PAZOPANIB HYDROCHLORIDE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C21H23N7O2S.ClH
Molecular Weight	473.979
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Cl.CN(C1=CC2=NN(C)C(C)=C2C=C1)C3=CC=NC(NC4=CC=C(C)C(=C4)S(N)(=O)=O)=N3

InChI

InChIKey=MQHIQUBXFFAOMK-UHFFFAOYSA-N

InChI=1S/C21H23N7O2S.ClH/c1-13-5-6-15(11-19(13)31(22,29)30)24-21-23-10-9-20(25-21)27(3)16-7-8-17-14(2)28(4)26-18(17)12-16;/h5-12H,1-4H3,(H2,22,29,30)(H,23,24,25);1H

HIDE SMILES / InChI

Molecular Formula	C21H23N7O2S
Molecular Weight	437.518
Charge	0
Count

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

Molecular Formula	ClH
Molecular Weight	36.461
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/2012/022465s-010S-012lbl.pdf
Curator's Comment: Description was created based on several sources, including http://adisinsight.springer.com/drugs/800016874 | https://www.ncbi.nlm.nih.gov/pubmed/26767042 | https://www.ncbi.nlm.nih.gov/pubmed/17620431

Pazopanib (VOTRIENT) is an orally bioavailable multi-targeted tyrosine kinase receptor inhibitor. Pazopanib inhibits vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2, VEGFR-3, platelet-derived growth factor receptor (PDGFR)-α and -β, fibroblast growth factor receptor (FGFR) -1 and -3, cytokine receptor (Kit), interleukin-2 receptor inducible T-cell kinase (Itk), leukocyte-specific protein tyrosine kinase (Lck), and transmembrane glycoprotein receptor tyrosine kinase (c-Fms). In an vitro study, pazopanib exerted anti-tumor effect through mechanisms including the Raf-MAPK/ERK (MEK)-extracellular signal-regulated kinase (ERK) pathway. It has good oral exposure and inhibits angiogenesis and tumor growth in mice. Pazopanib (VOTRIENT) was developed by GlaxoSmithKline for the treatment of solid tumours and age-related macular degeneration. However, Novartis acquired all the rights to the drug from GlaxoSmithKline. Pazopanib (VOTRIENT) is indicated for the treatment of patients with advanced renal cell carcinoma and advanced soft tissue sarcoma.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Fibroblast growth factor receptor 1 45 Target ID: CHEMBL3650 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17620431/	Inhibitor 8297	0.14 µM [IC50]
Fibroblast growth factor receptor 3 32 Target ID: CHEMBL2742 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17620431/	Inhibitor 8297	0.13 µM [IC50]
Macrophage colony stimulating factor receptor 24 Target ID: CHEMBL1844 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17620431/	Inhibitor 8297	0.146 µM [IC50]
Platelet-derived growth factor receptor alpha 30 Target ID: CHEMBL2007 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17620431/	Inhibitor 8297	0.071 µM [IC50]
Platelet-derived growth factor receptor beta 56 Target ID: CHEMBL1913 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17620431/	Inhibitor 8297	0.084 µM [IC50]
Stem cell growth factor receptor 53 Target ID: CHEMBL1936 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17620431/	Inhibitor 8297	0.074 µM [IC50]
Tyrosine-protein kinase ITK/TSK 4 Target ID: CHEMBL2959 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17620431/	Inhibitor 8297	0.43 µM [IC50]
Tyrosine-protein kinase LCK 12 Target ID: CHEMBL258 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17620431/	Inhibitor 8297	0.411 µM [IC50]
Vascular endothelial growth factor receptor 1 41 Target ID: CHEMBL1868 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17620431/	Inhibitor 8297	0.01 µM [IC50]
Vascular endothelial growth factor receptor 2 104 Target ID: CHEMBL279 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17620431/	Inhibitor 8297	0.03 µM [IC50]
Vascular endothelial growth factor receptor 3 41 Target ID: CHEMBL1955 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17620431/	Inhibitor 8297	0.047 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Renal cell carcinoma 31 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/022465s-010S-012lbl.pdf https://www.ncbi.nlm.nih.gov/pubmed/22341567	Primary		Approved 8429	VOTRIENT Approved Use VOTRIENT® is indicated for the treatment of patients with advanced renal cell carcinoma (RCC). VOTRIENT is indicated for the treatment of patients with advanced soft tissue sarcoma (STS) who have received prior chemotherapy. Limitation of Use: The efficacy of VOTRIENT for the treatment of patients with adipocytic STS or gastrointestinal stromal tumors has not been demonstrated. VOTRIENT is a kinase inhibitor indicated for the treatment of patients with: •advanced renal cell carcinoma. (1) •advanced soft tissue sarcoma who have received prior chemotherapy. (1) Limitation of Use: The efficacy of VOTRIENT for the treatment of patients with adipocytic soft tissue sarcoma or gastrointestinal stromal tumors has not been demonstrated. Launch Date 1.25591041E12
Soft tissue sarcoma 10 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/022465s-010S-012lbl.pdf https://www.ncbi.nlm.nih.gov/pubmed/23488774	Primary		Approved 8429	VOTRIENT Approved Use VOTRIENT® is indicated for the treatment of patients with advanced renal cell carcinoma (RCC). VOTRIENT is indicated for the treatment of patients with advanced soft tissue sarcoma (STS) who have received prior chemotherapy. Limitation of Use: The efficacy of VOTRIENT for the treatment of patients with adipocytic STS or gastrointestinal stromal tumors has not been demonstrated. VOTRIENT is a kinase inhibitor indicated for the treatment of patients with: •advanced renal cell carcinoma. (1) •advanced soft tissue sarcoma who have received prior chemotherapy. (1) Limitation of Use: The efficacy of VOTRIENT for the treatment of patients with adipocytic soft tissue sarcoma or gastrointestinal stromal tumors has not been demonstrated. Launch Date 1.25591041E12

