General Information of Drug (ID: DMIYDT4)

Drug Name
Cabozantinib
Synonyms Cabometyx; Cometriq
Indication
Disease Entry ICD 11 Status REF
Thyroid cancer 2D10 Approved [1], [2]
Ovarian cancer 2C73 Phase 2 [1], [2]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 2 Molecular Weight (mw) 501.5
Topological Polar Surface Area (xlogp) 5.4
Rotatable Bond Count (rotbonds) 8
Hydrogen Bond Donor Count (hbonddonor) 2
Hydrogen Bond Acceptor Count (hbondacc) 7
ADMET Property
Absorption Tmax
The time to maximum plasma concentration (Tmax) is 2-5 h [3]
Half-life
The concentration or amount of drug in body reduced by one-half in 55 hours [4]
Metabolism
The drug is metabolized via the CYP3A4 and CYP2C9 [3]
Vd
The volume of distribution (Vd) of drug is 349 L [5]
Chemical Identifiers
Formula
C28H24FN3O5
IUPAC Name
1-N-[4-(6,7-dimethoxyquinolin-4-yl)oxyphenyl]-1-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide
Canonical SMILES
COC1=CC2=C(C=CN=C2C=C1OC)OC3=CC=C(C=C3)NC(=O)C4(CC4)C(=O)NC5=CC=C(C=C5)F
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)
InChIKey
ONIQOQHATWINJY-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
25102847
ChEBI ID
CHEBI:72317
CAS Number
849217-68-1
DrugBank ID
DB08875
TTD ID
D0IQ6P
INTEDE ID
DR0254
ACDINA ID
D00087

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Proto-oncogene c-Met (MET) TTNDSF4 MET_HUMAN Inhibitor [2], [6]
Vascular endothelial growth factor receptor 2 (KDR) TTUTJGQ VGFR2_HUMAN Inhibitor [2], [6]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4)
Main DME
DE4LYSA CP3A4_HUMAN Substrate [7]
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Substrate [8]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Thyroid cancer
ICD Disease Classification 2D10
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Vascular endothelial growth factor receptor 2 (KDR) DTT KDR 1.98E-01 0.11 0.2
Proto-oncogene c-Met (MET) DTT MET 1.08E-03 -0.24 -0.4
Cytochrome P450 2C9 (CYP2C9) DME CYP2C9 1.90E-01 -9.81E-03 -5.96E-02
Cytochrome P450 3A4 (CYP3A4) DME CYP3A4 1.04E-02 6.29E-02 3.54E-01
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Same Disease as Cabozantinib
DDI Drug Name DDI Drug ID Severity Mechanism Disease REF
Lenvatinib DMB1IU4 Major Increased risk of prolong QT interval by the combination of Cabozantinib and Lenvatinib. Thyroid cancer [2D10] [45]
Coadministration of a Drug Treating the Disease Different from Cabozantinib (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Metreleptin DM1NOEK Moderate Increased metabolism of Cabozantinib caused by Metreleptin mediated induction of CYP450 enzyme. Acute diabete complication [5A2Y] [46]
Ivosidenib DM8S6T7 Major Increased risk of prolong QT interval by the combination of Cabozantinib and Ivosidenib. Acute myeloid leukaemia [2A60] [47]
Arn-509 DMT81LZ Major Increased metabolism of Cabozantinib caused by Arn-509 mediated induction of CYP450 enzyme. Acute myeloid leukaemia [2A60] [46]
Oliceridine DM6MDCF Major Increased risk of prolong QT interval by the combination of Cabozantinib and Oliceridine. Acute pain [MG31] [48]
Ivabradine DM0L594 Major Increased risk of ventricular arrhythmias by the combination of Cabozantinib and Ivabradine. Angina pectoris [BA40] [45]
Bedaquiline DM3906J Major Increased risk of prolong QT interval by the combination of Cabozantinib and Bedaquiline. Antimicrobial drug resistance [MG50-MG52] [49]
Levalbuterol DM5YBO1 Moderate Increased risk of ventricular arrhythmias by the combination of Cabozantinib and Levalbuterol. Asthma [CA23] [50]
