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Description
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.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: P04626
Gene ID: 2064.0
Gene Symbol: ERBB2
Target Organism: Homo sapiens (Human)
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
KADCYLA

Approved Use

indicated, 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 Date

1.36149126E12
PubMed

PubMed

TitleDatePubMed
An unusual citrate synthase from mango fruit.
1971 Aug 6
Recent advances in the development of anti-HER2 antibodies and antibody-drug conjugates.
2014 Dec
[Trastuzumab emtansine (Kadcyla(®)) approval in HER2-positive metastatic breast cancers].
2015 Apr
Trastuzumab emtansine in advanced human epidermal growth factor receptor 2-positive breast cancer.
2015 May
Patents

Patents

Sample Use Guides

The recommended dose of ado-trastuzumab emtansine (KADCYLA) is 3.6 mg/kg given as an intravenous infusion every 3 weeks (21-day cycle) until disease progression or unacceptable toxicity.
Route of Administration: Intravenous
In Vitro Use Guide
Unknown
Substance Class Protein
Created
by admin
on Fri Jul 07 00:12:22 UTC 2023
Edited
by admin
on Fri Jul 07 00:12:22 UTC 2023
Protein Type MONOCLONAL ANTIBODY
Protein Sub Type IGG1
Sequence Origin HUMANIZED MOUSE
Sequence Type COMPLETE
Record UNII
SE2KH7T06F
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ADO-TRASTUZUMAB EMTANSINE
DASH   VANDF  
FDA  
Preferred Name English
TRASTUZUMAB EMTANSINE
INN   MART.   MI   USAN   WHO-DD  
USAN   INN  
Official Name English
PRO-132365
Code English
KADCYLA
Brand Name English
TRASTUZUMAB EMTANSINE [JAN]
Common Name English
TRASTUZUMAB EMTANSINE [USAN]
Common Name English
TRASTUZUMAB-MCC-DM1
Code English
T-DM1
Code English
RG-3502
Code English
TRASTUZUMAB EMTANSINE [MI]
Common Name English
Trastuzumab emtansine [WHO-DD]
Common Name English
ADO-TRASTUZUMAB [VANDF]
Common Name English
trastuzumab emtansine [INN]
Common Name English
TRASTUZUMAB EMTANSINE [MART.]
Common Name English
PRO132365
Code English
TRASTUZUMAB EMTANSINE (GENETICAL RECOMBINATION)
JAN  
Official Name English
ADO-TRASTUZUMAB EMTANSINE [PURPLE BOOK CDER]
Common Name English
ADO-TRASTUZUMAB EMTANSINE [VANDF]
Common Name English
Classification Tree Code System Code
FDA ORPHAN DRUG 412213
Created by admin on Fri Jul 07 00:12:22 UTC 2023 , Edited by admin on Fri Jul 07 00:12:22 UTC 2023
NCI_THESAURUS C155712
Created by admin on Fri Jul 07 00:12:22 UTC 2023 , Edited by admin on Fri Jul 07 00:12:22 UTC 2023
WHO-VATC QL01XC14
Created by admin on Fri Jul 07 00:12:22 UTC 2023 , Edited by admin on Fri Jul 07 00:12:22 UTC 2023
WHO-ATC L01XC14
Created by admin on Fri Jul 07 00:12:22 UTC 2023 , Edited by admin on Fri Jul 07 00:12:22 UTC 2023
EMA ASSESSMENT REPORTS KADCYLA (AUTHORIZED: BREAST NEOLPLASMA)
Created by admin on Fri Jul 07 00:12:22 UTC 2023 , Edited by admin on Fri Jul 07 00:12:22 UTC 2023
