Vesatolimod (GS-9620) | TLR7 Agonist

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CAS No. :	1228585-88-3
Formula :	C₂₂H₃₀N₆O₂
M.W :	410.51
SMILES Code :	O=C1NC2=C(N)N=C(OCCCC)N=C2N(CC3=CC=CC(CN4CCCC4)=C3)C1
Synonyms :	GS-9620
MDL No. :	MFCD25372045
InChI Key :	VFOKSTCIRGDTBR-UHFFFAOYSA-N
Pubchem ID :	46241268

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

RAW264.7 cells	0.59 µM	48 hours	Evaluated the inhibitory effect of TLR7 agonists on murine norovirus replication, showing GS-9620 effectively inhibited viral replication	PMC5923118
SH-SY5Y cells	1–50 µM	48 hours	To evaluate the inhibitory effect of Vesatolimod on EV-D68 replication in SH-SY5Y cells, results showed Vesatolimod significantly suppressed viral protein VP1 synthesis and progeny virus production.	PMC11237570
BEAS-2B cells	1–50 µM	48 hours	To evaluate the inhibitory effect of Vesatolimod on EV-D68 replication in BEAS-2B cells, results showed Vesatolimod significantly suppressed viral protein VP1 synthesis and progeny virus production.	PMC11237570
A549 cells	1, 10, 50, 100 µM	48 hours	To evaluate the inhibitory effect of Vesatolimod on EV-D68 replication, results showed Vesatolimod significantly inhibited EV-D68 replication (EC50 = 0.1427 µM) without significant cytotoxicity.	PMC11237570
Monocyte-derived dendritic cells (MDDCs)	1000 nM	48 hours to 6 days	To evaluate the effect of Vesatolimod on HIV-specific T-cell proliferation and cytokine secretion. Results showed that Vesatolimod increased the secretion of IFNγ, IP10, MIP-1α, and MIP-1β, and enhanced T-cell proliferation.	PMC9961394
CD4+ T cells	1000 nM	5 days	To evaluate the activation effect of GS-9620 on CD4+ T cells and the killing effect of PGT121 on HIV-1-infected CD4+ T cells. Results showed that GS-9620 activated CD4+ T cells and NK cells, and the combination of PGT121 and GS-9620 significantly enhanced the killing of HIV-1-infected CD4+ T cells.	PMC6237629
OvCa236 primary ovarian cancer cells	40 µM (IC50)	72 hours	Evaluate the cytotoxicity of Vesatolimod on primary ovarian cancer cells	PMC7930250
SKOV3WT ovarian cancer cells	40 µM (IC50)	72 hours	Evaluate the cytotoxicity of Vesatolimod on ovarian cancer cells	PMC7930250

Rhesus macaques	SIVmac251 infection model	Oral gavage	0.05 mg/kg, 0.15 mg/kg	Every other week for 14 weeks (Study 1) or 23 weeks (Study 2)	To evaluate the impact of TLR7 agonists on the viral reservoir in SIV-infected rhesus macaques. Results showed that TLR7 agonists induced transient viremia and reduced viral DNA.	PMC5973480
Rhesus macaques	SIVmac251 infection model	Oral	0.1 mg/kg	Every 2 weeks for 10 doses	Evaluate the efficacy of Ad26/MVA therapeutic vaccination combined with vesatolimod, showing virologic control in ~42% of animals after ART discontinuation	PMC9117189
Rhesus monkeys	SHIV-SF162P3 infection model	Oral	0.15 mg/kg	Every 2 weeks for 10 administrations (from week 96 to week 114)	To evaluate the effect of PGT121 combined with GS-9620 on delaying viral rebound in SHIV-SF162P3-infected rhesus monkeys. Results showed that the combination of PGT121 and GS-9620 significantly delayed viral rebound time and reduced viral DNA levels.	PMC6237629
Rhesus macaques	RT-SHIV infection model	Oral	0.15 mg/kg	Once a week for three months	To evaluate whether Vesatolimod as an immune activator could promote viral remission when added to early ART. Results showed no viral rebound in any animals post-treatment, and viral remission was maintained despite CD8+ T cell depletion.	PMC11618496
Rhesus macaques	SHIV-SF162P3 infection model	Oral	0.15 mg/kg	Every 2 weeks from weeks 50 to 58 and from weeks 64 to 72, total of ten doses	To evaluate the virologic control effect of Vesatolimod combined with active and passive immunization after ART interruption. Results showed that 70% of animals in the combined treatment group achieved virologic control post-ART interruption.	PMC9203527
Rhesus macaques	SIVmac239X infection model	Oral gavage	0.15 mg/kg and 0.5 mg/kg	Every two weeks, total of 12 doses	To evaluate the immunologic and virologic effects of GS-9620 in SIV-infected rhesus macaques. Results showed transient upregulation of ISGs, increases in plasma cytokines, and immune cell activation, but no measurable increases in plasma viremia or viral RNA/DNA ratios in PBMCs or tissues.	PMC6629134
Chimpanzee	Chronic hepatitis B model	Oral	1 mg/kg and 2 mg/kg	Two treatment cycles	GS-9620 treatment significantly altered the liver and PBMC transcriptomes of chimpanzees chronically infected with HBV, induced genes associated with HBV clearance, and formed lymphoid aggregates predominantly composed of CD8+ T cells and B cells.	PMC9940657
Chimpanzees	Chronic HBV infection	Oral	1 mg/kg and 2 mg/kg	Every other day, three times per week, for 4 weeks	To evaluate the antiviral efficacy of GS-9620 in chimpanzees with chronic HBV infection. Results showed that short-term oral administration of GS-9620 provided long-term suppression of serum and liver HBV DNA, with a mean maximum reduction of viral DNA by 2.2 logs, and reductions of greater than 1 log persisted for months after the end of administration.	PMC3691056
NMRI nude mice	SKOV3WT ovarian cancer xenograft model	Intraperitoneal injection	5 mg/kg	Four times at 4-day intervals	Evaluate the effect of Vesatolimod alone or in combination with romidepsin on tumor growth and metastasis	PMC7930250

