated cognitive deficits with acute dosing, but these effects disappeared after subchronic dosing and even impaired normal cognition. GSM-2 significantly ameliorated cognitive deficits without affecting normal cognition. | PMC6621706 |
Rats | Wistar rats | Oral | 40 mg/kg | Once daily for 21 days | To investigate the effect of Avagacestat on PS1 levels in rat brains, results showed that Avagacestat significantly increased PS1 protein levels in the brain. | PMC5948247 |
Mice | CCl4-induced liver fibrosis model | intraperitoneal injection | 10 mg/kg | once daily for 2 days | Significantly attenuated liver fibrosis, reduced HSC activation and inflammatory M1 macrophages, while upregulated suppressive M2 macrophages | PMC4677309 |
Rats and dogs | Wild-type rats and beagle dogs | Oral | 1, 3, 10, 30 mg/kg (rats); 2 mg/kg (dogs) | Single dose | Significantly reduced Aβ40 levels in brain, plasma, and cerebrospinal fluid | PMC4007960 |
Clinical Trial:
NCT Number | Conditions | Phases | Recruitment | Completion Date | Locations |
NCT00901498 | Alzheimer's Disease ... More >> Healthy Less << | Phase 1 | Completed | - | United States, New Jersey ... More >> Mds Pharma Services (Us) Inc. Neptune, New Jersey, United States, 07753 Less << |
NCT00810147 | Alzheimer's Disease | Phase 2 | Completed | - | - |
NCT00828646 | Healthy | Phase 1 | Completed | - | Japan ... More >> Local Institution Yokohama, Kanagawa, Japan, 2320064 Less << |
NCT00726726 | Alzheimer Disease | Phase 1 | Completed | - | United States, New Jersey ... More >> Bristol-Myers Squibb Clinical Pharmacology Unit Hamilton, New Jersey, United States, 08690 Less << |
NCT01079819 | Alzheimer's Disease | Phase 1 | Completed | - | United States, California ... More >> West Coast Clinical Trials, Llc Cypress, California, United States, 90630 California Clinical Trials Medical Group Glendale, California, United States, 91206 United States, New Jersey Iberica Clinical Research Center Eatontown, New Jersey, United States, 07724 Less << |
NCT00979316 | Alzheimer Disease | Phase 1 | Completed | - | United States, Arizona ... More >> Mds Pharma Services (Us), Inc Tempe, Arizona, United States, 85283 Less << |
NCT01002079 | Alzheimer Disease | Phase 1 | Completed | - | India ... More >> Local Institution Bangalore, India, 560100 Less << |
NCT01454115 | Alzheimer's Disease | Phase 1 | Completed | - | - |
NCT01057030 | Alzheimer Disease | Phase 1 | Completed | - | United States, California ... More >> California Clinical Trials Medical Group Glendale, California, United States, 91206 Less << |
NCT00860275 | Alzheimer Disease | Phase 1 | Completed | - | United States, Texas ... More >> Ppd Development, Lp Austin, Texas, United States, 78744 Less << |
NCT01039194 | Alzheimer Disease | Phase 1 | Completed | - | United States, Maryland ... More >> Parexel International - Baltimore Epcu Baltimore, Maryland, United States, 21225 Less << |
NCT00890890 | Alzheimer's Disease | Phase 2 | Terminated | - | - |
NCT01042314 | Alzheimer Disease | Phase 1 | Completed | - | United States, Maryland ... More >> Parexel International - Baltimore Epcu Baltimore, Maryland, United States, 21225 Less << |
Bio Calculators | ||||
Preparing Stock Solutions | ![]() |
1mg | 5mg | 10mg |
1 mM 5 mM 10 mM |
1.92mL 0.38mL 0.19mL |
9.60mL 1.92mL 0.96mL |
19.20mL 3.84mL 1.92mL |
Tags: Avagacestat | BMS-708163 | BMS708163 | BMS 708163 | γ-secretase | Notch | Gamma secretase | γ-secretase inhibitor | Aβ42 inhibition | Aβ40 inhibition | NICD inhibition | Alzheimer’s disease | CYP2C19 inhibition | 1146699-66-2
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P265 | Wash skin thouroughly after handling. |
P270 | Do not eat, drink or smoke when using this product. |
P271 | Use only outdoors or in a well-ventilated area. |
P272 | Contaminated work clothing should not be allowed out of the workplace. |
P273 | Avoid release to the environment. |
P280 | Wear protective gloves/protective clothing/eye protection/face protection. |
P281 | Use personal protective equipment as required. |
P282 | Wear cold insulating gloves/face shield/eye protection. |
P283 | Wear fire/flame resistant/retardant clothing. |
P284 | Wear respiratory protection. |
P285 | In case of inadequate ventilation wear respiratory protection. |
P231 + P232 | Handle under inert gas. Protect from moisture. |
P235 + P410 | Keep cool. Protect from sunlight. |
Response | |
Code | Phrase |
P301 | IF SWALLOWED: |
P304 | IF INHALED: |
P305 | IF IN EYES: |
P306 | IF ON CLOTHING: |
P307 | IF exposed: |
P308 | IF exposed or concerned: |
P309 | IF exposed or if you feel unwell: |
P310 | Immediately call a POISON CENTER or doctor/physician. |
P311 | Call a POISON CENTER or doctor/physician. |
P312 | Call a POISON CENTER or doctor/physician if you feel unwell. |
