Identification

Name
Cabozantinib
Accession Number
DB08875  (DB05153)
Type
Small Molecule
Groups
Approved
Description

Cabozantinib was approved in 2012 and is a non-specific tyrosine kinase inhibitor. It is marketed as Cometriq, which is indicated for the treatment of metastatic medullary thyroid cancer. It's label includes a black box warning of gastrointestinal perforations, fistulas, and hemorrhage. The FDA approved cabozantinib as Cabometyx for patients with advanced renal cell carcinoma in April 2016.

Structure
Thumb
Synonyms
Not Available
External IDs
BMS 907351 / BMS907351 / XL 184 / XL-184 / XL184
Product Ingredients
IngredientUNIICASInChI Key
Cabozantinib malateDR7ST46X581140909-48-3HFCFMRYTXDINDK-WNQIDUERSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
CabometyxTablet60 mg/1OralExelixis2016-04-25Not applicableUs
CabometyxTablet20 mg/1OralExelixis2016-04-25Not applicableUs
CabometyxTablet40 mg/1OralExelixis2016-04-25Not applicableUs
CometriqCapsule20 mg/1OralExelixis2012-11-292016-10-13Us
CometriqCapsule20 mg/1OralExelixis2012-11-29Not applicableUs
CometriqKitExelixis2012-11-29Not applicableUs
CometriqCapsule20 mgOralTmc Pharma Services Ltd.2014-03-21Not applicableEu
CometriqKitExelixis2012-11-29Not applicableUs
CometriqCapsule20 mgOralTmc Pharma Services Ltd.2014-03-21Not applicableEu
Categories
UNII
1C39JW444G
CAS number
849217-68-1
Weight
Average: 501.514
Monoisotopic: 501.169999048
Chemical Formula
C28H24FN3O5
InChI Key
ONIQOQHATWINJY-UHFFFAOYSA-N
InChI
InChI=1S/C28H24FN3O5/c1-35-24-15-21-22(16-25(24)36-2)30-14-11-23(21)37-20-9-7-19(8-10-20)32-27(34)28(12-13-28)26(33)31-18-5-3-17(29)4-6-18/h3-11,14-16H,12-13H2,1-2H3,(H,31,33)(H,32,34)
IUPAC Name
N'1-{4-[(6,7-dimethoxyquinolin-4-yl)oxy]phenyl}-N1-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide
SMILES
COC1=CC2=C(C=C1OC)C(OC1=CC=C(NC(=O)C3(CC3)C(=O)NC3=CC=C(F)C=C3)C=C1)=CC=N2

Pharmacology

Indication

For the treatment of metastatic medullary thyroid cancer and for the treatment of patients with advanced renal cell carcinoma (RCC) who have received prior anti-angiogenic therapy.

Structured Indications
Pharmacodynamics

Cabozantinib suppresses metastasis, angiogenesis, and oncognesis by inhibiting receptor tyrosine kinases.

Mechanism of action

Cabozantinib inhibits specific receptor tyrosine kinases such as VEGFR-1, -2 and -3, KIT, TRKB, FLT-3, AXL, RET, MET, and TIE-2.

TargetActionsOrganism
AHepatocyte growth factor receptor
antagonist
Human
AVascular endothelial growth factor receptor 2
antagonist
Human
AProto-oncogene tyrosine-protein kinase receptor Ret
antagonist
Human
Absorption

After oral administration, peak plasma concentration was achieved in 2-5 hours.

Volume of distribution

The volume of distribution is 349L.

Protein binding

Cabozantinib has extensive plasma protein binding (≥ 99.7%).

Metabolism

Cabozantinib is metabolized mostly by CYP3A4 and, to a minor extent, by CYP2C9. Both enzyme produce an N-oxide metabolite.

Route of elimination

Cabozantinib is eliminated mostly by the feces (54%) and also by the urine (27%).

Half life

Cabozantinib has a long half-life of 55 hours.

Clearance

At steady state, the clearance is 4.4 L/hr.

