Ibudilast (KC-404) | Phosphodiesterase Inhibitor

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CAS No. :	50847-11-5
Formula :	C₁₄H₁₈N₂O
M.W :	230.31
SMILES Code :	CC(C)C(C1=C2C=CC=CN2N=C1C(C)C)=O
Synonyms :	KC-404; AV-411; MN-166
MDL No. :	MFCD00864808
InChI Key :	ZJVFLBOZORBYFE-UHFFFAOYSA-N
Pubchem ID :	3671

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

RAW264.7 macrophage cell line	10 μM	12 hours	To evaluate the inhibitory effect of Ibudilast on doxorubicin-induced cytotoxicity. Results showed that Ibudilast significantly suppressed doxorubicin-induced cell death.	PMC6715615
C2C12 skeletal muscle myoblasts	10 μM	24 hours	To evaluate the inhibitory effect of Ibudilast on doxorubicin-induced atrophy in skeletal muscle myoblasts. Results showed that Ibudilast significantly suppressed doxorubicin-induced cell atrophy.	PMC6715615
H9c2 rat cardiac myoblasts	10 μM	24 hours	To evaluate the inhibitory effect of Ibudilast on doxorubicin-induced cytotoxicity in cardiac myoblasts. Results showed that Ibudilast significantly suppressed doxorubicin-induced cell death.	PMC6715615
Rat insulinoma cells (INS1)	10 μM	24-48 hours	Ibudilast and calpain inhibitor XI reversed the deficits observed in WFS1-KO cells, including lowering resting cytosolic calcium levels, restoring cell viability, and glucose-stimulated insulin secretion	PMC7382278
Rat astrocytes	10 – 100 μM	30 minutes	To investigate the protective effect of Ibudilast against H2O2-induced apoptosis, results showed that Ibudilast significantly attenuated H2O2-induced decrease in cell viability, inhibited cytochrome c release, caspase-3 activation, DNA ladder formation, and nuclear condensation	PMC1572853
RAW264.7 cells	100 ng/mL	5 days	LPS significantly increased the expression levels of osteoclast-associated molecules such as cathepsin K and TRAP.	PMC7865869
VTA dopamine neurons	10 μM	6-10 minutes	Enhanced GABAergic inhibition and prevented cocaine self-administration-induced changes in inhibitory synaptic plasticity	PMC8656241
RN1 cells	195 μM	7 days	To evaluate the effect of combined Ibudilast and TMZ treatment on cell cycle and apoptosis, results showed significant increase in G1 cell cycle arrest and apoptosis.	PMC6393433
Peripheral blood mononuclear cells (PBMC)	10 nM to 10 μM		To evaluate the inhibitory effect of AV411 and AV1013 on rhMIF-induced PBMC migration. Results showed that AV411 significantly inhibited PBMC migration at concentrations as low as 10 nM, while AV1013 showed significant inhibition only at 10 μM.	PMC2895110
MC3T3-E1 cells	100 ng/mL		LPS significantly inhibited MC3T3-E1 cell differentiation, including reductions in alkaline phosphatase (ALP) levels and calcium deposition, as well as decreased osteopontin secretion.	PMC7865869

