Pazopanib Property

Melting point:

285-289°C (dec.)

Boiling point:

728.8±70.0 °C(Predicted)

Density 

1.40

Flash point:

359℃

storage temp. 

Refrigerator

solubility 

Aqueous Acid (Slightly), DMSO (Slightly, Heated), Methanol (Slightly, Heated)

pka

10.19±0.60(Predicted)

form 

Yellow powder.

color 

White to Beige

Safety

Risk Statements 

43-62/63

Safety Statements 

36/37/39-28B

HS Code 

29350090

Hazardous Substances Data

444731-52-6(Hazardous Substances Data)

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Danger

Hazard statements

H373May cause damage to organs through prolonged or repeated exposure

H411Toxic to aquatic life with long lasting effects

Precautionary statements

P202Do not handle until all safety precautions have been read and understood.

P260Do not breathe dust/fume/gas/mist/vapours/spray.

P273Avoid release to the environment.

P280Wear protective gloves/protective clothing/eye protection/face protection.

P308+P313IF exposed or concerned: Get medical advice/attention.

P391Collect spillage. Hazardous to the aquatic environment

Pazopanib Chemical Properties,Usage,Production

product description

Pazopanib(444731-52-6) is researched and developed by a GlaxoSmithKline ,it is a novel oral vascular generation inhibitor which may interfere stubborn tumor survival and new blood vessels generation growth needed .Targeting vascular endothelial growth factor receptor (VEGFR),it works by inhibiting angiogenesis of tumor blood supply.it is suitable for advanced renal cell carcinoma ( a discovery of cancer cells in the renal tubules), soft tissue sarcoma (STS), epithelial ovarian cancer and non-small cell lung cancer (NSCLC) treatment.
Minnesota Rochester, Mayo Clinical Research Clinical Research Center researches show that pazopanib (trade name Votrient) can effectively cure thyroid cancer,and can make half of the patients tumor volume reduced, compared to the commonly used drugs ,it is more prolonged stable ,and can be maintained for a considerable period of treatment, the drug has the highest response rate in treatment of thyroid cancer so far.
The US Food and Drug Administration (FDA) approved on October 19, 2009 that pazopanib (trade name Votrient) is listed ,the sixth approved drug treatment of kidney cancer since 2005. In 2009, approximately 49,000 patients were diagnosed with renal cell carcinoma, 11,000 patients died of the disease.
June 15, 2010, pazopanib, EU conditionally approved it for advanced renal cell cancer and first-line treatment in patients with previously received cytokine therapy. Once the European Commits to give final marketing authorization for this drug, GlaxoSmithKline will have exclusive marketing rights pazopanib for ten years.

The efficacy of the treatment of advanced renal cell carcinoma

In order to investigate the efficacy of molecule targeting drug tyrosine kinase inhibitor pazopanib which inhibist the angiogenesis in patients with advanced renal cell carcinoma, People's Liberation Army General Hospital, in June 2006 to May 2007, the participation of pazopanib in patients with advanced renal cell carcinoma randomized clinical drug trials of outpatient 14 cases, were divided into pazopanib group (n = 10) and placebo group ( 4 cases), were treated with pazopanib 800mg/d and placebo after 12 weeks of treatment duration, according to the results of CT scan before and after medication , efficacy was determined .
The results showed that the reduced average ratios of measurable disease focus of pazopanib and placebo patients were 27.6%,-2.8% (P <O.05); the disease control rate of pazopanib and placebo groups were 100% and 25%, respectively. Conclusions confirmed that molecule targeting drug tyrosine kinase inhibitor pazopanib which inhibist the angiogenesis can have a significant therapeutic effect and high security on metastatic renal cell carcinoma in a short period of time.
A clinical trail study phase I showed that compared with placebo, pazopanib can reduce the risk of death and tumor progression by 54%. Overall,in the product group of patients ,disease progression-free survival (PFS) mean survival time was 9.2 months ,in the placebo group was 4.2 months. In previously treated patients who had not received in this product group average survival time was 11.1 months in the placebo group was 2.8 months; previously received cytokine therapy patients, pazopanib group survived an average of 7.4 months, the placebo group was 4.2 months.
The above information is edited by the chemicalbook of Tian Ye.

