| Catalog No. | HC589016 |
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| Species reactivity | Human |
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| Applications | ELISA, Bioactivity: FACS, Functional assay, Research in vivo |
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| Host species | Human |
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| Isotype | IgG2-kappa |
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| Expression system | Mammalian Cells |
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| Clonality | Monoclonal |
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| Target | MAdCAM-1, hMAdCAM-1, MADCAM1, Mucosal addressin cell adhesion molecule 1 |
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| Endotoxin level | Please contact the lab for this information. |
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| Purity | >95% purity as determined by SDS-PAGE. |
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| Purification | Protein A/G purified from cell culture supernatant. |
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| Accession | Q13477 |
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| Form | Liquid |
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| Storage buffer | 0.01M PBS, pH 7.4. |
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| Stability and Storage | Use a manual defrost freezer and avoid repeated freeze-thaw cycles. Store at 4°C for short-term storage (1-2 weeks). Store at -20°C for up to 12 months. For long-term storage, store at -80°C. |
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| Alternate Names | PF-00547659, PF-547659, SHP647, 2098790-40-8 |
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| Background | Ontamalimab (SHP647) is a fully human, immunoglobulin G2 , antihuman mucosal addressin cell adhesion molecule-1 (MAdCAM-1) monoclonal antibody being developed for the treatment of ulcerative colitis (UC) and Crohn's disease (CD). A population pharmacokinetic/pharmacodynamic (PK/PD) analysis was conducted using clinical phase 2 study data to evaluate the PK and PD of ontamalimab following subcutaneous administrations of 7.5, 22.5, 75, and 225 mg every 4 weeks in patients with moderate to severe UC or CD. A total of 440 patients with UC (n = 249; 56.6%) or CD (n = 191; 43.4%) were included in the analysis. A 2-compartment model with parallel linear and nonlinear elimination adequately characterized concentration-time profiles of ontamalimab. The apparent clearance and volume of distribution were 0.0127 L/h (0.305 L/day) and 6.53 L, respectively. Apparent clearance and volume of distribution were mainly dependent on baseline albumin and body weight, respectively. No differences in the PK properties of ontamalimab were observed between patients with UC or CD. The presence of antidrug antibodies did not impact the PK of ontamalimab. Nonlinear elimination occurred at very low concentrations and was unlikely to contribute to the elimination half-life under steady-state conditions. A linear PK/PD model described the relationship between ontamalimab and free MAdCAM-1. Minimum concentrations of ontamalimab at steady state following 75 mg every 4 weeks were associated with >95% suppression of circulating free MAdCAM-1. The PK/PD properties characterized support phase 3 testing in UC and CD.
• A microbiota-modulated checkpoint directs immunosuppressive intestinal T cells into cancers., PMID:37289890
• Mucosal addressin cell adhesion molecule-1 (MAdCAM-1). Its binding motif for alpha 4 beta 7 and role in experimental colitis., PMID:9379078
• Targeting Endothelial Ligands: ICAM-1/alicaforsen, MAdCAM-1., PMID:29757363
• Anti-MADCAM therapy for ulcerative colitis., PMID:31709847
• Domain 1 of mucosal addressin cell adhesion molecule has an I1-set fold and a flexible integrin-binding loop., PMID:23297416
• Targeting mucosal addressin cellular adhesion molecule (MAdCAM)-1 to noninvasively image experimental Crohn's disease., PMID:16401463
• Differential expression of mucosal addressin cell adhesion molecule-1 (MAdCAM-1) in ulcerative colitis and Crohn's disease., PMID:12100519
• Human mucosal addressin cell adhesion molecule-1 is preferentially expressed in intestinal tract and associated lymphoid tissue., PMID:9212736
• Nano-targeting of mucosal addressin cell adhesion molecule-1 identifies bowel inflammation foci in murine model., PMID:28621606
• Mucosal addressin cell adhesion molecule (MAdCAM-1) expression is upregulated in the cirrhotic liver and immunolocalises to the peribiliary plexus and lymphoid aggregates., PMID:23839340
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| Note | For research use only. Not suitable for clinical or therapeutic use. |
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