ripretinib 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |

Stem definitionDrug idCAS RN
tyrosine kinase inhibitors 5394 1442472-39-0

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • ripretinib
  • qinlock
  • DCC-2618
Ripretinib is a tyrosine kinase inhibitor that inhibits KIT proto-oncogene receptor tyrosine kinase (KIT) and platelet derived growth factor receptor A (PDGFRA) kinase, including wild type, primary, and secondary mutations. Ripretinib also inhibits other kinases in vitro, such as PDGFRB, TIE2, VEGFR2, and BRAF
  • Molecular weight: 510.37
  • Formula: C24H21BrFN5O2
  • CLOGP: 5.06
  • LIPINSKI: 1
  • HAC: 7
  • HDO: 3
  • TPSA: 86.36
  • ALOGS: -4.94
  • ROTB: 5
  • Status: ONP
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
0.15 g O

ADMET properties:

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

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 4.409 High 1
caco2-efflux Caco-2 efflux ratio (BA/AB) 7.244 High 1
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 22.594 10^-6 cm/s High 1
dh-clint Dog hepatocyte intrinsic clearance 9.141 uL/min/10^6 cells High 1
dppb Dog plasma protein binding (% unbound) 0.250 % High 1
fcs-ppb Fetal calf serum protein binding (% unbound) 1.150 % High 1
herg hERG pIC50 5.154 pIC50 High 1
hh-clint Human hepatocyte intrinsic clearance 6.152 uL/min/10^6 cells High 1
hlm-clint Human liver microsomal intrinsic clearance 23.121 uL/min/mg protein High 1
hppb Human plasma protein binding (% unbound) 0.200 % High 1
kinase-safety-class ABL1,ABL2,ACVR2A,ACVR2B,ACVRL1,AKT3,ALK,AURKA,AURKB,AURKC,AXL,BLK,BMX,BRAF,BTK,CAMK2B,CAMK2D,CDK1,CDK16,CDK19,CDK2,CDK5,CDK7,CDK9,CHEK1,CSF1R,CSK,DDR1,DYRK1B,EGFR,EIF2AK3,EPHA2,EPHB1,EPHB3,EPHB4,ERBB2,ERBB4,FGFR1,FLT1,FLT3,FLT4,FYN,GAK,GRK2,GSK3B,IKBKB,INSR,IRAK1,ITK,JAK1,JAK2,KDR,KIT,LCK,LYN,MAP2K1,MAP2K4,MAP2K6,MAP3K1,MAP3K10,MAP3K11,MAP3K2,MAP3K21,MAP3K3,MAP3K7,MAP4K1,MAP4K2,MAP4K3,MAP4K5,MAPK1,MAPK10,MAPK11,MAPK12,MAPK14,MAPK7,MAPK8,MAPK9,MAPKAPK2,MARK4,MELK,MET,MINK1,MST1R,MTOR,NTRK1,NTRK2,NTRK3,PDGFRB,PDK1,PDK2,PDK4,PIK3CA,PIK3CB,PIK3CD,PIK3CG,PRKCD,PRKDC,PTK6,RET,RIPK3,RPS6KA1,SIK2,SIK3,SRC,STK10,STK33,SYK,TEK,TNIK,TTK,TYRO3,ULK1,ULK2,YES1 114
kinase-selectivity-class ABL2,ACVR2A,ACVR2B,ALK,AURKA,AURKB,AURKC,AXL,BLK,BMX,BRAF,BTK,CAMK2B,CAMK2D,CDK1,CDK6,CDK7,CDK9,CLK4,CSF1R,CSK,DDR1,EGFR,EIF2AK3,EPHA2,EPHB3,EPHB4,ERBB2,FGFR1,FGFR4,FLT1,FLT3,FLT4,FYN,GAK,GSK3A,GSK3B,INSR,IRAK1,JAK1,JAK2,KDR,KIT,LCK,LRRK2,LYN,MAP2K1,MAP2K4,MAP2K6,MAP3K10,MAP3K11,MAP3K2,MAP3K21,MAP3K7,MAP4K1,MAP4K3,MAP4K5,MAPK1,MAPK11,MAPK12,MAPK14,MAPK7,MAPKAPK2,MARK4,MELK,MET,MINK1,MST1R,MTOR,NTRK1,NTRK3,PAK1,PAK4,PDGFRB,PDK1,PDK4,PIK3CD,PRKCD,PRKDC,RET,SIK2,SIK3,SRC,STK10,STK33,SYK,TEK,TNIK,TTK,TYRO3,ULK1,YES1 92
mdck-mdr1-bcrp-efflux MDCK-MDR1-BCRP efflux ratio 34.041 High 1
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 31.189 High 1
mh-clint Mouse hepatocyte intrinsic clearance 45.290 High 1
mppb Mouse plasma protein binding (% unbound) 0.220 High 1
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 36.475 High 1
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pppb Pig plasma protein binding (% unbound) 1.090 % High 1
rat-kpuu-brain Rat brain Kpuu 0.067 % High 1
rh-clint Rat hepatocyte intrinsic clearance 16.672 uL/min/10^6 cells High 1
rh-fuinc Rat hepatocyte fraction unbound in incubation 2.260 % High 1
rppb Rat plasma protein binding (% unbound) 0.220 % High 1
solubility-dd Solubility at pH 7.4 in DMSO 0.565 uM High 1

