1Z105
Based on 1 Customer Validation
1Z105 is an orally active TLR4/MD2 agonist, immunostimulant and vaccine adjuvant. 1Z105 activates NF-κB via the MyD88/TRIF pathway in a CD14-independent manner, with EC50 values of 0.63 µM and 0.77 µM for inducing IL-6 and IL-12 in mBMDCs, respectively. 1Z105 promotes dendritic cell maturation, antigen uptake and cross-presentation; when used alone, it induces Th2-IgG1, while combined with the TLR7 agonist 1V270, it synergistically induces balanced Th1/Th2 responses and provides low-reactogenic protection against homologous, heterologous and heterosubtypic influenza. 1Z105 prevents LPS (HY-D1056A1)- and galactosamine-induced liver injury as well as autoantibody-driven arthritis in mice. 1Z105 can be used in studies related to influenza virus infection, inflammation, and LPS/galactosamine-induced liver injury.
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- Pureza: 99.83%
- No. CAS: 1438280-73-9
- Fòrmula: C25H26N4O2S
- Peso molecular:446.56
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Almacenamiento:Powder -20°C, 3 years ; In solvent -80°C, 6 months , -20°C, 1 month
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Actividad biológica
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Chemical Information
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Actividad biológica
Descripciòn
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MD2 |
TLR4 |
IL-8 0.63 μM (EC50) |
IL-6 0.77 μM (EC50) |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| HEK293 | EC50 |
8.26 μM
Compound: 1
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Agonist activity at human TLR4 expressed in HEK293 blue cells assessed as induction of NF-kappaB activation-mediated SEAP production after 20 to 24 hrs by colorimetric assay
Agonist activity at human TLR4 expressed in HEK293 blue cells assessed as induction of NF-kappaB activation-mediated SEAP production after 20 to 24 hrs by colorimetric assay
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[PMID: 29049886] |
In Vitro
1Z105 (1-10 µM; 20 h) stimulates NF-κB activation in HEK-Blue™ mTLR4 cells, with an EC50 of 7.49 µM[1].
1Z105 (1-10 µM; 20 h) stimulates NF-κB activation in HEK-Blue™ hTLR4 cells, with an EC50 of 1445 µM[1].
1Z105 (2-10 μM; overnight) enhances the expression of co-stimulatory molecules CD40 and CD86 in bone marrow-derived dendritic cells from wild-type C57BL/6 mice in a TLR4-dependent manner[2].
1Z105 (20-24 h) activates the NF-κB signaling pathway in murine TLR4 HEK Blue™ cells[3].
1Z105 (5 µM; overnight) induces IL-8 secretion in human peripheral blood mononuclear cells, with a level lower than that of 2B182C[1].
1Z105 (5 µM) stimulates murine bone marrow-derived dendritic cells to secrete IL-12 and IL-6, with EC50 values of 0.77 µM and 0.63 µM, respectively[1].
1Z105 (10 μM; 18 h) activates human monocyte-derived dendritic cells in vitro, inducing them to release proinflammatory cytokines including IL-1β, IL-6, IL-8, IL-12p70 and TNF-α[2].
1Z105 (1 µM; 20 h) induces the expression of CD40 and CD86 in mouse bone marrow-derived dendritic cells, but their expression levels are lower than those of 2B182C[1].
1Z105 (2 μM; overnight) enhances antigen cross-presentation from bone marrow-derived dendritic cells of wild-type C57BL/6 mice to OT-1 CD8+ T cells in vitro[2].
1Z105 (18 h) potently induces IL-6 (EC50 = 0.27 μM) and type I interferons (EC50 = 1.9 μM) in mouse bone marrow-derived dendritic cells[3].
1Z105 (0.63 μM; pre-treatment) desensitized mouse bone marrow-derived macrophages to subsequent LPS-induced IL-6 secretion[3].
1Z105 (2.5 μM; overnight pre-treatment) attenuated IL-6 secretion by mouse bone marrow-derived dendritic cells induced by various MyD88-dependent TLR ligands[3].
1Z105 (10 μM; 24 h) exhibits no cytotoxicity in HepG2 cells[3].
1Z105 (10 μM) exhibits only extremely low cytotoxicity in mouse bone marrow-derived dendritic cells[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:Mouse BMDCs cells
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Concentration:5 µM
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Incubation Time:overnight
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Result:It induced human peripheral blood mononuclear cells to secrete IL-8, and the IL-8 level was lower than that induced by 2B182C.
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Cell Line:wild-type C57BL/6 mouse bone marrow-derived dendritic cells (mBMDCs), CFSE-labeled OT-1 CD8+ T cells
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Concentration:2 μM
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Incubation Time:overnight (mBMDCs); 3 days (co-culture with T cells)
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Result:Induced proliferation of OT-1 CD8+ T cells, indicating efficient processing of extracellular OVA via the MHC class I pathway, with activity similar to the positive control MPLA.
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Cell Line:HepG2 human hepatocellular carcinoma cells
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Concentration:10 μM
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Incubation Time:24 h
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Result:Maintained cell viability at 99% compared to vehicle control, indicating no cytotoxicity at this concentration.
