U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula 2C26H24N8O2.C2H6O
Molecular Weight 1007.1108
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TUCATINIB HEMIETHANOLATE

SMILES

CCO.CC1=C(OC2=CC3=NC=NN3C=C2)C=CC(NC4=C5C=C(NC6=NC(C)(C)CO6)C=CC5=NC=N4)=C1.CC7=C(OC8=CC9=NC=NN9C=C8)C=CC(NC%10=C%11C=C(NC%12=NC(C)(C)CO%12)C=CC%11=NC=N%10)=C7

InChI

InChIKey=UGAFQGGOUGJBMF-UHFFFAOYSA-N
InChI=1S/2C26H24N8O2.C2H6O/c2*1-16-10-17(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;1-2-3/h2*4-12,14-15H,13H2,1-3H3,(H,32,33)(H,27,29,31);3H,2H2,1H3

HIDE SMILES / InChI
Molecular Formula C26H24N8O2
Molecular Weight 480.5212
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE
Molecular Formula C2H6O
Molecular Weight 46.0684
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
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

2020
691
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
8504
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Phase II
1147
Unknown

Approved Use

Unknown
Primary
Phase II
1147
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
790 ng/mL
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/29955792
300 mg 2 times / day steady-state, oral
dose: 300 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
TUCATINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
2920 ng × h/mL
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/29955792
300 mg 2 times / day steady-state, oral
dose: 300 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
TUCATINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
5.5 h
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/29955792
300 mg 2 times / day steady-state, oral
dose: 300 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
TUCATINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
2.9%
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213411s000lbl.pdf
TUCATINIB plasma
Homo sapiens
Doses

Doses

DosePopulationAdverse events​
300 mg 2 times / day steady, oral
Recommended
Dose: 300 mg, 2 times / day
Route: oral
Route: steady
Dose: 300 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213411s000lbl.pdf
unhealthy, 54 years (range: 22 - 82 years)
Health Status: unhealthy
Age Group: 54 years (range: 22 - 82 years)
Sex: M+F
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213411s000lbl.pdf
Disc. AE: Hepatotoxicity, Diarrhea...
AEs leading to
discontinuation/dose reduction:
Hepatotoxicity (1.5%)
Diarrhea (1%)
Hepatotoxicity (8%)
Diarrhea (6%)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213411s000lbl.pdf
800 mg 2 times / day steady, oral
Highest studied dose
Dose: 800 mg, 2 times / day
Route: oral
Route: steady
Dose: 800 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/28053023
unhealthy, 58 years (range: 31–77 years)
Health Status: unhealthy
Age Group: 58 years (range: 31–77 years)
Sex: M+F
Sources:
https://pubmed.ncbi.nlm.nih.gov/28053023
DLT: Alanine aminotransferase increased, Aspartate aminotransferase increased...
Dose limiting toxicities:
Alanine aminotransferase increased (grade 3, 2 patients)
Aspartate aminotransferase increased (grade 3, 2 patients)
Sources:
https://pubmed.ncbi.nlm.nih.gov/28053023
600 mg 2 times / day steady, oral
MTD
Dose: 600 mg, 2 times / day
Route: oral
Route: steady
Dose: 600 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/28053022
unhealthy, 58 years (range: 31–77 years)
Health Status: unhealthy
Age Group: 58 years (range: 31–77 years)
Sex: M+F
Sources:
https://pubmed.ncbi.nlm.nih.gov/28053022
Other AEs: Diarrhea, Nausea...
Other AEs:
Diarrhea (grade 1-2, 26%)
Nausea (grade 1-2, 33%)
Fatigue (grade 1-2, 19%)
Vomiting (grade 1-2, 3%)
Acne (grade 3, 4%)
Dermatitis acneiform (grade 3, 4%)
Skin exfoliation (grade 3, 4%)
Alanine aminotransferase increased (grade 3, 4%)
Aspartate aminotransferase increased (grade 2, 11%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/28053022
AEs

