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Synonyms: 5F9vcMMAE [6] | MLN-0264 | MLN0264 | TAK-264 | TAK264
Compound class:
Antibody
Comment: Indusatumab vedotin was a clinical lead antibody-drug conjugate (ADC). It comprises an anti-guanylate cyclase 2C (GUCY2C) antibody linked to the synthetic antineoplastic toxin monomethyl auristatin E (MMAE, aka vedotin; PubChem CID 11542188).
Peptide sequence information for this antibody is available from its IMGT/mAb-DB record. A BLAST search of patented peptide sequences reveals that the heavy and light chain variable regions of indusatumab are identical to SEQ ID NO: 18 and SEQ ID NO: 20 respectively, from patent US8785600 B2 [6]. The patent also describes the toxin conjugation methodology. 
Ligand Activity Visualisation ChartsThese are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts. ✖ |
| No information available. |
Summary of Clinical Use  |
| Indusatumab vedotin was advanced to Phase 2 clinical trial for its potential to treat pancreatic and stomach adenocarcinomas and cancer of the gastroesophageal junction expressing guanylyl cyclase C, but development has since been terminated (for business reasons, not because of safety or efficacy concerns). Phase 2 results have been published [1-2]. |
| Mechanism Of Action and Pharmacodynamic Effects |
| In normal tissue GUCY2C is expressed on the apical membranes of intestinal epithelial cells [4-5], but is segregated from the systemic compartment by the intestinal barrier. GUCY2C is over-expressed in primary and metastatic colorectal tumors [3-4,7], and in view of its separation from the systemic compartment this protein represents an effective therapeutic target for immunotoxins which could treat and prevent colorectal cancer metastases without damaging normal tissues. Indusatumab vedotin targets GUCY2C-expressing cancer cells and delivers its toxic payload on internalisation. |
| Clinical Trials | |||||
| Clinical Trial ID | Title | Type | Source | Comment | References |
| NCT02202785 | A Study of MLN0264 in Patients With Pancreatic Cancer | Phase 2 Interventional | Takeda | 2 | |
| NCT01577758 | Phase 1 Study of MLN0264 in Adult Patients With Advanced Gastrointestinal Malignancies Expressing Guanylyl Cyclase C | Phase 1 Interventional | Takeda | 1 | |
