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

Stem definitionDrug idCAS RN
tyrosine kinase inhibitors 5750 1194506-26-7

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • fruquintinib
  • HMPL-013
  • fruzaqla
Fruquintinib is a small molecule kinase inhibitor of vascular endothelial growth factor receptors (VEGFR)-1, -2, and -3 with IC50 values of 33, 35, and 0.5 nM, respectively. In vitro studies showed fruquintinib inhibited VEGF-mediated endothelial cell proliferation and tubular formation. In vitro and in vivo studies showed fruquintinib inhibited VEGF-induced VEGFR-2 phosphorylation. In vivo studies showed fruquintinib inhibited tumor growth in a tumor xenograft mouse model of colon cancer.
  • Molecular weight: 393.40
  • Formula: C21H19N3O5
  • CLOGP: 3.85
  • LIPINSKI: 0
  • HAC: 8
  • HDO: 1
  • TPSA: 95.71
  • ALOGS:
  • ROTB: 5
  • Status: ONP
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
3.75 mg O

ADMET properties:

None

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 2.585 High 1
caco2-efflux Caco-2 efflux ratio (BA/AB) 0.826 High 1
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 45.604 10^-6 cm/s High 1
dh-clint Dog hepatocyte intrinsic clearance 3.214 uL/min/10^6 cells High 1
dppb Dog plasma protein binding (% unbound) 14.040 % High 1
fcs-ppb Fetal calf serum protein binding (% unbound) 38.630 % High 1
herg hERG pIC50 4.364 pIC50 High 1
hh-clint Human hepatocyte intrinsic clearance 1.107 uL/min/10^6 cells High 1
hlm-clint Human liver microsomal intrinsic clearance 3.767 uL/min/mg protein High 1
hppb Human plasma protein binding (% unbound) 5.150 % High 1
kinase-safety-class ABL1,ABL2,ACVR2B,ACVRL1,AURKA,AURKB,AURKC,AXL,BLK,BRAF,CSF1R,CSK,DDR1,EGFR,EIF2AK3,EPHA2,EPHB4,ERBB2,FLT1,FLT3,FLT4,KDR,KIT,LCK,LYN,MAP3K21,MAPK7,NTRK1,PDGFRB,PDK1,PDK2,PDK4,PIK3CA,PIK3CD,PIK3CG,PRKDC,PTK6,RET,RIPK3,SRC,SYK,TTK,YES1 43
kinase-selectivity-class ACVR2B,AURKA,AXL,BLK,BRAF,CSF1R,CSK,DDR1,EGFR,ERBB2,FLT1,FLT4,IRAK3,KDR,KIT,LYN,PDGFRB,PDK4,PLK4,RIPK3 20
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 3.289 High 1
mh-clint Mouse hepatocyte intrinsic clearance 5.483 High 1
mppb Mouse plasma protein binding (% unbound) 7.440 High 1
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 6.561 High 1
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pppb Pig plasma protein binding (% unbound) 13.650 % High 1
rh-clint Rat hepatocyte intrinsic clearance 1.963 uL/min/10^6 cells High 1
rh-fuinc Rat hepatocyte fraction unbound in incubation 64.430 % High 1
rppb Rat plasma protein binding (% unbound) 4.780 % High 1
solubility-dd Solubility at pH 7.4 in DMSO 15.596 uM High 1

Approvals:

DateAgencyCompanyOrphan
Nov. 8, 2023 FDA TAKEDA PHARMS USA

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
Myelosuppression 258.83 38.36 74 1372 53517 90573484
Death 191.34 38.36 107 1339 456444 90170557
Palmar-plantar erythrodysaesthesia syndrome 109.76 38.36 33 1413 27990 90599011
Proteinuria 106.84 38.36 31 1415 23260 90603741
Blood pressure increased 73.14 38.36 43 1403 197174 90429827
Hypertension 66.23 38.36 56 1390 457476 90169525
Hypothyroidism 44.20 38.36 20 1426 53107 90573894
Nephrotic syndrome 43.72 38.36 12 1434 7327 90619674

