Cabozantinib Fumarate

Details

Stereochemistry	ACHIRAL
Molecular Formula	C28H24FN3O5.C4H4O4
Molecular Weight	617.5778
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC(=O)\C=C\C(O)=O.COC1=CC2=NC=CC(OC3=CC=C(NC(=O)C4(CC4)C(=O)NC5=CC=C(F)C=C5)C=C3)=C2C=C1OC

InChI

InChIKey=LHGXFAKOHVXKPV-WLHGVMLRSA-N

InChI=1S/C28H24FN3O5.C4H4O4/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;5-3(6)1-2-4(7)8/h3-11,14-16H,12-13H2,1-2H3,(H,31,33)(H,32,34);1-2H,(H,5,6)(H,7,8)/b;2-1+

HIDE SMILES / InChI

Molecular Formula	C4H4O4
Molecular Weight	116.0722
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	1
Optical Activity	NONE

Molecular Formula	C28H24FN3O5
Molecular Weight	501.5057
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/203756s002lbl.pdf
Curator's Comment: description was created based on several sources, including http://www.ncbi.nlm.nih.gov/pubmed/?term=21606412

Cabozantinib (development code name XL184; marketed under the trade name Cometriq) is an orally bioavailable, small molecule receptor tyrosine kinase (RTK) inhibitor with potential antineoplastic activity. Cabozantinib strongly binds to and inhibits several RTKs, which are often overexpressed in a variety of cancer cell types, including hepatocyte growth factor receptor (MET), RET (rearranged during transfection), vascular endothelial growth factor receptor types 1 (VEGFR-1), 2 (VEGFR-2), and 3 (VEGFR-3), mast/stem cell growth factor (KIT), FMS-like tyrosine kinase 3 (FLT-3), TIE-2 (TEK tyrosine kinase, endothelial), tropomyosin-related kinase B (TRKB) and AXL. This may result in an inhibition of both tumor growth and angiogenesis, and eventually lead to tumor regression. Cabozantinib was granted orphan drug status by the U.S. Food and Drug Administration (FDA) in January 2011. It is currently undergoing clinical trials for the treatment of prostate, bladder, ovarian, brain, melanoma, breast, non-small cell lung, pancreatic, hepatocellular and kidney cancers.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Proto-oncogene tyrosine-protein kinase receptor Ret 7 Target ID: P07949 Gene ID: 5979.0 Gene Symbol: RET Target Organism: Homo sapiens (Human) Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/203756s002lbl.pdf	Inhibitor 8504	5.2 nM [IC50]
Hepatocyte growth factor receptor 56 Target ID: P08581 Gene ID: 4233.0 Gene Symbol: MET Target Organism: Homo sapiens (Human) Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/203756s002lbl.pdf	Inhibitor 8504	1.3 nM [IC50]
Vascular endothelial growth factor receptor 2 112 Target ID: P35968 Gene ID: 3791.0 Gene Symbol: KDR Target Organism: Homo sapiens (Human) Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/203756s002lbl.pdf	Inhibitor 8504	0.035 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Medullary thyroid cancer, metastatic 4 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/203756s004lbl.pdf	Primary		Approved 8583	COMETRIQ Approved Use COMETRIQ is the (S)-malate salt of cabozantinib. COMETRIQ is a kinase inhibitor indicated for the treatment of patients with progressive, metastatic medullary thyroid cancer Launch Date 2012
Renal cell carcinoma 33 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208692s002lbl.pdf	Primary		Approved 8583	CABOMETYX Approved Use CABOMETYX is the (S)-malate salt of cabozantinib. CABOMETYX is a kinase inhibitor indicated for the treatment of patients with advanced renal cell carcinoma (RCC). Launch Date 2016