C_max

Value	Dose	Analyte	Population
44.8 mg/L EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/31125423	800 mg 1 times / day multiple, oral dose: 800 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PAZOPANIB blood	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
50.2 mg/L EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/31125423	600 mg 1 times / day multiple, oral dose: 600 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PAZOPANIB blood	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED
58.1 μg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022465lbl.pdf	800 mg single, oral dose: 800 mg route of administration: Oral experiment type: SINGLE co-administered:	PAZOPANIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Analyte	Population
821 mg × h/L EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/31125423	800 mg 1 times / day multiple, oral dose: 800 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PAZOPANIB blood	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
895 mg × h/L EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/31125423	600 mg 1 times / day multiple, oral dose: 600 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PAZOPANIB blood	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED
1037 μg × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022465lbl.pdf	800 mg single, oral dose: 800 mg route of administration: Oral experiment type: SINGLE co-administered:	PAZOPANIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
1% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/022465s-010S-012lbl.pdf			PAZOPANIB plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
800 mg 1 times / day multiple, oral Recommended Dose: 800 mg, 1 times / day Route: oral Route: multiple Dose: 800 mg, 1 times / day Sources: PAZOPANIB Page: p. 61	unhealthy, 59 years n = 290 Health Status: unhealthy Condition: renal cell carcinoma Age Group: 59 years Sex: M+F Population Size: 290 Sources: PAZOPANIB Page: p. 61	Disc. AE: Proteinuria... AEs leading to discontinuation/dose reduction: Proteinuria (5 patients) Sources: PAZOPANIB Page: p. 61
800 mg 1 times / day multiple, oral Recommended Dose: 800 mg, 1 times / day Route: oral Route: multiple Dose: 800 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_MedR.pdf Page: p. 61	unhealthy, 59 years n = 290 Health Status: unhealthy Condition: renal cell carcinoma Age Group: 59 years Sex: M+F Population Size: 290 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_MedR.pdf Page: p. 61	Disc. AE: ALT increased, AST increased... AEs leading to discontinuation/dose reduction: ALT increased (11 patient) AST increased (11 patient) Bilirubin increased (11 patient) Myocardial infarction (6 patients) Ischemic stroke (6 patients) Transient ischemic attack (6 patients) Fatigue (5 patients) Diarrhea (7 patients) Anorexia (7 patients) Vomiting (7 patients) Proteinuria (3 patients) Hypertension (2 patients) Hemorrhage (2 patients) Confusion (12 patients) Infection (12 patients) Hand-and-foot syndrome (12 patients) Edema (12 patients) Dehydration (12 patients) Anemia (12 patients) Anxiety (12 patients) Convulsion (12 patients) Atrial fibrillation (12 patients) Hypertension (20 patients) Gastrointestinal disturbance (17 patients) Liver function test abnormal (16 patients) Fatigue (10 patients) Hematologic disorder (4 patients) Rash (5 patients) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_MedR.pdf Page: p. 61