Parmacokinetics
| Species | Dose | Route | Bioavailability | Tmax |
|---|---|---|---|---|
| Mice[4] | 1 μmol | p.o. | 11 % | 60 min |
In Vivo
1Z105 (89.4 μg/dose; intramuscular injection; single administration on day 0), when used as an adjuvant in combination with rPR/8 HA, induces rapid, Th2-biased protective immunity against lethal homologous influenza A virus challenge in BALB/c mice, while exhibiting antigen-sparing activity[2].
1Z105 (89.4 μg/dose; intramuscular injection; single administration on day 0), when used as an adjuvant for rCal/09 HA, induces protective immunity against lethal pandemic H1N1 influenza virus challenge in BALB/c mice[2].
1Z105 (89.4 μg/dose; intramuscular injection; single administration on day 0), when used as an adjuvant in combination with rVN/04 HA, induces protective immunity against lethal avian H5N1 influenza virus challenge in BALB/c mice[2].
1Z105 (89.4 μg/dose; intramuscular injection; single administration on day 0), when used as an adjuvant in combination with rPR/8 HA, induces long-lasting protective immunity against lethal homologous influenza A virus challenge in BALB/c mice[2].
1Z105 (89.4 μg/dose; intramuscular injection; single administration on day 0) acts as an adjuvant to enhance the immunogenicity of Fluzone and reduce the morbidity of BALB/c mice after challenge with heterologous influenza B virus[2].
1Z105 (89.4 μg per dose; intramuscular injection; administered in three sequential immunizations) acts as an adjuvant combined with sequential cHA immunization to induce cross-subtype antibody responses targeting the conserved stem region of influenza virus HA in BALB/c mice[2].
1Z105 (200 nM; intramuscular injection; day 0 and day 21), acting as an adjuvant, synergizes with the TLR7 ligand 1V270 against inactivated influenza A virus to enhance antigen-specific IgG2a responses in BALB/c mice[1].
1Z105 (89.4 μg/dose; intramuscular injection; days 0 and 14) acts as an adjuvant for OVA and induces a robust Th2-associated IgG1 antibody response in C57BL/6 mice[2].
1Z105 (89.4 μg/dose; intramuscular injection; single administration), when administered without co-administration of antigens, induced only mild local and systemic pro-inflammatory responses in BALB/c mice[2].
1Z105 (0.5 μM per mouse) protects over 80% of mice from lethal LPS/D-galactosamine-induced liver injury and reduces associated TNF release; no mouse mortality is observed when it is administered in combination with D-galactosamine[3].
1Z105 (1-5 μM; p.o.) inhibits LPS-induced TNF release in mice, and does not induce significant proinflammatory cytokines at effective doses[3].
1Z105 (5 μM; oral administration; once every other day) significantly alleviates paw swelling and joint tissue damage in a mouse model of autoantibody-induced arthritis[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:BALB/c wild-type mice (6-8-week-old, female)[1]
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Dosage:89.4 μg/dose
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Administration:i.m.; single dose
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Result:Enhanced the seroresponse to all three Fluzone® viral components (A/Brisbane/59/2007 (H1N1), A/Uruguay/716/2007 (H3N2), and B/Brisbane/60/2008 (Victoria lineage)) as measured by ELISA, alongside 1V270, their combination, and AddaVax.\nInduced minimal cellular infiltration (mononuclear and a few polynuclear cells) at the injection site, with significantly lower local expression of proinflammatory cytokines IL-6, KC, and MCP-1, and lower systemic circulating levels of IL-6 and KC compared to AddaVax.
This minimal local and systemic inflammation was shared with 1V270 and their combination.
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Animal Model:BALB/c (female, 6-8 weeks old, immunized with inactivated influenza A virus)[1]
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Dosage:40 nM/injection; 200 nM/injection
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Administration:i.m.; days 0 and 21
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Result:Induced anti-HA IgG1, anti-NA IgG1, anti-HA IgG2a, and anti-NA IgG2a responses at 40 nmol/injection.
Induced elevated anti-HA IgG1 and anti-NA IgG1 responses, along with anti-HA IgG2a and anti-NA IgG2a responses at 200 nmol/injection.
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Animal Model:BALB/c (female, 6-8 weeks old, immunized with inactivated influenza A virus combined with TLR7 ligand 1V270)[1]
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Dosage:200 nM/injection
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Administration:i.m.; days 0 and 21
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Result:Induced anti-HA IgG1 and anti-NA IgG1 levels equivalent to those induced by 1V270 alone.
Induced anti-HA IgG2a and anti-NA IgG2a levels that were lower than those induced by 1V270 combined with 2B182C but higher than those induced by 1V270 alone.
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Animal Model:C57BL/6 wild-type mice (7- to 9-week-old)[1]
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Dosage:89.4 μg/dose
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Administration:i.m.; on days 0 and 14
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Result:Induced significantly higher antigen-specific IgG1 serum antibody titers than OVA alone, with a Th2-skewed immune profile (low IgG2a/IgG1 ratio).