Toxicity

Cabozantinib has a black box warning of serious gastrointestinal fistulas and perforations, and potentially fatal hemoptysis and gastrointestinal hemorrhage.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AbirateroneThe metabolism of Cabozantinib can be decreased when combined with Abiraterone.Approved
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Cabozantinib.Approved
AcetyldigoxinAcetyldigoxin may decrease the cardiotoxic activities of Cabozantinib.Experimental
AmiodaroneThe serum concentration of Cabozantinib can be increased when it is combined with Amiodarone.Approved, Investigational
AprepitantThe serum concentration of Cabozantinib can be increased when it is combined with Aprepitant.Approved, Investigational
AtazanavirThe serum concentration of Cabozantinib can be increased when it is combined with Atazanavir.Approved, Investigational
AtomoxetineThe metabolism of Cabozantinib can be decreased when combined with Atomoxetine.Approved
BevacizumabBevacizumab may increase the cardiotoxic activities of Cabozantinib.Approved, Investigational
BoceprevirThe serum concentration of Cabozantinib can be increased when it is combined with Boceprevir.Approved, Withdrawn
BortezomibThe metabolism of Cabozantinib can be decreased when combined with Bortezomib.Approved, Investigational
BosentanThe serum concentration of Cabozantinib can be decreased when it is combined with Bosentan.Approved, Investigational
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel is combined with Cabozantinib.Approved
CapecitabineThe metabolism of Cabozantinib can be decreased when combined with Capecitabine.Approved, Investigational
CarbamazepineThe serum concentration of Cabozantinib can be decreased when it is combined with Carbamazepine.Approved, Investigational
CholecalciferolThe metabolism of Cabozantinib can be decreased when combined with Cholecalciferol.Approved, Nutraceutical
ClarithromycinThe serum concentration of Cabozantinib can be increased when it is combined with Clarithromycin.Approved
ClemastineThe metabolism of Cabozantinib can be decreased when combined with Clemastine.Approved
ClotrimazoleThe metabolism of Cabozantinib can be decreased when combined with Clotrimazole.Approved, Vet Approved
CobicistatThe serum concentration of Cabozantinib can be increased when it is combined with Cobicistat.Approved
ConivaptanThe serum concentration of Cabozantinib can be increased when it is combined with Conivaptan.Approved, Investigational
CrisaboroleThe metabolism of Cabozantinib can be decreased when combined with Crisaborole.Approved
CrizotinibThe metabolism of Cabozantinib can be decreased when combined with Crizotinib.Approved
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Cabozantinib.Approved, Investigational
CyclosporineThe metabolism of Cabozantinib can be decreased when combined with Cyclosporine.Approved, Investigational, Vet Approved
CymarinCymarin may decrease the cardiotoxic activities of Cabozantinib.Experimental
DabrafenibThe serum concentration of Cabozantinib can be decreased when it is combined with Dabrafenib.Approved
DarunavirThe serum concentration of Cabozantinib can be increased when it is combined with Darunavir.Approved
DasatinibThe serum concentration of Cabozantinib can be increased when it is combined with Dasatinib.Approved, Investigational
DeferasiroxThe serum concentration of Cabozantinib can be decreased when it is combined with Deferasirox.Approved, Investigational
DelavirdineThe metabolism of Cabozantinib can be decreased when combined with Delavirdine.Approved
DeslanosideDeslanoside may decrease the cardiotoxic activities of Cabozantinib.Approved
DexamethasoneThe serum concentration of Cabozantinib can be decreased when it is combined with Dexamethasone.Approved, Investigational, Vet Approved
DigitoxinDigitoxin may decrease the cardiotoxic activities of Cabozantinib.Approved, Investigational
DigoxinDigoxin may decrease the cardiotoxic activities of Cabozantinib.Approved
DihydroergotamineThe metabolism of Cabozantinib can be decreased when combined with Dihydroergotamine.Approved
DiltiazemThe metabolism of Cabozantinib can be decreased when combined with Diltiazem.Approved
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with Cabozantinib.Approved, Investigational
DosulepinThe metabolism of Cabozantinib can be decreased when combined with Dosulepin.Approved
DoxycyclineThe metabolism of Cabozantinib can be decreased when combined with Doxycycline.Approved, Investigational, Vet Approved
DronedaroneThe metabolism of Cabozantinib can be decreased when combined with Dronedarone.Approved
EfavirenzThe metabolism of Cabozantinib can be decreased when combined with Efavirenz.Approved, Investigational
ErythromycinThe metabolism of Cabozantinib can be decreased when combined with Erythromycin.Approved, Vet Approved
