PAZOPANIB: LATEST VEGFR INHIBITOR

by Selleckchem | May 22 2012

PAZOPANIB: INTRODUCTION
A very famous pharmaceutical company named GlaxoSmithKline is the manufacturer of an important anticancer drug Pazopanib Votrient known as Pazopanib VEGFR inhibitor and is selling it under the trade name Votrient. Pazopanib is a good source of anti-angiogenic activity that inhibits VEGF, R1, VEGFR2 and VEGFR3 along with the β subtypes and c-kit RTKs and PDGFR-a. Pazopanib is a very small molecule that got fame in just in recent years by exhibiting its potential activity in case of different types of cancers. PazopanibVEGFR-PDGFR inhibitor is indeed one of those important inhibitors which are now approved for the use at clinical level [1]. Pazopanib structure reveals the presence of a sulfonamide group. One can buy Pazopanib from supplier Pazopanib by paying Pazopanib price that is around $100 per a 25 mg packing under the trade name Votrient or GW786034. Its price may vary among the suppliers. Pazopanib solubility is best observed in DMSO but it is completely insoluble in ethanol and water. It is stable for almost two years if stored at -20oC. The values for Pazopanib IC50 for efficient VEGF-2, VEGF-3 and VEGFR1 inhibitions are found to be 30 nM, 47 nM and 10 nM respectively. Pazopanib IC50 for some closely related kinases like PDGFR-beta.c-Kit, c-fms and FGF R1, Pazopanib IC50 was observed to be 85 nM, 74 nM, 146 nM and 140 nM respectively.

PAZOPANIB: IN VITRO AND IN VIVO TRIALS
The discovery and initial screening of PazopanibVotrient has developed a very good thought for Pazopanib production and its use at clinical level [2]. Pazopanib is easily tolerable, manageable and have a safe toxicity profile and good pharmacokinetic properties that has promoted its value and demand for clinical studies [3]. The steady-state concentration of Pazopanib that is derived from its preclinical trials has corroborated its anti-cancer activities and its pharmacodynamics in phase I trials [4]. In vitro cultures of multiple myeloma cells it was studied that both tumor and endothelial cells are targeted by the Pazopanib GW786034 [5]. Pazopanib is also found to be very good in targeting choroidalneovascularization or CNV in models of mice [6]. Noninvasive assessment of Pazopanib was performed by molecular imaging technique [7] and this approach can b further utilized. A recent report tells that B-Raf protein in breast cancer cell lines and melanoma are targeted by Pazopanib c-Kit inhibitor [8]. A combined therapy of Lapatinib and Pazopanib in case of non-small cell lung cancer or NSCLC has exhibited valuable effectiveness [9]. While a combination of Topotecan and Pazopanib was found to be effective in models of mice having advanced pediatric solid tumors [10].

CLINICAL SUCCESS OF PAZOPANIB
Clinical trials phase III are being carried out for Pazopanib GW786034 against tissue and bone sarcoma [11]. It gave promising results in renal cell carcinoma patients under clinical trials phase II [12]. Very encouraging results were obtained when Pazopanib was used against patients of advanced or metastatic renal cell cancer in studies of phase II [13]. It can also be used as a monotherapeutic agent while its combinational therapy with Lapatinib was very promising and enhance its demand in field of combinational therapies [14]. In castration-sensitive patients of prostate cancer, a clinical study of phase II Pazopanib has shown great efficiency [15]. Patients under clinical trials of phase I and II in case of pre-treated and recurrent ovarian cancer, good synergistic effects were observed by inducing Pazopanib and Cyclophosphamide combined [16]. Pazopanib clinical trial phase II against the Asian patients suffering from metastatic or recurrent nasopharyngeal carcinoma [17].

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