PF-06940434
PF-06940434 (ADWA-11) is a monoclonal antibody targeting integrin αvβ8. PF-06940434 inhibits αvβ8-mediated TGF-β activation. PF-06940434 increases the accumulation of tumor-infiltrating CD8+ T cells and upregulates the expression of granzyme B and TNF-γ. PF-06940434 blocks the inhibitory effect of CD4+CD25+ T cells on the cytotoxic activity of tumor CD8+ T cells. PF-06940434 enhances the anti-tumor efficacy of combination therapies with other immunomodulators or radiotherapy and induces long-term anti-tumor immunity. PF-06940434 can be used in the research of squamous cell carcinoma, breast cancer, colon cancer, and prostate adenocarcinoma.
For research use only. We do not sell to patients.
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
- Protocols
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
Description
IC50 & Target
[1]|
αvβ8 |
In Vitro
PF-06940434 (0.067-66.67 pM) potently inhibits αvβ8-mediated cell adhesion to TGF-β1 latency-associated peptide in SNB19 human glioblastoma cells[1].
PF-06940434 (0.067-66.67 pM; 16 h) potently blocks αvβ8-mediated TGF-β activation in a co-culture system of SNB229 human glioblastoma cells and TMLC reporter cells[1].
PF-06940434 (48 h) blocks the suppressive effect of TRAMPC2 tumor-derived CD25+/CD4+ T cells on CD8+ T cell-mediated TRAMPC2 tumor cell killing in a 48-hour in vitro co-culture assay[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
In Vivo
PF-06940434 (10 mg/kg; i.p.; days 0 and 7) monotherapy induces complete tumor regression in 10% of mice with mammary carcinoma, enhances intratumoral CD8+ T cell cytotoxic function, inhibits TGF-β signaling, and elicits long-term anti-tumor immunity[1].
PF-06940434 (10 mg/kg; i.p.; days 0 and 7) monotherapy potently inhibits prostate adenocarcinoma tumor growth, increases intratumoral CD8+ T cell accumulation and cytotoxic gene expression, and inhibits TGF-β signaling[1].
PF-06940434 (10 mg/kg; i.p.; days 0 and 7) inhibits prostate adenocarcinoma tumor growth and improves survival in wild-type littermate mice, with no additive effect in mice with T cell-specific Itgb8 deletion[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:FVB/NJ (equal numbers of male and female; subcutaneous injection of 1.5×104 CCK168 cells to induce squamous cell carcinoma)[1]
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Dosage:10 mg/kg
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Administration:i.p.; days 0 and 7
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Result:Induced tumor regression in most mice, with 4 of 10 mice showing complete tumor regression.
Significantly increased the percentage of intratumoral CD8+ T cells, the percentage of CD8+ T cells expressing granzyme B, and the percentage of CD4+ and CD8+ T cells expressing interferon-γ (IFNγ).
Significantly reduced SMAD3 phosphorylation (pSMAD3) in whole-tumor lysates.
Significantly upregulated mRNA expression of granzyme B, IFNγ, and Fas ligand in intratumoral CD8+ T cells.
Prevented tumor formation in re-challenged mice, indicating long-term anti-tumor immunity.
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Animal Model:BALB/c (female; orthotopic injection of 5×104 EMT6 cells into the fourth mammary fat pad to induce mammary carcinoma)[1]
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Dosage:10 mg/kg
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Administration:i.p.; days 0 and 7
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Result:Induced complete tumor regression in 2 of 20 mice.
Significantly increased the percentage of intratumoral CD8+ T cells, the percentage of CD8+ T cells expressing granzyme B, and the percentage of CD4+ and CD8+ T cells expressing IFNγ.
Significantly reduced pSMAD3 in whole-tumor lysates.
Significantly upregulated mRNA expression of granzyme B, IFNγ, granzyme A, and Fas ligand in intratumoral CD8+ T cells.
Prevented tumor formation in re-challenged mice, indicating long-term anti-tumor immunity.
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Animal Model:C57BL/6J (male; subcutaneous injection of 1×106 TRAMPC2 cells with matrigel to induce prostate adenocarcinoma)[1]
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Dosage:10 mg/kg
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Administration:i.p.; days 0 and 7
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Result:Markedly reduced tumor growth.
Significantly increased the percentage of intratumoral CD8+ T cells, the percentage of CD8+ T cells expressing granzyme B, and the percentage of CD4+ and CD8+ T cells expressing IFNγ.
Significantly reduced pSMAD3 in whole-tumor lysates.
Significantly upregulated mRNA expression of granzyme B, IFNγ, granzyme A, and Fas ligand in intratumoral CD8+ T cells.
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Animal Model:C57BL/6J (male, Itgb8-f/f littermates; subcutaneous injection of 1×106 TRAMPC2 cells with matrigel to induce prostate adenocarcinoma)[1]
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Dosage:10 mg/kg
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Administration:i.p.; days 0 and 7
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Result:Significantly inhibited tumor growth and enhanced survival in Itgb8-f/f littermates.
Showed no additional benefit in CD4-Cre;Itgb8-f/f mice (with T cell-specific Itgb8 deletion).
Chemical Information
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SMILES
[PF-06940434]
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Synonyms
ADWA-11
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Protocols
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RNA extraction experimental
By lysing cells, releasing RNA, and removing impurities such as proteins and DNA, high-purity RNA products are finally obtained. The commonly used traditional method is the guanidine isothiocyanate/phenol/chloroform method (Trizol), which is suitable for a variety of animal materials including animal tissues, microorganisms, cultured cells, etc., and most plant materials.
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Cell Cytotoxicity Assay
Cytotoxicity assays are usually based on the assessment of cell membrane damage, which can also be indirectly detected by measuring cell viability. Detection methods include MTT assay, CKK-8 assay, LDH assay and ATP assay, etc.
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Breast Cancer Modeling
Breast cancer is a heterogeneous cancer, and it has been distinguished into four subtypes: luminal A, luminal B, HER2-positive and basal-like. Molecular mutations, epigenetic alterations, hormone exposure and immune microenvironment are related to the progression of breast cancer.
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Cell Viability Determination by MTT Colorimetric Assay
The following protocol uses the MTT colorimetric assay as a classic literature-established method for assessing cell viability/metabolic activity in cultured mammalian cells. MTT[3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] is reduced by metabolically active cells to a colored formazan product; the amount of formazan is quantified spectrophotometrically and provides an indirect measure of metabolically active viable cells. Importantly, MTT reduction reflects cellular oxidoreductase/metabolic activity rather than an absolute direct count of living cells, so changes in cellular metabolism can alter the signal independently of cell number.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
PF-06940434 Related Classifications
HY-P992519 Related Classifications
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