EtravirineThe metabolism of Cabozantinib can be decreased when combined with Etravirine.Approved
FloxuridineThe metabolism of Cabozantinib can be decreased when combined with Floxuridine.Approved
FluconazoleThe metabolism of Cabozantinib can be decreased when combined with Fluconazole.Approved
FluorouracilThe metabolism of Cabozantinib can be decreased when combined with Fluorouracil.Approved
FluvastatinThe metabolism of Cabozantinib can be decreased when combined with Fluvastatin.Approved
FluvoxamineThe metabolism of Cabozantinib can be decreased when combined with Fluvoxamine.Approved, Investigational
FosamprenavirThe metabolism of Cabozantinib can be decreased when combined with Fosamprenavir.Approved
FosaprepitantThe serum concentration of Cabozantinib can be increased when it is combined with Fosaprepitant.Approved
FosphenytoinThe serum concentration of Cabozantinib can be decreased when it is combined with Fosphenytoin.Approved
Fusidic AcidThe serum concentration of Cabozantinib can be increased when it is combined with Fusidic Acid.Approved
GemfibrozilThe metabolism of Cabozantinib can be decreased when combined with Gemfibrozil.Approved
GitoformateGitoformate may decrease the cardiotoxic activities of Cabozantinib.Experimental
IdelalisibThe serum concentration of Cabozantinib can be increased when it is combined with Idelalisib.Approved
ImatinibThe metabolism of Cabozantinib can be decreased when combined with Imatinib.Approved
IndinavirThe serum concentration of Cabozantinib can be increased when it is combined with Indinavir.Approved
IrbesartanThe metabolism of Cabozantinib can be decreased when combined with Irbesartan.Approved, Investigational
IsavuconazoniumThe metabolism of Cabozantinib can be decreased when combined with Isavuconazonium.Approved, Investigational
IsradipineThe metabolism of Cabozantinib can be decreased when combined with Isradipine.Approved
ItraconazoleThe serum concentration of Cabozantinib can be increased when it is combined with Itraconazole.Approved, Investigational
IvacaftorThe serum concentration of Cabozantinib can be increased when it is combined with Ivacaftor.Approved
KetoconazoleThe serum concentration of Cabozantinib can be increased when it is combined with Ketoconazole.Approved, Investigational
Lanatoside CLanatoside C may decrease the cardiotoxic activities of Cabozantinib.Experimental
LeflunomideThe metabolism of Cabozantinib can be decreased when combined with Leflunomide.Approved, Investigational
LobeglitazoneThe metabolism of Cabozantinib can be decreased when combined with Lobeglitazone.Approved, Investigational
LopinavirThe serum concentration of Cabozantinib can be increased when it is combined with Lopinavir.Approved
LosartanThe metabolism of Cabozantinib can be decreased when combined with Losartan.Approved
LovastatinThe metabolism of Cabozantinib can be decreased when combined with Lovastatin.Approved, Investigational
LuliconazoleThe serum concentration of Cabozantinib can be increased when it is combined with Luliconazole.Approved
ManidipineThe metabolism of Cabozantinib can be decreased when combined with Manidipine.Approved, Investigational
MetildigoxinMetildigoxin may decrease the cardiotoxic activities of Cabozantinib.Experimental
MidostaurinThe metabolism of Cabozantinib can be decreased when combined with Midostaurin.Approved
MifepristoneThe serum concentration of Cabozantinib can be increased when it is combined with Mifepristone.Approved, Investigational
NefazodoneThe serum concentration of Cabozantinib can be increased when it is combined with Nefazodone.Approved, Withdrawn
NelfinavirThe serum concentration of Cabozantinib can be increased when it is combined with Nelfinavir.Approved
NetupitantThe serum concentration of Cabozantinib can be increased when it is combined with Netupitant.Approved
NevirapineThe serum concentration of Cabozantinib can be decreased when it is combined with Nevirapine.Approved
NicardipineThe metabolism of Cabozantinib can be decreased when combined with Nicardipine.Approved
NilotinibThe metabolism of Cabozantinib can be decreased when combined with Nilotinib.Approved, Investigational
OlaparibThe metabolism of Cabozantinib can be decreased when combined with Olaparib.Approved
OleandrinOleandrin may decrease the cardiotoxic activities of Cabozantinib.Experimental, Investigational
OmeprazoleThe metabolism of Cabozantinib can be decreased when combined with Omeprazole.Approved, Investigational, Vet Approved
OsimertinibThe serum concentration of Cabozantinib can be increased when it is combined with Osimertinib.Approved
OuabainOuabain may decrease the cardiotoxic activities of Cabozantinib.Approved
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Cabozantinib.Approved, Vet Approved
PalbociclibThe serum concentration of Cabozantinib can be increased when it is combined with Palbociclib.Approved
