PAZOPANIB – THE LATEST CLINICAL VEGFR INHIBITOR

by Selleckchem | May 10 2012

PAZOPANIB: INTRODUCTION
Pazopanib VEGFR inhibitor is compound manufactured by a famous pharmacuetical company GlaxoSmithKline under the trading name of Votrient, is a potential source of anti-angiogenic activity which inhibits R1, VEGF, VEGF R3 and VEGF R2 along with β subtypes and PDGFR-a and c-kit RTKs. Pazopanib is a small molecule which got famous in recent years when it showed potential activity in various types of tumors. PazopanibVEGFR-PDGFR inhibitor is actually one of those few inhibitor molecules that are approved for their use at clinical levels [1]. Its structure revealed the presence of sulfonamide group in it. One can purchase Pazopanib to supplier Pazopanib under the trading name Votrient or GW786034 by paying the price around $100 for a 25 mg vial. Pazopanib price may vary from supplier to supplier. Pazopanib solubility is very good in DMSO but not in water and ethanol. Its stability is for almost 2 years when stored at -20oC. Pazopanib IC50 for efficient VEGF R1, VEGF -2, VEGF -3 inhibitions is actually 10 nM, 30nM and 47 nM respectively. For closely related kinase enzymes for example PDGFR-beta, FGF R1, c-Kit and c-fms, Pazopanib IC50 was recorded as 85 nM, 140 nM, 74 nM and 146 nM, respectively.

PAZOPANIB: IN VIVO AND IN VITRO TRIALS
The discovery of Pazopanib Votrient and its initial screening has generated a good thought for its production and use in clinical trials [2]. Its easily manageable, tolerable and safe toxicity profile along with better pharmacokinetic properties has promoted its demand for clinical trials [3]. Derived from preclinical trials of Pazopanib, its steady-state concentration corroborated its anti-tumor activities and pharmacodynamics in clinical trials of phase I [4]. In in vitro systems of multiple myeloma cell lines, Pazopanib GW786034 was found to target both endothelial cells and tumor cells [5]. This drug is also found to be very successful in targeting CNV or choroidal neovascularizationin models of mice [6]. Pazopanib’s noninvasive assessment was performed successfully by using molecular imaging technique [7] and this knowledge can further be utilized. According to a recent report, Pazopanib c-Kit inhibitor can target B-Rafin protein in melanoma and breast cancer cell lines [8]. Combination of Pazopanib and Lapatinib in NSCLC or non-small cell lung cancer has shown valuable effectiveness [9]. Combination of Pazopanib and Topotecan was found to be very effective in mice model suffering from advanced pediatric solid tumor [10].

PAZOPANIB: CLINICAL SUCCESS
Pazopanib GW786034 has now under phase III clinical trials against bone sarcoma and tissue sarcoma [11]. It promised valuable results in patients of renal cell carcinoma trials of phase II [12]. Its results of phase II trials against patients of metastatic or advanced form of renal cell cancer were found to be very encouraging [13]. It can be used as a monotherapeutic agent and its combination along with Lapatinib was found to be very promising treatment which promoted its demand as a combinational therapies [14] . In patients of prostate cancer who were castration-sensitive, a phase II Pazopanib clinical trial has shown remarkable efficiency [15]. Very good synergistic effects were observed in patients of pre-treated and recurrent ovarian cancer under phase I or II trials, by the induction of Cyclophosphamide and Pazopanib in combination [16]. This drug, Pazopanib is also found to be use in phase II trials for treating the Asian patients having metastatic or recurrent nasopharyngeal carcinoma [17].

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