C_max

Value	Dose	Co-administered	Analyte	Population
554 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/27139820	140 mg single, oral dose: 140 mg route of administration: Oral experiment type: SINGLE co-administered:		CABOZANTINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
58300 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/27139820	140 mg single, oral dose: 140 mg route of administration: Oral experiment type: SINGLE co-administered:		CABOZANTINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
112 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/27139820	140 mg single, oral dose: 140 mg route of administration: Oral experiment type: SINGLE co-administered:		CABOZANTINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
0.3% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208692s000lbl.pdf			CABOZANTINIB plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
250 mg 1 times / day multiple, oral Highest studied dose Dose: 250 mg, 1 times / day Route: oral Route: multiple Dose: 250 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/21606412/	unhealthy, median age 56 years Health Status: unhealthy Age Group: median age 56 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/21606412/	Other AEs: Aspartate aminotransferase increased, Palmar-plantar erythrodysesthesia syndrome... Other AEs: Aspartate aminotransferase increased (grade 3, 16.7%) Palmar-plantar erythrodysesthesia syndrome (grade 3, 16.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/21606412/
265 mg 1 times / day multiple, oral Highest studied dose Dose: 265 mg, 1 times / day Route: oral Route: multiple Dose: 265 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/21606412/	unhealthy, median age 56 years Health Status: unhealthy Age Group: median age 56 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/21606412/	Other AEs: Mucositis... Other AEs: Mucositis (grade 2, 20%) Sources: https://pubmed.ncbi.nlm.nih.gov/21606412/
175 mg 1 times / day multiple, oral MTD Dose: 175 mg, 1 times / day Route: oral Route: multiple Dose: 175 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/21606412/	unhealthy, median age 56 years Health Status: unhealthy Age Group: median age 56 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/21606412/	Sources: https://pubmed.ncbi.nlm.nih.gov/21606412/
162.5 mg 1 times / day multiple, oral Dose: 162.5 mg, 1 times / day Route: oral Route: multiple Dose: 162.5 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/21606412/	unhealthy, median age 56 years Health Status: unhealthy Age Group: median age 56 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/21606412/	Other AEs: Diarrhea, Fatigue... Other AEs: Diarrhea (grade 3, 8%) Fatigue (grade 3, 13%) Decreased appetite (grade 3, 3%) Nausea (grade 3, 3%) Palmar-plantar erythrodysesthesia syndrome (grade 3, 20%) Aspartate aminotransferase increased (grade 3, 5%) Alanine aminotransferase increased (grade 3, 5%) Weight decreased (grade 3, 3%) Hypertension (grade 3, 5%) Lipase increased (grade 3, 18%) Blood amylase increased (grade 3, 8%) Sources: https://pubmed.ncbi.nlm.nih.gov/21606412/
175 mg 1 times / day multiple, oral Dose: 175 mg, 1 times / day Route: oral Route: multiple Dose: 175 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/21606412/	unhealthy, median age 56 years Health Status: unhealthy Age Group: median age 56 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/21606412/	Other AEs: Pulmonary embolism... Other AEs: Pulmonary embolism (grade 4) Sources: https://pubmed.ncbi.nlm.nih.gov/21606412/
11.52 mg/kg 1 times / day multiple, oral Dose: 11.52 mg/kg, 1 times / day Route: oral Route: multiple Dose: 11.52 mg/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/21606412/	unhealthy, median age 56 years Health Status: unhealthy Age Group: median age 56 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/21606412/	Other AEs: Palmar-plantar erythrodysesthesia syndrome, Aspartate aminotransferase increased... Other AEs: Palmar-plantar erythrodysesthesia syndrome (grade 3, 33.3%) Aspartate aminotransferase increased (grade 3, 33.3%) Alanine aminotransferase increase (grade 3, 33.3%) Lipase increased (grade 3, 33.3%) Sources: https://pubmed.ncbi.nlm.nih.gov/21606412/