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
Myelosuppression 266.02 35.16 89 1724 40372 42579150
Death 132.69 35.16 128 1685 471057 42148465
Palmar-plantar erythrodysaesthesia syndrome 125.82 35.16 43 1770 20539 42598983
Proteinuria 117.38 35.16 42 1771 22941 42596581
Hypertension 82.41 35.16 63 1750 167141 42452381
Dysphonia 80.92 35.16 34 1779 28416 42591106
Decreased appetite 62.29 35.16 57 1756 193080 42426442
Metastases to liver 41.37 35.16 18 1795 16308 42603214
Asthenia 39.91 35.16 54 1759 280739 42338783
Fatigue 35.71 35.16 65 1748 435576 42183946

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
Myelosuppression 549.81 36.34 164 2425 94176 110492534
Proteinuria 233.83 36.34 70 2519 39948 110546762
Palmar-plantar erythrodysaesthesia syndrome 210.72 36.34 65 2524 40960 110545750
Death 145.79 36.34 124 2465 698745 109887965
Hypertension 115.31 36.34 95 2494 509989 110076721
Nephrotic syndrome 92.90 36.34 27 2562 13804 110572906
Decreased appetite 78.03 36.34 74 2515 475772 110110938
Hypothyroidism 75.70 36.34 36 2553 72863 110513847
Blood pressure increased 64.17 36.34 51 2538 258322 110328388
Dysphonia 59.56 36.34 31 2558 75898 110510812
Platelet count decreased 58.30 36.34 46 2543 230397 110356313
Renal impairment 48.46 36.34 38 2551 188407 110398303
White blood cell count decreased 38.05 36.34 36 2553 229354 110357356
Asthenia 36.67 36.34 61 2528 688938 109897772

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC L01EK04 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
PROTEIN KINASE INHIBITORS
Vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors
MeSH PA D000092004 Tyrosine Kinase Inhibitors
MeSH PA D000970 Antineoplastic Agents
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D047428 Protein Kinase Inhibitors
CHEBI has role CHEBI:35610 antineoplastic agent
CHEBI has role CHEBI:62434 EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor
CHEBI has role CHEBI:65207 vascular endothelial growth factor receptor antagonist
CHEBI has role CHEBI:231911 renoprotective agent

Related Drugs by ATC class:

L01EK Vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors 3 drugs
apatinibaxitinibtivozanib

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

DiseaseRelationSNOMED_IDDOID
Metastatic colorectal cancer (mCRC) indication 781076008




