What is the mechanism of action for the DM4 payload?

DM4 is a maytansinoid, structurally similar to rifamycin and geldanamycin. It binds to tubulin at or near the vinblastine-binding site. This binding interferes with microtubule formation and depolymerizes already formed microtubules, inducing mitotic arrest in the intoxicated cells.

What does the FOLR1 gene encode?

The FOLR1 gene encodes a member of the folate receptor family. These receptors bind folic acid and its reduced derivatives, transporting 5-methyltetrahydrofolate into cells. The protein is either anchored to membranes via a glycosyl-phosphatidylinositol linkage or exists in a soluble form.

Anti-FOLR1 (M9346A)-sulfo-SPDB-DM4 ADC

CAT#: ADC-119LCT

This ADC product is composed of an anti-FOLR1 antibody (clone M9346A) conjuagated via a sulfo-SPDB linker to DM4 (M9346A-sulfo-SPDB-DM4). It has demonstrated a response in Ovarian cancer, NSCLC treatment by a MOA (Mechanism of Action) of Depolymerize Microtubules.

Gene Expression

Subcellular Location Figure 1 IF staining of human cell line HeLa

Immunofluorescent staining of human cell line HeLa shows localization to nuclear membrane.

* Image credit: Image credit: Human Protein Atlas https://v21.proteinatlas.org/images/77030/1659_B3_2_selected.jpg

RNA Expression Figure 2 RNA cell line category: Group enriched (HeLa, RPTEC TERT1)

Cell lines ordered by descending RNA expression order.

* Image credit: Image credit: Human Protein Atlas https://v21.proteinatlas.org/ENSG00000110195-FOLR1

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Specifications

Antibody Overview
Humanized Antibody M9346A (Anti-FOLR1)

Clone
M9346A

Linker
sulfo-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
The protein encoded by this gene is a member of the folate receptor family. Members of this gene family bind folic acid and its reduced derivatives, and transport 5-methyltetrahydrofolate into cells. This gene product is a secreted protein that either anchors to membranes via a glycosyl-phosphatidylinositol linkage or exists in a soluble form. Mutations in this gene have been associated with neurodegeneration due to cerebral folate transport deficiency. Due to the presence of two promoters, multiple transcription start sites, and alternative splicing, multiple transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Oct 2009]

Alternative Names
FOLR1; folate receptor 1 (adult); FBP; FOLR; folate receptor alpha; FR-alpha; KB cells FBP; folate binding protein; folate receptor, adult; adult folate-binding protein; ovarian tumor-associated antigen MOv18;

Gene ID
2348

UniProt ID
A0A024R5H1

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Breast cancer biomarkers at key points during disease progression

High Affinity FOLR1 Targeting

We utilized this ADC to target Folate Receptor 1 in our ovarian cancer research lines. The antibody clone M9346A binds effectively to the receptor, which transports 5-methyltetrahydrofolate. This product has allowed us to explore the potential of FOLR1 as a portal for delivering cytotoxic payloads like DM4.

Effective DM4 Payload Action

The combination of the sulfo-SPDB linker and the DM4 payload works very well in this conjugate. We observed the expected mitotic arrest in treated cells, confirming that the maytansinoid is effectively interfering with microtubule formation. The chemically labile disulfide linkage provided consistent release profiles in our assays.

Q&As

What is the mechanism of action for the DM4 payload?

A: DM4 is a maytansinoid, structurally similar to rifamycin and geldanamycin. It binds to tubulin at or near the vinblastine-binding site. This binding interferes with microtubule formation and depolymerizes already formed microtubules, inducing mitotic arrest in the intoxicated cells.
What does the FOLR1 gene encode?

A: The FOLR1 gene encodes a member of the folate receptor family. These receptors bind folic acid and its reduced derivatives, transporting 5-methyltetrahydrofolate into cells. The protein is either anchored to membranes via a glycosyl-phosphatidylinositol linkage or exists in a soluble form.

View the frequently asked questions answered by Creative Biolabs Support.

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Datasheet

Datasheet - ADC-119LCT.pdf

MSDS

MSDS - ADC-119LCT.pdf

COA

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