Approvals:

DateAgencyCompanyOrphan
May 15, 2020 FDA DECIPHERA PHARMS
Nov. 18, 2021 EMA DECIPHERA PHARMACEUTICALS (NETHERLANDS) B.V.

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
Extra dose administered 226.35 36.96 50 1960 9068 90617369
Disease progression 214.91 36.96 92 1918 156523 90469914
Underdose 196.81 36.96 65 1945 53952 90572485
Palmar-plantar erythrodysaesthesia syndrome 107.00 36.96 35 1975 27988 90598449
Alopecia 91.06 36.96 80 1930 494991 90131446
Neoplasm progression 84.07 36.96 33 1977 44453 90581984
Hospitalisation 63.70 36.96 38 1972 128062 90498375
Adverse event 58.81 36.96 35 1975 117383 90509054
Incorrect dosage administered 51.01 36.96 12 1998 2848 90623589
Hyperkeratosis 49.37 36.96 14 1996 6914 90619523
Fatigue 48.54 36.96 89 1921 1153934 89472503
Inappropriate schedule of product administration 46.28 36.96 33 1977 149900 90476537
Death 43.65 36.96 52 1958 456499 90169938
Metastases to liver 42.81 36.96 18 1992 28789 90597648
Malignant neoplasm progression 38.78 36.96 26 1984 106844 90519593

FDA Adverse Event Reporting System (Male)

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
Extra dose administered 392.71 44.15 85 2282 5584 42613384
Disease progression 221.51 44.15 122 2245 143534 42475434
Alopecia 188.44 44.15 68 2299 29208 42589760
Underdose 171.21 44.15 55 2312 16611 42602357
Fatigue 111.77 44.15 128 2239 435513 42183455
Adverse event 88.12 44.15 37 2330 23603 42595365
Incorrect dosage administered 81.76 44.15 19 2348 1699 42617269
Malignant neoplasm progression 70.98 44.15 54 2313 108346 42510622
Neoplasm progression 65.46 44.15 32 2335 28968 42590000
Death 64.18 44.15 102 2265 471083 42147885
Inappropriate schedule of product administration 61.04 44.15 47 2320 95855 42523113
Hospitalisation 57.55 44.15 41 2326 74289 42544679
Hair texture abnormal 52.64 44.15 10 2357 334 42618634
Palmar-plantar erythrodysaesthesia syndrome 50.32 44.15 24 2343 20558 42598410

