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:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 2 Bocci G, Oprea TI, Benet LZ

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 701.98 29.10 587 6248 714779 62767408
Palmar-plantar erythrodysaesthesia syndrome 322.04 29.10 113 6722 22902 63459285
Metastases to central nervous system 181.84 29.10 64 6771 13041 63469146
Disease progression 163.25 29.10 122 6713 122636 63359551
Unevaluable event 150.49 29.10 84 6751 51302 63430885
Nausea 148.65 29.10 299 6536 854172 62628015
Hospice care 146.41 29.10 48 6787 7884 63474303
Product dose omission issue 143.79 29.10 150 6685 234163 63248024
Fatigue 137.14 29.10 296 6539 887732 62594455
Hospitalisation 96.43 29.10 77 6758 85004 63397183
Hyperbilirubinaemia 80.49 29.10 34 6801 11280 63470907
Death 74.11 29.10 139 6696 374242 63107945
Hepatic cytolysis 73.47 29.10 35 6800 15372 63466815
Decreased appetite 73.36 29.10 111 6724 250941 63231246
Malignant neoplasm progression 65.86 29.10 61 6774 82060 63400127
Radiotherapy 61.32 29.10 13 6822 386 63481801
Vomiting 55.29 29.10 158 6677 559459 62922728
Skin discolouration 48.80 29.10 37 6798 37791 63444396
Dry skin 43.17 29.10 41 6794 56846 63425341
Gamma-glutamyltransferase abnormal 40.61 29.10 9 6826 330 63481857
Metastases to lung 40.44 29.10 22 6813 12728 63469459
Blood lactate dehydrogenase abnormal 39.71 29.10 9 6826 366 63481821
Illness 38.45 29.10 36 6799 49023 63433164
Carcinoembryonic antigen increased 37.95 29.10 12 6823 1753 63480434
Dehydration 34.93 29.10 65 6770 173289 63308898
Neuropathy peripheral 34.14 29.10 51 6784 113616 63368571
Brain neoplasm 34 29.10 14 6821 4352 63477835
Memory impairment 33.07 29.10 48 6787 104210 63377977
Constipation 33.06 29.10 74 6761 224869 63257318
Skin exfoliation 32.57 29.10 31 6804 43071 63439116
Botryomycosis 31.57 29.10 5 6830 26 63482161
Herpangina 31.25 29.10 5 6830 28 63482159
Blood bilirubin increased 30.54 29.10 28 6807 37112 63445075
Brain operation 30.50 29.10 8 6827 601 63481586
Faeces soft 30.43 29.10 14 6821 5678 63476509
Condition aggravated 29.89 29.10 4 6831 402213 63079974
Cell death 29.67 29.10 11 6824 2590 63479597
Epilepsy 29.55 29.10 24 6811 27041 63455146
Liver function test increased 29.47 29.10 26 6809 32785 63449402
Gram stain positive 29.38 29.10 5 6830 43 63482144

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
Palmar-plantar erythrodysaesthesia syndrome 169.47 32.57 56 2420 33078 79708834
Diarrhoea 159.20 32.57 163 2313 880326 78861586
Hepatic cytolysis 107.84 32.57 38 2438 27113 79714799
Metastases to central nervous system 97.12 32.57 31 2445 16344 79725568
Hyperbilirubinaemia 84.86 32.57 31 2445 24487 79717425
Disease progression 66.68 32.57 51 2425 184311 79557601
Blood lactate dehydrogenase abnormal 53.64 32.57 9 2467 267 79741645
Carcinoembryonic antigen increased 50.07 32.57 12 2464 2197 79739715
Gamma-glutamyltransferase abnormal 46.57 32.57 9 2467 597 79741315
Metastases to lung 41.52 32.57 17 2459 18146 79723766
Unevaluable event 41.00 32.57 24 2452 55561 79686351
Hospice care 39.23 32.57 14 2462 10310 79731602
Product dose omission issue 38.98 32.57 43 2433 247494 79494418
Herpangina 37.32 32.57 5 2471 29 79741883
Cell death 36.72 32.57 11 2465 4688 79737224
Malignant neoplasm progression 35.17 32.57 31 2445 135959 79605953
Botryomycosis 34.16 32.57 5 2471 59 79741853
Epilepsy 33.76 32.57 19 2457 40841 79701071