PentobarbitalThe serum concentration of Cabozantinib can be decreased when it is combined with Pentobarbital.Approved, Vet Approved
PeruvosidePeruvoside may decrease the cardiotoxic activities of Cabozantinib.Experimental
PhenobarbitalThe serum concentration of Cabozantinib can be decreased when it is combined with Phenobarbital.Approved
PhenytoinThe serum concentration of Cabozantinib can be decreased when it is combined with Phenytoin.Approved, Vet Approved
PosaconazoleThe serum concentration of Cabozantinib can be increased when it is combined with Posaconazole.Approved, Investigational, Vet Approved
PrimidoneThe serum concentration of Cabozantinib can be decreased when it is combined with Primidone.Approved, Vet Approved
ProscillaridinProscillaridin may decrease the cardiotoxic activities of Cabozantinib.Experimental
PyrimethamineThe metabolism of Cabozantinib can be decreased when combined with Pyrimethamine.Approved, Vet Approved
QuinineThe metabolism of Cabozantinib can be decreased when combined with Quinine.Approved
RanolazineThe metabolism of Cabozantinib can be decreased when combined with Ranolazine.Approved, Investigational
RifabutinThe serum concentration of Cabozantinib can be decreased when it is combined with Rifabutin.Approved
RifampicinThe serum concentration of Cabozantinib can be decreased when it is combined with Rifampicin.Approved
RifapentineThe serum concentration of Cabozantinib can be decreased when it is combined with Rifapentine.Approved
RitonavirThe serum concentration of Cabozantinib can be increased when it is combined with Ritonavir.Approved, Investigational
SaquinavirThe serum concentration of Cabozantinib can be increased when it is combined with Saquinavir.Approved, Investigational
SecobarbitalThe metabolism of Cabozantinib can be increased when combined with Secobarbital.Approved, Vet Approved
SildenafilThe metabolism of Cabozantinib can be decreased when combined with Sildenafil.Approved, Investigational
SiltuximabThe serum concentration of Cabozantinib can be decreased when it is combined with Siltuximab.Approved
SimeprevirThe serum concentration of Cabozantinib can be increased when it is combined with Simeprevir.Approved
SorafenibThe metabolism of Cabozantinib can be decreased when combined with Sorafenib.Approved, Investigational
St. John's WortThe serum concentration of Cabozantinib can be decreased when it is combined with St. John's Wort.Investigational, Nutraceutical
StiripentolThe serum concentration of Cabozantinib can be increased when it is combined with Stiripentol.Approved
SulfadiazineThe metabolism of Cabozantinib can be decreased when combined with Sulfadiazine.Approved, Vet Approved
SulfamethoxazoleThe metabolism of Cabozantinib can be decreased when combined with Sulfamethoxazole.Approved
SulfisoxazoleThe metabolism of Cabozantinib can be decreased when combined with Sulfisoxazole.Approved, Vet Approved
TelaprevirThe serum concentration of Cabozantinib can be increased when it is combined with Telaprevir.Approved, Withdrawn
TelithromycinThe serum concentration of Cabozantinib can be increased when it is combined with Telithromycin.Approved
TicagrelorThe metabolism of Cabozantinib can be decreased when combined with Ticagrelor.Approved
TiclopidineThe metabolism of Cabozantinib can be decreased when combined with Ticlopidine.Approved
TocilizumabThe serum concentration of Cabozantinib can be decreased when it is combined with Tocilizumab.Approved
TolbutamideThe metabolism of Cabozantinib can be decreased when combined with Tolbutamide.Approved
TopiroxostatThe metabolism of Cabozantinib can be decreased when combined with Topiroxostat.Approved, Investigational
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Cabozantinib.Approved, Investigational
TrimethoprimThe metabolism of Cabozantinib can be decreased when combined with Trimethoprim.Approved, Vet Approved
Valproic AcidThe metabolism of Cabozantinib can be decreased when combined with Valproic Acid.Approved, Investigational
ValsartanThe metabolism of Cabozantinib can be decreased when combined with Valsartan.Approved, Investigational
VenlafaxineThe metabolism of Cabozantinib can be decreased when combined with Venlafaxine.Approved
VerapamilThe metabolism of Cabozantinib can be decreased when combined with Verapamil.Approved
VoriconazoleThe serum concentration of Cabozantinib can be increased when it is combined with Voriconazole.Approved, Investigational
ZafirlukastThe metabolism of Cabozantinib can be decreased when combined with Zafirlukast.Approved, Investigational
ZiprasidoneThe metabolism of Cabozantinib can be decreased when combined with Ziprasidone.Approved
Food Interactions
  • Avoid grapefruit juice. Combination may increase levels of cabozantinib. Also avoid all other strong CYP3A4 inhibitors.

