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PCSK9
Anti-PCSK9 (Lodelcizumab)-SMCC-DM1 ADC

Anti-PCSK9 (Lodelcizumab)-SMCC-DM1 ADC (CAT#: ADC-W-1688)

This ADC product is comprised of an anti-PCSK9 monoclonal antibody conjugated via a SMCC linker to DM1. The DM1 is targeted to certain cancers by immunerecognition and delivered into cancer cells via receptor mediated endocytosis. Within the cell, DM1 binds to tubulins, interrupts microtubule dynamics, and subsequently, induces cell death.

ADC Target
ADC Antibody
ADC Linker
ADC payload drug

Name
PCSK9

Alternative Names
PCSK9; proprotein convertase subtilisin/kexin type 9; HCHOLA3, hypercholesterolemia, autosomal dominant 3; FH3; NARC 1; NARC1; NARC-1; HCHOLA3;

Target Entrez Gene ID
353175

Target UniProt ID
Q8NBP7

Overview
This gene encodes a member of the subtilisin-like proprotein convertase family, which includes proteases that process protein and peptide precursors trafficking through regulated or constitutive branches of the secretory pathway. The encoded protein undergoes an autocatalytic processing event with its prosegment in the ER and is constitutively secreted as an inactive protease into the extracellular matrix and trans-Golgi network. It is expressed in liver, intestine and kidney tissues and escorts specific receptors for lysosomal degradation. It plays a role in cholesterol and fatty acid metabolism. Mutations in this gene have been associated with autosomal dominant familial hypercholesterolemia. Alternative splicing results in multiple transcript variants.

Overview
Humanized Anti-PCSK9 IgG1-kappa antibody, Lodelcizumab

Generic name
Lodelcizumab

Host animal
Mouse

Name
SMCC (N-succinimidyl 4-(Nmaleimidomethyl)cyclohexane-1-carboxylate)

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.

Name
DM1 (N2'-Deacetyl-N2'-(3-mercapto-1-oxopropyl)maytansine)

Description
Derived from Maytansinoid,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.

For Research Use Only. NOT FOR CLINICAL USE.

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CAMouse™-Fully Human Antibody Generation Platform

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Same Target Same Linker Same Payload

CAT#	Product Name	Linker	Payload
ADC-W-2231	Anti-PCSK9 (Bococizumab)-MC-Vc-PAB-MMAE ADC	MC-Vc-PAB (maleimidocaproyl-valine-citrulline-p-aminobenzoyloxycarbonyl)	MMAE
ADC-W-2313	Anti-PCSK9 (Ralpancizumab)-SPDB-DM4 ADC	SPDB (N-succinimidyl-4-(2-pyridyldithio)butyrate)	DM4 (N2'-Deacetyl-N2'-(4-mercapto-4-methyl-1-oxopentyl)maytansine)
ADC-W-2380	Anti-PCSK9 (Evolocumab)-MC-MMAF ADC	MC (maleimidocaproyl)	MMAF
ADC-W-2379	Anti-PCSK9 (Evolocumab)-SPDB-DM4 ADC	SPDB (N-succinimidyl-4-(2-pyridyldithio)butyrate)	DM4 (N2'-Deacetyl-N2'-(4-mercapto-4-methyl-1-oxopentyl)maytansine)
ADC-W-2232	Anti-PCSK9 (Bococizumab)-MC-Vc-PAB-SN38 ADC	MC-Vc-PAB (maleimidocaproyl-valine-citrulline-p-aminobenzoyloxycarbonyl)	SN-38 (7-ethyl-10-hydroxycamptothecin)

CAT#	Product Name	Linker	Payload
ADC-W-473	Anti-CD37-SMCC-DM1 ADC	SMCC (N-succinimidyl 4-(Nmaleimidomethyl)cyclohexane-1-carboxylate)	DM1 (N2’-Deacetyl-N2’-(3-mercapto-1-oxopropyl)maytansine)
ADC-W-2583	Anti-EGFR (Zalutumumab)-SMCC-DM1 ADC	SMCC (N-succinimidyl 4-(Nmaleimidomethyl)cyclohexane-1-carboxylate)	DM1 (N2'-Deacetyl-N2'-(3-mercapto-1-oxopropyl)maytansine)
ADC-W-495	Anti-EGFR (J2898A)-SMCC-DM1 ADC	SMCC (N-succinimidyl 4-(Nmaleimidomethyl)cyclohexane-1-carboxylate)	DM1 (N2’-Deacetyl-N2’-(3-mercapto-1-oxopropyl)maytansine)
ADC-W-2610	Anti-MS4A1 (Rituximab)-SMCC-DM1 ADC	SMCC (N-succinimidyl 4-(Nmaleimidomethyl)cyclohexane-1-carboxylate)	DM1 (N2'-Deacetyl-N2'-(3-mercapto-1-oxopropyl)maytansine)
ADC-W-2589	Anti-EGFR (Cetuximab)-SMCC-DM1 ADC	SMCC (N-succinimidyl 4-(Nmaleimidomethyl)cyclohexane-1-carboxylate)	DM1 (N2'-Deacetyl-N2'-(3-mercapto-1-oxopropyl)maytansine)

CAT#	Product Name	Linker	Payload
ADC-W-2610	Anti-MS4A1 (Rituximab)-SMCC-DM1 ADC	SMCC (N-succinimidyl 4-(Nmaleimidomethyl)cyclohexane-1-carboxylate)	DM1 (N2'-Deacetyl-N2'-(3-mercapto-1-oxopropyl)maytansine)
ADC-W-2548	Anti-CD74-SMCC-DM1 ADC	SMCC (N-succinimidyl 4-(Nmaleimidomethyl)cyclohexane-1-carboxylate)	DM1 (N2'-Deacetyl-N2'-(3-mercapto-1-oxopropyl)maytansine)
ADC-W-2565	Anti-MUC16 (Sofituzumab)-SMCC-DM1 ADC	SMCC (N-succinimidyl 4-(Nmaleimidomethyl)cyclohexane-1-carboxylate)	DM1 (N2'-Deacetyl-N2'-(3-mercapto-1-oxopropyl)maytansine)
ADC-W-2554	Anti-CD79B (Polatuzumab )-SMCC-DM1 ADC	SMCC (N-succinimidyl 4-(Nmaleimidomethyl)cyclohexane-1-carboxylate)	DM1 (N2'-Deacetyl-N2'-(3-mercapto-1-oxopropyl)maytansine)
ADC-W-2560	Anti-MSLN (Anetumab )-SMCC-DM1 ADC	SMCC (N-succinimidyl 4-(Nmaleimidomethyl)cyclohexane-1-carboxylate)	DM1 (N2'-Deacetyl-N2'-(3-mercapto-1-oxopropyl)maytansine)

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