100 mg 1 times / day multiple, oral Studied dose Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203756lbl.pdf https://pubmed.ncbi.nlm.nih.gov/28352985/	unhealthy, median age 64.8 years Health Status: unhealthy Age Group: median age 64.8 years Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203756lbl.pdf https://pubmed.ncbi.nlm.nih.gov/28352985/	Disc. AE: Large intestine perforation, Intracranial hemorrhage... AEs leading to discontinuation/dose reduction: Large intestine perforation (7.7%) Intracranial hemorrhage (7.7%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203756lbl.pdf https://pubmed.ncbi.nlm.nih.gov/28352985/
60 mg 1 times / day multiple, oral Recommended Dose: 60 mg, 1 times / day Route: oral Route: multiple Dose: 60 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208692Orig1s000MedR.pdf	unhealthy, median age of 62.5 years Health Status: unhealthy Age Group: median age of 62.5 years Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208692Orig1s000MedR.pdf	Disc. AE: Fatigue, Asthenia... Other AEs: Fatigue, Asthenia... AEs leading to discontinuation/dose reduction: Fatigue (1.2%) Asthenia (0.9%) Death (grade 5, 0.6%) Diarrhea (0.9%) Vomiting (0.6%) Nausea (0.3%) Constipation (0.3%) Anal fistula (0.3%) Dry mouth (0.3%) Dysphagia (0.3%) Gastrointestinal perforation (0.3%) Pancreatitis (0.3%) Palmar-plantar erythrodysesthesia syndrome (0.3%) Pain in extremity (0.6%) Proteinuria (0.9%) Renal failure (0.3%) Decreased appetite (1.8%) Dehydration (0.3%) Hyperkalemia (0.3%) Adenocarcinoma (0.3%) Leiomyoma (0.3%) Anal abscess (0.3%) Anorectal cellulitis (0.3%) Device related infection (0.3%) AST increased (0.3%) Weight decreased (0.3%) Cardiac failure (0.3%) Ventricular arrhythmia (0.3%) Hepatitis cholestatic (0.3%) Muscle spasticity (0.3%) Pneumothorax (0.3%) Pulmonary embolism (0.3%) Asthenia (grade 3, 0.6%) Anal fistula (grade 3, 0.3%) Gastrointestinal perforation (grade 3, 0.3%) Pancreatitis (grade 3, 0.3%) Pain in extremity (grade 3, 0.3%) Proteinuria (grade 3, 0.9%) Renal failure (grade 3, 0.3%) Decreased appetite (grade 3, 0.9%) Hyperkalemia (grade 3, 0.3%) Anal abscess (grade 3, 0.3%) Anorectal cellulitis (grade 3, 0.3%) Device related infection (grade 3, 0.3%) Weight decreased (grade 3, 0.3%) Hepatitis cholestatic (grade 3, 0.3%) Pneumothorax (grade 3, 0.3%) Pulmonary embolism (grade 3, 0.3%) Diarrhea (16%) Palmar-plantar erythrodysesthesia syndrome (11%) Fatigue (10%) Hypertension (7.6%) Diarrhea (grade 3, 5.1%) Palmar-plantar erythrodysesthesia syndrome (grade 3, 4.2%) Fatigue (grade 3, 3.6%) Hypertension (grade 3, 6%) Diarrhea (22%) Palmar-plantar erythrodysesthesia syndrome (14%) Fatigue (12%) Nausea (8.5%) Decreased appetite (7.6%) Vomiting (7.6%) Hypertension (5.1%) Diarrhea (grade 3, 8.2%) Palmar-plantar erythrodysesthesia syndrome (grade 3, 7.3%) Fatigue (grade 3, 4.8%) Nausea (grade 3, 1.2%) Decreased appetite (grade 3, 1.2%) Vomiting (grade 3, 1.2%) Hypertension (grade 3, 4.5%) Other AEs: Fatigue (grade 3, 9.1%) Asthenia (grade 3, 4.2%) General physical health deterioration (grade 3, 2.1%) Diarrhea (grade 3, 11.5%) Nausea (grade 3, 3.9%) Abdominal pain (grade 3, 3.6%) Stomatitis (grade 3, 2.4%) Vomiting (grade 3, 2.1%) Palmar-plantar erythrodysesthesia syndrome (grade 3, 8.2%) Hypertension (grade 3, 14.8%) Anemia (grade 3, 5.4%) Dyspnea (grade 3, 3%) Pleural effusion (grade 3, 2.7%) Pulmonary embolism (grade 3, 2.4%) Pneumonia (grade 3, 1.5%) Hypomagnesemia (grade 3, 4.8%) Hypokalemia (grade 3, 4.5%) Hyponatremia (grade 3, 3.9%) Hypophosphatemia (grade 3, 3.6%) Decreased appetite (grade 3, 2.7%) Hypocalcemia (grade 3, 1.8%) Back pain (grade 3, 2.1%) Syncope (grade 3, 1.5%) Proteinuria (grade 3, 2.4%) Lipase increased (grade 3, 2.7%) ALT increased (grade 3, 2.4%) AST increased (grade 3, 1.8%) Weight decreased (grade 3, 1.8%) Blood bilirubin increased (grade 3, 1.5%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208692Orig1s000MedR.pdf
200 mg 1 times / day multiple, oral Dose: 200 mg, 1 times / day Route: oral Route: multiple Dose: 200 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203756lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203756lbl.pdf	Other AEs: Memory impairment, Mental status changes... Other AEs: Memory impairment (grade 3) Mental status changes (grade 3) Cognitive disturbance (grade 3) Weight loss (grade 2) Blood urea nitrogen increased (grade 1) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203756lbl.pdf