Pexidartinib DMS2J0Z Moderate Increased metabolism of Cabozantinib caused by Pexidartinib mediated induction of CYP450 enzyme. Bone/articular cartilage neoplasm [2F7B] [46]
Talazoparib DM1KS78 Moderate Decreased clearance of Cabozantinib due to the transporter inhibition by Talazoparib. Breast cancer [2C60-2C6Y] [51]
Tucatinib DMBESUA Major Decreased metabolism of Cabozantinib caused by Tucatinib mediated inhibition of CYP450 enzyme. Breast cancer [2C60-2C6Y] [52]
PF-04449913 DMSB068 Major Increased risk of prolong QT interval by the combination of Cabozantinib and PF-04449913. Chronic myelomonocytic leukaemia [2A40] [45]
Olodaterol DM62B78 Moderate Increased risk of prolong QT interval by the combination of Cabozantinib and Olodaterol. Chronic obstructive pulmonary disease [CA22] [53]
Vilanterol DMF5EK1 Moderate Increased risk of ventricular arrhythmias by the combination of Cabozantinib and Vilanterol. Chronic obstructive pulmonary disease [CA22] [50]
Levomilnacipran DMV26S8 Moderate Increased risk of bleeding by the combination of Cabozantinib and Levomilnacipran. Chronic pain [MG30] [54]
Regorafenib DMHSY1I Major Increased risk of bleeding by the combination of Cabozantinib and Regorafenib. Colorectal cancer [2B91] [45]
Osilodrostat DMIJC9X Major Increased risk of prolong QT interval by the combination of Cabozantinib and Osilodrostat. Cushing syndrome [5A70] [45]
Lumacaftor DMCLWDJ Major Increased metabolism of Cabozantinib caused by Lumacaftor mediated induction of CYP450 enzyme. Cystic fibrosis [CA25] [46]
MK-8228 DMOB58Q Moderate Decreased metabolism of Cabozantinib caused by MK-8228 mediated inhibition of CYP450 enzyme. Cytomegaloviral disease [1D82] [55]
Vortioxetine DM6F1PU Moderate Increased risk of bleeding by the combination of Cabozantinib and Vortioxetine. Depression [6A70-6A7Z] [54]
Ingrezza DMVPLNC Major Increased risk of prolong QT interval by the combination of Cabozantinib and Ingrezza. Dystonic disorder [8A02] [45]
Stiripentol DMMSDOY Moderate Decreased metabolism of Cabozantinib caused by Stiripentol mediated inhibition of CYP450 enzyme. Epilepsy/seizure [8A61-8A6Z] [55]
Eslicarbazepine DMZREFQ Moderate Increased metabolism of Cabozantinib caused by Eslicarbazepine mediated induction of CYP450 enzyme. Epilepsy/seizure [8A61-8A6Z] [46]
Tazemetostat DMWP1BH Moderate Increased metabolism of Cabozantinib caused by Tazemetostat mediated induction of CYP450 enzyme. Follicular lymphoma [2A80] [46]
Ripretinib DM958QB Moderate Decreased clearance of Cabozantinib due to the transporter inhibition by Ripretinib. Gastrointestinal stromal tumour [2B5B] [52]
Avapritinib DMK2GZX Major Increased risk of bleeding by the combination of Cabozantinib and Avapritinib. Gastrointestinal stromal tumour [2B5B] [45]
Fostemsavir DM50ILT Major Increased risk of prolong QT interval by the combination of Cabozantinib and Fostemsavir. Human immunodeficiency virus disease [1C60-1C62] [45]
Cobicistat DM6L4H2 Major Decreased metabolism of Cabozantinib caused by Cobicistat mediated inhibition of CYP450 enzyme. Human immunodeficiency virus disease [1C60-1C62] [52]
Aliskiren DM1BV7W Moderate Decreased clearance of Cabozantinib due to the transporter inhibition by Aliskiren. Hypertension [BA00-BA04] [56]
Lesinurad DMUR64T Moderate Increased metabolism of Cabozantinib caused by Lesinurad mediated induction of CYP450 enzyme. Inborn purine/pyrimidine/nucleotide metabolism error [5C55] [46]
Berotralstat DMWA2DZ Major Decreased clearance of Cabozantinib due to the transporter inhibition by Berotralstat. Innate/adaptive immunodeficiency [4A00] [57]
