tucatinib 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
tyrosine kinase inhibitors 5389 937263-43-9

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • tucatinib
  • tukysa
  • ARRY-380
  • ONT-380
Tucatinib is a tyrosine kinase inhibitor of HER2. In vitro, tucatinib inhibits phosphorylation of HER2 and HER3, resulting in inhibition of downstream MAPK and AKT signaling and cell proliferation, and showed anti-tumor activity in HER2 expressing tumor cells. In vivo, tucatinib inhibited the growth of HER2 expressing tumors. The combination of tucatinib and trastuzumab showed increased anti-tumor activity in vitro and in vivo compared to either drug alone
  • Molecular weight: 480.53
  • Formula: C26H24N8O2
  • CLOGP: 5.19
  • LIPINSKI: 1
  • HAC: 10
  • HDO: 2
  • TPSA: 110.85
  • ALOGS: -5.08
  • ROTB: 5

  • Status: ONP

  • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
0.60 g O

ADMET properties:

None

Approvals:

DateAgencyCompanyOrphan
Feb. 11, 2021 EMA SEAGEN B.V
April 17, 2020 FDA SEATTLE GENETICS

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Diarrhoea 605.05 31.13 488 4767 587988 50011881
Product dose omission issue 171.67 31.13 146 5109 183692 50416177
Palmar-plantar erythrodysaesthesia syndrome 157.53 31.13 64 5191 20034 50579835
Nausea 153.92 31.13 266 4989 705132 49894737
Unevaluable event 153.51 31.13 81 5174 45985 50553884
Hospice care 150.12 31.13 45 5210 5727 50594142
Fatigue 131.38 31.13 249 5006 707352 49892517
Disease progression 116.51 31.13 89 5166 95777 50504092
Hospitalisation 102.71 31.13 72 5183 67865 50532004
Metastases to central nervous system 99.01 31.13 39 5216 11243 50588626
Decreased appetite 79.77 31.13 101 5154 200822 50399047
Illness 61.99 31.13 36 5219 24504 50575365
Death 61.52 31.13 116 5139 325263 50274606
Radiotherapy 59.10 31.13 12 5243 298 50599571
Skin discolouration 54.82 31.13 37 5218 32720 50567149
Dry skin 49.95 31.13 39 5216 43152 50556717
Vomiting 44.44 31.13 126 5129 460632 50139237
Constipation 41.08 31.13 71 5184 185637 50414232
Skin exfoliation 38.09 31.13 30 5225 33582 50566287
Memory impairment 38.07 31.13 44 5211 79316 50520553
Brain neoplasm 36.47 31.13 14 5241 3759 50596110
Faeces soft 35.40 31.13 14 5241 4070 50595799
Brain operation 32 31.13 8 5247 515 50599354
Botryomycosis 31.75 31.13 5 5250 26 50599843
Herpangina 31.43 31.13 5 5250 28 50599841

FDA Adverse Event Reporting System (Male)

None

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Diarrhoea 116.17 33.32 105 1252 722599 63774776
Palmar-plantar erythrodysaesthesia syndrome 61.42 33.32 23 1334 28796 64468579
Product dose omission issue 58.04 33.32 41 1316 194706 64302669
Unevaluable event 52.08 33.32 24 1333 50465 64446910
Hospice care 44.36 33.32 13 1344 7612 64489763
Disease progression 42.52 33.32 30 1327 141650 64355725
Herpangina 39.27 33.32 5 1352 29 64497346
Hepatic cytolysis 36.54 33.32 13 1344 14036 64483339
Botryomycosis 36.11 33.32 5 1352 59 64497316

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC L01EH03 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
PROTEIN KINASE INHIBITORS
Human epidermal growth factor receptor 2 (HER2) tyrosine kinase inhibitors
MeSH PA D000970 Antineoplastic Agents
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D047428 Protein Kinase Inhibitors
FDA MoA N0000020001 Tyrosine Kinase Inhibitors
FDA EPC N0000175605 Kinase Inhibitor
FDA MoA N0000185503 P-Glycoprotein Inhibitors
FDA MoA N0000187062 Cytochrome P450 2C8 Inhibitors
FDA MoA N0000190114 Cytochrome P450 3A Inhibitors

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Metastatic human epidermal growth factor 2 positive carcinoma of breast indication 459391000124109