References

General References
  1. Durante C, Russo D, Verrienti A, Filetti S: XL184 (cabozantinib) for medullary thyroid carcinoma. Expert Opin Investig Drugs. 2011 Mar;20(3):407-413. doi: 10.1517/13543784.2011.559163. [PubMed:21314233]
  2. Choueiri TK, Escudier B, Powles T, Mainwaring PN, Rini BI, Donskov F, Hammers H, Hutson TE, Lee JL, Peltola K, Roth BJ, Bjarnason GA, Geczi L, Keam B, Maroto P, Heng DY, Schmidinger M, Kantoff PW, Borgman-Hagey A, Hessel C, Scheffold C, Schwab GM, Tannir NM, Motzer RJ: Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma. N Engl J Med. 2015 Nov 5;373(19):1814-23. doi: 10.1056/NEJMoa1510016. Epub 2015 Sep 25. [PubMed:26406150]
  3. Krajewska J, Olczyk T, Jarzab B: Cabozantinib for the treatment of progressive metastatic medullary thyroid cancer. Expert Rev Clin Pharmacol. 2016;9(1):69-79. doi: 10.1586/17512433.2016.1102052. Epub 2015 Nov 4. [PubMed:26536165]
  4. Grullich C: Cabozantinib: a MET, RET, and VEGFR2 tyrosine kinase inhibitor. Recent Results Cancer Res. 2014;201:207-14. doi: 10.1007/978-3-642-54490-3_12. [PubMed:24756794]
External Links
KEGG Drug
D10062
PubChem Compound
25102847
PubChem Substance
347827806
ChemSpider
25948202
BindingDB
50021574
ChEBI
72317
ChEMBL
CHEMBL2105717
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Cabozantinib
ATC Codes
L01XE26 — Cabozantinib
FDA label
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Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1Active Not RecruitingTreatmentChildhood Solid Neoplasm / Childhood Thyroid Gland Medullary Carcinoma / Recurrent Childhood Central Nervous System Neoplasm / Recurrent Malignant Solid Neoplasm / Recurrent Melanoma / Recurrent Thyroid Gland Carcinoma / Refractory Malignant Solid Neoplasm / Thyroid Gland Medullary Carcinoma1
1Active Not RecruitingTreatmentCcRCC / Clear Cell Renal Cell Carcinoma / RCC / Renal Cancers / Renal Cell Adenocarcinoma1
1Active Not RecruitingTreatmentMalignant Neoplasm of Pancreas1
1Active Not RecruitingTreatmentProstate Cancer1
1CompletedTreatmentAdenocarcinoma, Prostate1
1CompletedTreatmentCancers / Lung Cancer Non-Small Cell Cancer (NSCLC) / Tumors, Solid1
1CompletedTreatmentCancers / Malignant Lymphomas / Thyroid Carcinoma1
1CompletedTreatmentFollicular Thyroid Cancer / Huerthle Cell Thyroid Cancer / Renal Cell Adenocarcinoma / Thyroid Papillary Carcinoma1
1CompletedTreatmentGiant Cell Glioblastoma / Glioblastomas / Gliosarcoma1
1CompletedTreatmentHealthy Volunteers / Hepatic Impairment1
1CompletedTreatmentHealthy Volunteers / Impaired Renal Function1
1CompletedTreatmentMultiple Myeloma (MM)1
1CompletedTreatmentNeoplasms1
1CompletedTreatmentRefractory Acute Myeloid Leukemia / Relapsed Acute Myeloid Leukemia1
1Not Yet RecruitingTreatmentLocally Advanced Hepatocellular Carcinoma1
1Not Yet RecruitingTreatmentRenal Cell Adenocarcinoma1
1RecruitingTreatmentAdult Solid Neoplasm / Advanced Malignant Neoplasm / Advanced Malignant Solid Neoplasm / Human Immunodeficiency Virus (HIV) Infections / Metastatic Malignant Neoplasm / Metastatic Malignant Solid Neoplasm / Recurrent Malignant Neoplasm / Recurrent Malignant Solid Neoplasm / Solid Neoplasms / Unresectable Malignant Neoplasm / Unresectable Solid Neoplasm1
1RecruitingTreatmentClear Cell Renal Cell Carcinoma / Malignant Reproductive System Neoplasm / Malignant Urinary System Neoplasm / Metastatic Malignant Neoplasm in the Bone / Metastatic Penile Carcinoma / Metastatic Urethral Neoplasm / Metastatic Urothelial Carcinoma of the Renal Pelvis and Ureter / Progressive Neoplastic Disease / Recurrent Bladder Carcinoma / Recurrent Urethra Carcinoma / Recurrent Urothelial Carcinoma of the Renal Pelvis and Ureter / Regional Urothelial Carcinoma of the Renal Pelvis and Ureter / Renal Pelvis Urothelial Carcinoma / Solid Neoplasms / Squamous Cell Carcinoma of the Penis / Stage III Bladder Adenocarcinoma / Stage III Bladder Squamous Cell Carcinoma / Stage III Bladder Urothelial Carcinoma / Stage III Penile Cancer / Stage III Renal Cell Cancer / Stage III Renal Pelvis Carcinoma / Stage III Ureter Cancer / Stage III Urethral Cancer / Stage IIIa Penile Cancer / Stage IIIb Penile Cancer / Stage IV Bladder Adenocarcinoma / Stage IV Bladder Squamous Cell Carcinoma / Stage IV Bladder Urothelial Carcinoma / Stage IV Penile Cancer / Stage IV Renal Cell Cancer / Stage IV Renal Pelvis Carcinoma / Stage IV Ureter Cancer / Stage IV Urethral Cancer / Ureter Urothelial Carcinoma / Urethral Urothelial Carcinoma1
1RecruitingTreatmentColorectal Cancers1
