Depatuxizumab mafodotin

Identification

Name
Depatuxizumab mafodotin
Accession Number
DB11731
Description

Depatuxizumab/Denintuzumab mafodotin has been used in trials studying the treatment of Lymphoma, Gliosarcoma, Glioblastoma, Malignant Glioma, Squamous Cell Tumors, and Glioblastoma Multiforme.

Type
Biotech
Groups
Investigational
Synonyms
  • Denintuzumab mafodotin
  • Depatuxizumab mafodotin
External IDs
  • 1399672-02-6
  • ABT-414
  • SGN-19A
  • SGN-CD 19A
  • SGN-CD19A

Pharmacology

Indication

No approved indication.

Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
Learn More
Pharmacodynamics

Selectively targets cancer cells expressing mutant epidermal growth factor receptor (EGFR) vIII or over expressing wild type EGFR 1. Depatuxizumab mafodotin acts on these cells to inhibit microtuble polymerization thus disrupting mitosis and vesicular trafficking 2

Mechanism of action

Depatuxizumab is a chimeric monoclonal antibody for EGFR which is linked to monomethyl aurastatin F via a maleimidocaproyl linker (mafodotin) 1. Once delivered to the cancer cell, the mafodotin component is able to bind to tubulin and inhibit the exchange of GDP for GTP necessary for the polymerization of tubulin subunits to form microtubules. The inhibition of microtubule polymerization disrupts mitosis and interferes with vesicle trafficking in the cancer cell 3 2.

TargetActionsOrganism
NEpidermal growth factor receptor
antibody
Humans
ATubulin beta chain
nucleotide exchange blocker
Humans
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half-life
Not Available
Clearance
Not Available
Adverse Effects
Learn about our commercial Adverse Effects data.
Learn More
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbciximabThe risk or severity of adverse effects can be increased when Abciximab is combined with Depatuxizumab mafodotin.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Depatuxizumab mafodotin.
AlemtuzumabThe risk or severity of adverse effects can be increased when Alemtuzumab is combined with Depatuxizumab mafodotin.
AlirocumabThe risk or severity of adverse effects can be increased when Alirocumab is combined with Depatuxizumab mafodotin.
Anthrax immune globulin humanThe risk or severity of adverse effects can be increased when Anthrax immune globulin human is combined with Depatuxizumab mafodotin.
Antilymphocyte immunoglobulin (horse)The risk or severity of adverse effects can be increased when Antilymphocyte immunoglobulin (horse) is combined with Depatuxizumab mafodotin.
Antithymocyte immunoglobulin (rabbit)The risk or severity of adverse effects can be increased when Antithymocyte immunoglobulin (rabbit) is combined with Depatuxizumab mafodotin.
Asfotase alfaThe risk or severity of adverse effects can be increased when Asfotase alfa is combined with Depatuxizumab mafodotin.
AtezolizumabThe risk or severity of adverse effects can be increased when Atezolizumab is combined with Depatuxizumab mafodotin.
AvelumabThe risk or severity of adverse effects can be increased when Depatuxizumab mafodotin is combined with Avelumab.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

    Learn more
  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

    Learn more
  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

    Learn more
  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

    Learn more
Food Interactions
Not Available

Products

Categories

Drug Categories
Classification
Not classified

Chemical Identifiers

UNII
F3R7A4P04N
CAS number
1585973-65-4

References

General References
  1. Phillips AC, Boghaert ER, Vaidya KS, Mitten MJ, Norvell S, Falls HD, DeVries PJ, Cheng D, Meulbroek JA, Buchanan FG, McKay LM, Goodwin NC, Reilly EB: ABT-414, an Antibody-Drug Conjugate Targeting a Tumor-Selective EGFR Epitope. Mol Cancer Ther. 2016 Apr;15(4):661-9. doi: 10.1158/1535-7163.MCT-15-0901. Epub 2016 Feb 4. [PubMed:26846818]
  2. Waight AB, Bargsten K, Doronina S, Steinmetz MO, Sussman D, Prota AE: Structural Basis of Microtubule Destabilization by Potent Auristatin Anti-Mitotics. PLoS One. 2016 Aug 12;11(8):e0160890. doi: 10.1371/journal.pone.0160890. eCollection 2016. [PubMed:27518442]
  3. Bai RL, Pettit GR, Hamel E: Binding of dolastatin 10 to tubulin at a distinct site for peptide antimitotic agents near the exchangeable nucleotide and vinca alkaloid sites. J Biol Chem. 1990 Oct 5;265(28):17141-9. [PubMed:2211617]
PubChem Compound
71300933
PubChem Substance
347828090
ChemSpider
57523411
Wikipedia
Depatuxizumab_mafodotin