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 8.87 Basic
pKa2 5.0 Basic
pKa3 3.09 Basic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
150MG TUKYSA SEAGEN N213411 April 17, 2020 RX TABLET ORAL 7452895 Nov. 16, 2024 TREATMENT OF BREAST CANCER INCLUDING HER2 (ERBB2)-POSITIVE OR -OVEREXPRESSING BREAST CANCER
50MG TUKYSA SEAGEN N213411 April 17, 2020 RX TABLET ORAL 7452895 Nov. 16, 2024 TREATMENT OF BREAST CANCER INCLUDING HER2 (ERBB2)-POSITIVE OR -OVEREXPRESSING BREAST CANCER
150MG TUKYSA SEAGEN N213411 April 17, 2020 RX TABLET ORAL 9693989 May 9, 2027 TREATMENT OF BREAST CANCER INCLUDING HER2 (ERBB2)-POSITIVE OR -OVEREXPRESSING BREAST CANCER
50MG TUKYSA SEAGEN N213411 April 17, 2020 RX TABLET ORAL 9693989 May 9, 2027 TREATMENT OF BREAST CANCER INCLUDING HER2 (ERBB2)-POSITIVE OR -OVEREXPRESSING BREAST CANCER
150MG TUKYSA SEAGEN N213411 April 17, 2020 RX TABLET ORAL 9457093 Oct. 12, 2032 TREATMENT OF BREAST CANCER INCLUDING HER2 (ERBB2)-POSITIVE OR -OVEREXPRESSING BREAST CANCER
50MG TUKYSA SEAGEN N213411 April 17, 2020 RX TABLET ORAL 9457093 Oct. 12, 2032 TREATMENT OF BREAST CANCER INCLUDING HER2 (ERBB2)-POSITIVE OR -OVEREXPRESSING BREAST CANCER

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
150MG TUKYSA SEAGEN N213411 April 17, 2020 RX TABLET ORAL April 17, 2025 NEW CHEMICAL ENTITY
50MG TUKYSA SEAGEN N213411 April 17, 2020 RX TABLET ORAL April 17, 2025 NEW CHEMICAL ENTITY
150MG TUKYSA SEAGEN N213411 April 17, 2020 RX TABLET ORAL April 17, 2027 INDICATED FOR USE IN COMBINATION WITH TRASTUZUMAB AND CAPECITABINE FOR TREATMENT OF ADULT PATIENTS WITH METASTATIC HER2-POSITIVE BREAST CANCER AND BRAIN METASTASES, WHO HAVE RECEIVED ONE OR MORE PRIOR ANTI-HER2-BASED REGIMENS IN THE METASTIC SETTING
50MG TUKYSA SEAGEN N213411 April 17, 2020 RX TABLET ORAL April 17, 2027 INDICATED FOR USE IN COMBINATION WITH TRASTUZUMAB AND CAPECITABINE FOR TREATMENT OF ADULT PATIENTS WITH METASTATIC HER2-POSITIVE BREAST CANCER AND BRAIN METASTASES, WHO HAVE RECEIVED ONE OR MORE PRIOR ANTI-HER2-BASED REGIMENS IN THE METASTIC SETTING

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
ERBB2/ERBB3 Kinase INHIBITOR IC50 8.16 SCIENTIFIC LITERATURE DRUG LABEL
Epidermal growth factor receptor Kinase INHIBITOR IC50 6.35 IUPHAR
Ferrochelatase, mitochondrial Enzyme Kd 5.41 CHEMBL
Ribosyldihydronicotinamide dehydrogenase [quinone] Enzyme Kd 5.61 CHEMBL
Myosin-14 Enzyme Kd 6.73 CHEMBL
Receptor tyrosine-protein kinase erbB-4 Kinase INHIBITOR IC50 6.50 SCIENTIFIC LITERATURE
Receptor-interacting serine/threonine-protein kinase 3 Kinase Kd 5.97 CHEMBL

External reference:

IDSource
234248D0HH UNII
C4519167 UMLSCUI
CHEMBL3989868 ChEMBL_ID
51039094 PUBCHEM_CID
DB11652 DRUGBANK_ID
D11141 KEGG_DRUG
9922 IUPHAR_LIGAND_ID
2361285 RXNORM
333110 MMSL
38332 MMSL
d09542 MMSL
871698009 SNOMEDCT_US
871715004 SNOMEDCT_US
4039346 VANDF
018332 NDDF
C000705452 MESH_SUPPLEMENTAL_RECORD_UI
9997 INN_ID

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
TUKYSA HUMAN PRESCRIPTION DRUG LABEL 1 51144-001 TABLET 50 mg ORAL NDA 29 sections
TUKYSA HUMAN PRESCRIPTION DRUG LABEL 1 51144-001 TABLET 50 mg ORAL NDA 29 sections
TUKYSA HUMAN PRESCRIPTION DRUG LABEL 1 51144-002 TABLET 150 mg ORAL NDA 29 sections
TUKYSA HUMAN PRESCRIPTION DRUG LABEL 1 51144-002 TABLET 150 mg ORAL NDA 29 sections