Code System Code Type Description
IUPHAR
6928
Created by admin on Fri Jul 07 00:12:22 UTC 2023 , Edited by admin on Fri Jul 07 00:12:22 UTC 2023
PRIMARY
DRUG BANK
DB05773
Created by admin on Fri Jul 07 00:12:22 UTC 2023 , Edited by admin on Fri Jul 07 00:12:22 UTC 2023
PRIMARY
EVMPD
SUB35467
Created by admin on Fri Jul 07 00:12:22 UTC 2023 , Edited by admin on Fri Jul 07 00:12:22 UTC 2023
PRIMARY
LACTMED
Ado-Trastuzumab Emtansine
Created by admin on Fri Jul 07 00:12:22 UTC 2023 , Edited by admin on Fri Jul 07 00:12:22 UTC 2023
PRIMARY
ChEMBL
CHEMBL1743082
Created by admin on Fri Jul 07 00:12:22 UTC 2023 , Edited by admin on Fri Jul 07 00:12:22 UTC 2023
PRIMARY
NCI_THESAURUS
C82492
Created by admin on Fri Jul 07 00:12:22 UTC 2023 , Edited by admin on Fri Jul 07 00:12:22 UTC 2023
PRIMARY
CAS
1018448-65-1
Created by admin on Fri Jul 07 00:12:22 UTC 2023 , Edited by admin on Fri Jul 07 00:12:22 UTC 2023
PRIMARY
MERCK INDEX
M11006
Created by admin on Fri Jul 07 00:12:22 UTC 2023 , Edited by admin on Fri Jul 07 00:12:22 UTC 2023
PRIMARY Merck Index
SMS_ID
100000128434
Created by admin on Fri Jul 07 00:12:22 UTC 2023 , Edited by admin on Fri Jul 07 00:12:22 UTC 2023
PRIMARY
DRUG CENTRAL
4990
Created by admin on Fri Jul 07 00:12:22 UTC 2023 , Edited by admin on Fri Jul 07 00:12:22 UTC 2023
PRIMARY
RXCUI
1371041
Created by admin on Fri Jul 07 00:12:22 UTC 2023 , Edited by admin on Fri Jul 07 00:12:22 UTC 2023
PRIMARY RxNorm
WIKIPEDIA
TRASTUZUMAB EMTANSINE
Created by admin on Fri Jul 07 00:12:22 UTC 2023 , Edited by admin on Fri Jul 07 00:12:22 UTC 2023
PRIMARY
FDA UNII
SE2KH7T06F
Created by admin on Fri Jul 07 00:12:22 UTC 2023 , Edited by admin on Fri Jul 07 00:12:22 UTC 2023
PRIMARY
USAN
WW-66
Created by admin on Fri Jul 07 00:12:22 UTC 2023 , Edited by admin on Fri Jul 07 00:12:22 UTC 2023
PRIMARY
JAPANESE REVIEW
KADCYLA
Created by admin on Fri Jul 07 00:12:22 UTC 2023 , Edited by admin on Fri Jul 07 00:12:22 UTC 2023
PRIMARY APPROVED SEPTEMBER 2013
INN
9295
Created by admin on Fri Jul 07 00:12:22 UTC 2023 , Edited by admin on Fri Jul 07 00:12:22 UTC 2023
PRIMARY
LACTMED
Trastuzumab Emtansine
Created by admin on Fri Jul 07 00:12:22 UTC 2023 , Edited by admin on Fri Jul 07 00:12:22 UTC 2023
PRIMARY
DAILYMED
SE2KH7T06F
Created by admin on Fri Jul 07 00:12:22 UTC 2023 , Edited by admin on Fri Jul 07 00:12:22 UTC 2023
PRIMARY
ChEMBL
CHEMBL2109399
Created by admin on Fri Jul 07 00:12:22 UTC 2023 , Edited by admin on Fri Jul 07 00:12:22 UTC 2023
PRIMARY
From To
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
N 1_300
N 2_300
Related Record Type Details
PARENT -> CONJUGATE
Related Record Type Details
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
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Molecular Formula CHEMICAL
Volume of Distribution PHARMACOKINETIC
MOL_WEIGHT:ESTIMATED(SDS-PAGE) CHEMICAL