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Details

Stereochemistry ACHIRAL
Molecular Formula C26H24N8O2
Molecular Weight 480.5212
Optical Activity UNSPECIFIED
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TUCATINIB

SMILES

CC1=C(OC2=CC3=NC=NN3C=C2)C=CC(NC4=C5C=C(NC6=NC(C)(C)CO6)C=CC5=NC=N4)=C1

InChI

InChIKey=SDEAXTCZPQIFQM-UHFFFAOYSA-N
InChI=1S/C26H24N8O2/c1-16-10-17(5-7-22(16)36-19-8-9-34-23(12-19)28-15-30-34)31-24-20-11-18(4-6-21(20)27-14-29-24)32-25-33-26(2,3)13-35-25/h4-12,14-15H,13H2,1-3H3,(H,32,33)(H,27,29,31)

HIDE SMILES / InChI

Molecular Formula C26H24N8O2
Molecular Weight 480.5212
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description

TUCATINIB (ONT-380 or ARRY-380) is an orally active, reversible and selective small-molecule HER2 inhibitor invented by Array and licensed to Cascadian Therapeutics (previously named Oncothyreon) for development, manufacturing and commercialization. HER2, a growth factor receptor that is over-expressed in multiple cancers, including breast, ovarian, and stomach cancer. HER2 mediates cell growth, differentiation and survival, and tumors that overexpress HER2 are more aggressive and historically have been associated with poorer overall survival compared with HER2-negative cancers. ONT-380 is highly active as a single agent and in combination with both chemotherapy and Herceptin® (trastuzumab) in xenograft models of HER2+ breast cancer, including models of CNS metastases that were refractory to Tykerb® (lapatinib) or neratinib treatment. In a Phase 1 single agent clinical study, ONT-380 administered orally twice a day was well tolerated and demonstrated anti-tumor activity in heavily pre-treated HER2+ breast cancer patients with metastatic disease. Based on the strength of these preclinical and clinical trials, ONT-380 is advancing in one Phase 2 and three Phase 1b combination trials in patients with metastatic breast cancer. A second study reported the CNS activity of ONT-380 in combination with either T-DM1 or trastuzumab or capecitabine. Patients with brain metastases assessable for response were included in the combined analysis. Responses and clinical benefit in the CNS were reported with the three combinations tested, supporting future development of the drug for this particular indication.

CNS Activity

Originator

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions
PubMed

PubMed

TitleDatePubMed
Emerging Therapeutic Options for HER2-Positive Breast Cancer.
2016
Phase I Study of ONT-380, a HER2 Inhibitor, in Patients with HER2+-Advanced Solid Tumors, with an Expansion Cohort in HER2+ Metastatic Breast Cancer (MBC).
2017 Jul 15
Patents

Sample Use Guides

In Vivo Use Guide
Phase 2 Study of tucatinib in combination with capecitabine & trastuzumab in patients with advanced HER2+ breast cancer: Tucatinib 300 mg or placebo will be given orally twice daily (PO BID).
Route of Administration: Oral
Substance Class Chemical
Created
by admin
on Mon Oct 21 23:01:16 UTC 2019
Edited
by admin
on Mon Oct 21 23:01:16 UTC 2019
Record UNII
234248D0HH
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
TUCATINIB
INN   USAN   WHO-DD  
INN   USAN  
Official Name English
TUCATINIB [USAN]
Common Name English
TUCATINIB [WHO-DD]
Common Name English
IRBINITINIB
Common Name English
ONT-380
Code English
4,6-QUINAZOLINEDIAMINE, N6-(4,5-DIHYDRO-4,4-DIMETHYL-2-OXAZOLYL)-N4-(3-METHYL-4-((1,2,4)TRIAZOLO(1,5-A)PYRIDIN-7-YLOXY)PHENYL)-
Systematic Name English
TUCATINIB [INN]
Common Name English
ARRY-380
Code English
N6-(4,4-DIMETHYL-4,5-DIHYDROOXAZOL-2-YL)-N4-(3-METHYL-4-((1,2,4)TRIAZOLO(1,5-A)PYRIDIN-7-YLOXY)PHENYL)QUINAZOLINE-4,6-DIAMINE
Systematic Name English
Classification Tree Code System Code
FDA ORPHAN DRUG 570716
Created by admin on Mon Oct 21 23:01:16 UTC 2019 , Edited by admin on Mon Oct 21 23:01:16 UTC 2019
NCI_THESAURUS C2167
Created by admin on Mon Oct 21 23:01:16 UTC 2019 , Edited by admin on Mon Oct 21 23:01:16 UTC 2019
FDA ORPHAN DRUG 571216
Created by admin on Mon Oct 21 23:01:16 UTC 2019 , Edited by admin on Mon Oct 21 23:01:16 UTC 2019
FDA ORPHAN DRUG 603217
Created by admin on Mon Oct 21 23:01:16 UTC 2019 , Edited by admin on Mon Oct 21 23:01:16 UTC 2019
Code System Code Type Description
ChEMBL
CHEMBL3545380
Created by admin on Mon Oct 21 23:01:16 UTC 2019 , Edited by admin on Mon Oct 21 23:01:16 UTC 2019
PRIMARY
INN
9997
Created by admin on Mon Oct 21 23:01:16 UTC 2019 , Edited by admin on Mon Oct 21 23:01:16 UTC 2019
PRIMARY
CAS
937263-43-9
Created by admin on Mon Oct 21 23:01:16 UTC 2019 , Edited by admin on Mon Oct 21 23:01:16 UTC 2019
PRIMARY
NCI_THESAURUS
C77896
Created by admin on Mon Oct 21 23:01:16 UTC 2019 , Edited by admin on Mon Oct 21 23:01:16 UTC 2019
PRIMARY
EVMPD
SUB177913
Created by admin on Mon Oct 21 23:01:16 UTC 2019 , Edited by admin on Mon Oct 21 23:01:16 UTC 2019
PRIMARY
NCI_THESAURUS
C77896
Created by admin on Mon Oct 21 23:01:16 UTC 2019 , Edited by admin on Mon Oct 21 23:01:16 UTC 2019
PRIMARY
PUBCHEM
51039094
Created by admin on Mon Oct 21 23:01:16 UTC 2019 , Edited by admin on Mon Oct 21 23:01:16 UTC 2019
PRIMARY
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TARGET -> INHIBITOR
SELECTIVE
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ACTIVE MOIETY