600 mg 1 times / day multiple, oral MTD Dose: 600 mg, 1 times / day Route: oral Route: multiple Dose: 600 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/21831954	unhealthy, 61 years (range: 38–76 years) n = 8 Health Status: unhealthy Condition: Hepatocellular Carcinoma Age Group: 61 years (range: 38–76 years) Sex: M+F Population Size: 8 Sources: https://pubmed.ncbi.nlm.nih.gov/21831954	DLT: Neutropenia, Aspartate aminotransferase increased... Other AEs: Diarrhea, Hypertension... Dose limiting toxicities: Neutropenia (grade 2, 1 patient) Aspartate aminotransferase increased (grade 2, 1 patient) Hyperbilirubinemia (grade 2, 1 patient) Other AEs: Diarrhea (all grades, 50%) Hypertension (grade 3, 13%) AST increased (grade 3, 13%) ALT increased (all grades, 25%) Cough (all grades, 13%) Skin hypopigmentation (all grades, 50%) Weight decrease (all grades, 25%) Alopecia (all grades, 13%) Dizziness (all grades, 13%) Hyperbilirubinemia (all grades, 25%) Abdominal distension (all grades, 25%) Abdominal pain (all grades, 25%) Fatigue (all grades, 13%) Leukopenia (all grades, 13%) Muscle spasms (all grades, 25%) Upper respiratory tract infection (all grades, 13%) Hypercholesterolemia (grade 3, 13%) Gastrointestinal hemorrhage (grade 4, 13%) Hypoglycemia (grade 4, 13%) Transaminases increased (grade 4, 13%) Sources: https://pubmed.ncbi.nlm.nih.gov/21831954
800 mg 1 times / day multiple, oral Dose: 800 mg, 1 times / day Route: oral Route: multiple Dose: 800 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/21831954	unhealthy, 61 years (range: 38–76 years) n = 5 Health Status: unhealthy Condition: Hepatocellular Carcinoma Age Group: 61 years (range: 38–76 years) Sex: M+F Population Size: 5 Sources: https://pubmed.ncbi.nlm.nih.gov/21831954	DLT: Aspartate aminotransferase increase, Malaise... Dose limiting toxicities: Aspartate aminotransferase increase (grade 3, 2 patients) Malaise (grade 3, 2 patients) ALT increased (grade 3, 2 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/21831954
800 mg 1 times / day multiple, oral Recommended Dose: 800 mg, 1 times / day Route: oral Route: multiple Dose: 800 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022465lbl.pdf	unhealthy, adult Health Status: unhealthy Condition: advanced renal cell carcinoma Age Group: adult Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022465lbl.pdf	Other AEs: Hepatotoxicity... Other AEs: Hepatotoxicity (severe\|grade 5) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022465lbl.pdf
2000 mg 1 times / day multiple, oral Highest studied dose Dose: 2000 mg, 1 times / day Route: oral Route: multiple Dose: 2000 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022465lbl.pdf https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_MedR.pdf	unhealthy n = 3 Health Status: unhealthy Population Size: 3 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022465lbl.pdf https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_MedR.pdf	DLT: Fatigue... Dose limiting toxicities: Fatigue (grade 3, 1 patient) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022465lbl.pdf https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_MedR.pdf
1000 mg 1 times / day multiple, oral Dose: 1000 mg, 1 times / day Route: oral Route: multiple Dose: 1000 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022465lbl.pdf https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_MedR.pdf	unhealthy n = 3 Health Status: unhealthy Population Size: 3 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022465lbl.pdf https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_MedR.pdf	DLT: Hypertension... Dose limiting toxicities: Hypertension (grade 3, 1 patient) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022465lbl.pdf https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_MedR.pdf

