NGM-438
Based on 1 Customer Validation
NGM-438 is a humanized monoclonal antibody antagonist of LAIR1, with a Ka of 0.26 nM for human LAIR1 and 4.28 nM for cynomolgus monkey LAIR1. NGM-438 blocks the binding of LAIR1 to its Collagen ligand and antagonizes the Collagen-induced LAIR1 signaling pathway. NGM-438 reverses FcγR signaling inhibition in myeloid cells, induces dendritic cells to secrete TNFα, promotes T cell proliferation, and triggers myeloid inflammation and allogeneic T cell responses. NGM-438 sensitizes refractory mouse lung cancer to PD-1 blockade, increases the content of intratumoral CD8+ T cells and the expression of inflammatory genes. NGM-438 is applicable to research related to solid tumors, refractory solid tumors and non-small cell lung cancer.
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- Pureté: 99.74%
- Masse moléculaire:144.92 kDa
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Stockage:
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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Activité biologique
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Chemical Information
- Pureté et documentation
- Références
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Help & FAQs
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Activité biologique
Human IgG1 kappa
Human
LAIR-1
NGM-438 exhibits an IC50 of 3.41 nM and 3.05 nM, respectively, in the human and cynomolgus monkey LAIR1-Fc: type 1 collagen blocking enzyme-linked immunosorbent assay, and an EC50 of 0.38 nM and 13.7 nM, respectively, in the human and cynomolgus monkey immune cell binding assay[1].
NGM-438 binds to recombinant human and cynomolgus monkey LAIR1 with high affinity, with Kd values of 0.26 nM and 4.28 nM, respectively[2].
NGM-438 (overnight treatment) potently and dose-dependently blocks the binding of LAIR1 to Collagen (HY-NP003), and inhibits Collagen-induced GFP expression in LAIR1-GFP reporter cells exposed to various collagen substrates[2].
NGM-438 (for 2 days) abrogates the inhibitory effect of Collagen on myeloid inflammation, induces human monocyte-derived dendritic cells (moDCs) to secrete CCL3, CCL4 and IL1RN in a dose-dependent manner, and reprograms the expression of immunosuppressive SAM genes to an inflammatory phenotype[2].
NGM-438 (overnight treatment) reverses the inhibitory effect of Collagen on FcR-driven myeloid inflammation, and induces dose-dependent TNFα secretion by human monocyte-derived dendritic cells (moDCs)[2].
Combination of NGM-438 (administered for 4-5 days) with anti-PD-1 reverses Collagen-mediated T cell proliferation inhibition and promotes the secretion of proinflammatory cytokines in human allogeneic MLR assays[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:129/Sv (6-8 week old, male and female; subcutaneous syngeneic implantation of 1×106 344SQ Kras/p53 mutant NSCLC cells)[2]
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Dosage:10 mg/kg
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Administration:i.p.; twice per week
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Result:Significantly reduced primary tumor volume and metastatic lung nodule count compared to single-agent anti-PD-1 or single-agent NGM438 surrogate.
Increased intratumoral CD8+ T cell content, frequency of effector/memory and granzyme B+ CD8+ T cells, and reduced CD8+ T cell exhaustion marker expression.
Induced a significant increase in iNOS+ MHCII-high macrophages at week 2.
Increased apoptotic cells via TUNEL staining and reduced proliferation via Ki67 staining in primary tumors, as well as increased CD8/granzyme-B expression.
Upregulated interferon-induced genes including Ccl8, Cxcl9, Cxcl10, Cxcl11, Mx1, Ifi44, Ifit1, Gbp3, Gbp4, and Gbp5 in tumors.
| NCT Number | Sponsor | Condition | Start Date |
Phase
|
|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Unconjugated
The product can be reconstituted/diluted with sterile PBS or saline.
ELISA, FACS, Functional assay
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Immobilized Human LAIR1/CD305 Protein,Fc Tag can bind NGM-438. The EC50 for this effect is 66.71 ng/mL. -
Flow Cytometry analysis of THP-1 cells labelling LAIR-1 (red) with NGM-438 (HY-P991193). Cells were fixed with 4% paraformaldehyde and permeabilised with 90% methanol. Then cells were stained with the primary antibody at 1/200 dilution for an hour at 4℃. Goat Anti-Human IgG H&L (AF488) (HY-P83776) was used as the secondary antibody at 1/1,000 dilution for 30 minutes at 4℃. Human IgG1 kappa (HY-P99001, blue) was used as the isotype control, cells without incubation with primary antibody were used as the unlabeled control (black).
Chemical Information
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Appearance Liquid
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Masse moléculaire 144.92 kDa
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Color Colorless to light yellow
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SMILES
N/A
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Livraison
Shipping with dry ice.
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Formulation
Please refer to the lot-specific COA for specific buffer information.
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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureté et documentation
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Fiche technique (262 KB)
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SDS (251 KB)
- English - EN (251 KB)
- Français - FR (251 KB)
- Deutsch - DE (251 KB)
- Norwegian - NO (251 KB)
- Español - ES (251 KB)
- Swedish - SV (251 KB)
- Italian - IT (251 KB)
- Korean - KR (251 KB)
- Portuguese - PT (251 KB)
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Inhibitory Antibodies User Guide (603 KB)
Références
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
NGM-438 Related Classifications
HY-P991193 Related Classifications
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