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
Extra dose administered 395.22 36.28 86 2873 12073 110574267
Underdose 226.96 36.28 79 2880 63475 110522865
Disease progression 220.53 36.28 114 2845 243920 110342420
Alopecia 141.49 36.28 99 2860 364654 110221686
Incorrect dosage administered 128.69 36.28 28 2931 3890 110582450
Fatigue 120.51 36.28 154 2805 1215804 109370536
Palmar-plantar erythrodysaesthesia syndrome 112.45 36.28 42 2917 40983 110545357
Inappropriate schedule of product administration 112.31 36.28 69 2890 203568 110382772
Hospitalisation 104.20 36.28 58 2901 142435 110443905
Malignant neoplasm progression 103.55 36.28 62 2897 174505 110411835
Death 97.91 36.28 106 2853 698763 109887577
Neoplasm progression 87.65 36.28 40 2919 64555 110521785
Adverse event 60.17 36.28 37 2922 108772 110477568
Surgery 51.08 36.28 24 2935 41259 110545081
Hyperkeratosis 46.87 36.28 15 2944 9224 110577116
Metastases to liver 45.10 36.28 21 2938 35365 110550975
Muscle spasms 40.08 36.28 43 2916 278114 110308226

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC L01EX19 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
PROTEIN KINASE INHIBITORS
Other protein kinase inhibitors
FDA MoA N0000020028 Platelet-derived Growth Factor alpha Receptor Inhibitors
FDA MoA N0000020034 Stem Cell Factor (KIT) Receptor Inhibitors
FDA EPC N0000175605 Kinase Inhibitor
FDA MoA N0000185503 P-Glycoprotein Inhibitors
FDA MoA N0000187062 Cytochrome P450 2C8 Inhibitors
FDA MoA N0000190113 Breast Cancer Resistance Protein Inhibitors
CHEBI has role CHEBI:35610 antineoplastic agent

Related Drugs by ATC class:

L01EX Other protein kinase inhibitors 21 drugs
avapritinibcabozantinibcapivasertibentrectinibgilteritiniblarotrectiniblenvatinibmidostaurinnintedanibpazopanibpexidartinibpralsetinib show all 21 →

Drug Use | Suggest Off label Use Form| |View source of the data|

DiseaseRelationSNOMED_IDDOID
Gastrointestinal stromal tumor indication 420120006 DOID:9253