Fisher transgenic 344-AD rats	Transgenic rat model of Alzheimer’s disease	Oral (via rodent chow)	10 mg/kg	Once daily for 6 months	To evaluate the effects of Ibudilast on cognitive behavior and hippocampal pathology in transgenic rats with Alzheimer’s disease. Results showed that Ibudilast treatment significantly mitigated spatial learning and memory deficits, reduced hippocampal (hilar subregion) amyloid plaque and tau paired-helical filament load, and microgliosis. Additionally, RNA sequencing analysis revealed that Ibudilast treatment differentially affected gene expression levels of the TLR and ubiquitin-proteasome pathways in male and female transgenic rats.	PMC10226755
C57BL/6 mice	Doxorubicin-induced systemic tissue wasting model	Intraperitoneal injection	10 mg/kg	Continuous administration for 2 weeks	To evaluate the inhibitory effect of Ibudilast on doxorubicin-induced systemic tissue wasting. Results showed that Ibudilast significantly suppressed doxorubicin-induced body weight loss and tissue wasting.	PMC6715615
Mice	Genetic demyelination model	Intraperitoneal injection	10 mg/kg	Daily from PND30 to PND45	To evaluate the effect of Ibudilast on demyelination and clinical symptoms	PMC1112612
Mice	SOD1G93A and FUSR521C transgenic mice	Oral	12 mg/kg	Once daily, starting from 4 weeks after birth	To study the effects of Ibudilast on ALS Mice models, results showed Ibudilast enhanced the protective effects of NR and PT on survival and neuromotor functions	PMC10903100
Sprague-Dawley rats	Morphine dependence and withdrawal model	Intraperitoneal injection	7.5mg/kg	Twice daily for 7 days	AV411 significantly reduced naloxone-precipitated morphine withdrawal behaviors and potentiated acute opioid analgesia.	PMC2662518
Chick	Excitotoxic retinal damage model	Intravitreal injection	1 × 10−5 mg/mL to 4.0 mg/mL	Single injection, evaluated 24 hours later	Evaluate the protective effect of Ibudilast on excitotoxic retinal damage	PMC11920683
C57BL/6NCrlBltw mice	Femoral defect model	Intraperitoneal injection	4 mg/kg	3 consecutive days	Ibudilast mitigated LPS-induced delayed bone healing, promoting bone bridge formation and mature osteocyte formation.	PMC7865869
Long-Evans rats	Cocaine self-administration model	Intraperitoneal injection	1, 3, 10 mg/kg	Single dose, tested 30 minutes after administration	Dose-dependently reduced cocaine self-administration and restored E/I balance in VTA dopamine neurons	PMC8656241
Rats	Cocaine behavioral sensitization model	Intraperitoneal injection	7.5 and 10 mg/kg	Twice daily for 3 days and once on test day	Ibudilast reversed the expression of cocaine-induced behavioral sensitization, returning behavior to levels seen after acute exposure, but not below. In male rats, distance travelled in the center of the test arena and rearing only showed sensitization, and ibudilast reversed these behaviors to levels seen after acute cocaine exposure. In female rats, 7.5 mg/kg ibudilast reduced center distance travelled below levels seen after acute cocaine exposure.	PMC5404892
C57BL/6 mice	Folic acid-induced acute kidney injury model	Intraperitoneal injection	10 mg/kg	Twice daily for two consecutive days	Ibudilast ameliorates folic acid-induced acute kidney injury by blocking pyroptosis through TLR4-mediated NF-κB and MAPK signaling pathways, reducing inflammation.	PMC8139578
C57BL/6J mice	Methamphetamine-induced locomotor activity model	Subcutaneous injection	1.8-13 mg/kg	Twice daily for 7 days	Ibudilast significantly reduced the acute, chronic, and sensitization effects of methamphetamine-induced locomotor activity	PMC3973724
Long-Evans hooded rats	Methamphetamine self-administration model	Intraperitoneal injection	2.5 and 7.5 mg/kg	Twice daily on the last two days of extinction and once on the test day	To evaluate the effects of AV411 on footshock- and methamphetamine-induced reinstatement of drug-seeking behavior. AV411 significantly reduced footshock-induced reinstatement responses (2.5 and 7.5 mg/kg) and methamphetamine-induced reinstatement responses (7.5 mg/kg).	PMC2878837
Long-Evans hooded rats	Methamphetamine self-administration model	Intraperitoneal injection	1, 7.5, 10 mg/kg	Twice daily for three consecutive days	To evaluate the effects of Ibudilast on methamphetamine self-administration behavior. Results showed that Ibudilast significantly reduced the number of responses maintained by 0.03 mg/kg/inf methamphetamine.	PMC3593742
Mice	Fmr1 KO mice	Intraperitoneal injection	6 mg/kg	Once or twice daily for 14 days	Ibudilast significantly improved cognitive deficits in Fmr1 KO mice, including performance in novel object recognition, social recognition, and object location memory tests. Additionally, Ibudilast partially ameliorated anxiety-like behaviors.	PMC10789243
Balb/c nude mice	RN1 patient-derived xenograft model	Oral gavage	5 mg/kg and 20 mg/kg	Daily administration until all control mice died	To evaluate the effect of combined Ibudilast and TMZ treatment on survival time, results showed significant extension of survival time.	PMC6393433

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CAS No.: 50847-11-5

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CAS No.: 50847-11-5

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Precautionary Statements-General

Prevention

Response

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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	4.34mL 0.87mL 0.43mL	21.71mL 4.34mL 2.17mL	43.42mL 8.68mL 4.34mL
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