Adverse reactions

Diarrhea, hypertension, hair color change, nausea, loss of appetite, vomiting, fatigue, weakness, headache, abdominal pain and so on.
Cause serious liver problems, so health care workers should take blood tests to monitor liver function before using the drug in patients and during treatment of patients.
Hazardous to the fetus,people during pregnancy are forbid using this drug.
Pazopanib can also lead to arrhythmias, during treatment patients should have regular electrocardiogram measuring heart rate, and regular blood tests to monitor electrolytes since an electrolyte imbalance will also play a role in arrhythmia.

Description

Pazopanib is a multi-kinase inhibitor that inhibits the VEGF receptors VEGFR1, VEGFR2, and VEGFR3 (IC₅₀s = 10, 30, and 47 nM, respectively, in a cell-free enzyme assay). It also inhibits PDGFRα, PDGFRβ, and c-Kit (IC₅₀s = 71, 84, and 74 nM, respectively, in a cell-free enzyme assay) as well as additional receptor tyrosine kinases. Pazopanib inhibits upregulation of the surface adhesion proteins ICAM-1 and VCAM-1 induced by VEGF in multiple myeloma cells cocultured with human umbilical vein endothelial cells (HUVECs) and decreases multiple myeloma cell adhesion to HUVECs. It also inhibits proliferation of multiple myeloma cells cocultured with HUVECs. Pazopanib (30 and 100 mg/kg) reduces tumor growth, induces apoptosis, decreases angiogenesis, and increases survival in a multiple myeloma mouse xenograft model. Formulations containing pazopanib have been used in the treatment of cancer.

Chemical Properties

Off-White Solid

Characteristics

Class: receptor tyrosine kinase
Treatment: RCC, STS
Oral bioavailability = 14–39%
Elimination half-life = 31 h
Protein binding > 99.9%

Uses

An oral angiogenesis inhibitor targeting VEGFR and PDGFR.

Uses

Pazopanib Hydrochloride (GW786034, Votrient, Armala) is a novel multi-target inhibitor of VEGFR1, VEGFR2, VEGFR3, PDGFR, FGFR, c-Kit and c-Fms with IC50 of 10 nM, 30 nM, 47 nM, 84 nM, 74 nM, 140 nM and 146 nM, respectively.

Uses

Pazopanib is a potent and selective multi-targeted receptor tyrosine kinase inhibitor of VEGFR1, VEGFR2, VEGFR3, PDGFR-α/β, and c-Kit.

Uses

Pazopanib is a novel multi-target inhibitor of VEGFR1, VEGFR2, VEGFR3, PDGFR, FGFR, c-Kit and c-Fms with IC50 of 10 nM, 30 nM, 47 nM, 84 nM, 74 nM, 140 nM and 146 nM, respectively.

Definition

ChEBI: A pyrimidine that is 5-(pyrimidin-2-yl}amino-2-methylbenzenesulfonamide substituted at position 4 by a (2,3-dimethylindazol-6-yl)(methyl)amino group. Used as its hydrochloride salt for treatment of kidney cancer.

Clinical Use

Tyrosine kinase inhibitor:
Treatment of metastatic renal cell carcinoma and soft tissue sarcoma

target

VEGFR1

Drug interactions

Potentially hazardous interactions with other drugs
Antibacterials: avoid with clarithromycin, rifampicin and telithromycin.
Antifungals: avoid with itraconazole, ketoconazole and voriconazole.
Antipsychotics: avoid with clozapine (increased risk of agranulocytosis).
Antivirals: avoid with atazanavir, boceprevir, indinavir, ritonavir and saquinavir.
Grapefruit juice: avoid concomitant administration.
Avoid concomitant use with other inhibitors or inducers of CYP3A4. Dose alterations may be required.

Metabolism

Metabolism primarily by CYP3A4, with minor contributions from CYP1A2 and CYP2C8. The four principle pazopanib metabolites account for only 6% of the exposure in plasma. One of these metabolites inhibits the proliferation of VEGF-stimulated human umbilical vein endothelial cells with a similar potency to that of pazopanib, the others are 10- to 20-fold less active.
Therefore, activity of pazopanib is mainly dependent on parent pazopanib exposure.
Elimination is mostly via the faeces.