1RecruitingTreatmentFumarate Hydratase (FH)-Deficient Tumors / Lung Cancer Non-Small Cell Cancer (NSCLC) / Mesothelioma / Renal Cell Adenocarcinoma / Succinate Dehydrogenase (SDH)-Deficient Gastrointestinal Stromal Tumors (GIST) / Succinate Dehydrogenase (SDH)-Deficient Non-gastrointestinal Stromal Tumors / Triple-Negative Breast Cancer (TNBC) / Tumors Harboring Amplifications in the cMyc Gene / Tumors Harboring Isocitrate Dehydrogenase-1 (IDH1) and IDH2 Mutations / Tumors, Solid1
1TerminatedTreatmentRecurrent Melanoma / Stage IIIA Melanoma / Stage IIIB Melanoma / Stage IIIc Melanoma / Stage IV Melanoma / Unspecified Adult Solid Tumor, Protocol Specific1
1, 2Active Not RecruitingTreatmentProstatic Neoplasms1
1, 2CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
1, 2CompletedTreatmentRelapsed Or Refractory Multiple Myeloma1
1, 2Not Yet RecruitingTreatmentMetastatic Renal Cell Carcinoma1
1, 2Not Yet RecruitingTreatmentMultiple Myeloma (MM) / Refractory Multiple Myeloma / Relapsed/Refractory Multiple Myeloma1
1, 2RecruitingTreatmentHepatocellular,Carcinoma1
1, 2RecruitingTreatmentRenal Cell Adenocarcinoma / Transitional Cell Carcinoma1
2Active Not RecruitingDiagnosticBone Metastases / Castrate-resistant Prostate Cancer (CRPC) / Recurrent Prostate Cancer / Stage IV Prostate Cancer1
2Active Not RecruitingTreatmentCancer, Breast1
2Active Not RecruitingTreatmentCarcinoid Tumors / Progressive Neuroendocrine Tumors of pancreatic origin1
2Active Not RecruitingTreatmentClear Cell Renal Cell Carcinoma / Metastatic Renal Cell Cancer / Stage III Renal Cell Cancer / Stage IV Renal Cell Cancer1
2Active Not RecruitingTreatmentFallopian Tube Clear Cell Adenocarcinoma / Ovarian Clear Cell Adenocarcinoma / Recurrent Fallopian Tube Carcinoma / Recurrent Ovarian Carcinoma / Recurrent Primary Peritoneal Carcinoma1
2Active Not RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC) / Recurrent Non-Small Cell Lung Carcinoma / Stage IV Non-Small Cell Lung Cancer1
2Active Not RecruitingTreatmentLung Cancers / Solid Tumor (Not Breast or Prostate Cancers)1
2Active Not RecruitingTreatmentNeurofibromatosis / NF1 / Plexiform Neurofibromas1
2Active Not RecruitingTreatmentNeoplasms, Kidney / Transitional Cell Carcinoma / Ureteral Neoplasms / Urethral Neoplasms / Urinary Bladder Neoplasms1
2Active Not RecruitingTreatmentNeuroendocrine Carcinoma of the Skin / Skin Cancers1
2Active Not RecruitingTreatmentPoorly Differentiated Thyroid Gland Carcinoma / Recurrent Thyroid Gland Carcinoma / Stage I Thyroid Gland Follicular Carcinoma / Stage I Thyroid Gland Papillary Carcinoma / Stage II Thyroid Gland Follicular Carcinoma / Stage II Thyroid Gland Papillary Carcinoma / Stage III Thyroid Gland Follicular Carcinoma / Stage III Thyroid Gland Papillary Carcinoma / Stage IVA Thyroid Gland Follicular Carcinoma / Stage IVA Thyroid Gland Papillary Carcinoma / Stage IVB Thyroid Gland Follicular Carcinoma / Stage IVB Thyroid Gland Papillary Carcinoma / Stage IVC Thyroid Gland Follicular Carcinoma / Stage IVC Thyroid Gland Papillary Carcinoma / Tall Cell Variant Thyroid Gland Papillary Carcinoma / Thyroid Gland Oncocytic Follicular Carcinoma1
2Active Not RecruitingTreatmentProstate Cancer1
2Active Not RecruitingTreatmentRecurrent Fallopian Tube Carcinoma / Recurrent Ovarian Carcinoma / Recurrent Primary Peritoneal Carcinoma1
2Active Not RecruitingTreatmentRecurrent Non-Small Cell Lung Carcinoma / Stage IV Non-Small Cell Lung Cancer / Stage IV Non-Small Cell Lung Cancer AJCC v71
2Active Not RecruitingTreatmentRecurrent Uveal Melanoma / Stage III Uveal Melanoma / Stage IIIA Uveal Melanoma / Stage IIIB Uveal Melanoma / Stage IIIC Uveal Melanoma / Stage IV Uveal Melanoma1
2CompletedTreatmentAstrocytic Tumors1
2CompletedTreatmentBile Duct Carcinoma / Cholangiocarcinoma of the Extrahepatic Bile Duct / Intrahepatic Cholangiocarcinoma1
2CompletedTreatmentCancer, Breast1
2CompletedTreatmentCancers / Tumors, Solid1
2CompletedTreatmentGlioblastoma Multiforme1
2CompletedTreatmentProstate Cancer1
2Not Yet RecruitingTreatmentAdvanced Renal Cell Carcinoma1
2Not Yet RecruitingTreatmentCancer, Breast1
