DescriptionSources: http://www.ncbi.nlm.nih.gov/pubmed/?term=25568875Curator's Comment: description was created based on several sources, including
http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/125427s096lbl.pdf
Sources: http://www.ncbi.nlm.nih.gov/pubmed/?term=25568875
Curator's Comment: description was created based on several sources, including
http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/125427s096lbl.pdf
Trastuzumab emtansine (ado-trastuzumab emtansine, trade name Kadcyla) is a combination between a monoclonal antibody and a small-molecule drug. Each molecule of trastuzumab emtansine consists of a single trastuzumab molecule with several molecules of DM1, a cytotoxic maytansinoid, attached. SMCC, or succinimidyl trans-4-(maleimidylmethyl)cyclohexane-1-carboxylate, is a heterobifunctional crosslinker, a type of chemical reagent that contains two reactive functional groups, a succinimide ester and a maleimide. The succinimide group of SMCC reacts with the free amino group of a lysine residue in the trastuzumab molecule and the maleimide moiety of SMCC links to the free sulfhydryl group of DM1, forming a covalent bond between the antibody and the DM1. Each trastuzumab molecule may be linked to zero to eight DM1 molecules (3.5 on average). Trastuzumab emtansine is an antibody-drug conjugate consisting of the recombinant anti-epidermal growth factor receptor 2 (HER2) monoclonal antibody trastuzumab conjugated to the maytansinoid DM1. The trastuzumab moiety of this ADC binds to HER2 on tumor cell surface surfaces; upon internalization, the DM1 moiety is released and binds to tubulin, thereby disrupting microtubule assembly/disassembly dynamics and inhibiting cell division and the proliferation of cancer cells that overexpress HER2. Linkage of antibody and drug through a nonreducible linker has been reported to contribute to the improved efficacy and reduced toxicity of this ADC compared to similar ADCs constructed with reducible linkers. Trastuzumab emtansine is used for the treatment of patients with HER2-positive, metastatic breast cancer who previously received rastuzumab and a taxane, separately or in combination. Patients should have either: received prior therapy for metastatic disease, or developed disease recurrence during or within six months of completing adjuvant therapy. Ado-trastuzumab emtansine is marketed under the brand name Kadcyla and is indicated for use in HER2-positive, metastatic breast cancer patients who have already used taxane and/or trastuzumab for metastatic disease or had their cancer recur within 6 months of adjuvant treatment. The FDA label has two precautions. First that ado-trastuzumab emtansine and trastuzumab cannot be interchanged. Second that there is a black box warning of serious side effects such as hepatotoxicity, embryo-fetal toxicity, and cardiac toxicity.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
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Target ID: P04626 Gene ID: 2064.0 Gene Symbol: ERBB2 Target Organism: Homo sapiens (Human) Sources: http://www.ncbi.nlm.nih.gov/pubmed/?term=25568875 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
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Primary | KADCYLA Approved Useindicated, as a single agent, for the treatment of patients with HER2-positive, metastatic breast cancer who previously received trastuzumab and a taxane, separately or in combination. Patients should have either received prior therapy for metastatic disease, or developed disease recurrence during or within six months of completing adjuvant therapy Launch Date2013 |
Substance Class |
Protein
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Protein Type | MONOCLONAL ANTIBODY |
Protein Sub Type | IGG1 |
Sequence Origin | HUMANIZED MOUSE |
Sequence Type | COMPLETE |
Record UNII |
SE2KH7T06F
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Validated (UNII)
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FDA ORPHAN DRUG |
412213
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NCI_THESAURUS |
C155712
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WHO-VATC |
QL01XC14
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EMA ASSESSMENT REPORTS |
KADCYLA (AUTHORIZED: BREAST NEOLPLASMA)
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DB05773
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SUB35467
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Ado-Trastuzumab Emtansine
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CHEMBL1743082
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C82492
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1018448-65-1
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m11006
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100000128434
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4990
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1371041
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TRASTUZUMAB EMTANSINE
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SE2KH7T06F
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WW-66
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KADCYLA
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PRIMARY | APPROVED SEPTEMBER 2013 | ||
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9295
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Trastuzumab Emtansine
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SE2KH7T06F
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CHEMBL2109399
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1_22 | 1_96 |
1_147 | 1_203 |
1_223 | 3_214 |
1_229 | 2_229 |
1_232 | 2_232 |
1_264 | 1_324 |
1_370 | 1_428 |
2_22 | 2_96 |
2_147 | 2_203 |
2_223 | 4_214 |
2_264 | 2_324 |
2_370 | 2_428 |
3_23 | 3_88 |
3_134 | 3_194 |
4_23 | 4_88 |
4_134 | 4_194 |
Glycosylation Type | MAMMALIAN |
Glycosylation Link Type | Site |
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N | 1_300 |
N | 2_300 |
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PARENT -> CONJUGATE |
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Related Record | Type | Details | ||
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METABOLITE ACTIVE -> PARENT |
INTERNALIZATION FOLLOWED BY PROTEOLYTIC DIGESTION FORMS ACTIVE METABOLITE WHICH IS UNABLE TO MIGRATE OUT OF CELL LEADING TO AN ENHANCED SAFETY PROFILE
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Related Record | Type | Details | ||
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ACTIVE MOIETY |
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Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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Molecular Formula | CHEMICAL |
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Volume of Distribution | PHARMACOKINETIC |
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MOL_WEIGHT:ESTIMATED(SDS-PAGE) | CHEMICAL |
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