Polyethylene glycol DM4I1JP Moderate Increased risk of ventricular arrhythmias by the combination of Cabozantinib and Polyethylene glycol. Irritable bowel syndrome [DD91] [45]
Naloxegol DML0B41 Minor Decreased clearance of Cabozantinib due to the transporter inhibition by Naloxegol. Large intestine motility disorder [DB32] [58]
Brigatinib DM7W94S Moderate Increased metabolism of Cabozantinib caused by Brigatinib mediated induction of CYP450 enzyme. Lung cancer [2C25] [46]
Ceritinib DMB920Z Major Decreased metabolism of Cabozantinib caused by Ceritinib mediated inhibition of CYP450 enzyme. Lung cancer [2C25] [52]
PF-06463922 DMKM7EW Moderate Increased metabolism of Cabozantinib caused by PF-06463922 mediated induction of CYP450 enzyme. Lung cancer [2C25] [46]
Osimertinib DMRJLAT Major Increased risk of prolong QT interval by the combination of Cabozantinib and Osimertinib. Lung cancer [2C25] [59]
Selpercatinib DMZR15V Major Increased risk of prolong QT interval by the combination of Cabozantinib and Selpercatinib. Lung cancer [2C25] [45]
GDC-0199 DMH0QKA Major Decreased clearance of Cabozantinib due to the transporter inhibition by GDC-0199. Mature B-cell leukaemia [2A82] [52]
IPI-145 DMWA24P Moderate Decreased metabolism of Cabozantinib caused by IPI-145 mediated inhibition of CYP450 enzyme. Mature B-cell leukaemia [2A82] [55]
Acalabrutinib DM7GCVW Major Increased risk of bleeding by the combination of Cabozantinib and Acalabrutinib. Mature B-cell lymphoma [2A85] [60]
Ibrutinib DMHZCPO Major Increased risk of bleeding by the combination of Cabozantinib and Ibrutinib. Mature B-cell lymphoma [2A85] [55]
Ponatinib DMYGJQO Major Increased risk of bleeding by the combination of Cabozantinib and Ponatinib. Mature B-cell lymphoma [2A85] [61]
Arry-162 DM1P6FR Major Increased risk of bleeding by the combination of Cabozantinib and Arry-162. Melanoma [2C30] [55]
Vemurafenib DM62UG5 Major Increased risk of prolong QT interval by the combination of Cabozantinib and Vemurafenib. Melanoma [2C30] [56]
LGX818 DMNQXV8 Major Increased risk of prolong QT interval by the combination of Cabozantinib and LGX818. Melanoma [2C30] [45]
Dabrafenib DMX6OE3 Moderate Increased metabolism of Cabozantinib caused by Dabrafenib mediated induction of CYP450 enzyme. Melanoma [2C30] [45]
Siponimod DM2R86O Major Increased risk of ventricular arrhythmias by the combination of Cabozantinib and Siponimod. Multiple sclerosis [8A40] [52]
Ozanimod DMT6AM2 Major Increased risk of ventricular arrhythmias by the combination of Cabozantinib and Ozanimod. Multiple sclerosis [8A40] [62]
Fedratinib DM4ZBK6 Moderate Decreased metabolism of Cabozantinib caused by Fedratinib mediated inhibition of CYP450 enzyme. Myeloproliferative neoplasm [2A20] [55]
Ruxolitinib DM7Q98D Major Increased risk of bleeding by the combination of Cabozantinib and Ruxolitinib. Myeloproliferative neoplasm [2A20] [55]
Vorapaxar DMA16BR Major Increased risk of bleeding by the combination of Cabozantinib and Vorapaxar. Myocardial infarction [BA41-BA43] [55]
Entrectinib DMMPTLH Major Increased risk of prolong QT interval by the combination of Cabozantinib and Entrectinib. Non-small cell lung cancer [2C25] [45]
Rucaparib DM9PVX8 Major Increased risk of prolong QT interval by the combination of Cabozantinib and Rucaparib. Ovarian cancer [2C73] [45]
MK-4827 DMLYGH4 Moderate Increased risk of bleeding by the combination of Cabozantinib and MK-4827. Ovarian cancer [2C73] [45]
