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Details

Stereochemistry ACHIRAL
Molecular Formula C21H23N7O2S
Molecular Weight 437.518
Optical Activity UNSPECIFIED
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of PAZOPANIB

SMILES

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=CUIHSIWYWATEQL-UHFFFAOYSA-N
InChI=1S/C21H23N7O2S/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)

HIDE SMILES / InChI

Description

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

Approval Year

TargetsConditions
PubMed

PubMed

TitleDatePubMed
Targeted therapy in the treatment of metastatic renal cell cancer.
2009
Major clinical research advances in gynecologic cancer 2009.
2009 Dec
Impact of anti-angiogenic treatments on metastatic renal cell carcinoma.
2009 Dec
Pazopanib: therapeutic developments.
2009 Dec
Tyrosine kinase inhibitors and the thyroid.
2009 Dec
Pazopanib: an antiangiogenic drug in perspective.
2009 Nov
Selective inhibition of retinal angiogenesis by targeting PI3 kinase.
2009 Nov 17
Pazopanib for the treatment of renal cell carcinoma and other malignancies.
2009 Sep
Targeting angiogenesis with multitargeted tyrosine kinase inhibitors in the treatment of non-small cell lung cancer.
2010
Antiangiogenic therapy and mechanisms of tumor resistance in malignant glioma.
2010
Everolimus (RAD001) in the treatment of advanced renal cell carcinoma: a review.
2010
Anticancer Role of PPARgamma Agonists in Hematological Malignancies Found in the Vasculature, Marrow, and Eyes.
2010
Targeting signal transduction pathways in metastatic breast cancer: a comprehensive review.
2010
Targeted therapies in epithelial ovarian cancer.
2010
A current review of targeted therapeutics for ovarian cancer.
2010
Potent preclinical impact of metronomic low-dose oral topotecan combined with the antiangiogenic drug pazopanib for the treatment of ovarian cancer.
2010 Apr
Bridging the gap between cytotoxic and biologic therapy with metronomic topotecan and pazopanib in ovarian cancer.
2010 Apr
Pazopanib-induced hyperbilirubinemia is associated with Gilbert's syndrome UGT1A1 polymorphism.
2010 Apr 27
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
Plethora of agents, plethora of targets, plethora of side effects in metastatic renal cell carcinoma.
2010 Aug
Analytical control of process impurities in Pazopanib hydrochloride by impurity fate mapping.
2010 Aug 1
Prognostic factors in patients treated with VEGF-targeted therapies.
2010 Feb
Noninvasive assessment of tumor VEGF receptors in response to treatment with pazopanib: a molecular imaging study.
2010 Feb
Angiogenesis inhibitors in the management of breast cancer.
2010 Feb
Anti-angiogenesis agents in metastatic or recurrent cervical cancer.
2010 Feb
Prognostic stratification of patients with advanced renal cell carcinoma treated with sunitinib: comparison with the Memorial Sloan-Kettering prognostic factors model.
2010 Feb 18
Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial.
2010 Feb 20
StatBite: FDA oncology drug product approvals in 2009.
2010 Feb 24
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
Molecular basis for the treatment of renal cell carcinoma.
2010 Jan
Pazopanib.
2010 Jan
VEGF signalling inhibition-induced proteinuria: Mechanisms, significance and management.
2010 Jan
Efficacy and safety of pazopanib in patients with metastatic renal cell carcinoma.
2010 Jan 20
New therapeutic strategies for renal cell carcinoma.
2010 Jan-Feb
An exploratory study of sunitinib plus paclitaxel as first-line treatment for patients with advanced breast cancer.
2010 Jul
[Antiangionic drugs in soft tissue sarcoma].
2010 Jun
Pazopanib: an oral multitargeted tyrosine kinase inhibitor for use in renal cell carcinoma.
2010 Jun
Current status of vascular endothelial growth factor inhibition in age-related macular degeneration.
2010 Jun
Bevacizumab salvage therapy following progression in high-grade glioma patients treated with VEGF receptor tyrosine kinase inhibitors.
2010 Jun
Recent advances and future directions in the management of metastatic renal cell carcinoma.
2010 Mar
[Management of metastatic HER2-positive breast cancer: present and future].
2010 Mar
Anti-angiogenic tyrosine kinase inhibitors: what is their mechanism of action?
2010 Mar
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
Pazopanib: a multikinase inhibitor with activity in advanced renal cell carcinoma.
2010 May
Targeted therapy and hand-foot skin reaction in advanced renal cell carcinoma.
2010 May
The complexity of the complicity of mast cells in cancer.
2010 May
Antitumor and antiangiogenic effect of the dual EGFR and HER-2 tyrosine kinase inhibitor lapatinib in a lung cancer model.
