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 8228	0.14 µM [IC50]
Fibroblast growth factor receptor 3 32 Target ID: CHEMBL2742 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17620431/	Inhibitor 8228	0.13 µM [IC50]
Macrophage colony stimulating factor receptor 23 Target ID: CHEMBL1844 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17620431/	Inhibitor 8228	0.146 µM [IC50]
Platelet-derived growth factor receptor alpha 30 Target ID: CHEMBL2007 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17620431/	Inhibitor 8228	0.071 µM [IC50]
Platelet-derived growth factor receptor beta 55 Target ID: CHEMBL1913 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17620431/	Inhibitor 8228	0.084 µM [IC50]
Stem cell growth factor receptor 52 Target ID: CHEMBL1936 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17620431/	Inhibitor 8228	0.074 µM [IC50]
Tyrosine-protein kinase ITK/TSK 4 Target ID: CHEMBL2959 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17620431/	Inhibitor 8228	0.43 µM [IC50]
Tyrosine-protein kinase LCK 11 Target ID: CHEMBL258 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17620431/	Inhibitor 8228	0.411 µM [IC50]
Vascular endothelial growth factor receptor 1 40 Target ID: CHEMBL1868 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17620431/	Inhibitor 8228	0.01 µM [IC50]
Vascular endothelial growth factor receptor 2 102 Target ID: CHEMBL279 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17620431/	Inhibitor 8228	0.03 µM [IC50]
Vascular endothelial growth factor receptor 3 40 Target ID: CHEMBL1955 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17620431/	Inhibitor 8228	0.047 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Renal cell carcinoma 30 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/022465s-010S-012lbl.pdf https://www.ncbi.nlm.nih.gov/pubmed/22341567	Primary		Approved 8360	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 8360	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 1709 inhibitor 1579 inducer 768	inhibitor 1752	inhibitor 1837	inhibitor 1599

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1509 CYP2B6 799 CYP2C8 901 CYP2C19 1463 CYP2E1 876 P-gp 1437 UGT1A1 204 OATP1B1 781	CYP1A2 1032 CYP2C8 688 P-gp 1527	CYP2B6 538 CYP1A2 689

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP2C8 955	inhibitor 3240 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 1537	inhibitor 3240 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 1909	inhibitor 3240 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 985	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_ClinPharmR.pdf#page=32 Page: 32.0	moderate [IC50 15 uM]
CYP1A2 1673	inhibitor 3240 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 964	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_ClinPharmR.pdf#page=32 Page: 32.0	moderate [IC50 17 uM]
CYP2D6 1875	inhibitor 3240 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 1803	inhibitor 3240 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 985	inducer 1542 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_ClinPharmR.pdf#page=32 Page: 32,33	moderate
CYP3A4 1909	inducer 1542 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 1673	inducer 1542 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_ClinPharmR.pdf#page=33 Page: 33.0	no
P-gp 1626	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_ClinPharmR.pdf#page=34 Page: 34.0	no
OATP1B1 796	inhibitor 3240 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 3240 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 1709	substrate 3326 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 1032	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_ClinPharmR.pdf#page=32 Page: 32.0	minor
CYP2C8 688	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_ClinPharmR.pdf#page=32 Page: 32.0	minor
P-gp 1527	substrate 3326 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 1632	inhibitor 1613 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
Recent advances in systemic therapy. When HER2 is not the target: advances in the treatment of HER2-negative metastatic breast cancer.	2009	19744307
Recent advances in systemic therapy: Advances in systemic therapy for HER2-positive metastatic breast cancer.	2009	19664181
Emerging pharmacologic therapies for wet age-related macular degeneration.	2009	19622904
Anti-VEGF therapy as adjuvant therapy: clouds on the horizon?	2009	19519950
Response to antiangiogenesis therapy in a patient with advanced adult-type testicular granulosa cell tumor.	2009 Aug	19777766
Systemic therapy of advanced urothelial cancer.	2009 Aug	19408129
Major clinical research advances in gynecologic cancer 2009.	2009 Dec	20041096
Impact of anti-angiogenic treatments on metastatic renal cell carcinoma.	2009 Dec	19954291
Tyrosine kinase inhibitors and the thyroid.	2009 Dec	19942148
Metastatic renal cell carcinoma: recent advances in the targeted therapy era.	2009 Dec	19748725
Synergistic proapoptotic effects of the two tyrosine kinase inhibitors pazopanib and lapatinib on multiple carcinoma cell lines.	2009 Dec 3	19749798
Pazopanib, a multikinase angiogenesis inhibitor, in patients with relapsed or refractory advanced soft tissue sarcoma: a phase II study from the European organisation for research and treatment of cancer-soft tissue and bone sarcoma group (EORTC study 62043).	2009 Jul 1	19451427
Phase I trial of pazopanib in patients with advanced cancer.	2009 Jun 15	19509175
[Chemotherapy for breast cancer refractory to anthracycline, taxane or trastuzumab].	2009 May	19461171
Vascular endothelial growth factor-targeted therapy in metastatic renal cell carcinoma.	2009 May 15	19402073
Vascular endothelial growth factor inhibition is not an effective therapeutic strategy for relapsed or refractory multiple myeloma: a phase 2 study of pazopanib (GW786034).	2009 May 7	19423744
Pazopanib: an antiangiogenic drug in perspective.	2009 Nov	19903063
New treatment approaches in renal cell carcinoma.	2009 Nov	19752718
Selective inhibition of retinal angiogenesis by targeting PI3 kinase.	2009 Nov 17	19924235
Myelosuppression and kinase selectivity of multikinase angiogenesis inhibitors.	2009 Nov 17	19844230
Pazopanib for the treatment of renal cell carcinoma and other malignancies.	2009 Sep	19956806
Response to a novel multitargeted tyrosine kinase inhibitor pazopanib in metastatic Merkel cell carcinoma.	2009 Sep 10	19564526
VEGFR1 activity modulates myeloid cell infiltration in growing lung metastases but is not required for spontaneous metastasis formation.	2009 Sep 18	19763275
Analytical control of genotoxic impurities in the pazopanib hydrochloride manufacturing process.	2009 Sep 8	19427156
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
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
Plethora of agents, plethora of targets, plethora of side effects in metastatic renal cell carcinoma.	2010 Aug	20163917
Prognostic factors in patients treated with VEGF-targeted therapies.	2010 Feb	20386528
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
Molecular basis for the treatment of renal cell carcinoma.	2010 Jan	20080466
Pazopanib.	2010 Jan	20043026
New therapeutic strategies for renal cell carcinoma.	2010 Jan-Feb	20359144
[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
Bevacizumab salvage therapy following progression in high-grade glioma patients treated with VEGF receptor tyrosine kinase inhibitors.	2010 Jun	20156808
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
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 `Wed Jul 05 23:56:47 UTC 2023` Edited by `admin` on `Wed Jul 05 23:56:47 UTC 2023`
Record UNII	33Y9ANM545
Record Status	`Validated (UNII)`
Record Version

Download

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