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CAS No. :	300816-15-3
Formula :	C₂₅H₂₇N₃O₃
M.W :	417.50
SMILES Code :	O=C1OC2(CCN(CCC3=C(C)OC(C4=CC=CC=C4)=N3)CC2)C5=CC(C)=CC=C5N1
MDL No. :	MFCD09038564
InChI Key :	ODNICNWASXKNNQ-UHFFFAOYSA-N
Pubchem ID :	9953769

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302-H315-H319-H335
Precautionary Statements:	P261-P305+P351+P338

SIM-A9 cells	100 µM	12 hours	To evaluate the effect of RS504393 on ethanol-induced MCP-1/CCR2 signaling in SIM-A9 cells. Results showed that RS504393 significantly reduced ethanol-induced increase in MCP-1 expression.	J Neuroinflammation. 2018 Jul 5;15(1):197.
Mouse dorsal root ganglion neurons	10 µM	3 minutes	To evaluate the effect of CCR2 antagonist on TRPV1 sensitization, results showed that 10 μM RS 504393 significantly reduced the proportion of Berk SS neurons responding to 5 nM capsaicin	Pain. 2018 Aug;159(8):1652-1663

C57BL/6 mice	Ethanol-exposed developing brain model	Subcutaneous injection	1 mg/kg	Two injections, 24 hours and 0.5 hours prior to ethanol exposure	To evaluate the effect of RS504393 on ethanol-induced neuroinflammation and neurodegeneration in the developing brain. Results showed that RS504393 significantly reduced ethanol-induced neuroapoptosis, microglial activation, and expression of pro-inflammatory cytokines.	J Neuroinflammation. 2018 Jul 5;15(1):197.
Mice	Bone cancer pain model	Intrathecal administration	1-3 μg	5 administrations, 48, 36, 24, 12, and 1 hour before	Inhibition of tumor-induced thermal hyperalgesia, reduction of astroglial activation in the superficial laminae of the spinal cord	Cell Mol Neurobiol. 2014 Jan;34(1):143-56
Mice	Unilateral ureteral obstruction model	Oral	2 mg/kg	Twice a day, starting from 3 days before ureteral ligation until the day of sacrifice	To evaluate the therapeutic effects of RS-504393 on renal interstitial fibrosis, results showed that RS-504393 reduced renal interstitial fibrosis and macrophage infiltration	Am J Pathol. 2004 Jul;165(1):237-46
Mice	Pressure overload-induced heart failure model	Subcutaneous injection	2 mg/kg	Once daily for 1 or 6 weeks	Blocking CCR2+ monocyte recruitment during pressure overload modified the proportion of macrophage subsets within the pathological heart and preserved lymphatic network from remodeling.	Sci Rep. 2021 Aug 19;11(1):16801
CD1 mice	Inflammatory pain model	Intrathecal injection	20 μg	Single dose	RS504393 reversed CFA-induced heat hyperalgesia	Neurosci Bull. 2018 Feb;34(1):13-21
Wistar rats	Chronic constriction injury (CCI) model of the sciatic nerve	Intrathecal injection	20 μg/5μl	Preemptive administration at 16 h and 1 h before CCI, then once daily for 7 days	RS504393 not only attenuated CCI-induced tactile and thermal hypersensitivity but also enhanced the analgesic effects of morphine and buprenorphine by reducing the mRNA and/or protein levels of pronociceptive factors such as IL-1beta, IL-18, IL-6, and iNOS in neuropathic pain.	J Neuroimmune Pharmacol. 2017 Sep;12(3):402-419
Mice	Berkeley sickle mice (Berk SS)	Subcutaneous injection	3 mg/kg	Single administration, 30 minutes prior to behavioral testing	To evaluate the effect of CCR2 antagonist on mechanical and cold hypersensitivity in SCD mice, results showed that 3 mg/kg RS 504393 significantly alleviated mechanical and cold hypersensitivity in Berk SS mice	Pain. 2018 Aug;159(8):1652-1663
C57BL/6J male mice	Subarachnoid hemorrhage model	Intraperitoneal injection	3 mg/kg/day	Once daily for 24 hours	To investigate the effects of RS504393 on neurological deficits, brain edema, blood-brain barrier permeability, neuroinflammation, and neuronal apoptosis after SAH. Results showed that RS504393 significantly improved neurological scores, reduced brain edema and BBB disruption, and decreased the expression of inflammatory and apoptotic factors.	J Neuroinflammation. 2022 Dec 25;19(1):312
DBA mice	Collagen-induced arthritis model	Intraperitoneal injection	4 mg/kg	Every 48 hours for 2 weeks	To evaluate the effect of CCR2 SMI on arthritis development, results showed CCR2 SMI alone or in combination with MTX reduced bone resorption and OCP frequency	Front Immunol. 2021 Dec 3;12:767231
Mice	Destabilization of the medial meniscus (DMM) surgery-induced osteoarthritis model	Oral gavage	4 mg/kg/day	Once daily for 12 weeks	To evaluate the effect of RS-504393 on the development of osteoarthritis in mice. Results showed that RS-504393 significantly attenuated cartilage damage, synovitis, and osteophyte formation, and reduced the accumulation of F4/80+ macrophages in the synovium.	Ann Rheum Dis. 2017 May;76(5):914-922.
Mice	Destabilization of medial meniscus (DMM) model	Oral	4mg/kg/day	Once daily for 1-4 weeks, 4-8 weeks, or 8-12 weeks	Early CCR2 blockade (1-4 weeks) significantly reduced cartilage and bone damage and alleviated pain responses; delayed treatment was less effective.	Osteoarthritis Cartilage. 2017 Jun;25(6):914-925

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CAS No.: 300816-15-3

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CAS No.: 300816-15-3

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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