P313 | Get medical advice/attention. |
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P337 | If eye irritation persists: |
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P340 | Remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P341 | If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P342 | If experiencing respiratory symptoms: |
P350 | Gently wash with plenty of soap and water. |
P351 | Rinse cautiously with water for several minutes. |
P352 | Wash with plenty of soap and water. |
P353 | Rinse skin with water/shower. |
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P362 | Take off contaminated clothing and wash before reuse. |
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P370 | In case of fire: |
P371 | In case of major fire and large quantities: |
P372 | Explosion risk in case of fire. |
P373 | DO NOT fight fire when fire reaches explosives. |
P374 | Fight fire with normal precautions from a reasonable distance. |
P376 | Stop leak if safe to do so. Oxidising gases (section 2.4) 1 |
P377 | Leaking gas fire: Do not extinguish, unless leak can be stopped safely. |
P378 | |
P380 | Evacuate area. |
P381 | Eliminate all ignition sources if safe to do so. |
P390 | Absorb spillage to prevent material damage. |
P391 | Collect spillage. Hazardous to the aquatic environment |
P301 + P310 | IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician. |
P301 + P312 | IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell. |
P301 + P330 + P331 | IF SWALLOWED: Rinse mouth. Do NOT induce vomiting. |
P302 + P334 | IF ON SKIN: Immerse in cool water/wrap in wet bandages. |
P302 + P350 | IF ON SKIN: Gently wash with plenty of soap and water. |
P303 + P361 + P353 | IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower. |
P304 + P312 | IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell. |
P304 + P340 | IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing. |
P304 + P341 | IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P305 + P351 + P338 | IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. |
P306 + P360 | IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes. |
P307 + P311 | IF exposed: call a POISON CENTER or doctor/physician. |
P308 + P313 | IF exposed or concerned: Get medical advice/attention. |
P309 + P311 | IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician. |
P332 + P313 | IF SKIN irritation occurs: Get medical advice/attention. |
P333 + P313 | IF SKIN irritation or rash occurs: Get medical advice/attention. |
P335 + P334 | Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages. |
P337 + P313 | IF eye irritation persists: Get medical advice/attention. |
P342 + P311 | IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician. |
P370 + P376 | In case of fire: Stop leak if safe to Do so. |
P370 + P378 | In case of fire: |
P370 + P380 | In case of fire: Evacuate area. |
P370 + P380 + P375 | In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion. |
P371 + P380 + P375 | In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion. |
Storage | |
Code | Phrase |
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P402 | Store in a dry place. |
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P413 | |
P420 | Store away from other materials. |
P422 | |
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P403 + P235 | Store in a well-ventilated place. Keep cool. |
P410 + P403 | Protect from sunlight. Store in a well-ventilated place. |
P410 + P412 | Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF. |
P411 + P235 | Keep cool. |
Disposal | |
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Physical hazards | |
Code | Phrase |
H200 | Unstable explosive |
H201 | Explosive; mass explosion hazard |
H202 | Explosive; severe projection hazard |
H203 | Explosive; fire, blast or projection hazard |
H204 | Fire or projection hazard |
H205 | May mass explode in fire |
H220 | Extremely flammable gas |
H221 | Flammable gas |
H222 | Extremely flammable aerosol |
H223 | Flammable aerosol |
H224 | Extremely flammable liquid and vapour |
H225 | Highly flammable liquid and vapour |
H226 | Flammable liquid and vapour |
H227 | Combustible liquid |
H228 | Flammable solid |
H229 | Pressurized container: may burst if heated |
H230 | May react explosively even in the absence of air |
H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
H240 | Heating may cause an explosion |
H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
H250 | Catches fire spontaneously if exposed to air |
H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
H270 | May cause or intensify fire; oxidizer |
H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
Code | Phrase |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
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