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737 inhibitor 1587 inducer 781	inhibitor 1767	inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 CYP2B6 810 CYP2C8 911 CYP2C19 1478 CYP2E1 882 P-gp 1461 UGT1A1 204 OATP1B1 788	CYP1A2 1054 CYP2C8 693 P-gp 1537	CYP2B6 547 CYP1A2 701

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_ClinPharmR.pdf#page=32 Page: 32.0	moderate [IC50 10 uM]	weak (co-administration study) Comment: AUC of paclitaxel (CYP3A4 and CYP2C8 substrate) increased by 26%, decreased paclitaxel clearance by 14%, and increased paclitaxel Cmax by 31%; Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_ClinPharmR.pdf#page=32 Page: 32.0
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_ClinPharmR.pdf#page=32 Page: 32,36	moderate [IC50 11 uM]	no (co-administration study) Comment: no effect Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_ClinPharmR.pdf#page=32 Page: 32,36
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_ClinPharmR.pdf#page=33 Page: 33,37	moderate [IC50 11 uM]	weak (co-administration study) Comment: pazopanib increased the AUC of CYP3A4 substrate (midazolam) by 32%; AUC of paclitaxel (CYP3A4 and CYP2C8 substrate) increased by 26%, decreased paclitaxel clearance by 14%, and increased paclitaxel Cmax by 31%; Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_ClinPharmR.pdf#page=33 Page: 33,37
CYP2B6 1001	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_ClinPharmR.pdf#page=32 Page: 32.0	moderate [IC50 15 uM]
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_ClinPharmR.pdf#page=32 Page: 32,36	moderate [IC50 16 uM]	no (co-administration study) Comment: no effect Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_ClinPharmR.pdf#page=32 Page: 32,36
CYP2E1 970	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_ClinPharmR.pdf#page=32 Page: 32.0	moderate [IC50 17 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_ClinPharmR.pdf#page=32 Page: 32,37	moderate [IC50 18 uM]	yes (co-administration study) Comment: increased the AUC of CYP2D6 substrate (dextromethorphan) by 64% Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_ClinPharmR.pdf#page=32 Page: 32,37
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_ClinPharmR.pdf#page=32 Page: 32,36	moderate [IC50 7.9 uM]	no (co-administration study) Comment: no effect Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_ClinPharmR.pdf#page=32 Page: 32,36
CYP2B6 1001	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_ClinPharmR.pdf#page=32 Page: 32,33	moderate
CYP3A4 1925	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_ClinPharmR.pdf#page=32 Page: 32,33,37	moderate	weak (co-administration study) Comment: pazopanib increased the AUC of CYP3A4 substrate (midazolam) by 32%; AUC of paclitaxel (CYP3A4 and CYP2C8 substrate) increased by 26%, decreased paclitaxel clearance by 14%, and increased paclitaxel Cmax by 31%; Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_ClinPharmR.pdf#page=32 Page: 32,33,37
CYP1A2 1692	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_ClinPharmR.pdf#page=33 Page: 33.0	no
P-gp 1650	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_ClinPharmR.pdf#page=34 Page: 34.0	no
OATP1B1 803	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_ClinPharmR.pdf#page=34 Page: 34.0	yes [IC50 0.79 uM]
UGT1A1 254	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_ClinPharmR.pdf#page=34 Page: 34,4	yes [IC50 1.2 uM]	yes (pharmacogenomic study) Comment: Certain UGT1A1 genotypes are associated with an increase in the risk of pazopanib induced hyperbilirubinemia. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_ClinPharmR.pdf#page=34 Page: 34,4

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP3A4 1737	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_ClinPharmR.pdf#page=32 Page: 32,35	major	yes (co-administration study) Comment: pazopanib AUC (0-t), Cmax, and half-life were increased 1.47, 2.21, and 2.81 fold, respectively; Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_ClinPharmR.pdf#page=32 Page: 32,35
CYP1A2 1054	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_ClinPharmR.pdf#page=32 Page: 32.0	minor
CYP2C8 693	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_ClinPharmR.pdf#page=32 Page: 32.0	minor
P-gp 1537	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_ClinPharmR.pdf#page=34 Page: 34,35	yes	yes (co-administration study) Comment: AUC(0-t) and Cmax values of pazopanib are increased by 59 and 50%, respectively, when coadministered with lapatinib; Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_ClinPharmR.pdf#page=34 Page: 34,35