Triclabendazole DMPWGBR Major Increased risk of prolong QT interval by the combination of Cabozantinib and Triclabendazole. Parasitic worm infestation [1F90] [45]
Abametapir DM2RX0I Moderate Decreased metabolism of Cabozantinib caused by Abametapir mediated inhibition of CYP450 enzyme. Pediculosis [1G00] [63]
Macimorelin DMQYJIR Major Increased risk of prolong QT interval by the combination of Cabozantinib and Macimorelin. Pituitary gland disorder [5A60-5A61] [64]
Enzalutamide DMGL19D Major Increased metabolism of Cabozantinib caused by Enzalutamide mediated induction of CYP450 enzyme. Prostate cancer [2C82] [46]
Relugolix DMK7IWL Major Decreased clearance of Cabozantinib due to the transporter inhibition by Relugolix. Prostate cancer [2C82] [65]
Voxelotor DMCS6M5 Moderate Decreased metabolism of Cabozantinib caused by Voxelotor mediated inhibition of CYP450 enzyme. Sickle-cell disorder [3A51] [55]
Larotrectinib DM26CQR Moderate Decreased metabolism of Cabozantinib caused by Larotrectinib mediated inhibition of CYP450 enzyme. Solid tumour/cancer [2A00-2F9Z] [52]
LEE011 DMMX75K Major Increased risk of prolong QT interval by the combination of Cabozantinib and LEE011. Solid tumour/cancer [2A00-2F9Z] [56]
Pitolisant DM8RFNJ Major Increased risk of prolong QT interval by the combination of Cabozantinib and Pitolisant. Somnolence [MG42] [45]
Fostamatinib DM6AUHV Moderate Decreased metabolism of Cabozantinib caused by Fostamatinib mediated inhibition of CYP450 enzyme. Thrombocytopenia [3B64] [66]
Elagolix DMB2C0E Moderate Increased metabolism of Cabozantinib caused by Elagolix mediated induction of CYP450 enzyme. Uterine fibroid [2E86] [46]
Betrixaban DM2C4RF Major Increased risk of bleeding by the combination of Cabozantinib and Betrixaban. Venous thromboembolism [BD72] [55]
⏷ Show the Full List of 66 DDI Information of This Drug

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG
DIG Name DIG ID PubChem CID Functional Classification
Isopropyl alcohol E00070 3776 Antimicrobial preservative; Solvent
Stearic acid E00079 5281 Emulsifying agent; Solubilizing agent; Viscosity-controlling agent; lubricant
Ammonia E00007 222 Alkalizing agent
Beta-D-lactose E00099 6134 Diluent; Dry powder inhaler carrier; Lyophilization aid
Butyl alcohol E00011 263 Flavoring agent; Solvent
Carmellose sodium E00625 Not Available Disintegrant
Ferric hydroxide oxide yellow E00539 23320441 Colorant
Ferric oxide black E00522 16211978 Colorant
Ferrosoferric oxide E00231 14789 Colorant
Hydroxypropyl cellulose E00632 Not Available Binding agent; Coating agent; Emulsifying agent; Film/Membrane-forming agent; Modified-release agent; Suspending agent; Viscosity-controlling agent
Hypromellose E00634 Not Available Coating agent
Magnesium stearate E00208 11177 lubricant
Propylene glycol E00040 1030 Antimicrobial preservative; Humectant; Plasticizing agent; Solvent
Silicon dioxide E00670 Not Available Anticaking agent; Opacifying agent; Viscosity-controlling agent
Titanium dioxide E00322 26042 Coating agent; Colorant; Opacifying agent
Triacetin E00080 5541 Humectant; Plasticizing agent; Solvent
Haematite red E00236 14833 Colorant
Hydrophobic colloidal silica E00285 24261 Anticaking agent; Emulsion stabilizing agent; Glidant; Suspending agent; Viscosity-controlling agent
Ammonium hydroxide E00687 Not Available Alkalizing agent
Cellulose microcrystalline E00698 Not Available Adsorbent; Suspending agent; Diluent
Shellac E00695 Not Available Coating agent; Film/membrane-forming agent; Microencapsulating agent; Modified-release agent