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3CompletedTreatmentGlioblastoma Multiforme (GBM)1
2CompletedTreatmentGlioblastomas1
2TerminatedTreatmentDiffuse Large B-Cell Lymphoma (DLBCL) / Follicular Lymphoma, Grade 3b / Lymphoma, B-Cell / Lymphoma, Follicular, Grade 3b1
2TerminatedTreatmentDiffuse Large B-Cell Lymphoma (DLBCL) / Follicular Lymphoma, Grade 3b / Transformed Lymphoma / DLBCL1
2, 3Active Not RecruitingTreatmentGlioblastomas / Gliosarcoma1
1CompletedTreatmentBurkitt's Lymphoma / Diffuse Large B-Cell Lymphoma (DLBCL) / Follicular Lymphoma (FL) / Mantle Cell Lymphoma (MCL) / Precursor B-Cell Lymphoblastic Leukemia-Lymphoma1
1CompletedTreatmentBurkitt's Lymphoma / Precursor B-Cell Lymphoblastic Leukemia-Lymphoma1
1CompletedTreatmentGlioblastoma Multiforme (GBM)1
1CompletedTreatmentSquamous Cell Tumors1
1, 2CompletedTreatmentGlioblastoma Multiforme (GBM) / Gliomas, Malignant1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Not Available
Experimental Properties
Not Available

Targets

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Antibody
General Function
Ubiquitin protein ligase binding
Specific Function
Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses. Known ligands include EGF, TG...
Gene Name
EGFR
Uniprot ID
P00533
Uniprot Name
Epidermal growth factor receptor
Molecular Weight
134276.185 Da
References
  1. Phillips AC, Boghaert ER, Vaidya KS, Mitten MJ, Norvell S, Falls HD, DeVries PJ, Cheng D, Meulbroek JA, Buchanan FG, McKay LM, Goodwin NC, Reilly EB: ABT-414, an Antibody-Drug Conjugate Targeting a Tumor-Selective EGFR Epitope. Mol Cancer Ther. 2016 Apr;15(4):661-9. doi: 10.1158/1535-7163.MCT-15-0901. Epub 2016 Feb 4. [PubMed:26846818]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Nucleotide exchange blocker
General Function
Ubiquitin protein ligase binding
Specific Function
Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain.
Gene Name
TUBB
Uniprot ID
P07437
Uniprot Name
Tubulin beta chain
Molecular Weight
49670.515 Da
References
  1. Bai RL, Pettit GR, Hamel E: Binding of dolastatin 10 to tubulin at a distinct site for peptide antimitotic agents near the exchangeable nucleotide and vinca alkaloid sites. J Biol Chem. 1990 Oct 5;265(28):17141-9. [PubMed:2211617]
  2. Waight AB, Bargsten K, Doronina S, Steinmetz MO, Sussman D, Prota AE: Structural Basis of Microtubule Destabilization by Potent Auristatin Anti-Mitotics. PLoS One. 2016 Aug 12;11(8):e0160890. doi: 10.1371/journal.pone.0160890. eCollection 2016. [PubMed:27518442]

Drug created on October 20, 2016 14:43 / Updated on June 12, 2020 10:53

Logo pink
Are you a
new drug developer?
Contact us to learn more about our customized products and solutions.
Logo pink
Stay in the know!
As part of our commitment to providing the most up-to-date drug information, we will be releasing #DrugBankUpdates with our newly added curated drug pages.
#DrugBankUpdates