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CAS No. :	1527473-33-1
Formula :	C₁₇H₁₅N₅O
M.W :	305.33
SMILES Code :	N#CC1=CC=CC(C2=CNC3=NC=NC(N4CCOCC4)=C32)=C1
MDL No. :	MFCD28347838
InChI Key :	BHTWDJBVZQBRKP-UHFFFAOYSA-N
Pubchem ID :	72706840

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302
Precautionary Statements:	P280-P305+P351+P338

Midbrain dopaminergic neurons	30 nM	14 days	To test the effect of LRRK2 inhibitors on α-synuclein pathology in dopaminergic neurons, no significant changes were observed	Acta Neuropathol Commun. 2018 May 31;6(1):45
Primary mouse hippocampal neurons	30 nM	18 days	Inhibition of LRRK2 kinase activity, significantly reducing the formation of α-synuclein inclusions in G2019S-LRRK2-expressing neurons	J Neurosci. 2016 Jul 13;36(28):7415-27
Differentiated SHSY5Y cells	1 and 3 µM	2 hours	To evaluate the effect of PF-475 on MPTP-induced LRRK2 phosphorylation. Results showed that PF-475 significantly reduced p-Ser935 levels in a concentration-dependent manner.	iScience. 2024 Sep 16;27(10):110980
Mouse embryonic fibroblasts (MEFs)	150 nM	2 hours	To evaluate the effect of LRRK2 kinase inhibitors on early stages of autophagy, results showed that PF-06447475 treatment did not affect WIPI2 puncta formation	Cell Death Dis. 2023 Jul 15;14(7):436
SH-SY5Y cells	150 nM	2 hours	To evaluate the effect of LRRK2 kinase inhibitors on autophagy, results showed that PF-06447475 treatment did not affect autophagy	Cell Death Dis. 2023 Jul 15;14(7):436
Hippocampal neurons	5, 30, 120 nM	21 days	To test the effect of LRRK2 inhibitors on α-synuclein pathology, found that even robust LRRK2 inhibition is insufficient to reduce α-synuclein pathology	Acta Neuropathol Commun. 2018 May 31;6(1):45
RAW264.7 cells	1 and 10 µM	24, 48 and 72 hours	Tested the ability of PROTACs to degrade LRRK2, results showed PROTACs did not significantly reduce LRRK2 protein levels	ChemMedChem. 2021 Mar 18;16(6):959-965
WT PSEN1 DALNs	1 µM	4 days	PF-475 reduced basal levels of accumulated iAβ (-47%), oxDJ-1 (-58%), p-TAU (-50%), pS935-LRRK2 (-58%), and pS129-αSyn (-78%), but had no significant effect on apoptotic markers pS63-c-JUN and CC3.	Molecules. 2025 May 2;30(9):2034
PSEN1 I416T dopaminergic-like neurons (DALNs)	1 µM	4 days	PF-475 significantly reduced the accumulation of iAβ (-44%), decreased oxDJ-1 (-72%), and reduced p-TAU (-73%). Additionally, it decreased pS935-LRRK2 (-60%) and pS129-αSyn (-48%), and reduced the expression of apoptotic markers pS63-c-JUN (-18%) and CC3 (-41%).	Molecules. 2025 May 2;30(9):2034
DALNs (dopamine-like neurons)	1 µM	6 hours or 24 hours	To evaluate the effect of PF-06447475 on ROT-induced apoptosis and autophagy. Results showed that PF-06447475 almost completely inhibited the phosphorylation of p-S935-LRRK2, reduced the number of CC3-positive cells, and decreased the accumulation of lysosomes.	Int J Mol Sci. 2023 Oct 30;24(21):15744
SH-SY5Y cells	150 nM	6 weeks	To investigate the effects of long-term LRRK2 kinase inhibition on LRRK2 protein levels and S935 phosphorylation. Results showed sustained reduction in LRRK2 protein levels and S935 phosphorylation.	Mol Neurobiol. 2019 Aug;56(8):5273-5286
SH-SY5Y cells	150 nM	various time periods	To study the reversibility of LRRK2 kinase inhibition. Results showed complete recovery of S935 phosphorylation after inhibitor withdrawal, and full recovery of LRRK2 protein levels after 3 days.	Mol Neurobiol. 2019 Aug;56(8):5273-5286