⏷ Show the Full List of 21 Pharmaceutical Excipients of This Drug
Pharmaceutical Formulation
Formulation Name Drug Dosage Dosage Form Route
Cabozantinib 20 mg capsule 20 mg Oral Capsule Oral
Cabozantinib S-Malate eq 80mg base capsule eq 80mg base Capsule Oral
Cabozantinib S-Malate eq 20mg base capsule eq 20mg base Capsule Oral
Cabozantinib S-Malate eq 20mg base tablet eq 20mg base Tablet Oral
Cabozantinib S-Malate eq 40mg base tablet eq 40mg base Tablet Oral
Cabozantinib S-Malate eq 60mg base tablet eq 60mg base Tablet Oral
Cabozantinib 20 mg tablet 20 mg Oral Tablet Oral
Cabozantinib 40 mg tablet 40 mg Oral Tablet Oral
Cabozantinib 60 mg tablet 60 mg Oral Tablet Oral
Jump to Detail Pharmaceutical Formulation Page of This Drug

References

1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5887).
2 Clinical pipeline report, company report or official report of Exelixis (2011).
3 FDA approval: ado-trastuzumab emtansine for the treatment of patients with HER2-positive metastatic breast cancer. Clin Cancer Res. 2014 Sep 1;20(17):4436-41.
4 Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
5 An FDA phase I clinical trial of quinacrine sterilization (QS). Int J Gynaecol Obstet. 2003 Oct;83 Suppl 2:S45-9.
6 Tropomyosin receptor kinase inhibitors: an updated patent review for 2010-2016 - Part I.Expert Opin Ther Pat. 2017 Jun;27(6):733-751.
7 Practical management of adverse events associated with cabozantinib treatment in patients with renal-cell carcinoma. Onco Targets Ther. 2017 Oct 19;10:5053-5064.
8 FDA Label of Cabozantinib. The 2020 official website of the U.S. Food and Drug Administration.
9 Expression levels and activation of a PXR variant are directly related to drug resistance in osteosarcoma cell lines. Cancer. 2007 Mar 1;109(5):957-65.
10 Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
11 Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther. 2004 Sep;310(3):1062-75.
12 Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
13 Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
14 Potent mechanism-based inhibition of CYP3A4 by imatinib explains its liability to interact with CYP3A4 substrates. Br J Pharmacol. 2012 Apr;165(8):2787-98.
15 Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
16 The metabolism of zidovudine by human liver microsomes in vitro: formation of 3'-amino-3'-deoxythymidine. Biochem Pharmacol. 1994 Jul 19;48(2):267-76.
17 Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
18 Progesterone and testosterone hydroxylation by cytochromes P450 2C19, 2C9, and 3A4 in human liver microsomes. Arch Biochem Biophys. 1997 Oct 1;346(1):161-9.
19 Tamoxifen inhibits cytochrome P450 2C9 activity in breast cancer patients. J Chemother. 2006 Aug;18(4):421-4.
20 Characterization of the oxidative metabolites of 17beta-estradiol and estrone formed by 15 selectively expressed human cytochrome p450 isoforms. Endocrinology. 2003 Aug;144(8):3382-98.
21 Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
22 Drug-drug interactions with imatinib: an observational study. Medicine (Baltimore). 2016 Oct;95(40):e5076.
23 Drug interactions with calcium channel blockers: possible involvement of metabolite-intermediate complexation with CYP3A. Drug Metab Dispos. 2000 Feb;28(2):125-30.
24 New insights into the structural features and functional relevance of human cytochrome P450 2C9. Part I. Curr Drug Metab. 2009 Dec;10(10):1075-126.
25 A potential role for the estrogen-metabolizing cytochrome P450 enzymes in human breast carcinogenesis. Breast Cancer Res Treat. 2003 Dec;82(3):191-7.
26 A mechanistic approach to antiepileptic drug interactions. Ann Pharmacother. 1998 May;32(5):554-63.
27 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
28 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
29 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2021
30 Antitumor Activity of Amivantamab (JNJ-61186372), an EGFR-MET Bispecific Antibody, in Diverse Models of EGFR Exon 20 Insertion-Driven NSCLC. Cancer Discov. 2020 Aug;10(8):1194-1209.
31 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1815).
32 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
33 Beperminogene perplasmid for the treatment of critical limb ischemia. Expert Rev Cardiovasc Ther. 2014 Oct;12(10):1145-56.
34 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7948).
35 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
36 Preclinical overview of sorafenib, a multikinase inhibitor that targets both Raf and VEGF and PDGF receptor tyrosine kinase signaling.Mol Cancer Ther.2008 Oct;7(10):3129-40.
37 Anthranilic acid amides: a novel class of antiangiogenic VEGF receptor kinase inhibitors. J Med Chem. 2002 Dec 19;45(26):5687-93.
38 2006 drug approvals: finding the niche. Nat Rev Drug Discov. 2007 Feb;6(2):99-101.
39 Nat Rev Drug Discov. 2013 Feb;12(2):87-90.
40 A comparison of physicochemical property profiles of marketed oral drugs and orally bioavailable anti-cancer protein kinase inhibitors in clinical development. Curr Top Med Chem. 2007;7(14):1408-22.
41 Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
42 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services
43 Emerging drugs for ovarian cancer. Expert Opin Emerg Drugs. 2008 Sep;13(3):523-36.
44 YN968D1 is a novel and selective inhibitor of vascular endothelial growth factor receptor-2 tyrosine kinase with potent activity in vitro and in vivo. Cancer Sci. 2011 Jul;102(7):1374-80.
45 Cerner Multum, Inc. "UK Summary of Product Characteristics.".
46 Product Information. Cabometyx (cabozantinib). Exelixis Inc, S San Francisco, CA.
47 Product Information. Tibsovo (ivosidenib). Agios Pharmaceuticals, Cambridge, MA.
48 Product Information. Olinvyk (oliceridine). Trevena Inc, Chesterbrook, PA.
49 Product Information. Sirturo (bedaquiline). Janssen Pharmaceuticals, Titusville, NJ.
50 Product Information. Arcapta Neohaler (indacaterol). Novartis Pharmaceuticals, East Hanover, NJ.
51 Product Information. Talzenna (talazoparib). Pfizer U.S. Pharmaceuticals Group, New York, NY.
52 Cerner Multum, Inc. "Australian Product Information.".
53 Bengtsson B, Fagerstrom PO "Extrapulmonary effects of terbutaline during prolonged administration." Clin Pharmacol Ther 31 (1982): 726-32. [PMID: 7042176]
54 Alderman CP, Moritz CK, Ben-Tovim DI "Abnormal platelet aggregation associated with fluoxetine therapy." Ann Pharmacother 26 (1992): 1517-9. [PMID: 1482806]
55 Product Information. Cometriq (cabozantinib). Exelixis Inc, S San Francisco, CA.
56 Canadian Pharmacists Association.
57 Product Information. Orladeyo (berotralstat). BioCryst Pharmaceuticals Inc, Durham, NC.
58 Product Information. Movantik (naloxegol). Astra-Zeneca Pharmaceuticals, Wilmington, DE.
59 Product Information. Tagrisso (osimertinib). Astra-Zeneca Pharmaceuticals, Wilmington, DE.
60 Product Information. Calquence (acalabrutinib). Astra-Zeneca Pharmaceuticals, Wilmington, DE.
61 Product Information. Iclusig (ponatinib). Ariad Pharmaceuticals Inc, Cambridge, MA.
62 Product Information. Zeposia (ozanimod). Celgene Corporation, Summit, NJ.
63 Product Information. Xeglyze (abametapir topical). Dr. Reddy's Laboratories Inc, Upper Saddle River, NJ.
64 Product Information. Macrilen (macimorelin). Aeterna Zentaris, Charleston, SC.
65 Product Information. Orgovyx (relugolix). Myovant Sciences, Inc., Brisbane, CA.
66 Product Information. Tavalisse (fostamatinib). Rigel Pharmaceuticals, South San Francisco, CA.