2RecruitingTreatmentAdrenal Cortex Carcinoma / Adult Alveolar Soft Part Sarcoma / Adult Clear Cell Sarcoma of Soft Parts / Adult Hepatocellular Carcinoma / Adult Rhabdomyosarcoma / Adult Soft Tissue Sarcoma / Childhood Alveolar Soft Part Sarcoma / Childhood Central Nervous System Neoplasm / Childhood Clear Cell Sarcoma of Soft Parts / Childhood Hepatocellular Carcinoma / Childhood Rhabdomyosarcoma / Childhood Soft Tissue Sarcoma / Childhood Solid Neoplasm / Ewing's Sarcoma (ES) / Hepatoblastomas / Hepatocellular,Carcinoma / Recurrent Adrenal Cortex Carcinoma / Recurrent Adult Hepatocellular Carcinoma / Recurrent Adult Soft Tissue Sarcoma / Recurrent Alveolar Soft Part Sarcoma / Recurrent Childhood Central Nervous System Neoplasm / Recurrent Childhood Hepatocellular Carcinoma / Recurrent Childhood Soft Tissue Sarcoma / Recurrent Ewing Sarcoma / Recurrent Hepatoblastoma / Recurrent Malignant Solid Neoplasm / Recurrent Rhabdomyosarcoma / Recurrent Solid Neoplasm / Renal Cell Adenocarcinoma / Renal Cell Carcinoma Recurrent / Thyroid Gland Medullary Carcinoma / Wilms' tumor1
2RecruitingTreatmentAnaplastic Astrocytoma (AA) / Glioblastoma Multiforme / High Grade Glioma (HGG) / Malignant Brain Tumors1
2RecruitingTreatmentBrain Tumor - Metastatic / Cancer, Breast1
2RecruitingTreatmentDifferentiated Thyroid Cancer (DTC) / Poorly Differentiated Thyroid Cancer1
2RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
2RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC) / Metastases to the Brain1
2RecruitingTreatmentMetastatic Ewing Sarcoma / Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor / Metastatic Osteosarcoma / Recurrent Ewing Sarcoma / Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor / Recurrent Osteosarcoma / Stage III Osteosarcoma / Stage III Osteosarcoma AJCC v7 / Stage IV Osteosarcoma / Stage IV Osteosarcoma AJCC v7 / Stage IVA Osteosarcoma / Stage IVA Osteosarcoma AJCC v7 / Stage IVB Osteosarcoma / Stage IVB Osteosarcoma AJCC v7 / Unresectable Ewing Sarcoma / Unresectable Osteosarcoma1
2RecruitingTreatmentMetastatic Gastrointestinal Stromal Tumor1
2RecruitingTreatmentNeuroendocrine Tumors1
2RecruitingTreatmentPancreatic Adenocarcinoma Metastatic1
2RecruitingTreatmentRare Tumor / Refractory Tumors1
2RecruitingTreatmentRefractory Soft Tissue Sarcomas1
2RecruitingTreatmentRenal Cell Carcinoma Recurrent / Stage III Renal Cell Cancer / Stage IV Renal Cell Cancer / Type 1 Papillary Renal Cell Carcinoma / Type 2 Papillary Renal Cell Carcinoma1
2RecruitingTreatmentUterine Sarcoma1
2SuspendedTreatmentEndometrial Adenosquamous Carcinoma / Endometrial Clear Cell Adenocarcinoma / Endometrial Mixed Adenocarcinoma / Endometrial Serous Adenocarcinoma / Metastatic Endometrioid Adenocarcinoma / Recurrent Uterine Corpus Carcinoma / Stage IV Uterine Corpus Cancer / Stage IVA Uterine Corpus Cancer / Stage IVB Uterine Corpus Cancer / Uterine Corpus Carcinosarcoma1
2TerminatedTreatmentCastration Resistant Prostate Cancer (CRPC) / Prostate Cancer / Prostatic Neoplasms1
2TerminatedTreatmentMetastatic Hormone Refractory Prostate Cancer1
3Active Not RecruitingTreatmentHepatocellular,Carcinoma1
3Active Not RecruitingTreatmentRenal Cell Adenocarcinoma1
3Active Not RecruitingTreatmentThyroid Cancers1
3CompletedTreatmentCastration Resistant Prostate Cancer (CRPC) / Pain / Prostate Cancer / Prostatic Neoplasms1
3RecruitingTreatmentRenal Cell Adenocarcinoma1
3TerminatedTreatmentCastration Resistant Prostate Cancer (CRPC) / Pain / Prostate Cancer / Prostatic Neoplasms1
4RecruitingTreatmentMedullary Thyroid Cancer (MTC)1
Not AvailableActive Not RecruitingTreatmentAdenocarcinoma of the Prostate / Castration-Resistant Prostate Cancer (CRPC) / Recurrent Prostate Cancer / Stage III Prostate Cancer / Stage IV Prostate Cancer1
Not AvailableActive Not RecruitingTreatmentAdenocarcinoma of the Prostate / Hormone-Resistant Prostate Cancer / Recurrent Prostate Cancer / Stage IV Prostate Cancer1
Not AvailableApproved for MarketingNot AvailableMedullary Thyroid Cancer (MTC)1
Not AvailableRecruitingDiagnosticAdvanced Cancers / Endocrine Tumors1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
TabletOral20 mg/1
TabletOral40 mg/1
TabletOral60 mg/1
CapsuleOral20 mg/1
CapsuleOral20 mg
Kit
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US8877776No2010-10-082030-10-08Us
US7579473No2004-09-242024-09-24Us
US8497284No2004-09-242024-09-24Us
US9724342No2013-07-092033-07-09Us
US9717720No2012-02-102032-02-10Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilityCOMETRIQ is practically insoluble in water.From FDA label.
Predicted Properties
PropertyValueSource
Water Solubility0.00199 mg/mLALOGPS
logP4.01ALOGPS
logP4.66ChemAxon
logS-5.4ALOGPS
pKa (Strongest Acidic)13.46ChemAxon
pKa (Strongest Basic)5.9ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area98.78 Å2ChemAxon
Rotatable Bond Count8ChemAxon
Refractivity136.12 m3·mol-1ChemAxon
Polarizability51.49 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0udi-0139180000-20096332e7e989d72392