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_PharmR.pdf#PAGE=68 Page: 68.0

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:71219	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:71219
MolPort	MolPort-006-827-156	https://www.molport.com/shop/molecule-link/MolPort-006-827-156
Selleck Chemicals	pazopanib	http://www.selleckchem.com/products/pazopanib.html
ZINC	ZINC000011617039	http://zinc15.docking.org/substances/ZINC000011617039
eMolecules	30151586	https://www.emolecules.com/cgi-bin/more?vid=30151586

PubMed

Title	Date	PubMed
Targeted therapy in the treatment of metastatic renal cell cancer.	2009	20130440
Major clinical research advances in gynecologic cancer 2009.	2009 Dec	20041096
Impact of anti-angiogenic treatments on metastatic renal cell carcinoma.	2009 Dec	19954291
Pazopanib: therapeutic developments.	2009 Dec	19954277
Tyrosine kinase inhibitors and the thyroid.	2009 Dec	19942148
Pazopanib: an antiangiogenic drug in perspective.	2009 Nov	19903063
Selective inhibition of retinal angiogenesis by targeting PI3 kinase.	2009 Nov 17	19924235
Pazopanib for the treatment of renal cell carcinoma and other malignancies.	2009 Sep	19956806
Targeting angiogenesis with multitargeted tyrosine kinase inhibitors in the treatment of non-small cell lung cancer.	2010	20427383
Antiangiogenic therapy and mechanisms of tumor resistance in malignant glioma.	2010	20414333
Everolimus (RAD001) in the treatment of advanced renal cell carcinoma: a review.	2010	20215359
Anticancer Role of PPARgamma Agonists in Hematological Malignancies Found in the Vasculature, Marrow, and Eyes.	2010	20204067
Targeting signal transduction pathways in metastatic breast cancer: a comprehensive review.	2010	20200040
Targeted therapies in epithelial ovarian cancer.	2010	20111741
A current review of targeted therapeutics for ovarian cancer.	2010	20069122
Potent preclinical impact of metronomic low-dose oral topotecan combined with the antiangiogenic drug pazopanib for the treatment of ovarian cancer.	2010 Apr	20371722
Bridging the gap between cytotoxic and biologic therapy with metronomic topotecan and pazopanib in ovarian cancer.	2010 Apr	20371710
Pazopanib-induced hyperbilirubinemia is associated with Gilbert's syndrome UGT1A1 polymorphism.	2010 Apr 27	20389299
Phase II trial of pazopanib (GW786034), an oral multi-targeted angiogenesis inhibitor, for adults with recurrent glioblastoma (North American Brain Tumor Consortium Study 06-02).	2010 Aug	20200024
Plethora of agents, plethora of targets, plethora of side effects in metastatic renal cell carcinoma.	2010 Aug	20163917
Analytical control of process impurities in Pazopanib hydrochloride by impurity fate mapping.	2010 Aug 1	20189340
Prognostic factors in patients treated with VEGF-targeted therapies.	2010 Feb	20386528
Noninvasive assessment of tumor VEGF receptors in response to treatment with pazopanib: a molecular imaging study.	2010 Feb	20165696
Angiogenesis inhibitors in the management of breast cancer.	2010 Feb	19952746
Anti-angiogenesis agents in metastatic or recurrent cervical cancer.	2010 Feb	19861227
Prognostic stratification of patients with advanced renal cell carcinoma treated with sunitinib: comparison with the Memorial Sloan-Kettering prognostic factors model.	2010 Feb 18	20163744
Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial.	2010 Feb 20	20100962
StatBite: FDA oncology drug product approvals in 2009.	2010 Feb 24	20145211
New weapons against kidney cancer. Two recent drug options appear to extend survival for kidney cancer patients who can't tolerate existing medications.	2010 Jan	20148481
Molecular basis for the treatment of renal cell carcinoma.	2010 Jan	20080466
Pazopanib.	2010 Jan	20043026
VEGF signalling inhibition-induced proteinuria: Mechanisms, significance and management.	2010 Jan	20006922
Efficacy and safety of pazopanib in patients with metastatic renal cell carcinoma.	2010 Jan 20	20008644
New therapeutic strategies for renal cell carcinoma.	2010 Jan-Feb	20359144
An exploratory study of sunitinib plus paclitaxel as first-line treatment for patients with advanced breast cancer.	2010 Jul	20032126
[Antiangionic drugs in soft tissue sarcoma].	2010 Jun	20483703
Pazopanib: an oral multitargeted tyrosine kinase inhibitor for use in renal cell carcinoma.	2010 Jun	20407031
Current status of vascular endothelial growth factor inhibition in age-related macular degeneration.	2010 Jun	20210371
Bevacizumab salvage therapy following progression in high-grade glioma patients treated with VEGF receptor tyrosine kinase inhibitors.	2010 Jun	20156808
Recent advances and future directions in the management of metastatic renal cell carcinoma.	2010 Mar	20184547
[Management of metastatic HER2-positive breast cancer: present and future].	2010 Mar	20176546
Anti-angiogenic tyrosine kinase inhibitors: what is their mechanism of action?	2010 Mar	20012482
Plasma cytokine and angiogenic factor profiling identifies markers associated with tumor shrinkage in early-stage non-small cell lung cancer patients treated with pazopanib.	2010 Mar 15	20215520
Pazopanib: a multikinase inhibitor with activity in advanced renal cell carcinoma.	2010 May	20469994
Targeted therapy and hand-foot skin reaction in advanced renal cell carcinoma.	2010 May	20113155
The complexity of the complicity of mast cells in cancer.	2010 May	20026421
Antitumor and antiangiogenic effect of the dual EGFR and HER-2 tyrosine kinase inhibitor lapatinib in a lung cancer model.	2010 May 11	20459769
Growth factors in multiple myeloma: a comprehensive analysis of their expression in tumor cells and bone marrow environment using Affymetrix microarrays.	2010 May 13	20465808
Everolimus and pazopanib: two new drugs for renal cell cancer.	2010 May 3	20431519
Initial assessment, surveillance, and management of blood pressure in patients receiving vascular endothelial growth factor signaling pathway inhibitors.	2010 May 5	20351338