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

None

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
50MG QINLOCK DECIPHERA PHARMS N213973 May 15, 2020 RX TABLET ORAL RE48731 June 7, 2032 TREATMENT OF GASTROINTESTINAL STROMAL TUMOR
50MG QINLOCK DECIPHERA PHARMS N213973 May 15, 2020 RX TABLET ORAL 10966966 Aug. 12, 2040 TREATMENT OF ADVANCED GASTROINTESTINAL STROMAL TUMOR IN PATIENTS HAVING PROGRESSED FROM A FIRST LINE ADMINISTRATION OF IMATINIB, A SECOND LINE ADMINISTRATION OF SUNITINIB, AND A THIRD LINE ADMINISTRATION OF REGORAFENIB
50MG QINLOCK DECIPHERA PHARMS N213973 May 15, 2020 RX TABLET ORAL 11266635 Aug. 12, 2040 TREATMENT OF GASTROINTESTINAL STROMAL TUMORS IN PATIENTS SUFFERING FROM PALMER-PLANTER ERYTHRODYSESTHESIA SYNDROME
50MG QINLOCK DECIPHERA PHARMS N213973 May 15, 2020 RX TABLET ORAL 11344536 Aug. 12, 2040 TREATMENT OF GASTROINTESTINAL STROMAL TUMORS IN PATIENTS SUFFERING FROM HYPERTENSION
50MG QINLOCK DECIPHERA PHARMS N213973 May 15, 2020 RX TABLET ORAL 11426390 Aug. 12, 2040 TREATMENT OF GASTROINTESTINAL STROMAL TUMORS IN PATIENTS BEING TREATED CONCURRENTLY WITH A CYP3A4 INHIBITOR
50MG QINLOCK DECIPHERA PHARMS N213973 May 15, 2020 RX TABLET ORAL 11433056 Aug. 12, 2040 METHOD OF TREATING GASTROINTESTINAL STROMAL TUMORS IN PATIENTS SUFFERING FROM GRADE 2 OR GRADE 3 MYALGIA WHILE BEING ADMINISTERED RIPRETINIB DAILY
50MG QINLOCK DECIPHERA PHARMS N213973 May 15, 2020 RX TABLET ORAL 11529336 Aug. 12, 2040 TREATMENT OF GASTROINTESTINAL STROMAL TUMORS IN PATIENTS SUFFERING FROM A GRADE 3 ADVERSE REACTION WHILE BEING ADMINISTERED RIPRETINIB DAILY
50MG QINLOCK DECIPHERA PHARMS N213973 May 15, 2020 RX TABLET ORAL 11534432 Aug. 12, 2040 TREATMENT OF ADVANCED GASTROINTESTINAL STROMAL TUMOR IN PATIENTS PREVIOUSLY ADMINISTERED AT LEAST THREE TYROSINE KINASE INHIBITORS, WHERE ONE OF THE KINASE INHIBITORS IS IMATINIB
50MG QINLOCK DECIPHERA PHARMS N213973 May 15, 2020 RX TABLET ORAL 11576904 Aug. 12, 2040 TREATMENT OF GASTROINTESTINAL STROMAL TUMORS IN PATIENTS SUFFERING FROM GRADE 2 OR GRADE 3 ARTHRALGIA WHILE BEING ADMINISTERED RIPRETINIB DAILY
50MG QINLOCK DECIPHERA PHARMS N213973 May 15, 2020 RX TABLET ORAL 11813251 Aug. 12, 2040 TREATMENT OF GASTROINTESTINAL STROMAL TUMOR WITH A WILD TYPE KIT MUTATION IN PATIENTS PREVIOUSLY ADMINISTERED THREE OR MORE KINASE INHIBITORS, WHERE ONE OF THE KINASE INHIBITORS IS IMATINIB
50MG QINLOCK DECIPHERA PHARMS N213973 May 15, 2020 RX TABLET ORAL 12023325 Aug. 12, 2040 TREATMENT OF ADVANCED GASTROINTESTINAL STROMAL TUMOR IN PATIENTS PREVIOUSLY ADMINISTERED IMATINIB
50MG QINLOCK DECIPHERA PHARMS N213973 May 15, 2020 RX TABLET ORAL 12023326 Aug. 12, 2040 TREATMENT OF GASTROINTESTINAL STROMAL TUMORS IN A PATIENT SUFFERING FROM GRADE 2 ARTHRALGIA WHILE BEING ADMINISTERED RIPRETINIB DAILY
50MG QINLOCK DECIPHERA PHARMS N213973 May 15, 2020 RX TABLET ORAL 12023327 Aug. 12, 2040 TREATMENT OF ADVANCED GASTROINTESTINAL STROMAL TUMOR IN PATIENTS PREVIOUSLY ADMINISTERED 4 LINES OF PRIOR THERAPY, WHERE THE FIRST LINE OF PRIOR THERAPY IS IMATINIB
50MG QINLOCK DECIPHERA PHARMS N213973 May 15, 2020 RX TABLET ORAL 12059410 Aug. 12, 2040 TREATMENT OF ADVANCED GASTROINTESTINAL STROMAL TUMOR IN PATIENTS HAVING PROGRESSED FROM A FIRST LINE ADMINISTRATION OF IMATINIB, A SECOND LINE ADMINISTRATION OF SUNITINIB, AND A THIRD LINE ADMINISTRATION OF REGORAFENIB
50MG QINLOCK DECIPHERA PHARMS N213973 May 15, 2020 RX TABLET ORAL 12059411 Aug. 12, 2040 TREATMENT OF GASTROINTESTINAL STROMAL TUMORS IN PATIENTS SUFFERING FROM PALMAR-PLANTAR ERYTHRODYSESTHESIA SYNDROME
50MG QINLOCK DECIPHERA PHARMS N213973 May 15, 2020 RX TABLET ORAL 12295944 Aug. 12, 2040 TREATMENT OF GASTROINTESTINAL STROMAL TUMORS IN A PATIENT SUFFERING FROM GRADE 3 ARTHRALGIA WHILE BEING ADMINISTERED RIPRETINIB DAILY
50MG QINLOCK DECIPHERA PHARMS N213973 May 15, 2020 RX TABLET ORAL 12318373 Aug. 12, 2040 TREATMENT OF GASTROINTESTINAL STROMAL TUMORS IN A PATIENT SUFFERING FROM GRADE 3 PALMAR-PLANTAR ERYTHRODYSESTHESIA WHILE BEING ADMINISTERED RIPETRINIB DAILY
50MG QINLOCK DECIPHERA PHARMS N213973 May 15, 2020 RX TABLET ORAL 11801237 Dec. 30, 2040 TREATMENT OF GASTROINTESTINAL STROMAL TUMOR
50MG QINLOCK DECIPHERA PHARMS N213973 May 15, 2020 RX TABLET ORAL 11969415 Dec. 30, 2040 TREATMENT OF GASTROINTESTINAL STROMAL TUMOR
50MG QINLOCK DECIPHERA PHARMS N213973 May 15, 2020 RX TABLET ORAL 12023328 Dec. 30, 2040 TREATMENT OF GASTROINTESTINAL STROMAL TUMOR COMPRISING ADMINISTERING ONCE DAILY, ONE OR MORE TABLETS COMPRISING RIPRETINIB
50MG QINLOCK DECIPHERA PHARMS N213973 May 15, 2020 RX TABLET ORAL 12064422 Dec. 30, 2040 TREATMENT OF GASTROINTESTINAL STROMAL TUMOR
50MG QINLOCK DECIPHERA PHARMS N213973 May 15, 2020 RX TABLET ORAL 11969414 Feb. 8, 2041 TREATMENT OF GASTROINTESTINAL STROMAL TUMORS IN PATIENTS BEING TREATED CONCURRENTLY WITH ITRACONAZOLE
50MG QINLOCK DECIPHERA PHARMS N213973 May 15, 2020 RX TABLET ORAL 11779572 Oct. 6, 2042 TREATMENT OF GASTROINTESTINAL STROMAL TUMORS IN PATIENTS HAVING PRE-EXISTING SEVERE HEPATIC IMPAIRMENT AND SUFFERING FROM AN ADVERSE EVENT WHILE BEING ADMINISTERED RIPRETINIB DAILY

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
50MG QINLOCK DECIPHERA PHARMS N213973 May 15, 2020 RX TABLET ORAL May 15, 2027 INDICATED FOR THE TREATMENT OF ADULT PATIENTS WITH ADVANCED GASTROINTESTINAL STROMAL TUMOR (GIST) WHO HAVE RECEIVED PRIOR TREATMENT WITH 3 OR MORE KINASE INHIBITORS, INCLUDING IMATINIB

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
Mast/stem cell growth factor receptor Kit Kinase INHIBITOR IC50 8.52 SCIENTIFIC LITERATURE DRUG LABEL
Platelet-derived growth factor receptor alpha Kinase INHIBITOR IC50 8.44 SCIENTIFIC LITERATURE DRUG LABEL
Platelet-derived growth factor receptor beta Kinase INHIBITOR IC50 8.05 DRUG LABEL
Vascular endothelial growth factor receptor 2 Kinase INHIBITOR IC50 8.47 DRUG LABEL
Macrophage colony-stimulating factor 1 receptor Kinase INHIBITOR IC50 6.91 DRUG LABEL
Angiopoietin-1 receptor Kinase INHIBITOR IC50 8.27 DRUG LABEL

External reference:

IDSource
D11353 KEGG_DRUG
9XW757O13D UNII
4039405 VANDF
C5139749 UMLSCUI
CHEBI:756647 CHEBI
CHEMBL4216467 ChEMBL_ID
71584930 PUBCHEM_CID
DB14840 DRUGBANK_ID
10808 INN_ID
C000707850 MESH_SUPPLEMENTAL_RECORD_UI
9175 IUPHAR_LIGAND_ID
874906002 SNOMEDCT_US
876860008 SNOMEDCT_US
334366 MMSL
38467 MMSL
d09563 MMSL
018369 NDDF
2369389 RXNORM
9XW757O13D INXIGHT DRUGS

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
QINLOCK HUMAN PRESCRIPTION DRUG LABEL 1 73207-101 TABLET 50 mg ORAL NDA 27 sections