CABOZANTINIB S-MALATE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C28H24FN3O5.C4H6O5
Molecular Weight	635.5931
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

O[C@@H](CC(O)=O)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=HFCFMRYTXDINDK-WNQIDUERSA-N

InChI=1S/C28H24FN3O5.C4H6O5/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;5-2(4(8)9)1-3(6)7/h3-11,14-16H,12-13H2,1-2H3,(H,31,33)(H,32,34);2,5H,1H2,(H,6,7)(H,8,9)/t;2-/m.0/s1

HIDE SMILES / InChI

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

Molecular Formula	C4H6O5
Molecular Weight	134.0874
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

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 6 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 8297	5.2 nM [IC50]
Hepatocyte growth factor receptor 54 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 8297	1.3 nM [IC50]
Vascular endothelial growth factor receptor 2 104 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 8297	0.035 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Medullary thyroid cancer 3 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/203756s002lbl.pdf	Secondary	Approved 8429	COMETRIQ Approved Use Indicated for the treatment of patients with progressive, metastatic medullary thyroid cancer (MTC) Launch Date 2012
Medullary thyroid cancer, metastatic 3 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/203756s004lbl.pdf	Primary	Approved 8429	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 31 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208692s002lbl.pdf	Primary	Approved 8429	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 n = 6 Health Status: unhealthy Condition: solid tumors Age Group: median age 56 years Sex: M+F Population Size: 6 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 n = 10 Health Status: unhealthy Condition: solid tumors Age Group: median age 56 years Sex: M+F Population Size: 10 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 n = 40 Health Status: unhealthy Condition: solid tumors Age Group: median age 56 years Sex: M+F Population Size: 40 Sources: https://pubmed.ncbi.nlm.nih.gov/21606412/	Sources: https://pubmed.ncbi.nlm.nih.gov/21606412/
162.5 mg 1 times / day multiple, oral (mean) 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 n = 40 Health Status: unhealthy Condition: solid tumors Age Group: median age 56 years Sex: M+F Population Size: 40 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 Condition: solid tumors 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 n = 3 Health Status: unhealthy Condition: solid tumors Age Group: median age 56 years Sex: M+F Population Size: 3 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 Co-administed with:: Erlotinib(50 mg; 1/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 n = 13 Health Status: unhealthy Condition: non-small cell lung cancer Age Group: median age 64.8 years Sex: M+F Population Size: 13 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 Page: 208692Orig1s000MedR.pdf - p.90	unhealthy, median age of 62.5 years n = 331 Health Status: unhealthy Condition: Renal Cell Carcinoma Age Group: median age of 62.5 years Sex: M+F Population Size: 331 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208692Orig1s000MedR.pdf Page: 208692Orig1s000MedR.pdf - p.90	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 Page: 208692Orig1s000MedR.pdf - p.90
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 n = 1 Health Status: unhealthy Condition: renal cell carcinoma Population Size: 1 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 1737 inhibitor 1587 inducer 781	substrate 1037 inhibitor 1767 inducer 389	inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C8 911 CYP2C19 1478 P-gp 1461 BCRP 699 BSEP 402 MRP2 383 OAT1 599 OAT3 642 OCT1 512 OATP1B1 788 OATP1B3 706	MRP2 205 OAT1 326 OCT1 327 OATP1B1 406 OATP1B3 350 MATE1 135 MATE2 96 P-gp 1537	CYP1A1 108 CYP1A2 701 CYP2B6 547 CYP2C8 168 CYP2C19 293