Patents

Sample Use Guides

In Vivo Use Guide

800 mg orally once daily without food (at least 1 hour before or 2 hours after a meal). Baseline moderate hepatic impairment – 200 mg orally once daily. Not recommended in patients with severe hepatic impairment.

Route of Administration: Oral

In Vitro Use Guide

Treatment of the KATO-III, OCUM-2M, SNU-16, and HSC-39 gastric cancer cell lines harboring FGFR2 amplification with pazopanib resulted in marked decreases of cell survival with IC50 in ranges of 0.1 to 2.0 uM, whereas the same treatment of those cell lines without FGFR2 amplification had no growth-inhibitory effects

Substance Class	Chemical Created by `admin` on `Fri Dec 15 16:30:57 UTC 2023` Edited by `admin` on `Fri Dec 15 16:30:57 UTC 2023`
Record UNII	33Y9ANM545
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

PAZOPANIB HYDROCHLORIDE

Official Name

English

PAZOPANIB HCL

Common Name

English

GW786034B

Code

English

Pazopanib hydrochloride [WHO-DD]

Common Name

English

PAZOPANIB HYDROCHLORIDE [MART.]

Common Name

English

BENZENESULFONAMIDE, 5-((4-((2,3-DIMETHYL-2H-INDAZOL-6-YL)METHYLAMINO)-2-PYRIMIDINYL)AMINO)-2-METHYL-, MONOHYDROCHLORIDE

Common Name

English

VOTRIENT

Brand Name

English

PAZOPANIB HYDROCHLORIDE [ORANGE BOOK]

Common Name

English

GW-786034B

Code

English

PAZOPANIB (AS HYDROCHLORIDE)

Common Name

English

PAZOPANIB MONOHYDROCHLORIDE

Common Name

English

PAZOPANIB HYDROCHLORIDE [USAN]

Common Name

English

PAZOPANIB HYDROCHLORIDE [MI]

Common Name

English

PAZOPANIB HYDROCHLORIDE [JAN]

Common Name

English

5-[[4-[(2,3-Dimethyl-2H-indazol-6-yl)methylamino]pyrimidin-2-yl]amino]-2-methylbenzenesulfonamide monohydrochloride

Systematic Name

English

Classification Tree Code System Code

NCI_THESAURUS

C1742