AEs

AESignificanceDosePopulation
Diarrhea 1%
Disc. AE
300 mg 2 times / day steady, oral
Recommended
Dose: 300 mg, 2 times / day
Route: oral
Route: steady
Dose: 300 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213411s000lbl.pdf
unhealthy, 54 years (range: 22 - 82 years)
Health Status: unhealthy
Age Group: 54 years (range: 22 - 82 years)
Sex: M+F
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213411s000lbl.pdf
Hepatotoxicity 1.5%
Disc. AE
300 mg 2 times / day steady, oral
Recommended
Dose: 300 mg, 2 times / day
Route: oral
Route: steady
Dose: 300 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213411s000lbl.pdf
unhealthy, 54 years (range: 22 - 82 years)
Health Status: unhealthy
Age Group: 54 years (range: 22 - 82 years)
Sex: M+F
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213411s000lbl.pdf
Diarrhea 6%
Disc. AE
300 mg 2 times / day steady, oral
Recommended
Dose: 300 mg, 2 times / day
Route: oral
Route: steady
Dose: 300 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213411s000lbl.pdf
unhealthy, 54 years (range: 22 - 82 years)
Health Status: unhealthy
Age Group: 54 years (range: 22 - 82 years)
Sex: M+F
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213411s000lbl.pdf
Hepatotoxicity 8%
Disc. AE
300 mg 2 times / day steady, oral
Recommended
Dose: 300 mg, 2 times / day
Route: oral
Route: steady
Dose: 300 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213411s000lbl.pdf
unhealthy, 54 years (range: 22 - 82 years)
Health Status: unhealthy
Age Group: 54 years (range: 22 - 82 years)
Sex: M+F
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213411s000lbl.pdf
Alanine aminotransferase increased grade 3, 2 patients
DLT, Disc. AE
800 mg 2 times / day steady, oral
Highest studied dose
Dose: 800 mg, 2 times / day
Route: oral
Route: steady
Dose: 800 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/28053023
unhealthy, 58 years (range: 31–77 years)
Health Status: unhealthy
Age Group: 58 years (range: 31–77 years)
Sex: M+F
Sources:
https://pubmed.ncbi.nlm.nih.gov/28053023
Aspartate aminotransferase increased grade 3, 2 patients
DLT, Disc. AE
800 mg 2 times / day steady, oral
Highest studied dose
Dose: 800 mg, 2 times / day
Route: oral
Route: steady
Dose: 800 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/28053023
unhealthy, 58 years (range: 31–77 years)
Health Status: unhealthy
Age Group: 58 years (range: 31–77 years)
Sex: M+F
Sources:
https://pubmed.ncbi.nlm.nih.gov/28053023
Fatigue grade 1-2, 19%
600 mg 2 times / day steady, oral
MTD
Dose: 600 mg, 2 times / day
Route: oral
Route: steady
Dose: 600 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/28053022
unhealthy, 58 years (range: 31–77 years)
Health Status: unhealthy
Age Group: 58 years (range: 31–77 years)
Sex: M+F
Sources:
https://pubmed.ncbi.nlm.nih.gov/28053022
Diarrhea grade 1-2, 26%
600 mg 2 times / day steady, oral
MTD
Dose: 600 mg, 2 times / day
Route: oral
Route: steady
Dose: 600 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/28053022
unhealthy, 58 years (range: 31–77 years)
Health Status: unhealthy
Age Group: 58 years (range: 31–77 years)
Sex: M+F
Sources:
https://pubmed.ncbi.nlm.nih.gov/28053022
Vomiting grade 1-2, 3%
600 mg 2 times / day steady, oral
MTD
Dose: 600 mg, 2 times / day
Route: oral
Route: steady
Dose: 600 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/28053022
unhealthy, 58 years (range: 31–77 years)
Health Status: unhealthy
Age Group: 58 years (range: 31–77 years)
Sex: M+F
Sources:
https://pubmed.ncbi.nlm.nih.gov/28053022
Nausea grade 1-2, 33%
600 mg 2 times / day steady, oral
MTD
Dose: 600 mg, 2 times / day
Route: oral
Route: steady
Dose: 600 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/28053022
unhealthy, 58 years (range: 31–77 years)
Health Status: unhealthy
Age Group: 58 years (range: 31–77 years)
Sex: M+F
Sources:
https://pubmed.ncbi.nlm.nih.gov/28053022
Aspartate aminotransferase increased grade 2, 11%
600 mg 2 times / day steady, oral
MTD
Dose: 600 mg, 2 times / day
Route: oral
Route: steady
Dose: 600 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/28053022
unhealthy, 58 years (range: 31–77 years)
Health Status: unhealthy
Age Group: 58 years (range: 31–77 years)
Sex: M+F
Sources:
https://pubmed.ncbi.nlm.nih.gov/28053022
Acne grade 3, 4%
600 mg 2 times / day steady, oral
MTD
Dose: 600 mg, 2 times / day
Route: oral
Route: steady
Dose: 600 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/28053022
unhealthy, 58 years (range: 31–77 years)
Health Status: unhealthy
Age Group: 58 years (range: 31–77 years)
Sex: M+F
Sources:
https://pubmed.ncbi.nlm.nih.gov/28053022
Alanine aminotransferase increased grade 3, 4%
600 mg 2 times / day steady, oral
MTD
Dose: 600 mg, 2 times / day
Route: oral
Route: steady
Dose: 600 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/28053022
unhealthy, 58 years (range: 31–77 years)
Health Status: unhealthy
Age Group: 58 years (range: 31–77 years)
Sex: M+F
Sources:
https://pubmed.ncbi.nlm.nih.gov/28053022
Dermatitis acneiform grade 3, 4%
600 mg 2 times / day steady, oral
MTD
Dose: 600 mg, 2 times / day
Route: oral
Route: steady
Dose: 600 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/28053022
unhealthy, 58 years (range: 31–77 years)
Health Status: unhealthy
Age Group: 58 years (range: 31–77 years)
Sex: M+F
Sources:
https://pubmed.ncbi.nlm.nih.gov/28053022
Skin exfoliation grade 3, 4%
600 mg 2 times / day steady, oral
MTD
Dose: 600 mg, 2 times / day
Route: oral
Route: steady
Dose: 600 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/28053022
unhealthy, 58 years (range: 31–77 years)
Health Status: unhealthy
Age Group: 58 years (range: 31–77 years)
Sex: M+F
Sources:
https://pubmed.ncbi.nlm.nih.gov/28053022
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG
inhibitor
2438
inhibitor
2217

