Anti-FcRL5 (10A8)-SPDB-DM4 ADC
CAT#: ADC-117LCT
This ADC product is composed of an anti-FcRL5 antibody (clone 10A8) conjuagated via a SPDB linker to DM4 (10A8-SPDB-DM4). It has demonstrated a response in multiple myeloma treatment by a MOA (Mechanism of Action) of Depolymerize Microtubules.
Gene Expression
RNA Expression
Figure 1 RNA cell line category: Group enriched (U-266/70, U-698)
Cell lines ordered by descending RNA expression order.
* Image credit: Image credit: Human Protein Atlas https://v21.proteinatlas.org/ENSG00000143297-FCRL5
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Specifications
- Clone
- 10A8
- Linker
- SPDB
- Linker Class/Description
- Disulfide Linkers are extensively exploited as a chemically labile linkage. Since the release of disulfide-linked drugs requires a cytoplasmic thiol cofactor, such as glutathione (GSH). Disulfides maintain stable at physiological pH and only when ADCs are internalized inside cells, the cytosol provides reducing environment including intracellular enzyme protein disulfide isomerase, or similar enzymes, drugs can be released.
- Drug
- DM4 (N2'-Deacetyl-N2'-(4-mercapto-4-methyl-1-oxopentyl)maytansine)
- Drug Class/Description
- Maytansinoids are a group of cytotoxins structurally similar to rifamycin, geldanamycin, and ansatrienin. The eponymous natural cytotoxic agent maytansine is a 19-member lactam (ansa
macrolide) structure originally isolated from the Ethiopian shrub Maytenus ovatus. Maytansinoids can bind to tubulin at or near the vinblastine-binding site, which interfere the formation of microtubules and depolymerize already formed microtubules, inducing mitotic arrest in the intoxicated cells
Target
- Introduction
- This gene encodes a member of the immunoglobulin receptor superfamily and the Fc-receptor like family. This gene and several other Fc receptor-like gene members are clustered on the long arm of chromosome 1. The encoded protein is a single-pass type I membrane protein and contains 8 immunoglobulin-like C2-type domains. This gene is implicated in B cell development and lymphomagenesis. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Sep 2010]
- Alternative Names
- FCRL5; Fc receptor-like 5; CD307; FCRH5; IRTA2; BXMAS1; CD307e; PRO820; Fc receptor-like protein 5; fcR-like protein 5; fc receptor homolog 5; immune receptor translocation-associated protein 2; immunoglobulin superfamily receptor translocation associated 2 (IRTA2);
- Gene ID
- 83416
- UniProt ID
- Q96RD9
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Reliable Clone 10A8 Specificity
The anti-FcRL5 antibody clone 10A8 in this conjugate is highly effective for identifying FcRL5 positive cells in our multiple myeloma research. The binding specificity allows for clean data generation, and the subsequent internalization of the complex leads to the expected microtubule depolymerization effects via the DM4 payload.
Disulfide Linker Functionality
We focused our study on the release mechanism of the SPDB linker. This product demonstrated that the disulfide bond remains stable extracellularly but is efficiently cleaved by intracellular reduction. This triggered the release of the thiol-containing DM4, inducing mitotic arrest in our target cell lines as anticipated.
Q&As
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What is the mechanism of the DM4 payload?
A: DM4 is a maytansinoid cytotoxin. It binds to tubulin at or near the vinblastine-binding site. This action interferes with microtubule formation and depolymerizes existing microtubules, leading to mitotic arrest and subsequent cell death in the target cells.
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Under what conditions is the SPDB linker cleaved?
A: The SPDB linker contains a disulfide bond that is stable at physiological pH in the blood. However, it is chemically cleaved in the reducing environment of the cell cytoplasm, where high concentrations of thiol cofactors like glutathione are present.
View the frequently asked questions answered by Creative Biolabs Support.
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Datasheet
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COA
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