2010 May 11
Growth factors in multiple myeloma: a comprehensive analysis of their expression in tumor cells and bone marrow environment using Affymetrix microarrays.
2010 May 13
Everolimus and pazopanib: two new drugs for renal cell cancer.
2010 May 3
Initial assessment, surveillance, and management of blood pressure in patients receiving vascular endothelial growth factor signaling pathway inhibitors.
2010 May 5
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
Name Type Language
PAZOPANIB
DASH   EMA EPAR   INN   MI   VANDF   WHO-DD  
INN  
Official Name English
PAZOPANIB [WHO-DD]
Common Name English
PAZOPANIB [VANDF]
Common Name English
PAZOPANIB [EMA EPAR]
Common Name English
5-((4-((2,3-DIMETHYL-2H-INDAZOL-6-YL)(METHYL)AMINO)PYRIMIDIN-2-YL)AMINO)-2-METHYLBENZENESULFONAMIDE
Systematic Name English
GW786034
Code English
PAZOPANIB [INN]
Common Name English
PAZOPANIB [MI]
Common Name English
BENZENESULFONAMIDE, 5-((4-((2,3-DIMETHYL-2H-INDAZOL-6-YL)METHYLAMINO)-2-PYRIMIDINYL)AMINO)-2-METHYL-
Systematic Name English
Classification Tree Code System Code
NCI_THESAURUS C1967
Created by admin on Tue Oct 22 00:00:56 UTC 2019 , Edited by admin on Tue Oct 22 00:00:56 UTC 2019
EMA ASSESSMENT REPORTS VOTRIENT (AUTHORIZED: CARCINOMA, RENAL CELL)
Created by admin on Tue Oct 22 00:00:56 UTC 2019 , Edited by admin on Tue Oct 22 00:00:56 UTC 2019
WHO-ATC L01XE11
Created by admin on Tue Oct 22 00:00:56 UTC 2019 , Edited by admin on Tue Oct 22 00:00:56 UTC 2019
FDA ORPHAN DRUG 383912
Created by admin on Tue Oct 22 00:00:56 UTC 2019 , Edited by admin on Tue Oct 22 00:00:56 UTC 2019
WHO-VATC QL01XE11
Created by admin on Tue Oct 22 00:00:56 UTC 2019 , Edited by admin on Tue Oct 22 00:00:56 UTC 2019
LIVERTOX 742
Created by admin on Tue Oct 22 00:00:56 UTC 2019 , Edited by admin on Tue Oct 22 00:00:56 UTC 2019
NCI_THESAURUS C1742
Created by admin on Tue Oct 22 00:00:56 UTC 2019 , Edited by admin on Tue Oct 22 00:00:56 UTC 2019
NDF-RT N0000175605
Created by admin on Tue Oct 22 00:00:56 UTC 2019 , Edited by admin on Tue Oct 22 00:00:56 UTC 2019
FDA ORPHAN DRUG 293809
Created by admin on Tue Oct 22 00:00:56 UTC 2019 , Edited by admin on Tue Oct 22 00:00:56 UTC 2019
Code System Code Type Description
EVMPD
SUB29175
Created by admin on Tue Oct 22 00:00:56 UTC 2019 , Edited by admin on Tue Oct 22 00:00:56 UTC 2019
PRIMARY
ChEMBL
CHEMBL477772
Created by admin on Tue Oct 22 00:00:56 UTC 2019 , Edited by admin on Tue Oct 22 00:00:56 UTC 2019
PRIMARY
LactMed
444731-52-6
Created by admin on Tue Oct 22 00:00:56 UTC 2019 , Edited by admin on Tue Oct 22 00:00:56 UTC 2019
PRIMARY
PUBCHEM
10113978
Created by admin on Tue Oct 22 00:00:56 UTC 2019 , Edited by admin on Tue Oct 22 00:00:56 UTC 2019
PRIMARY
NDF-RT
N0000182137
Created by admin on Tue Oct 22 00:00:56 UTC 2019 , Edited by admin on Tue Oct 22 00:00:56 UTC 2019
PRIMARY Cytochrome P450 2D6 Inhibitors [MoA]
HSDB
444731-52-6
Created by admin on Tue Oct 22 00:00:56 UTC 2019 , Edited by admin on Tue Oct 22 00:00:56 UTC 2019
PRIMARY
WIKIPEDIA
PAZOPANIB
Created by admin on Tue Oct 22 00:00:56 UTC 2019 , Edited by admin on Tue Oct 22 00:00:56 UTC 2019
PRIMARY
MESH
C516667
Created by admin on Tue Oct 22 00:00:56 UTC 2019 , Edited by admin on Tue Oct 22 00:00:56 UTC 2019
PRIMARY
NDF-RT
N0000182141
Created by admin on Tue Oct 22 00:00:56 UTC 2019 , Edited by admin on Tue Oct 22 00:00:56 UTC 2019
PRIMARY Cytochrome P450 3A4 Inhibitors [MoA]
NDF-RT
N0000187062
Created by admin on Tue Oct 22 00:00:56 UTC 2019 , Edited by admin on Tue Oct 22 00:00:56 UTC 2019
PRIMARY Cytochrome P450 2C8 Inhibitors [MoA]
RXCUI
714438
Created by admin on Tue Oct 22 00:00:56 UTC 2019 , Edited by admin on Tue Oct 22 00:00:56 UTC 2019
PRIMARY RxNorm
CAS
444731-52-6
Created by admin on Tue Oct 22 00:00:56 UTC 2019 , Edited by admin on Tue Oct 22 00:00:56 UTC 2019
PRIMARY
EPA CompTox
444731-52-6
Created by admin on Tue Oct 22 00:00:56 UTC 2019 , Edited by admin on Tue Oct 22 00:00:56 UTC 2019
PRIMARY
MERCK INDEX
M8430
Created by admin on Tue Oct 22 00:00:56 UTC 2019 , Edited by admin on Tue Oct 22 00:00:56 UTC 2019
PRIMARY Merck Index
DRUG BANK
DB06589
Created by admin on Tue Oct 22 00:00:56 UTC 2019 , Edited by admin on Tue Oct 22 00:00:56 UTC 2019
PRIMARY
INN
8681
Created by admin on Tue Oct 22 00:00:56 UTC 2019 , Edited by admin on Tue Oct 22 00:00:56 UTC 2019
PRIMARY
IUPHAR
5698
Created by admin on Tue Oct 22 00:00:56 UTC 2019 , Edited by admin on Tue Oct 22 00:00:56 UTC 2019
PRIMARY
NCI_THESAURUS
C74547
Created by admin on Tue Oct 22 00:00:56 UTC 2019 , Edited by admin on Tue Oct 22 00:00:56 UTC 2019
PRIMARY