OverviewOther

Other InhibitorOther SubstrateOther Inducer
CYP3A
227

CYP2C8
1057

OCT2
779

MATE1
415

MATE2
267

P-gp
1741
CYP2C8
810

CYP3A
220

P-gp
2052

BCRP
697
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
P-gp
1932
 yes [IC50 20 uM]
yes (co-administration study)
Comment: Digoxin Cmax increased by 2.4-fold
Page: 81, 83
MATE2
267
 yes [Ki 0.135 uM]
yes (co-administration study)
Comment: Metformin Cmax increased by 1.1-fold
Page: 81, 83
CYP2C8
1117
 yes [Ki 0.17 uM]
yes (co-administration study)
Comment: Repaglinide Cmax increased by 1.7-fold
Page: 80, 83
MATE1
416
 yes [Ki 0.34 uM]
yes (co-administration study)
Comment: Metformin Cmax increased by 1.1-fold
Page: 81, 83
CYP3A
317
 yes [Ki 0.805 uM]
yes (co-administration study)
Comment: Midazolam Cmax increased by 3-fold
Page: 80, 83
OCT2
782
 yes [Ki 14.7 uM]
CYP2C9
2497
 yes [Ki 4.57 uM]
no (co-administration study)
Comment: No effect on tolbutamide Cmax or AUC
Page: 80, 83
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
BCRP
697
 yes
P-gp
2052
 yes
CYP3A
220
 yes
weak (co-administration study)
Comment: Itraconazole increased tucatinib Cmax by 1.3-fold; Rifampin decreased tucatinib Cmax by 37%
Page: 80, 83
CYP2C8
810
 yes
yes (co-administration study)
Comment: Gemfibrozil increased tucatinib Cmax by 1.6-fold; Rifampin decreased tucatinib Cmax by 37%
Page: 80, 83
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
hERG
2263
Sourcing

