What is the mechanism of action of dasatinib?

Dasatinib is a tyrosine kinase inhibitor. It inhibits Bcr-Abl and Src family tyrosine kinases. In the context of this ADC, it is used to selectively deliver immunosuppressive activity to T cells by inhibiting these pathways.

How is the dasatinib payload attached to the antibody?

Dasatinib is conjugated via a disulfide-cleavable linker. This linker consists of a peptide spacer to increase solubility and an alkoxyamine group for conjugation. The disulfide bond allows for release in the reducing intracellular environment.

Anti-CD184-dasatinib ADC

CAT#: ADC-077LZY

This ADC product is composed of an anti-CD184 antibody conjugated via linker to dasatinib (anti-CXCR4-dasatinib). It has demonstrated a response in immunosuppressive drug treatment by a MOA (Mechanism of Action) of selectively delivering dasatinib to human T cells with excellent in vitro immunosuppressive activity.

Gene Expression

RNA Expression Figure 1 RNA cell line category: Cell line enhanced (Daudi, JURKAT, Karpas-707, MOLT-4, REH, U-266/70, U-698)

Cell lines ordered by descending RNA expression order.

* Image credit: Image credit: Human Protein Atlas https://v21.proteinatlas.org/ENSG00000121966-CXCR4

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Specifications

Antibody Overview
Humanized Anti-CXCR4 IgG with an elongated CDR3H

Antibody Isotype
IgG

Antibody Conjugation
a dasatinib disulfide-cleavable linker consists of a peptide spacer unit to increase
solubility and
an alkoxyamine group for conjugation; the antibody is modified by adding S-4FB linker

Linker
disulfide-cleavable linkers

Linker Class/Description
Class: Chemically cleavable Linker-Disulfide Linker
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
dasatinib

Drug Class/Description
Class: dasatinib
Description: Dasatinib(trade name Sprycel.), also known as BMS-354825, is a cancer drug .It is an oral Bcr-Abl tyrosine kinase inhibitorand Src family tyrosine kinase inhibitor approved for first line use in patients with chronic myelogenous leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL)

Target

Introduction
This gene encodes a CXC chemokine receptor specific for stromal cell-derived factor-1. The protein has 7 transmembrane regions and is located on the cell surface. It acts with the CD4 protein to support HIV entry into cells and is also highly expressed in breast cancer cells. Mutations in this gene have been associated with WHIM (warts, hypogammaglobulinemia, infections, and myelokathexis) syndrome. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

Alternative Names
CXCR4; chemokine (C-X-C motif) receptor 4; FB22; HM89; LAP3; LCR1; NPYR; WHIM; CD184; LAP-3; LESTR; NPY3R; NPYRL; HSY3RR; NPYY3R; D2S201E; C-X-C chemokine receptor type 4; fusin; CD184 antigen; SDF-1 receptor; LPS-associated protein 3; neuropeptide Y receptor Y3; seven transmembrane helix receptor; stromal cell-derived factor 1 receptor; lipopolysaccharide-associated protein 3; seven-transmembrane-segment receptor, spleen; leukocyte-derived seven transmembrane domain receptor;

Gene ID
7852

UniProt ID
P61073

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Breast cancer biomarkers at key points during disease progression

Novel Kinase Inhibitor Delivery

This product offered a unique approach by delivering a kinase inhibitor, dasatinib, rather than a traditional toxin. We studied its effect on T cells and found it selectively delivered the drug, showing excellent in vitro immunosuppressive activity as described.

Effective Disulfide Cleavage

The disulfide-cleavable linker worked well in our intracellular reduction assays. It released the dasatinib payload effectively upon internalization into CXCR4-positive cells. The antibody modification with the S-4FB linker did not interfere with receptor binding.

Q&As

What is the mechanism of action of dasatinib?

A: Dasatinib is a tyrosine kinase inhibitor. It inhibits Bcr-Abl and Src family tyrosine kinases. In the context of this ADC, it is used to selectively deliver immunosuppressive activity to T cells by inhibiting these pathways.
How is the dasatinib payload attached to the antibody?

A: Dasatinib is conjugated via a disulfide-cleavable linker. This linker consists of a peptide spacer to increase solubility and an alkoxyamine group for conjugation. The disulfide bond allows for release in the reducing intracellular environment.

View the frequently asked questions answered by Creative Biolabs Support.

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Downloadable Resources

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Datasheet

Datasheet - ADC-077LZY.pdf

MSDS

MSDS - ADC-077LZY.pdf

COA

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