Drosophila melanogaster	Wild type (w[1118]) and TH > Lrrk2-RNAi transgenic flies	Oral	0.05, 0.075, 0.1 µM	15 days	To evaluate the effects of PF-475 on lifespan, locomotor activity, DAergic neuronal integrity, and lipid peroxidation in Drosophila melanogaster. Results showed PF-475 significantly prolonged lifespan, improved locomotor activity, and reduced lipid peroxidation.	Neurochem Res. 2024 Sep;49(9):2440-2452
CD1 mice	Moderate traumatic brain injury model	Intraperitoneal injection	1, 2.5 and 5 mg/kg	Once daily for 14 days	PF-06447475 significantly reduced histological damage and behavioral disturbances, showing an antidepressant effect and restoring changes in the copper/glutamate/N-methyl-D-aspartic acid receptor (Cu/NMDAR) system.	Cells. 2023 Mar 29;12(7):1040
Mice	BALB/c mice	Tail vein injection	10 mg/kg	Single dose, 45 minutes	Evaluate the effect of PF-06447475 on the biodistribution of [3H]LRRK2-IN-1 in mice, showing that 10 mg/kg PF-06447475 reduced the uptake of [3H]LRRK2-IN-1 by 54% in kidney and 62% in brain.	Mol Imaging Biol. 2017 Dec;19(6):837-845
CD1 mice	MPTP-induced Parkinson's disease model	Intraperitoneal injection	2.5, 5, and 10 mg/kg	Once daily for 7 days	To evaluate the effect of PF-475 on MPTP-induced Parkinson's disease in the central nervous system and gastrointestinal system. Results showed that PF-475 reduced brain α-synuclein accumulation, modulated the mitophagy pathway, and decreased pro-inflammatory markers and α-synuclein aggregates in colonic tissues.	iScience. 2024 Sep 16;27(10):110980
Male Sprague-Dawley rats	Traumatic brain injury (TBI) model	Intraperitoneal injection	3 mg/kg and 5 mg/kg	Administered at 1 hour post-TBI	PF-06447475 significantly reduced neuronal apoptosis, brain water content, and blood–brain barrier permeability at 12 h post-TBI and ameliorated neurological deficits at 72 h post-TBI.	Front Cell Neurosci. 2018 Mar 1;12:51
Rats	G2019S-LRRK2 transgenic rats and wild-type rats	Oral gavage	30 mg/kg	Twice daily for 4 weeks	To evaluate the in vivo inhibitory effect of PF-06447475 on LRRK2 kinase activity and its neuroprotective effects against neurodegeneration. Results showed that PF-06447475 significantly mitigated α-synuclein-induced dopaminergic neurodegeneration and neuroinflammation, with no adverse pathological effects observed in the lung, kidney, or liver after 4 weeks of treatment.	J Biol Chem. 2015 Aug 7;290(32):19433-44

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CAS No.: 1527473-33-1

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CAS No.: 1527473-33-1

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Product Details of PF-06447475

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Precautionary Statements-General

Prevention

Response

Storage

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Physical hazards

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Preparing Stock Solutions		1mg	5mg	10mg
Preparing Stock Solutions	1 mM 5 mM 10 mM	3.28mL 0.66mL 0.33mL	16.38mL 3.28mL 1.64mL	32.75mL 6.55mL 3.28mL
Dissolving Methods	Animal experiment Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn: in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day; The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound. Protocol 1 Protocol 2

Precautionary Statements-General
Code	Phrase
P101	If medical advice is needed,have product container or label at hand.
P102	Keep out of reach of children.
P103	Read label before use
Prevention
Code	Phrase
P201	Obtain special instructions before use.
P202	Do not handle until all safety precautions have been read and understood.
P210	Keep away from heat/sparks/open flames/hot surfaces. - No smoking.
P211	Do not spray on an open flame or other ignition source.
P220	Keep/Store away from clothing/combustible materials.
P221	Take any precaution to avoid mixing with combustibles
P222	Do not allow contact with air.
P223	Keep away from any possible contact with water, because of violent reaction and possible flash fire.
P230	Keep wetted
P231	Handle under inert gas.
P232	Protect from moisture.
P233	Keep container tightly closed.
P234	Keep only in original container.
P235	Keep cool
P240	Ground/bond container and receiving equipment.
P241	Use explosion-proof electrical/ventilating/lighting/equipment.
P242	Use only non-sparking tools.
P243	Take precautionary measures against static discharge.
P244	Keep reduction valves free from grease and oil.
P250	Do not subject to grinding/shock/friction.
P251	Pressurized container: Do not pierce or burn, even after use.
P260	Do not breathe dust/fume/gas/mist/vapours/spray.
P261	Avoid breathing dust/fume/gas/mist/vapours/spray.
P262	Do not get in eyes, on skin, or on clothing.
P263	Avoid contact during pregnancy/while nursing.
P264	Wash hands thoroughly after handling.
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.
P314	Get medical advice/attention if you feel unwell.
P315	Get immediate medical advice/attention.
P320
P302 + P352	IF ON SKIN: wash with plenty of soap and water.
P321
P322
P330	Rinse mouth.
P331	Do NOT induce vomiting.
P332	IF SKIN irritation occurs:
P333	If skin irritation or rash occurs:
P334	Immerse in cool water/wrap n wet bandages.
P335	Brush off loose particles from skin.
P336	Thaw frosted parts with lukewarm water. Do not rub affected area.
P337	If eye irritation persists:
P338	Remove contact lenses, if present and easy to do. Continue rinsing.
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.
P360	Rinse immediately contaminated clothing and skin with plenty of water before removing clothes.
P361	Remove/Take off immediately all contaminated clothing.
P362	Take off contaminated clothing and wash before reuse.
P363	Wash contaminated clothing before reuse.
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
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
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
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

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