Drug as perpetrator

Target	Modality	Activity
BCRP 773	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208692Orig1s000ClinPharmR.pdf#page=23 Page: -	no
BSEP 403	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208692Orig1s000ClinPharmR.pdf#page=23 Page: -	no
CYP1A2 1692	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208692Orig1s000ClinPharmR.pdf#page=34 Page: -	no
CYP2B6 1001	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208692Orig1s000ClinPharmR.pdf#page=34 Page: -	no
CYP2C19 1553	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208692Orig1s000ClinPharmR.pdf#page=34 Page: -	no
CYP2C8 965	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208692Orig1s000ClinPharmR.pdf#page=34 Page: -	no
CYP2C9 1819	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208692Orig1s000ClinPharmR.pdf#page=34 Page: -	no
CYP3A4 1925	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208692Orig1s000ClinPharmR.pdf#page=34 Page: -	no
MRP2 475	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208692Orig1s000ClinPharmR.pdf#page=23 Page: -	no
OAT1 603	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208692Orig1s000ClinPharmR.pdf#page=23 Page: -	no
OAT3 644	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208692Orig1s000ClinPharmR.pdf#page=23 Page: -	no
OATP1B1 803	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208692Orig1s000ClinPharmR.pdf#page=23 Page: -	no
OATP1B3 715	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208692Orig1s000ClinPharmR.pdf#page=23 Page: -	no
OCT1 543	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208692Orig1s000ClinPharmR.pdf#page=23 Page: -	no
P-gp 1650	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208692Orig1s000ClinPharmR.pdf#page=34 Page: -	yes [IC50 7 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208692Orig1s000ClinPharmR.pdf#page=34 Page: -	yes [IC50 >20 uM]
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208692Orig1s000ClinPharmR.pdf#page=34 Page: -	yes [Ki 10.4 uM]
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208692Orig1s000ClinPharmR.pdf#page=34 Page: -	yes [Ki 28.8 uM]
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208692Orig1s000ClinPharmR.pdf#page=34 Page: -	yes [Ki 282 uM]
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208692Orig1s000ClinPharmR.pdf#page=34 Page: -	yes [Ki 4.6 uM]
CYP1A1 218	inducer 1573 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 326	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208692Orig1s000ClinPharmR.pdf#page=23 Page: -	no
OATP1B1 406	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208692Orig1s000ClinPharmR.pdf#page=23 Page: -	no
OATP1B3 350	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208692Orig1s000ClinPharmR.pdf#page=23 Page: -	no
OCT1 327	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208692Orig1s000ClinPharmR.pdf#page=23 Page: -	no
P-gp 1537	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208692Orig1s000ClinPharmR.pdf#page=34 Page: -	no
MATE2 96	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208692Orig1s000ClinPharmR.pdf#page=23 Page: -	yes [IC50 3.2 uM]
MATE1 135	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208692Orig1s000ClinPharmR.pdf#page=23 Page: -	yes [IC50 5.94 uM]
MRP2 205	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208692Orig1s000ClinPharmR.pdf#page=35 Page: -	yes
CYP2C9 1037	substrate 3367 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 1737	substrate 3367 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 1647	inhibitor 1626 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
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
eMolecules	36516753	https://www.emolecules.com/cgi-bin/more?vid=36516753

PubMed

Title	Date	PubMed
Cabozantinib (XL184), a novel MET and VEGFR2 inhibitor, simultaneously suppresses metastasis, angiogenesis, and tumor growth.	2011 Dec	21926191
Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma.	2015 Nov 5	26406150

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 `Fri Dec 15 16:26:18 GMT 2023` Edited by `admin` on `Fri Dec 15 16:26:18 GMT 2023`
Record UNII	DR7ST46X58
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

CABOZANTINIB S-MALATE

Official Name

English

N-(4-((6,7-DIMETHOXYQUINOLIN-4-YL)OXY)PHENYL)-N'-(4-FLUOROPHENYL)CYCLOPROPANE-1,1-DICARBOXAMIDE MONO((2S)-2-HYDROXYBUTANEDIOATE)

Systematic Name

English

XL-184

Code

English

XL184

Code

English

BMS-907351

Code

English

CABOZANTINIB MALATE [JAN]

Common Name

English

CABOZANTINIB S-MALATE [ORANGE BOOK]

Common Name

English

CABOZANTINIB S-MALATE [USAN]

Common Name

English

CABOMETYX

Brand Name

English

BUTANEDIOIC ACID, 2-HYDROXY-, (2S)-, COMPD. WITH N-(4-((6,7-DIMETHOXY-4-QUINOLINYL)OXY)PHENYL)-N'-(4-FLUOROPHENYL)-1,1-CYCLOPROPANEDICARBOXAMIDE (1:1)

Common Name

English

Cabozantinib s-malate [WHO-DD]

Common Name

English

COMETRIQ

Brand Name

English

Classification Tree Code System Code

NCI_THESAURUS

C1967