🐶 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
1MG FRUZAQLA TAKEDA PHARMS USA N217564 Nov. 8, 2023 RX CAPSULE ORAL 8212033 May 9, 2028 TREATMENT OF PATIENTS WITH METASTATIC COLORECTAL CANCER WHO HAVE BEEN PREVIOUSLY TREATED WITH FLUOROPYRIMIDINE-, OXALIPLATIN-, AND IRINOTECAN-BASED CHEMOTHERAPY, ANTI-VEGF THERAPY, AND, IF RAS WILD-TYPE AND MEDICALLY APPROPRIATE, ANTI-EGFR THERAPY
5MG FRUZAQLA TAKEDA PHARMS USA N217564 Nov. 8, 2023 RX CAPSULE ORAL 8212033 May 9, 2028 TREATMENT OF PATIENTS WITH METASTATIC COLORECTAL CANCER WHO HAVE BEEN PREVIOUSLY TREATED WITH FLUOROPYRIMIDINE-, OXALIPLATIN-, AND IRINOTECAN-BASED CHEMOTHERAPY, ANTI-VEGF THERAPY, AND, IF RAS WILD-TYPE AND MEDICALLY APPROPRIATE, ANTI-EGFR THERAPY
1MG FRUZAQLA TAKEDA PHARMS USA N217564 Nov. 8, 2023 RX CAPSULE ORAL 10519142 Sept. 7, 2035 TREATMENT OF PATIENTS WITH METASTATIC COLORECTAL CANCER WHO HAVE BEEN PREVIOUSLY TREATED WITH FLUOROPYRIMIDINE-, OXALIPLATIN-, AND IRINOTECAN-BASED CHEMOTHERAPY, ANTI-VEGF THERAPY, AND, IF RAS WILD-TYPE AND MEDICALLY APPROPRIATE, ANTI-EGFR THERAPY
1MG FRUZAQLA TAKEDA PHARMS USA N217564 Nov. 8, 2023 RX CAPSULE ORAL 11046674 Sept. 7, 2035 TREATMENT OF PATIENTS WITH METASTATIC COLORECTAL CANCER WHO HAVE BEEN PREVIOUSLY TREATED WITH FLUOROPYRIMIDINE-, OXALIPLATIN-, AND IRINOTECAN-BASED CHEMOTHERAPY, ANTI-VEGF THERAPY, AND, IF RAS WILD-TYPE AND MEDICALLY APPROPRIATE, ANTI-EGFR THERAPY
5MG FRUZAQLA TAKEDA PHARMS USA N217564 Nov. 8, 2023 RX CAPSULE ORAL 10519142 Sept. 7, 2035 TREATMENT OF PATIENTS WITH METASTATIC COLORECTAL CANCER WHO HAVE BEEN PREVIOUSLY TREATED WITH FLUOROPYRIMIDINE-, OXALIPLATIN-, AND IRINOTECAN-BASED CHEMOTHERAPY, ANTI-VEGF THERAPY, AND, IF RAS WILD-TYPE AND MEDICALLY APPROPRIATE, ANTI-EGFR THERAPY
5MG FRUZAQLA TAKEDA PHARMS USA N217564 Nov. 8, 2023 RX CAPSULE ORAL 11046674 Sept. 7, 2035 TREATMENT OF PATIENTS WITH METASTATIC COLORECTAL CANCER WHO HAVE BEEN PREVIOUSLY TREATED WITH FLUOROPYRIMIDINE-, OXALIPLATIN-, AND IRINOTECAN-BASED CHEMOTHERAPY, ANTI-VEGF THERAPY, AND, IF RAS WILD-TYPE AND MEDICALLY APPROPRIATE, ANTI-EGFR THERAPY

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
1MG FRUZAQLA TAKEDA PHARMS USA N217564 Nov. 8, 2023 RX CAPSULE ORAL Nov. 8, 2028 NEW CHEMICAL ENTITY
5MG FRUZAQLA TAKEDA PHARMS USA N217564 Nov. 8, 2023 RX CAPSULE ORAL Nov. 8, 2028 NEW CHEMICAL ENTITY

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
Vascular endothelial growth factor receptor 1 Kinase INHIBITOR IC50 7.48 DRUG LABEL DRUG LABEL
Vascular endothelial growth factor receptor 2 Kinase INHIBITOR IC50 7.46 DRUG LABEL DRUG LABEL
Vascular endothelial growth factor receptor 3 Kinase INHIBITOR IC50 9.30 DRUG LABEL DRUG LABEL

External reference:

IDSource
CHEBI:229221 CHEBI
CHEMBL4303214 ChEMBL_ID
C000591844 MESH_SUPPLEMENTAL_RECORD_UI
9428 IUPHAR_LIGAND_ID
DB11679 DRUGBANK_ID
1363353001 SNOMEDCT_US
4042767 VANDF
C3640966 UMLSCUI
10348 INN_ID
44480399 PUBCHEM_CID
374215 MMSL
42177 MMSL
d10132 MMSL
018657 NDDF
49DXG3M5ZW UNII
2670179 RXNORM
D11977 KEGG_DRUG
49DXG3M5ZW INXIGHT DRUGS

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Fruzaqla HUMAN PRESCRIPTION DRUG LABEL 1 63020-210 CAPSULE 1 mg ORAL NDA 31 sections
Fruzaqla HUMAN PRESCRIPTION DRUG LABEL 1 63020-225 CAPSULE 5 mg ORAL NDA 31 sections