Sourcing

Vendor/AggregatorIDURL
001 Chemical
DY581239
https://www.001chemical.com/chem/937263-43-9
AA Blocks
AA00GTX3
https://www.aablocks.com/goods/Goods/detail?id=AA00GTX3
Aaron Chemicals
AR00GUOV
http://www.aaronchem.com/937263-43-9
abcr GmbH
AB479024
http://www.abcr.com/shop/en/AB479024
AbMole Bioscience
M10038
http://www.abmole.com/products/tucatinib.html
Achemtek
0102-014230
http://www.achemtek.com/937263-43-9
Adooq BioScience
A16413
https://www.adooq.com/arry-380-23502.html
Ambinter
Amb24123281
http://www.ambinter.com/reference/24123281
Angel Pharmatech
AG-19862
http://www.angelpharmatech.com/937263-43-9.html
Ark Pharm
AK548135
http://www.arkpharminc.com/products/937263-43-9.html
Ark Pharma Scientific Limited
A-0731
http://www.arkpharmtech.com/product/32682.html
BioChemPartner
BCP15983
http://www.biochempartner.com/937263-43-9-BCP15983
Boerchem
BC600725
http://www.boerchem.com/?product_43560.html
Chem Scene
CS-3906
http://www.chemscene.com/937263-43-9.html
Chemspace
CSSB00020668746
https://chem-space.com/CSSB00020668746
DC Chemicals
DC8771
http://www.dcchemicals.com/product_show-Irbinitinib_ARRY_380_.html
Debye Scientific
DB-130430
http://www.debyesci.com/cas_937263-43-9.html
eNovation Chemicals
D501838
https://www.enovationchem.com/ProductDetails.asp?ProductID=D501838
eNovation Chemicals
D549339
https://www.enovationchem.com/ProductDetails.asp?ProductID=D549339
eNovation Chemicals
Y0974435
https://www.enovationchem.com/ProductDetails.asp?ProductID=Y0974435
Excenen
EX-A1031
http://www.excenen.com/searchresultlist.php?id=937263-43-9
Lab Network
LN01288250
https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01288250
MedChem Express
HY-16069
https://www.medchemexpress.com/Irbinitinib.html
Molcore
MC581239
https://www.molcore.com/product/937263-43-9
Smolecule
S547973
http://www.smolecule.com/products/s547973
Sun-shine Chemical
Irbinitinib
http://www.sun-shinechem.com/Details/Irbinitinib/2223/937263-43-9.html
Synblock Inc
SB17126
http://www.synblock.com/product/937263-43-9.html
THE BioTek
bt-287490
https://www.thebiotek.com/product/inhibitors/bt-287490
Yuhao Chemical
RT10803
http://www.chemyuhao.com/937263-43-9.html
PubMed

PubMed

TitleDatePubMed
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).
2017-07-15
Emerging Therapeutic Options for HER2-Positive Breast Cancer.
2016
Patents

Patents

WO2013056183
2
WO2013142875
2

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
In Vitro Use Guide
Unknown
Substance Class Chemical
Created
by admin
on Wed Apr 02 10:11:08 GMT 2025
Edited
by admin
on Wed Apr 02 10:11:08 GMT 2025
Record UNII
CDZ29KT2FT
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
TUCATINIB HEMIETHANOLATE
Common Name English
Tucatinib hemiethanolate [WHO-DD]
Preferred Name English
ETHANOL, COMPD. WITH N6-(4,5-DIHYDRO-4,4-DIMETHYL-2-OXAZOLYL)-N4-(3-METHYL-4-((1,2,4)TRIAZOLO(1,5-A)PYRIDIN-7-YLOXY)PHENYL)-4,6-QUINAZOLINEDIAMINE (1:2)
Systematic Name English
Code System Code Type Description
FDA UNII
CDZ29KT2FT
Created by admin on Wed Apr 02 10:11:08 GMT 2025 , Edited by admin on Wed Apr 02 10:11:08 GMT 2025
PRIMARY
CAS
1429755-56-5
Created by admin on Wed Apr 02 10:11:08 GMT 2025 , Edited by admin on Wed Apr 02 10:11:08 GMT 2025
PRIMARY
SMS_ID
300000024838
Created by admin on Wed Apr 02 10:11:08 GMT 2025 , Edited by admin on Wed Apr 02 10:11:08 GMT 2025
PRIMARY
PUBCHEM
162623678
Created by admin on Wed Apr 02 10:11:08 GMT 2025 , Edited by admin on Wed Apr 02 10:11:08 GMT 2025
PRIMARY
Related Record Type Details
Structure of TUCATINIB
ANHYDROUS->SOLVATE
Structure of TUCATINIB
PARENT -> SALT/SOLVATE
Related Record Type Details
Structure of TUCATINIB
ACTIVE MOIETY
NIH
NCATS
PRIVACY NOTICE
ACCESSIBILITY
DISCLAIMER
HHS VULNERABILITY DISCLOSURE
For language access assistance, contact the NCATS Public Information Officer
National Center for Advancing Translational Sciences (NCATS),
6701 Democracy Boulevard, Bethesda MD 20892-4874 • 301-594-8966