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 | Suggest Off label Use Form| |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
150MG TUKYSA SEAGEN N213411 April 17, 2020 RX TABLET ORAL 11504370 March 25, 2033 TREATMENT OF BREAST CANCER INCLUDING HER2 (ERBB2)-POSITIVE OR -OVEREXPRESSING BREAST CANCER
50MG TUKYSA SEAGEN N213411 April 17, 2020 RX TABLET ORAL 11504370 March 25, 2033 TREATMENT OF BREAST CANCER INCLUDING HER2 (ERBB2)-POSITIVE OR -OVEREXPRESSING BREAST CANCER
150MG TUKYSA SEAGEN N213411 April 17, 2020 RX TABLET ORAL 11207324 April 27, 2038 COMBINATION TREATMENT OF COLORECTAL CANCER INCLUDING RAS WILD-TYPE HER2 (ERBB2)-POSITIVE OR -OVEREXPRESSING UNRESECTABLE OR METASTATIC COLORECTAL CANCER
50MG TUKYSA SEAGEN N213411 April 17, 2020 RX TABLET ORAL 11207324 April 27, 2038 COMBINATION TREATMENT OF COLORECTAL CANCER INCLUDING RAS WILD-TYPE HER2 (ERBB2)-POSITIVE OR -OVEREXPRESSING UNRESECTABLE OR METASTATIC COLORECTAL 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 Jan. 19, 2026 TUCATINIB IN COMBINATION WITH TRASTUZUMAB FOR THE TREATMENT OF ADULT PATIENTS WITH RAS WILD-TYPE, HER2-POSITIVE, UNRESECTABLE OR METASTATIC COLORECTAL CANCER THAT HAS PROGRESSED FOLLOWING TREATMENT WITH FLUOROPYRIMIDINE-, OXALIPLATIN-, AND IRINOTECAN-BASED CHEMOTHERAPY
50MG TUKYSA SEAGEN N213411 April 17, 2020 RX TABLET ORAL Jan. 19, 2026 TUCATINIB IN COMBINATION WITH TRASTUZUMAB FOR THE TREATMENT OF ADULT PATIENTS WITH RAS WILD-TYPE, HER2-POSITIVE, UNRESECTABLE OR METASTATIC COLORECTAL CANCER THAT HAS PROGRESSED FOLLOWING TREATMENT WITH FLUOROPYRIMIDINE-, OXALIPLATIN-, AND IRINOTECAN-BASED CHEMOTHERAPY
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
150MG TUKYSA SEAGEN N213411 April 17, 2020 RX TABLET ORAL Jan. 19, 2030 TREATMENT OF ADULT PATIENTS WITH RAS WILD-TYPE, HER2-POSITIVE UNRESECTABLE OR METASTATIC COLORECTAL CANCER THAT HAS PROGRESSED FOLLOWING TREATMENT WITH FLUOROPYRIMIDINE-, OXALIPLATIN-, AND IRINOTECAN-BASED CHEMOTHERAPY
50MG TUKYSA SEAGEN N213411 April 17, 2020 RX TABLET ORAL Jan. 19, 2030 TREATMENT OF ADULT PATIENTS WITH RAS WILD-TYPE, HER2-POSITIVE UNRESECTABLE OR METASTATIC COLORECTAL CANCER THAT HAS PROGRESSED FOLLOWING TREATMENT WITH FLUOROPYRIMIDINE-, OXALIPLATIN-, AND IRINOTECAN-BASED CHEMOTHERAPY

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
9997 INN_ID
D11141 KEGG_DRUG
9922 IUPHAR_LIGAND_ID
018332 NDDF
871698009 SNOMEDCT_US
871715004 SNOMEDCT_US
4039346 VANDF
2361285 RXNORM
333110 MMSL
38332 MMSL
d09542 MMSL
C000705452 MESH_SUPPLEMENTAL_RECORD_UI

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
TUKYSA HUMAN PRESCRIPTION DRUG LABEL 1 51144-001 TABLET 50 mg ORAL NDA 30 sections
TUKYSA HUMAN PRESCRIPTION DRUG LABEL 1 51144-001 TABLET 50 mg ORAL NDA 30 sections
TUKYSA HUMAN PRESCRIPTION DRUG LABEL 1 51144-001 TABLET 50 mg ORAL NDA 30 sections
TUKYSA HUMAN PRESCRIPTION DRUG LABEL 1 51144-002 TABLET 150 mg ORAL NDA 30 sections
TUKYSA HUMAN PRESCRIPTION DRUG LABEL 1 51144-002 TABLET 150 mg ORAL NDA 30 sections
TUKYSA HUMAN PRESCRIPTION DRUG LABEL 1 51144-002 TABLET 150 mg ORAL NDA 30 sections