What is the mechanism of the NCS payload?

Neocarzinostatin (NCS) is a macromolecular chromoprotein enediyne antitumor antibiotic. It functions by inducing both single- and double-strand breaks in DNA. This inhibits DNA synthesis and leads to cell death in the targeted cells.

What are the characteristics of the SPDP linker?

SPDP is a chemically cleavable disulfide linker. These linkers are exploited for their lability in reducing environments. While stable at physiological pH, the disulfide bond is cleaved by cytoplasmic thiol cofactors like glutathione once the ADC is internalized.

Anti-VEGFR2-SPDP-NCS ADC

CAT#: ADC-152LZY

This ADC product is composed of an anti-VEGFR2 antibody conjugated via SPDP linker to NCS (anti-VEGFR2-SPDP-NCS). It has demonstrated a response in Multiple myeloma (MM) treatment by a MOA (Mechanism of Action) of inhibiting DNA synthesis .

Gene Expression

Subcellular Location Figure 1 IF staining of human cell line HEL

Immunofluorescent staining of human cell line HEL shows localization to nuclear membrane & vesicles.

* Image credit: Image credit: Human Protein Atlas v21.proteinatlas.org/images/73577/1825_D8_31_cr5ac340707076b_selected.jpg

Normal Tissue Figure 2 Placenta

High expression

* Image credit: Image credit: Human Protein Atlas v21.proteinatlas.org/images/4028/11467_A_2_7_val_selected.jpg

Normal Tissue Figure 3 Colon

Endothelial cells Staining: Low Intensity: Weak Quantity:>75% Location: Cytoplasmic/ membranous Glandular cells Staining: Low Intensity: Moderate Quantity: <25% Location: Cytoplasmic/ membranous

* Image credit: Image credit: Human Protein Atlas v21.proteinatlas.org/images/4028/11467_A_8_3.jpg

Normal Tissue Figure 4 Kidney

Cells in glomeruli Staining: High Intensity: Strong Quantity: 75%-25% Location: Cytoplasmic/ membranous

* Image credit: Image credit: Human Protein Atlas v21.proteinatlas.org/images/4028/11467_A_7_5.jpg

Normal Tissue Figure 5 Testis

Leydig cells Staining: Low Intensity: Weak Quantity: 75%-25% Location: Cytoplasmic/ membranous

* Image credit: Image credit: Human Protein Atlas v21.proteinatlas.org/images/4028/11467_A_6_6.jpg

RNA Expression Figure 6 RNA cell line category: Group enriched (HUVEC TERT2, TIME)

Cell lines ordered by descending RNA expression order.

* Image credit: Image credit: Human Protein Atlas v21.proteinatlas.org/ENSG00000128052-KDR

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Specifications

Antibody Overview
Anti-VEGFR2 IgG

Antibody Isotype
IgG

Linker
SPDP(N-succinimidyl 3-[2-pyridyldithio]-propionate)

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
NCS

Drug Class/Description
Class: Neocarzinostatin
Description: Neocarzinostatin (NCS) is a macromolecular chromoprotein enediyne antitumor antibiotic secreted by Streptomyces macromomyceticus. It is a product naturally found as a complex of an enediyne chromophore and a 10-kDa protein and it can induce both single-and double-strand breaks in DNA.

Target

Introduction
Vascular endothelial growth factor (VEGF) is a major growth factor for endothelial cells. This gene encodes one of the two receptors of the VEGF. This receptor, known as kinase insert domain receptor, is a type III receptor tyrosine kinase. It functions as the main mediator of VEGF-induced endothelial proliferation, survival, migration, tubular morphogenesis and sprouting. The signalling and trafficking of this receptor are regulated by multiple factors, including Rab GTPase, P2Y purine nucleotide receptor, integrin alphaVbeta3, T-cell protein tyrosine phosphatase, etc.. Mutations of this gene are implicated in infantile capillary hemangiomas. [provided by RefSeq, May 2009]

Alternative Names
KDR; kinase insert domain receptor; FLK1; CD309; VEGFR; VEGFR2; vascular endothelial growth factor receptor 2; soluble VEGFR2; fetal liver kinase 1; fetal liver kinase-1; protein-tyrosine kinase receptor Flk-1; tyrosine kinase growth factor receptor; kinase insert domain receptor (a type III receptor tyrosine kinase);

Gene ID
3791

UniProt ID
A0A024RD88

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Breast cancer biomarkers at key points during disease progression

Unique DNA Damaging Payload

The use of Neocarzinostatin (NCS) as a payload in this ADC is a distinctive feature that fits our DNA damage repair research. NCS induces strand breaks in DNA, and delivering it via an anti-VEGFR2 antibody allows us to specifically study these effects in cells expressing the kinase insert domain receptor.

Verified VEGFR2 Interaction

This conjugate binds effectively to VEGFR2, the main mediator of VEGF-induced endothelial proliferation. The SPDP linker's disulfide bond is cleaved as expected in the reducing environment of the cytosol, releasing the payload. This product has been very useful for our multiple myeloma related cellular models.

Q&As

What is the mechanism of the NCS payload?

A: Neocarzinostatin (NCS) is a macromolecular chromoprotein enediyne antitumor antibiotic. It functions by inducing both single- and double-strand breaks in DNA. This inhibits DNA synthesis and leads to cell death in the targeted cells.
What are the characteristics of the SPDP linker?

A: SPDP is a chemically cleavable disulfide linker. These linkers are exploited for their lability in reducing environments. While stable at physiological pH, the disulfide bond is cleaved by cytoplasmic thiol cofactors like glutathione once the ADC is internalized.

View the frequently asked questions answered by Creative Biolabs Support.

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Downloadable Resources

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Datasheet

Datasheet - ADC-152LZY.pdf

MSDS

MSDS - ADC-152LZY.pdf

COA

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