Induced minimal OVA-specific IFN-γ release by restimulated splenocytes and low frequencies of IFN-γ-releasing T cells specific for OVA class I and class II peptides.
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Animal Model:BALB/c mice (6- to 8-week-old, female)[2]
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Dosage:89.4 μg/dose; 89.4 μg/dose (0.2 μg rPR/8 HA co-administration)
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Administration:i.m.; single dose on day 0
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Result:Induced rapid seroconversion to rPR/8 HA, with detectable antigen-specific total IgG, IgG1, and IgG2a serum antibody titers as early as 7 days post-immunization, and maintained robust titers through day 21.
Demonstrated a Th2-skewed immune profile (low IgG2a/IgG1 ratio).
Significantly reduced weight loss and provided 100% survival following lethal PR/8 virus challenge.
Minimized morbidity and mortality compared to the no-adjuvant control group receiving 5 μg rPR/8 HA, showing antigen-sparing properties.
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Animal Model:BALB/c mice (6- to 8-week-old, female)[2]
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Dosage:89.4 μg/dose
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Administration:i.m.; single dose on day 0
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Result:Enhanced antigen-specific IgG serum antibody titers compared to unadjuvanted rCal/09 HA.
Restricted weight loss and provided 100% survival following lethal challenge with the homologous pandemic H1N1 virus.\nEnhanced antigen-specific IgG serum antibody titers compared to unadjuvanted rVN/04 HA.
Significantly minimized weight loss and provided 100% survival following lethal H5N1 virus challenge.\nInduced a robust, sustained antigen-specific IgG serum antibody response that persisted for at least 18 weeks post-immunization, with detectable hemagglutination-inhibiting (HAI) titers by 6 weeks post-immunization.
Significantly reduced weight loss and provided 100% survival following lethal PR/8 virus challenge 18 weeks post-immunization.
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Animal Model:BALB/c mice (6- to 8-week-old, female)[2]
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Dosage:89.4 μg/dose
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Administration:i.m.; single dose on day 0
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Result:Enhanced antigen-specific IgG serum antibody titers to all three Fluzone components (A/Brisbane/59/2007 H1N1, A/Uruguay/716/2007 H3N2, B/Brisbane/60/2008).
Reduced weight loss on days 7 and 8 post-challenge with heterologous influenza B virus.
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Animal Model:BALB/c mice (6- to 8-week-old, female)[2]
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Dosage:89.4 μg/dose
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Administration:i.m.; three total doses at sequential immunizations
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Result:Induced significantly higher serum IgG titers reactive to heterosubtypic VN/04 H5 HA compared to the no-adjuvant control, with a Th2-skewed immune profile (low IgG2a/IgG1 ratio).
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Animal Model:BALB/c mice (6- to 8-week-old, female)[2]
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Dosage:89.4 μg/dose
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Administration:i.m.; single dose
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Result:Induced minimal cellular infiltration (few mononuclear and polynuclear cells) at the injection site.
Induced local proinflammatory cytokine (IL-6, KC, MCP-1) expression and systemic circulating cytokine (IL-6, KC) levels comparable to vehicle control and markedly lower than AddaVax-treated mice.
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Animal Model:C57BL/6 wild-type mice (7 to 9 weeks old)[3]
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Dosage:1 μM 5 μM
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Administration:p.o.
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Result:Significantly reduced serum TNF release after LPS challenge at 5 μmol dose.
Resulted in very low or undetectable levels of serum TNF, IL-6, or IP-10 at doses needed to suppress LPS stimulation via i.p. or p.o. administration.
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Animal Model:C57BL/6 wild-type mice (7 to 9 weeks old)[3]
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Dosage:5 μM
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Administration:p.o.; every other day
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Result:Significantly reduced paw swelling.
Decreased histological inflammation, bone erosion, and cartilage damage.
Chemical Information
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No. CAS 1438280-73-9
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Appearance Solid
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Peso molecular 446.56
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Fòrmula C25H26N4O2S
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Color White to off-white
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SMILES
O=C1C2=C(C3=C(N2C)C=CC=C3)N=C(N1C4=CC=CC=C4)SCC(NC5CCCCC5)=O
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Powder -20°C 3 years In solvent -80°C 6 months -20°C 1 month
Pureza y Documentación
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Ficha de datos (309 KB)
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SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
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Instrucciones de manejo (2659 KB)
Referencias
[2]. Goff PH, et al. Synthetic Toll-like receptor 4 (TLR4) and TLR7 ligands as influenza virus vaccine adjuvants induce rapid, sustained, and broadly protective responses. Journal of virology. 2015 Mar;89(6):3221-35. [Content Brief]
[3]. Hayashi T, et al. Novel synthetic toll-like receptor 4/MD2 ligands attenuate sterile inflammation. The Journal of pharmacology and experimental therapeutics. 2014 Aug;350(2):330-40. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
1Z105 Related Classifications
HY-117573 Related Classifications
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