How does the PBD payload damage DNA?

The PBD (pyrrolobenzodiazepine) dimer payload works by binding covalently to the minor groove of DNA. Specifically, it cross-links DNA strands at guanine residues. This damage prevents DNA replication and transcription, leading to potent cytotoxicity.

What is the composition of the linker?

The linker consists of a maleimidocaproyl (mc) group and a valine-alanine (val-ala) dipeptide. This peptide linker is enzymatically cleavable by lysosomal proteases, ensuring that the toxic payload is released primarily inside the target cell.

Anti-CD33 (h2H12ec)-Mc-vc-PBD ADC (SGN-CD33A)

CAT#: ADC-L033

This ADC product is composed of an anti-CD33 antibody (clone h2H12ec) conjuagated via a mc-val linker to SGD-1882 (h2H12ec-mc-val-SGD-1882). It has demonstrated a response in AML treatment by a MOA (Mechanism of Action) of Bind to DNA minor groove and cause DNA damage.

Gene Expression

Subcellular Location and Protein Expression Figure 1 IF staining of human cell line PC-3

Immunofluorescent staining of human cell line PC-3 shows localization to nucleoplasm & plasma membrane.

* Image credit: Image credit: Human Protein Atlas https://v21.proteinatlas.org/images/64807/1186_A4_3_selected.jpg

Subcellular Location and Protein Expression Figure 2 IHC staining of human lymph node

Immunohistochemical staining of human lymph node shows membranous and cytoplasmic positivity in germinal center cells and non-germinal center cells.

* Image credit: Image credit: Human Protein Atlas https://v21.proteinatlas.org/images/35832/113039_A_9_8_selected.jpg

Subcellular Location and Protein Expression Figure 3 IHC staining of human tonsil

Immunohistochemical staining of human tonsil shows cytoplasmic positivity in germinal center cells and non-germinal center cells.

* Image credit: Image credit: Human Protein Atlas https://v21.proteinatlas.org/images/11442/26430_A_6_8_selected.jpg

Subcellular Location and Protein Expression Figure 4 IF staining of human cell line RH-30

Immunofluorescent staining of human cell line RH-30 shows localization to nucleoplasm.

* Image credit: Image credit: Human Protein Atlas https://v21.proteinatlas.org/images/64807/1413_G6_1_red_green.jpg

Subcellular Location and Protein Expression Figure 5 IF staining of human cell line U-2 OS

Immunofluorescent staining of human cell line U-2 OS shows localization to nucleoplasm.

* Image credit: Image credit: Human Protein Atlas https://v21.proteinatlas.org/images/64807/1200_A4_2_red_green.jpg

Normal Tissue Figure 6 Kidney

Cells in tubules
Staining:Medium
Intensity: Strong
Quantity: <25%
Location: Cytoplasmic/membranous

* Image credit: Image credit: Human Protein Atlas https://v21.proteinatlas.org/images/79996/170702_A_9_5.jpg

Normal Tissue Figure 7 Lymph node

Non-germinal center cells
Staining:Medium
Intensity: Strong
Quantity: <25%
Location: Cytoplasmic/membranous

* Image credit: Image credit: Human Protein Atlas https://v21.proteinatlas.org/images/79996/170702_A_9_8.jpg

Normal Tissue Figure 8 Spleen

Cells in red pulp
Staining:Medium
Intensity: Moderate
Quantity:>75%
Location: Cytoplasmic/membranous

* Image credit: Image credit: Human Protein Atlas https://v21.proteinatlas.org/images/79996/170702_B_8_4.jpg

RNA Expression Figure 9 RNA cell line category: Cell line enhanced (HEL, HL-60, HMC-1, NB-4, RPMI-8226, THP-1, U-937)

Cell lines ordered by descending RNA expression order.

* Image credit: Image credit: Human Protein Atlas https://v21.proteinatlas.org/ENSG00000105383-CD33

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Specifications

Antibody Overview
Chimeric anti-CD33 monoclonal antibody, IgG1k

Clone
h2H12ec

Antibody Conjugation
Chimeric murine/human

Linker
mc-vc (maleimidocaproyl-valine-alanine)

Linker Class/Description
Peptide linkers, belonging to Enzymatically cleavable linkers, combine greater systemic stability with rapid enzymatic release of the drug in the target cell. The scission of peptidic bonds relies on lysosomal proteolytic enzymes, which have very low activities in blood due to endogenous inhibitors and the unfavorably high pH value of blood.

Drug
pyrrolobenzodiazepine (PBD) dimers SGD-1882

Drug Class/Description
Pyrrolobenzodiazepine (PBD) dimmers are highly cytotoxic DNA cross-linking agents. PBDs exert their biological activity through covalent binding via their N10-C11imine/carbinolamine moieties to the C2-amino position of a guanine residue within the minor groove of DNA.

Target

Introduction
CD33 or Siglec-3 is a transmembrane receptor expressed on cells of myeloid lineage. It is usually considered myeloid-specific, but it can also be found on some lymphoid cells.

Alternative Names
CD33; CD33 molecule; p67; SIGLEC3; SIGLEC-3

Gene ID
945

UniProt ID
P20138

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Breast cancer biomarkers at key points during disease progression

Highly Cytotoxic PBD

The PBD dimer payload (SGD-1882) in this ADC is incredibly potent against our AML cell lines. Its ability to cross-link DNA in the minor groove leads to cell death even in cells that might be resistant to other toxins. The h2H12ec antibody directs this potency specifically to CD33-positive cells.

Enzyme Cleavable Linker

The mc-val-ala linker system in this conjugate works very well. It provides stability in the culture media but is cleaved by lysosomal proteases upon internalization. This controlled release mechanism is essential for our experiments, allowing us to accurately assess the therapeutic window in our cellular models.

Q&As

How does the PBD payload damage DNA?

A: The PBD (pyrrolobenzodiazepine) dimer payload works by binding covalently to the minor groove of DNA. Specifically, it cross-links DNA strands at guanine residues. This damage prevents DNA replication and transcription, leading to potent cytotoxicity.
What is the composition of the linker?

A: The linker consists of a maleimidocaproyl (mc) group and a valine-alanine (val-ala) dipeptide. This peptide linker is enzymatically cleavable by lysosomal proteases, ensuring that the toxic payload is released primarily inside the target cell.

View the frequently asked questions answered by Creative Biolabs Support.

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Datasheet

Datasheet - ADC-L033.pdf

MSDS

MSDS - ADC-L033.pdf

COA

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