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CAS No.: 1228585-88-3

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CAS No.: 1228585-88-3

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NCT01590654	Hepatitis B	Phase 1	Completed	-	-
NCT03060447	HIV-1 Infection	Phase 1	Active, not recruiting	July 2020	United States, California ... More >> Mills Clinical Research Los Angeles, California, United States, 90069 Zuckerberg San Francisco General San Francisco, California, United States, 94110 United States, Florida Midway Immunology & Research Center Fort Pierce, Florida, United States, 34982 Orlando Immunology Center Orlando, Florida, United States, 32803 United States, Texas Central Texas Clinical Research Austin, Texas, United States, 78705 United States, Washington Peter Shalit, MD Seattle, Washington, United States, 98104 Less <<
NCT02258581	-		Terminated	-	-
NCT02579382	Chronic Hepatitis B	Phase 2	Active, not recruiting	October 2019	United States, California ... More >> Los Angeles, California, United States Palo Alto, California, United States San Diego, California, United States San Francisco, California, United States United States, Hawaii Honolulu, Hawaii, United States United States, Maryland Catonsville, Maryland, United States United States, Massachusetts Boston, Massachusetts, United States United States, New York Flushing, New York, United States United States, Pennsylvania Philadelphia, Pennsylvania, United States Canada, Ontario Toronto, Ontario, Canada Hong Kong Kowloon, Hong Kong Italy Bologna, Italy Milano, Italy Pisa, Italy San Giovanni Rotondo, Italy Korea, Republic of Daegu, Korea, Republic of Seoul, Korea, Republic of New Zealand Grafton, Auckland, New Zealand Taiwan Dalin, Taiwan Kaohsiung, Taiwan United Kingdom London, United Kingdom Less <<
NCT01591668	Hepatitis C	Phase 1	Completed	-	United States, Arkansas ... More >> Woodland International Research Group Little Rock, Arkansas, United States, 72211 United States, Florida Avail Clinical Research, LLC DeLand, Florida, United States, 32720 Orlando Clinical Research Center Orlando, Florida, United States, 32809 United States, Missouri Kansas City Gastroenterology and Hepatology Kansas City, Missouri, United States, 64131 United States, New Jersey Comprehensive Clinical Research Berlin, New Jersey, United States, 08009 CRI Worldwide, LLC Willingboro, New Jersey, United States, 08046 United States, New York CliniLabs New York, New York, United States, 10019 United States, Pennsylvania CRI Worldwide, LLC Philadelphia, Pennsylvania, United States, 19139 United States, Texas Alamo Medical Research San Antonio, Texas, United States, 78215 United States, Utah Lifetree Clinical Research Salt Lake City, Utah, United States, 84106 Puerto Rico Fundacion De Investigacion De Diego Santurce, Puerto Rico, 00909 Less <<
NCT01590641	Hepatitis B H... More >>BV Less <<	Phase 1	Completed	-	-
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NCT02858401	HIV-1 Infection	Phase 1	Active, not recruiting	June 2019	United States, California ... More >> Mills Clinical Research Los Angeles, California, United States, 90069 UCSD Antiviral Research Center (AVRC) San Diego, California, United States, 92103 United States, Florida Midway Immunology & Research Center Fort Pierce, Florida, United States, 34982 Orlando Immunology Center Recruiting Orlando, Florida, United States, 32803 United States, Ohio Ohio State University Infectious Diseases Research Columbus, Ohio, United States, 43210 United States, Pennsylvania University of Pittsburgh Pittsburgh, Pennsylvania, United States, 15213 United States, Texas Central Texas Clinical Research Austin, Texas, United States, 78705 United States, Washington Peter Shalit, MD Seattle, Washington, United States, 98104 Less <<

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