Taxonomy

Description
This compound belongs to the class of organic compounds known as diarylethers. These are organic compounds containing the dialkyl ether functional group, with the formula ROR', where R and R' are aryl groups.
Kingdom
Organic compounds
Super Class
Organic oxygen compounds
Class
Organooxygen compounds
Sub Class
Ethers
Direct Parent
Diarylethers
Alternative Parents
Quinolines and derivatives / Anilides / Phenoxy compounds / Anisoles / N-arylamides / Alkyl aryl ethers / Fluorobenzenes / Pyridines and derivatives / Aryl fluorides / Cyclopropanecarboxylic acids and derivatives
show 8 more
Substituents
Diaryl ether / Quinoline / Anilide / Phenoxy compound / Anisole / Phenol ether / N-arylamide / Alkyl aryl ether / Halobenzene / Fluorobenzene
show 21 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
organofluorine compound, dicarboxylic acid diamide, aromatic ether, quinolines (CHEBI:72317)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Protein tyrosine kinase activity
Specific Function
Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to hepatocyte growth factor/HGF ligand. Regulates many physiological processes including...
Gene Name
MET
Uniprot ID
P08581
Uniprot Name
Hepatocyte growth factor receptor
Molecular Weight
155540.035 Da
References
  1. Kurzrock R, Sherman SI, Ball DW, Forastiere AA, Cohen RB, Mehra R, Pfister DG, Cohen EE, Janisch L, Nauling F, Hong DS, Ng CS, Ye L, Gagel RF, Frye J, Muller T, Ratain MJ, Salgia R: Activity of XL184 (Cabozantinib), an oral tyrosine kinase inhibitor, in patients with medullary thyroid cancer. J Clin Oncol. 2011 Jul 1;29(19):2660-6. doi: 10.1200/JCO.2010.32.4145. Epub 2011 May 23. [PubMed:21606412]
  2. Yakes FM, Chen J, Tan J, Yamaguchi K, Shi Y, Yu P, Qian F, Chu F, Bentzien F, Cancilla B, Orf J, You A, Laird AD, Engst S, Lee L, Lesch J, Chou YC, Joly AH: Cabozantinib (XL184), a novel MET and VEGFR2 inhibitor, simultaneously suppresses metastasis, angiogenesis, and tumor growth. Mol Cancer Ther. 2011 Dec;10(12):2298-308. doi: 10.1158/1535-7163.MCT-11-0264. Epub 2011 Sep 16. [PubMed:21926191]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Vascular endothelial growth factor-activated receptor activity
Specific Function
Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD. Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and ...
Gene Name
KDR
Uniprot ID
P35968
Uniprot Name
Vascular endothelial growth factor receptor 2
Molecular Weight
151525.555 Da
References
  1. Kurzrock R, Sherman SI, Ball DW, Forastiere AA, Cohen RB, Mehra R, Pfister DG, Cohen EE, Janisch L, Nauling F, Hong DS, Ng CS, Ye L, Gagel RF, Frye J, Muller T, Ratain MJ, Salgia R: Activity of XL184 (Cabozantinib), an oral tyrosine kinase inhibitor, in patients with medullary thyroid cancer. J Clin Oncol. 2011 Jul 1;29(19):2660-6. doi: 10.1200/JCO.2010.32.4145. Epub 2011 May 23. [PubMed:21606412]
  2. Yakes FM, Chen J, Tan J, Yamaguchi K, Shi Y, Yu P, Qian F, Chu F, Bentzien F, Cancilla B, Orf J, You A, Laird AD, Engst S, Lee L, Lesch J, Chou YC, Joly AH: Cabozantinib (XL184), a novel MET and VEGFR2 inhibitor, simultaneously suppresses metastasis, angiogenesis, and tumor growth. Mol Cancer Ther. 2011 Dec;10(12):2298-308. doi: 10.1158/1535-7163.MCT-11-0264. Epub 2011 Sep 16. [PubMed:21926191]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Transmembrane receptor protein tyrosine kinase activity
Specific Function
Receptor tyrosine-protein kinase involved in numerous cellular mechanisms including cell proliferation, neuronal navigation, cell migration, and cell differentiation upon binding with glial cell de...
Gene Name
RET
Uniprot ID
P07949
Uniprot Name
Proto-oncogene tyrosine-protein kinase receptor Ret
Molecular Weight
124317.465 Da
References
  1. Kurzrock R, Sherman SI, Ball DW, Forastiere AA, Cohen RB, Mehra R, Pfister DG, Cohen EE, Janisch L, Nauling F, Hong DS, Ng CS, Ye L, Gagel RF, Frye J, Muller T, Ratain MJ, Salgia R: Activity of XL184 (Cabozantinib), an oral tyrosine kinase inhibitor, in patients with medullary thyroid cancer. J Clin Oncol. 2011 Jul 1;29(19):2660-6. doi: 10.1200/JCO.2010.32.4145. Epub 2011 May 23. [PubMed:21606412]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da

Drug created on May 12, 2013 18:12 / Updated on November 09, 2017 04:41