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946 inhibitor 2252 inducer 1087	substrate 1193 inhibitor 2438 inducer 440	inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C8 1057 CYP2C19 2057 P-gp 1741 BCRP 910 BSEP 550 MRP2 499 OAT1 725 OAT3 747 OCT1 620 OATP1B1 1079 OATP1B3 961	MRP2 252 OAT1 395 OCT1 393 OATP1B1 503 OATP1B3 435 MATE1 182 MATE2 98 P-gp 2052	CYP1A1 151 CYP1A2 832 CYP2B6 669 CYP2C8 198 CYP2C19 329

Drug as perpetrator

Target	Modality	Activity
BCRP 985	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208692Orig1s000ClinPharmR.pdf#page=23 Page: -	no
BSEP 554	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208692Orig1s000ClinPharmR.pdf#page=23 Page: -	no
CYP1A2 2333	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208692Orig1s000ClinPharmR.pdf#page=34 Page: -	no
CYP2B6 1160	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208692Orig1s000ClinPharmR.pdf#page=34 Page: -	no
CYP2C19 2141	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208692Orig1s000ClinPharmR.pdf#page=34 Page: -	no
CYP2C8 1117	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208692Orig1s000ClinPharmR.pdf#page=34 Page: -	no
CYP2C9 2497	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208692Orig1s000ClinPharmR.pdf#page=34 Page: -	no
CYP3A4 2633	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208692Orig1s000ClinPharmR.pdf#page=34 Page: -	no
MRP2 625	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208692Orig1s000ClinPharmR.pdf#page=23 Page: -	no
OAT1 730	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208692Orig1s000ClinPharmR.pdf#page=23 Page: -	no
OAT3 749	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208692Orig1s000ClinPharmR.pdf#page=23 Page: -	no
OATP1B1 1095	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208692Orig1s000ClinPharmR.pdf#page=23 Page: -	no
OATP1B3 970	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208692Orig1s000ClinPharmR.pdf#page=23 Page: -	no
OCT1 656	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208692Orig1s000ClinPharmR.pdf#page=23 Page: -	no
P-gp 1932	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208692Orig1s000ClinPharmR.pdf#page=34 Page: -	yes [IC50 7 uM]
CYP2D6 2546	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208692Orig1s000ClinPharmR.pdf#page=34 Page: -	yes [IC50 >20 uM]
CYP2C9 2497	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208692Orig1s000ClinPharmR.pdf#page=34 Page: -	yes [Ki 10.4 uM]
CYP2C19 2141	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208692Orig1s000ClinPharmR.pdf#page=34 Page: -	yes [Ki 28.8 uM]
CYP3A4 2633	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208692Orig1s000ClinPharmR.pdf#page=34 Page: -	yes [Ki 282 uM]
CYP2C8 1117	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208692Orig1s000ClinPharmR.pdf#page=34 Page: -	yes [Ki 4.6 uM]
CYP1A1 272	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208692Orig1s000ClinPharmR.pdf#page=34 Page: -	yes

