Structure of JNJ-7777120
CAS No.: 459168-41-3
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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.
JNJ-7777120 is a selective antagonist of histamine-4 receptor (H4R) with Ki of 4 ± 1 nM.
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CAS No. : | 459168-41-3 |
Formula : | C14H16ClN3O |
M.W : | 277.75 |
SMILES Code : | O=C(C(N1)=CC2=C1C=CC(Cl)=C2)N3CCN(C)CC3 |
MDL No. : | MFCD04343337 |
InChI Key : | HUQJRYMLJBBEDO-UHFFFAOYSA-N |
Pubchem ID : | 4908365 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Target |
|
In Vitro:
Cell Line
|
Concentration | Treated Time | Description | References |
Atopic dermatitis outer root sheath keratinocytes | 10μM | 48 hours | Stimulation with histamine or H4R agonist induced proliferation in atopic dermatitis keratinocytes, which was blocked by H4R antagonist JNJ7777120 | PMC4447893 |
H4R-transfected HaCaT keratinocytes | 10μM | 48 hours | Histamine stimulation induced proliferation in H4R-transfected HaCaT cells, which was blocked by H4R antagonist JNJ7777120 | PMC4447893 |
Human primary neonatal keratinocytes | 10μM | 48 hours | Stimulation with histamine or H4R agonist 4-MH induced keratinocyte proliferation, which was blocked by H4R-specific antagonist JNJ7777120 | PMC4447893 |
4T1 cells | 10 μmol/L | 48 hours | To evaluate the cellular uptake and antitumor effect of PP@T, results showed that PP@T significantly enhanced oxidative stress and apoptosis under ultrasound irradiation. | PMC7000401 |
Human retinal endothelial cells (HRECs) | 0.1–10 μM | 4 hours | To evaluate the effect of R-2-HG on endothelial cell migration, results showed that R-2-HG significantly enhanced the migration ability of HRECs. | PMC4128071 |
Mouse whole blood | 50 μM | 4 hours | To evaluate the effect of JNJ-7777120 on LPS-induced TNF production, results showed no inhibition of TNF production by JNJ-7777120 in vitro. | PMC3654183 |
In Vivo:
Species
|
Animal Model
|
Administration | Dosage | Frequency | Description | References |
C57BL/6 female mice | Experimental autoimmune encephalomyelitis (EAE) model | Intraperitoneal injection | 10 mg/kg | Once daily, starting from day 10 post-immunization until the end of the experiment (up to 28 days) | Evaluate the effect of JNJ7777120 on the clinical course of EAE, showing that JNJ7777120 treatment exacerbated EAE symptoms, increased spinal cord inflammation and demyelination, increased IFN-γ expression, and decreased IL-4 and IL-10 expression | PMC3764850 |
BALB/c mice | 4T1 TNBC model | Subcutaneous injection | 10 mg/kg | Once daily for 15 days | Evaluate the effect of JNJ-7777120 on tumor growth and immune modulation in the 4T1 TNBC model, results showed JNJ-7777120 non-significantly reduced tumor weight and spleen weight, while significantly decreasing the percentage of tumor-infiltrating CD4+ T lymphocytes and Tregs in TDLN | PMC7000401 |
Mice | Laser-induced choroidal neovascularization (CNV) model | Intravitreous injection | 1 μg | Injected immediately after laser injury and again on day 3 | To evaluate the effect of JNJ7777120 on CNV volume and pathological vessel leakage, results showed JNJ7777120 significantly reduced laser-induced CNV volume and pathological leakage without causing retinal toxicity. | PMC4128071 |
BALB/c mice | Carrageenan-induced pleurisy model | Intraperitoneal injection | 30 mg/kg | Single dose, lasting 4 hours | To evaluate the anti-inflammatory effects of JNJ-7777120 on carrageenan-induced pleurisy. Results showed that JNJ significantly reduced the number of T-cell subsets, GITR+ and GITR+IL-17A+ cells, and decreased the levels of Th1/Th17 cytokines, while up-regulating the expression of Th2 cytokines. | PMC4080953 |
BALB/c mice | LPS-induced inflammation model | Oral | 20 mg/kg | Single dose, LPS administered 30 minutes later | To evaluate the effect of JNJ-7777120 on LPS-induced TNF production, results showed significant inhibition of TNF production by JNJ-7777120. | PMC3654183 |
BALB/c female mice | OVA-induced sub-chronic airway inflammation model | Oral | 5 mg/kg, 20 mg/kg, 50 mg/kg | Once daily, initiated on day 36 through day 58 | Therapeutic H4R antagonism inhibited T cell infiltration into the lung and decreased Th2 cytokines IL-13 and IL-5. IL-13 dependent remodeling parameters such as GCH and lung collagen were reduced. Intervention with H4R antagonist also improved measures of central and peripheral airway dysfunction. | PMC2914735 |
Tags: JNJ-7777120 | JNJ7777120 | JNJ 7777120 | Histamine Receptor | SK-N-MC cells | mast cells | inflammation | BMMC | histamine H4 receptor antagonist | anti-inflammatory | antipruritic | neutrophil infiltration | mast cell migration | antipruritic | 459168-41-3
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P302 + P334 | IF ON SKIN: Immerse in cool water/wrap in wet bandages. |
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P303 + P361 + P353 | IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower. |
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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. |
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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. |
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P337 + P313 | IF eye irritation persists: Get medical advice/attention. |
P342 + P311 | IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician. |
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H362 | May cause harm to breast-fed children |
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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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