Drug as victim

Target	Modality	Activity	Clinical evidence
OAT1 395	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208692Orig1s000ClinPharmR.pdf#page=23 Page: -	no
OATP1B1 503	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208692Orig1s000ClinPharmR.pdf#page=23 Page: -	no
OATP1B3 435	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208692Orig1s000ClinPharmR.pdf#page=23 Page: -	no
OCT1 393	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208692Orig1s000ClinPharmR.pdf#page=23 Page: -	no
P-gp 2052	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208692Orig1s000ClinPharmR.pdf#page=34 Page: -	no
MATE2 98	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208692Orig1s000ClinPharmR.pdf#page=23 Page: -	yes [IC50 3.2 uM]
MATE1 182	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208692Orig1s000ClinPharmR.pdf#page=23 Page: -	yes [IC50 5.94 uM]
MRP2 252	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208692Orig1s000ClinPharmR.pdf#page=35 Page: -	yes
CYP2C9 1193	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208692Orig1s000ClinPharmR.pdf#page=33 Page: -	yes	no (co-administration study) Comment: Inhibition of CYP2C9 had a minimal effect on cabozantinib metabolite formation (i.e., a <20% reduction). Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208692Orig1s000ClinPharmR.pdf#page=33 Page: -
CYP3A4 1946	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208692Orig1s000ClinPharmR.pdf#page=33 Page: -	yes	yes (co-administration study) Comment: Inhibition of CYP3A4 reduced the formation of the XL184 N-oxide metabolite by >80%. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208692Orig1s000ClinPharmR.pdf#page=33 Page: -

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203756Orig1s000PharmR.pdf Page: -

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:72317	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:72317
eMolecules	36516753	https://www.emolecules.com/cgi-bin/more?vid=36516753
MolPort	MolPort-021-804-939	https://www.molport.com/shop/molecule-link/MolPort-021-804-939
Selleck Chemicals	XL184	http://www.selleckchem.com/products/XL184.html
ZINC	ZINC000070466416	http://zinc15.docking.org/substances/ZINC000070466416

PubMed

Title	Date	PubMed
Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma.	2015-11-05	26406150
Cabozantinib (XL184), a novel MET and VEGFR2 inhibitor, simultaneously suppresses metastasis, angiogenesis, and tumor growth.	2011-12	21926191

Patents

Sample Use Guides

In Vivo Use Guide

Recommended Dose: 140 mg orally, once daily

Route of Administration: Oral

In Vitro Use Guide

For in vitro assays, 10 mM cabozantinib stock solutions were prepared in dimethyl sulfoxide (DMSO) and diluted in the appropriate media.

Substance Class	Chemical Created by `admin` on `Wed Apr 02 19:09:43 GMT 2025` Edited by `admin` on `Wed Apr 02 19:09:43 GMT 2025`
Record UNII	L8G2779TE5
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

N-(4-((6, 7-Dimethoxyquinolin-4-yl)oxy)phenyl)-N-(4-fluorophenyl)cyclopropane-1, 1-dicarboxamide fumarate

Preferred Name

English

Cabozantinib Fumarate

Common Name

English

Code System Code Type Description

CAS

3039845-68-3

Created by admin on Wed Apr 02 19:09:43 GMT 2025 , Edited by admin on Wed Apr 02 19:09:43 GMT 2025

NON-SPECIFIC STOICHIOMETRY

FDA UNII

L8G2779TE5

Created by admin on Wed Apr 02 19:09:43 GMT 2025 , Edited by admin on Wed Apr 02 19:09:43 GMT 2025

PRIMARY

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Amount: