1. Protein Tyrosine Kinase/RTK
    Autophagy
  2. VEGFR
    c-Kit
    PDGFR
    Autophagy

Pazopanib (Synonyms: GW786034)

Cat. No.: HY-10208 Purity: 99.44%
Data Sheet SDS Handling Instructions

Pazopanib is a novel multi-target inhibitor of VEGFR1, VEGFR2, VEGFR3, PDGFRβ, c-Kit, FGFR1, and c-Fms with IC50 of 10, 30, 47, 84, 74, 140 and 146 nM, respectively.

For research use only. We do not sell to patients.
Pazopanib Chemical Structure

Pazopanib Chemical Structure

CAS No. : 444731-52-6

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Other Forms of Pazopanib:

    Pazopanib purchased from MCE. Usage Cited in: Cell Physiol Biochem. 2016;38(3):926-38.

    Arithmetic means±SEM (n=16) of erythrocyte annexin-V-binding following incubation for 48 hours to Ringer solution without (white bar) or with (black bars) Pazopanib (10-50 µg/mL).
    • Biological Activity

    • Protocol

    • Technical Information

    • Purity & Documentation

    • References

    Description

    Pazopanib is a novel multi-target inhibitor of VEGFR1, VEGFR2, VEGFR3, PDGFRβ, c-Kit, FGFR1, and c-Fms with IC50 of 10, 30, 47, 84, 74, 140 and 146 nM, respectively.

    IC50 & Target

    IC50: 10 nM (VEGFR1), 30 nM (VEGFR2), 47 nM (VEGFR3), 74 nM (c-Kit), 84 nM (PDGFRβ), 140 nM (FGFR1), 146 nM (c-Fms)[1]

    In Vitro

    Pazopanib shows good potency against all the human VEGFR receptors with an IC50 of 10, 30, and 47 nM for VEGFR-1, -2, and -3, respectively. Significant activity is also seen against the closely related tyrosine receptor kinases PDGFRβ, c-Kit, FGF-R1, and c-fms with IC50s of 84, 74, 140, and 146 nM, respectively. In cellular assays, in addition to inhibiting the VEGF-induced proliferation of HUVECs, Pazopanib potently inhibits VEGF-induced phosphorylation of VEGFR-2 in HUVEC cells with an IC50 of ~8 nM. Pazopanib possesses good pharmacokinetics in rat, dog, and monkey with low clearances (1.4-1.7 mL/min/kg) and good oral bioavailabilities (72, 47, 65%) dosed at 10, 1, and 5 mg/kg, respectively. The cytochrome P450 profile is also improved with inhibition >10 μM against the isozymes tested, with the exception of 2C9 (7.9 μM)[1].

    In Vivo

    Treatment of mice with 100 mg/kg of Pazopanib twice daily for five days results in significant inhibition in the degree of vascularization. The antiangiogenic activity of Pazopanib is examined in mice bearing established human xenografts (200−250 mm3) using HT29 (colon carcinoma), A375P (melanoma), and HN5 (head and neck carcinoma) tumors following a standard three-week course of therapy. The HN5 and HT29 xenografts responded better at all doses compared to the A375P model, which is historically more resistant to VEGFR-2 inhibitors. As support that the observed inhibition of xenograft growth is working through an antiangiogenic rather than antitumor mechanism, no antiproliferative activity is observed below 10 μM for Pazopanib against these human tumor lines (HT29, HN5, A375P) growing in serum-containing media. No significant effect on the body weight of mice is observed, and the animals appeared healthy and active throughout the study duration[1]. The quantity of adherent leukocytes in the Pazopanib eye drops group is less than untreated diabetic animals and more than the healthy animals. Average leukocytes adhered to the retinal vasculature in healthy animals is 37.2±7.8, whereas diabetic animals have an average value of 102±15.6, approximately 3-fold higher than healthy animals. Animals treated with 0.5 % w/v Pazopanib suspension demonstrate 69.5±9.5 leukocytes adhered in their retinal vasculature, which is found to be significantly lower than diabetic animals[2].

    Clinical Trial
    NCT Number Sponsor Condition Start Date Phase
    NCT00401583 GlaxoSmithKline Solid Tumor Cancer|Carcinoma, Renal Cell July 2006 Phase 1
    NCT00281632 GlaxoSmithKline Malignant Tumor of Peritoneum|Ovarian Cancer|Neoplasms, Ovarian|Fallopian Tube Cancer March 2006 Phase 2
    NCT00158782 GlaxoSmithKline Carcinoma, Renal Cell|Cancer September 2004 Phase 1
    NCT01049776 Illinois CancerCare, P.C. Non Small Cell Lung Cancer January 2010 Phase 2
    NCT00244764 GlaxoSmithKline Carcinoma, Renal Cell October 2005 Phase 2
    NCT00256880 GlaxoSmithKline Carcinoma, Renal Cell January 2005 Phase 2
    NCT00478725 GlaxoSmithKline Carcinoma, Renal Cell|Cancer July 2007 Phase 1
    NCT01956669 Novartis Pharmaceuticals|Children's Oncology Group|Novartis Solid Tumours October 9, 2014 Phase 2
    NCT00358384 GlaxoSmithKline Psoriasis|Plaque Psoriasis September 2005 Phase 1
    NCT00945477 Illinois CancerCare, P.C. Prostate Cancer July 2009 Phase 2
    NCT00549328 GlaxoSmithKline Lung Cancer, Non-Small Cell February 2008 Phase 2
    NCT01108055 Sandy Srinivas|GlaxoSmithKline|Stanford University Bladder Cancer|Bladder (Urothelial, Transitional Cell) Cancer|Bladder (Urothelial, Transitional Cell) Cancer Superficial (Non-Invasive)|Bladder (Urothelial, Transitional Cell) Cancer Resectable (Pre-Cystectomy)|Bladder (Urothelial, Transitional Cell) Cancer Metastatic or Unresectable April 2010 Phase 2
    NCT00430781 GlaxoSmithKline Neoplasms, Uterine Cervix|Metastatic Cervical Cancer November 2006 Phase 2
    NCT00363194 GlaxoSmithKline Cancer September 2006 Phase 1
    NCT00722293 GlaxoSmithKline Neoplasms, Breast July 2008 Phase 1
    NCT00674024 National Cancer Institute (NCI)|National Institutes of Health Clinical Center (CC) Neoplasms|Lymphoma October 7, 2008 Phase 1
    NCT01051700 GlaxoSmithKline Age Related Macular Degeneration January 2010 Phase 1
    NCT01130623 National Cancer Institute (NCI)|National Institutes of Health Clinical Center (CC) Sarcoma|Neuroblastoma|Wilms Tumor|Osteosarcoma|Brain Tumor May 10, 2010 Phase 1
    NCT00347919 GlaxoSmithKline Neoplasms, Breast July 2006 Phase 2
    NCT00678977 GlaxoSmithKline Lung Cancer, Non-Small Cell April 2008 Phase 1
    NCT00561795 GlaxoSmithKline Primary Peritoneal Carcinoma|Tumor|Epithelial Ovarian Cancer|Uterine Disease|Cervix Diseases|Neoplasms, Ovarian|Cancer September 2007 Phase 2
    NCT01361334 University Hospital Muenster|Novartis Acute Myeloid Leukemia June 2011 Phase 2
    NCT01072890 University of California, Davis|GlaxoSmithKline|Pfizer Solid Tumors February 2010 Phase 1
    NCT01521715 iOMEDICO AG|Novartis Pharmaceuticals Locally Advanced and/or Metastatic Renal Cell Carcinoma|Carcinoma, Renal Cell|Clear-cell Metastatic Renal Cell Carcinoma January 24, 2012 Phase 4
    NCT01642017 Institut Claudius Regaud|GlaxoSmithKline Metastatic Cancer (Different Solid Tumour Types) March 2015 Phase 1
    NCT01430572 M.D. Anderson Cancer Center|GlaxoSmithKline|National Comprehensive Cancer Network Advanced Cancers|Solid Tumors October 2011 Phase 1
    NCT01577784 Associació per a la Recerca Oncologica, Spain|Trial Form Support S.L. Metastatic Renal Cell Carcinoma April 2012 Phase 2
    NCT01600573 JSehouli|GlaxoSmithKline|Charite University, Berlin, Germany Ovarian Cancer May 2012 Phase 1|Phase 2
    NCT02795819 Virginia Commonwealth University|Arno Therapeutics|National Cancer Institute (NCI) Renal Cell Carcinoma|Soft Tissue Sarcoma|Metastatic Disease July 8, 2016 Phase 1
    NCT01253369 Dana-Farber Cancer Institute|Massachusetts General Hospital|Brigham and Women's Hospital|Beth Israel Deaconess Medical Center|GlaxoSmithKline Small Cell Lung Cancer|Lung Cancer|SCLC June 2010 Phase 2
    NCT01545817 Novartis Carcinoma, Renal Cell April 2012 Phase 2
    NCT01392352 Cambridge University Hospitals NHS Foundation Trust|University of Cambridge|GlaxoSmithKline Renal Cell Carcinoma|Soft Tissue Sarcoma|Glioblastoma|Ovarian Cancer|Cervical Cancer|Breast Cancer|Non-small Cell Lung Cancer|Small Cell Lung Cancer|Pancreatic Cancer|Melanoma|Gastrointestinal Cancer April 2011 Phase 2
    NCT01975519 Tracon Pharmaceuticals Inc. Advanced Soft Tissue Sarcoma December 2013 Phase 1|Phase 2
    NCT01130805 Samsung Medical Center Gastric Cancer December 2010 Phase 2
    NCT02324803 Southern China Urology Cancer Consortium Self Efficacy|Adverse Drug Event|Carcinoma, Renal Cell July 2014 Phase 2
    NCT01107665 University of California, Irvine|GlaxoSmithKline Stage III Melanoma|Stage IV Melanoma|Unresectable Melanoma August 2010 Phase 2
    NCT02138526 Radboud University Cancer June 2014 Phase 1
    NCT01257750 Massachusetts Eye and Ear Infirmary Corneal Neovascularization November 2010 Phase 1|Phase 2
    NCT01743482 Fondazione IRCCS Istituto Nazionale dei Tumori, Milano|GlaxoSmithKline Germ Cell Tumors|Measurable Disease|Relapse or Progression After 2 or 3 Chemotherapy Regimens.|Relapse or Progression After High-dose Chemotherapy. January 2013 Phase 2
    NCT01339871 M.D. Anderson Cancer Center Advanced Cancer April 20, 2011 Phase 1
    NCT01330966 Vector Oncology|GlaxoSmithKline Chondrosarcoma|Metastatic Chondrosarcoma April 2011 Phase 2
    NCT02193152 Washington University School of Medicine Carcinoma, Non-Small Cell Lung|Non-Small Cell Lung Cancer|Nonsmall Cell Lung Cancer April 27, 2015 Phase 1
    NCT02303028 The Hospital for Sick Children|C17 Council Solid Tumors|Central Nervous System Tumors March 2015 Phase 1|Phase 2
    NCT01759303 Vector Oncology|GlaxoSmithKline Osteosarcoma|Metastatic Osteosarcoma April 2013 Phase 2
    NCT01542047 New Mexico Cancer Care Alliance|GlaxoSmithKline Cancer, Metastatic August 2012 Phase 1
    NCT02279576 Spanish Oncology Genito-Urinary Group Penile Squamous Cell Carcinoma Stage IV January 2015 Phase 2
    NCT00929903 National Cancer Institute (NCI) Childhood Central Nervous System Choriocarcinoma|Childhood Central Nervous System Embryonal Tumor|Childhood Central Nervous System Germ Cell Tumor|Childhood Central Nervous System Germinoma|Childhood Central Nervous System Mixed Germ Cell Tumor|Childhood Central Nervous System Teratoma|Childhood Central Nervous System Yolk Sac Tumor|Metastatic Childhood Soft Tissue Sarcoma|Recurrent Childhood Brain Stem Glioma|Recurrent Childhood Central Nervous System Embryonal Tumor|Recurrent Childhood Soft Ti June 2009 Phase 1
    NCT01506596 Vector Oncology|Novartis Liposarcoma|Surgically Unresectable Liposarcoma|Metastatic Liposarcoma March 2012 Phase 2
    NCT01361113 UNC Lineberger Comprehensive Cancer Center|GlaxoSmithKline Renal Cell Carcinoma June 2011 Phase 2
    NCT02113826 Seoul National University Hospital|Seoul National University Bundang Hospital|Asan Medical Center|Samsung Medical Center|Severance Hospital Metastatic Alveolar Soft Part Sarcoma April 2014 Phase 2
    NCT01012362 Masonic Cancer Center, University of Minnesota|GlaxoSmithKline Breast Cancer|Lung Cancer|Colon Cancer|Pancreatic Cancer|Head and Neck Cancer|Kidney Cancer|Sarcoma|Hepatocellular Cancer December 2009 Phase 1
    NCT01813136 Centre Leon Berard|GlaxoSmithKline Thyroid Carcinoma March 2013 Phase 2
    NCT02203760 University Medicine Greifswald|GlaxoSmithKline|medac GmbH Relapsed or Metastatic Uterine Leiomyosarcomas or Carcinosarcomas September 2013 Phase 2
    NCT01265940 Prof. Dr. Thomas Otto|Lukas-Krankenhaus GmbH Advanced Urothelial Cancer of Bladder After Failure of Platinum-containing Therapy. March 2011 Phase 1|Phase 2
    NCT01179269 Loyola University|GlaxoSmithKline Non-small Cell Lung Cancer March 2010 Phase 2
    NCT00350727 GlaxoSmithKline Glioma December 2006 Phase 2
    NCT01608009 Imperial College London|GlaxoSmithKline Ovarian Neoplasm July 2012 Phase 1
    NCT00334282 GlaxoSmithKline Carcinoma, Renal Cell April 2006 Phase 3
    NCT01064310 Novartis Pharmaceuticals|Novartis Carcinoma, Renal Cell May 17, 2010 Phase 3
    NCT00731211 SCRI Development Innovations, LLC|GlaxoSmithKline Renal Cell Carcinoma September 2008 Phase 2
    NCT00370513 GlaxoSmithKline Carcinoma, Hepatic Cell|Liver Cancer December 2006 Phase 1
    NCT01238770 Priv.-Doz. Dr. med. Joachim Rom|University Hospital Heidelberg Epithelial Ovarian Cancer November 2010 Phase 1|Phase 2
    NCT03149120 New York University School of Medicine|Bristol-Myers Squibb Soft Tissue Sarcomas October 2017 Phase 2
    NCT01543802 Heidelberg University|Universitätsmedizin Mannheim|Klinikum Frankfurt Höchst|German Cancer Research Center|GlaxoSmithKline|University Hospital Heidelberg Sarcoma, Soft-tissue April 2013 Phase 2
    NCT02055690 Heather Driscoll|Novartis|Mateon Therapeutics|East and North Hertfordshire NHS Trust|The Christie NHS Foundation Trust Ovarian Neoplasms|Neoplasms, Ovarian|Ovarian Cancer September 2014 Phase 1|Phase 2
    NCT01649778 Novartis Pharmaceuticals|Novartis Carcinoma, Renal Cell July 19, 2012
    NCT01797874 Samsung Medical Center SCLC June 2013 Phase 2
    NCT01205230 GlaxoSmithKline Cancer September 2010 Phase 4
    NCT01235962 Novartis Pharmaceuticals|Novartis Cancer November 30, 2010 Phase 3
    NCT01498458 German Breast Group Metastatic Breast Cancer October 2010 Phase 1
    NCT02066285 Grupo Espanol de Investigacion en Sarcomas Solitary Fibrous Tumor|Extraskeletal Myxoid Chondrosarcoma June 2014 Phase 2
    NCT01876082 Institut Bergonié Progressive Desmoids Tumors July 2012 Phase 2
    NCT01059656 Assistance Publique - Hôpitaux de Paris|GlaxoSmithKline Dermatofibrosarcomas of DARIER FERRAND(DFSP) July 2010 Phase 2
    NCT02575066 The Netherlands Cancer Institute Sarcoma|Soft Tissue Sarcomas January 2016 Phase 2
    NCT02393820 UNICANCER Salivary Gland Carcinoma August 2013 Phase 2
    NCT02331498 Centre Antoine Lacassagne|GlaxoSmithKline Glioblastoma Multiforme June 2015 Phase 1|Phase 2
    NCT01436227 M.D. Anderson Cancer Center|Novartis Von Hippel-Lindau Syndrome January 2012 Phase 2
    NCT00866528 GlaxoSmithKline Lung Cancer, Non-Small Cell July 2009 Phase 1
    NCT01613846 Technische Universität München Renal Cell Carcinoma May 2012 Phase 3
    NCT00387205 Novartis Pharmaceuticals|Novartis Carcinoma, Renal Cell June 2006 Phase 1
    NCT01767636 Mayo Clinic|National Cancer Institute (NCI) Carcinoma of the Collecting Ducts of Bellini|Chromophobe Renal Cell Carcinoma|Kidney Medullary Carcinoma|Kidney Oncocytoma|Metastatic Renal Cell Cancer|Papillary Renal Cell Carcinoma|Recurrent Renal Cell Carcinoma|Sarcomatoid Renal Cell Carcinoma|Stage IV Renal Cell Cancer May 16, 2013 Phase 2
    NCT02300545 Washington University School of Medicine Sarcoma, Soft Tissue|Soft Tissue Sarcoma April 8, 2015 Phase 2
    NCT01247571 National Cancer Institute (NCI) Recurrent Uterine Corpus Sarcoma|Uterine Carcinosarcoma January 2011 Phase 2
    NCT01552356 National Cancer Institute (NCI) Solid Neoplasm March 19, 2012 Phase 1
    NCT01692496 Grupo Espanol de Investigacion en Sarcomas|GlaxoSmithKline Advanced and / or Metastatic Liposarcoma January 2013 Phase 2
    NCT01713296 Hellenic Oncology Research Group SCLC November 2011 Phase 2
    NCT00459381 National Cancer Institute (NCI) Adult Giant Cell Glioblastoma|Adult Glioblastoma|Adult Gliosarcoma|Recurrent Adult Brain Tumor May 2007 Phase 2
    NCT01513187 Spanish Oncology Genito-Urinary Group|GlaxoSmithKline Advanced Renal Cell Carcinoma September 2010 Phase 1|Phase 2
    NCT01027598 SCRI Development Innovations, LLC|GlaxoSmithKline|OSI Pharmaceuticals Non Small Cell Lung Cancer January 2010 Phase 2
    NCT01262820 UNC Lineberger Comprehensive Cancer Center|GlaxoSmithKline Lung Cancer December 2010 Phase 2
    NCT01165385 UNICANCER Solid Tumors|Metastatic Cancer June 2010 Phase 1
    NCT01566747 Cancer Trials Ireland|Novartis Renal Cell Carcinoma March 2011 Phase 2
    NCT02207309 Ludwig-Maximilians - University of Munich Sarcoma December 2014 Phase 2
    NCT01524848 Scandinavian Sarcoma Group|GlaxoSmithKline Gastrointestinal Stromal Tumors February 2012 Phase 2
    NCT02729194 University of Michigan Cancer Center Carcinoma, Renal Cell June 2016 Early Phase 1
    NCT01548144 M.D. Anderson Cancer Center Advanced Cancers April 2012 Phase 1
    NCT00625846 National Cancer Institute (NCI) Recurrent Thyroid Gland Carcinoma|Stage III Differentiated Thyroid Gland Carcinoma|Stage III Thyroid Gland Medullary Carcinoma|Stage IVA Differentiated Thyroid Gland Carcinoma|Stage IVA Thyroid Gland Medullary Carcinoma|Stage IVA Thyroid Gland Undifferentiated (Anaplastic) Carcinoma|Stage IVB Differentiated Thyroid Gland Carcinoma|Stage IVB Thyroid Gland Medullary Carcinoma|Stage IVB Thyroid Gland Undifferentiated (Anaplastic) Carcinoma|Stage IVC Differentiated Thyroid Gland Carcinoma|Stage IVC February 22, 2008 Phase 2
    NCT01622660 Memorial Sloan Kettering Cancer Center|GlaxoSmithKline Bladder Cancer June 2012 Phase 2
    NCT01855724 Hellenic Cooperative Oncology Group|GlaxoSmithKline Cholangiocarcinoma|Gallbladder Carcinoma|Biliary Carcinoma June 2013 Phase 2
    NCT00454363 National Cancer Institute (NCI) Gastrin-Producing Neuroendocrine Tumor|Lung Carcinoid Tumor|Metastatic Digestive System Neuroendocrine Tumor G1|Multiple Endocrine Neoplasia Type 1|Pancreatic Glucagonoma|Pancreatic Insulinoma|Pancreatic Polypeptide Tumor|Recurrent Digestive System Neuroendocrine Tumor G1|Recurrent Pancreatic Neuroendocrine Carcinoma|Regional Digestive System Neuroendocrine Tumor G1|Somatostatin-Producing Neuroendocrine Tumor March 2007 Phase 2
    NCT01280201 Grupo Espanol de Tumores Neuroendocrinos Advanced/Metastatic Neuroendocrine Tumors December 2010 Phase 2
    NCT01158521 Case Comprehensive Cancer Center Clear Cell Renal Cell Carcinoma|Stage I Renal Cell Cancer|Stage II Renal Cell Cancer|Stage III Renal Cell Cancer June 2010 Phase 2
    NCT01391611 Kristen Ganjoo|GlaxoSmithKline|Stanford University Gastrointestinal Stromal Tumor (GIST) July 2011 Phase 2
    NCT01995981 Radboud University|GlaxoSmithKline Sarcoma, Soft Tissue December 2013
    NCT01466972 Hope Rugo, MD|GlaxoSmithKline|University of California, San Francisco Breast Cancer|Breast Neoplasm April 2012 Phase 2
    NCT02383251 ARCAGY/ GINECO GROUP|Novartis Ovarian Cancer June 2015 Phase 2
    NCT01340794 National Cancer Institute (NCI) Extra-Adrenal Paraganglioma|Metastatic Adrenal Gland Pheochromocytoma|Paraganglioma|Recurrent Adrenal Gland Pheochromocytoma May 2011 Phase 2
    NCT02367651 GlaxoSmithKline Sarcoma, Soft Tissue June 2015 Phase 2
    NCT01438554 Sidney Kimmel Comprehensive Cancer Center|National Comprehensive Cancer Network|Novartis Solid Tumors|Thyroid Cancer|Soft-tissue Sarcoma|Cholangiocarcinoma October 2011 Phase 1
    NCT02089802 Interessenverband zur Qualitätssicherung der Arbeit niedergelassener Uro-Onkologen in Deutschland e.|OnkoDataMed GmbH Locally Advanced Renal Cell Carcinoma|Metastatic Renal Cell Carcinoma February 2014 Phase 2
    NCT01154062 GlaxoSmithKline Macular Degeneration August 2010 Phase 1
    NCT00367679 GlaxoSmithKline Non-Small Cell Lung Cancer|Lung Cancer, Non-Small Cell November 2006 Phase 2
    NCT01035658 SCRI Development Innovations, LLC|GlaxoSmithKline Ovarian Cancer|Fallopian Tube Cancer|Peritoneal Carcinoma January 2010 Phase 1|Phase 2
    NCT02307474 Case Comprehensive Cancer Center|National Cancer Institute (NCI) Clear Cell Renal Cell Carcinoma|Renal Cell Carcinoma September 2015
    NCT01080248 Washington University School of Medicine Pancreatic Cancer August 2010 Phase 2
    NCT00866697 Novartis Pharmaceuticals|GlaxoSmithKline|Novartis Neoplasms, Ovarian May 26, 2009 Phase 3
    NCT01323400 Centre Leon Berard|GlaxoSmithKline GIST March 2011 Phase 2
    NCT01442662 UNICANCER Leiomyosarcoma September 2011 Phase 2
    NCT01418001 Memorial Sloan Kettering Cancer Center|National Comprehensive Cancer Network|University of California, Los Angeles|Washington University School of Medicine|Northwestern University Sarcoma|Leiomyosarcoma|Malignant Peripheral Nerve Sheath Tumor|Malignant Fibrous|Histiocytoma/Undifferentiated Pleomorphic Sarcoma August 2011 Phase 1|Phase 2
    NCT01716416 Washington University School of Medicine Squamous Cell Carcinoma of the Head and Neck May 31, 2013 Phase 1
    NCT00861913 National Cancer Institute (NCI) Recurrent Melanoma|Stage IV Skin Melanoma April 3, 2009 Phase 2
    NCT01099540 Samsung Medical Center Neuroendocrine Tumor April 2010 Phase 2
    NCT01413113 University of Washington|GlaxoSmithKline|National Cancer Institute (NCI)|National Comprehensive Cancer Network Recurrent Thyroid Cancer|Stage IVA Follicular Thyroid Cancer|Stage IVA Papillary Thyroid Cancer|Stage IVB Follicular Thyroid Cancer|Stage IVB Papillary Thyroid Cancer|Stage IVC Follicular Thyroid Cancer|Stage IVC Papillary Thyroid Cancer December 2011 Phase 1
    NCT01184326 Dana-Farber Cancer Institute|Beth Israel Deaconess Medical Center|Brigham and Women's Hospital|GlaxoSmithKline|Novartis Solid Tumor|Kidney Cancer September 2010 Phase 1
    NCT01449825 GlaxoSmithKline Carcinoma, Renal Cell December 2010
    NCT02691767 Samsung Medical Center Refractory Solid Tumors May 2016
    NCT02348398 M.D. Anderson Cancer Center|GlaxoSmithKline Cervical Cancer August 2016 Phase 2
    NCT01407562 Rutgers, The State University of New Jersey|National Cancer Institute (NCI)|Rutgers Cancer Institute of New Jersey|GlaxoSmithKline Unspecified Adult Solid Tumor - Protocol Specific|Breast Cancer - Female August 2011 Phase 1
    NCT01377298 National Taiwan University Hospital|GlaxoSmithKline Head and Neck Squamous Cell Carcinoma June 2011 Phase 2
    NCT00612456 GlaxoSmithKline Macular Degeneration March 2008 Phase 2
    NCT03200717 Novartis Pharmaceuticals|Novartis Advanced Renal Cell Carcinoma|Metastatic Renal Cell Carcinoma August 17, 2017 Phase 2
    NCT01454804 M.D. Anderson Cancer Center Advanced Cancers October 2011 Phase 1
    NCT02342600 Sarcoma Alliance for Research through Collaboration|Novartis Gastrointestinal Stromal Tumors January 2017 Phase 2
    NCT00659555 GlaxoSmithKline Macular Degeneration|Age-related Macular Degeneration April 2008 Phase 1
    NCT00509587 National Cancer Institute (NCI) Breast Cancer|Recurrent Breast Cancer|Stage IV Breast Cancer June 2007 Phase 2
    NCT00732420 GlaxoSmithKline Solid Tumours September 2008 Phase 1
    NCT02204371 GlaxoSmithKline Telangiectasia, Hereditary Hemorrhagic February 25, 2015 Phase 2
    NCT02014636 Novartis Pharmaceuticals|Merck Sharp & Dohme Corp.|Novartis Carcinoma, Renal Cell December 27, 2013 Phase 1|Phase 2
    NCT01610206 Linda R Duska|Novartis|University of Virginia Ovarian Cancer|Fallopian Tube Cancer|Peritoneal Cancer September 2012 Phase 2
    NCT02357810 Northwestern University|GlaxoSmithKline|National Cancer Institute (NCI) Adult Liposarcoma|Metastatic Liposarcoma|Metastatic Osteosarcoma|Recurrent Adult Soft Tissue Sarcoma|Recurrent Liposarcoma|Recurrent Osteosarcoma|Stage IV Adult Soft Tissue Sarcoma February 2015 Phase 2
    NCT02601209 National Cancer Institute (NCI) High Grade Sarcoma|Metastatic Leiomyosarcoma|Metastatic Malignant Peripheral Nerve Sheath Tumor|Metastatic Synovial Sarcoma|Metastatic Undifferentiated Pleomorphic Sarcoma|Myxofibrosarcoma|Recurrent Leiomyosarcoma|Recurrent Malignant Peripheral Nerve Sheath Tumor|Recurrent Synovial Sarcoma|Recurrent Undifferentiated Pleomorphic Sarcoma|Uterine Corpus Leiomyosarcoma November 30, 2015 Phase 1|Phase 2
    NCT00861029 GlaxoSmithKline Carcinoma, Renal Cell|Solid Tumors March 2009 Phase 1
    NCT02810756 The Netherlands Cancer Institute Pharmacokinetics of Pazopanib September 15, 2016 Early Phase 1
    NCT00387764 GlaxoSmithKline Carcinoma, Renal Cell September 2006 Phase 3
    NCT00471536 National Cancer Institute (NCI) Distal Urethral Cancer|Proximal Urethral Cancer|Recurrent Bladder Cancer|Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter|Recurrent Urethral Cancer|Stage IV Bladder Cancer|Transitional Cell Carcinoma of the Bladder|Urethral Cancer Associated With Invasive Bladder Cancer August 2008 Phase 2
    NCT01262014 Grupo Español de Investigación en Cáncer de Ovario Platinum-resistant Advanced Ovarian Cancer December 2010 Phase 2
    NCT00450879 National Cancer Institute (NCI) Male Breast Carcinoma|Recurrent Breast Carcinoma|Stage IA Breast Cancer|Stage IB Breast Cancer|Stage IIA Breast Cancer|Stage IIB Breast Cancer|Stage IIIA Breast Cancer January 2007 Phase 1
    NCT01639911 University of Illinois at Chicago|Millennium Pharmaceuticals, Inc. Malignant Neoplasm of Breast|CNS Malignancy|Malignant Neoplasm of Gastrointestinal Tract|Genitourinary Neoplasms Malignancy and Gender Unspecified|Head and Neck Neoplasms|Melanoma|Malignant Neoplasm of Thorax August 14, 2013 Phase 1
    NCT00454142 National Cancer Institute (NCI) Recurrent Lymphoepithelioma of the Nasopharynx|Recurrent Squamous Cell Carcinoma of the Nasopharynx|Stage IV Lymphoepithelioma of the Nasopharynx|Stage IV Squamous Cell Carcinoma of the Nasopharynx August 2007 Phase 2
    NCT00558103 GlaxoSmithKline Neoplasms, Breast December 2007 Phase 2
    NCT00486642 National Cancer Institute (NCI) Hormone-Resistant Prostate Cancer|Recurrent Prostate Carcinoma September 2007 Phase 2
    NCT00619424 GlaxoSmithKline Advanced Solid Tumours|Cancer|Lung Cancer, Non-Small Cell November 2007 Phase 1
    NCT01684397 Roswell Park Cancer Institute|National Cancer Institute (NCI)|GlaxoSmithKline Clear Cell Renal Cell Carcinoma|Stage IV Renal Cell Cancer October 5, 2012 Phase 1|Phase 2
    NCT01538238 Samsung Medical Center Locally Advanced or Metastatic Non-clear Cell Type Renal Cell Carcinoma May 2, 2012 Phase 2
    NCT01485042 Herbert Hurwitz, MD|National Comprehensive Cancer Network|GlaxoSmithKline|Threshold Pharmaceuticals|Duke University Solid Tumors December 2011 Phase 1
    NCT02555748 Institut Claudius Regaud|University Hospital, Bordeaux Metastatic Renal Cell Cancer October 2015 Phase 4
    NCT01465659 Northwestern University|Robert H. Lurie Cancer Center|National Comprehensive Cancer Network|GlaxoSmithKline Pancreatic Alpha Cell Carcinoma|Pancreatic Beta Islet Cell Carcinoma|Pancreatic Delta Cell Carcinoma|Pancreatic G-cell Carcinoma|Recurrent Islet Cell Carcinoma November 2011 Phase 1|Phase 2
    NCT01832259 University of Utah|Novartis Adenocarcinoma of the Prostate August 2013 Phase 2
    NCT00540943 GlaxoSmithKline Neoplasms, Colorectal|Colorectal Cancer July 2007 Phase 1
    NCT00516672 GlaxoSmithKline Carcinoma, Renal Cell September 2007 Phase 1
    NCT00387387 GlaxoSmithKline Neoplasms, Colorectal|Colorectal Cancer October 2006 Phase 1
    NCT02212015 Heidelberg University|Universitätsmedizin Mannheim|HELIOS Klinikum Berlin-Buch|University Hospital Dresden|Universitätsklinikum Hamburg-Eppendorf|University Hospital, Essen|Hannover Medical School|Klinikum der Universitaet Muenchen, Grosshadern|Medical University of Vienna|Medical University of Graz|Medical University Innsbruck|GlaxoSmithKline Angiosarcoma July 2014 Phase 2
    NCT00454571 National Cancer Institute (NCI) Recurrent Prostate Cancer June 2006 Phase 2
    NCT01060514 Northwestern University|Robert H. Lurie Cancer Center Metastatic Non Small Cell Lung Cancer|Metastatic Breast Cancer February 2010 Phase 1
    NCT01385228 Daniel George, MD|GlaxoSmithKline|Duke University Prostate Cancer June 2011 Phase 1
    NCT00297258 GlaxoSmithKline Sarcoma, Soft Tissue November 2005 Phase 2
    NCT01599832 University of Chicago|National Cancer Institute (NCI) Clear Cell Renal Cell Carcinoma|Recurrent Renal Cell Cancer|Stage IV Renal Cell Cancer June 2012
    NCT02378142 Gynecologic Oncology Group|GlaxoSmithKline Uterine Leiomyosarcoma March 2015 Phase 2
    NCT01227928 GlaxoSmithKline Neoplasms, Ovarian September 2010 Phase 2
    NCT01072214 GlaxoSmithKline Macular Degeneration March 2010 Phase 1
    NCT01392183 M.D. Anderson Cancer Center|Novartis Kidney Cancer October 2012 Phase 2
    NCT01713972 Manisha Shah|National Comprehensive Cancer Network|Ohio State University Comprehensive Cancer Center Unspecified Adult Solid Tumor, Protocol Specific November 19, 2012 Phase 1
    NCT01532687 OHSU Knight Cancer Institute|National Cancer Institute (NCI) Adult Alveolar Soft Part Sarcoma|Adult Angiosarcoma|Adult Desmoplastic Small Round Cell Tumor|Adult Epithelioid Hemangioendothelioma|Adult Epithelioid Sarcoma|Adult Extraskeletal Myxoid Chondrosarcoma|Adult Extraskeletal Osteosarcoma|Adult Fibrosarcoma|Adult Leiomyosarcoma|Adult Liposarcoma|Adult Malignant Mesenchymoma|Adult Malignant Peripheral Nerve Sheath Tumor|Adult Rhabdomyosarcoma|Adult Synovial Sarcoma|Adult Undifferentiated Pleomorphic Sarcoma|Malignant Adult Hemangiopericytoma|Recurrent March 2012 Phase 2
    NCT00871403 GlaxoSmithKline Lung Cancer, Non-Small Cell July 2009 Phase 2
    NCT01503372 Charite University, Berlin, Germany Advanced Gastric Cancer November 2011 Phase 2
    NCT01985295 The Netherlands Cancer Institute|GlaxoSmithKline Sarcoma,Soft Tissue June 2010 Phase 1
    NCT00753688 GlaxoSmithKline Sarcoma, Soft Tissue October 2008 Phase 3
    NCT01157091 City of Hope Medical Center Clear Cell Renal Cell Carcinoma|Recurrent Renal Cell Cancer|Stage IV Renal Cell Cancer November 2010 Phase 2
    NCT01841736 National Cancer Institute (NCI) Atypical Carcinoid Tumor|Foregut Carcinoid Tumor|Hindgut Carcinoid Tumor|Lung Carcinoid Tumor|Metastatic Carcinoid Tumor|Metastatic Digestive System Neuroendocrine Tumor G1|Midgut Carcinoid Tumor|Recurrent Digestive System Neuroendocrine Tumor G1|Regional Digestive System Neuroendocrine Tumor G1 June 21, 2013 Phase 2
    NCT01394211 University of Arizona|National Cancer Institute (NCI)|GlaxoSmithKline Estrogen Receptor-positive Breast Cancer|Human Epidermal Growth Factor 2 Negative Carcinoma of Breast|Male Breast Cancer|Recurrent Breast Cancer|Stage II Breast Cancer|Stage IIIA Breast Cancer|Stage IIIB Breast Cancer July 13, 2011 Phase 2
    NCT01313663 GlaxoSmithKline Lung Cancer, Small Cell February 2011 Phase 2
    NCT01472081 Bristol-Myers Squibb|Ono Pharmaceutical Co. Ltd Renal Cell Carcinoma|Clear-cell Metastatic Renal Cell Carcinoma January 2012 Phase 1
    NCT01402271 European Organisation for Research and Treatment of Cancer - EORTC Fallopian Tube Cancer|Ovarian Cancer|Primary Peritoneal Cavity Cancer July 2012 Phase 1|Phase 2
    NCT00720941 Novartis Pharmaceuticals|Novartis Carcinoma, Renal Cell August 14, 2008 Phase 3
    NCT01236547 National Cancer Institute (NCI) Thyroid Gland Undifferentiated (Anaplastic) Carcinoma October 28, 2010 Phase 2
    NCT01575548 National Cancer Institute (NCI) Clear Cell Renal Cell Carcinoma|Recurrent Renal Cell Carcinoma|Stage IV Renal Cell Cancer August 8, 2012 Phase 3
    NCT01147822 Novartis Pharmaceuticals|Novartis Carcinoma, Renal Cell May 19, 2010 Phase 2
    NCT02956798 University of Texas Southwestern Medical Center Carcinoma, Renal Cell July 15, 2017 Phase 2
    NCT01468922 National Cancer Institute (NCI)|National Institutes of Health Clinical Center (CC) Sarcoma|Stomach Neoplasms|Neoplasms October 24, 2011 Phase 1
    NCT02282579 Spanish Oncology Genito-Urinary Group Metastatic Renal Cell Carcinoma October 2014
    NCT01446809 University of Washington|National Cancer Institute (NCI) Stage IIA Adult Soft Tissue Sarcoma|Stage III Adult Soft Tissue Sarcoma|Stage IV Adult Soft Tissue Sarcoma April 2012
    NCT00827372 Indiana University Lymphedema January 2009 Phase 2
    NCT00849472 GlaxoSmithKline|NSABP Foundation Inc Neoplasms, Breast July 2009 Phase 2
    NCT00800345 Vector Oncology|GlaxoSmithKline Gynecologic Tumors April 2009 Phase 1
    NCT01593748 Medical University of South Carolina|Novartis Sarcoma May 2012 Phase 2
    NCT01462630 Fox Chase Cancer Center|National Cancer Institute (NCI) Adult Angiosarcoma|Recurrent Adult Soft Tissue Sarcoma|Stage III Adult Soft Tissue Sarcoma|Stage IV Adult Soft Tissue Sarcoma November 3, 2011 Phase 2
    NCT01468909 National Cancer Institute (NCI) Recurrent Fallopian Tube Carcinoma|Recurrent Ovarian Carcinoma|Recurrent Primary Peritoneal Carcinoma December 2011 Phase 2
    NCT00463320 GlaxoSmithKline Macular Degeneration|Age-related Macular Degeneration March 2007 Phase 1
    NCT01446224 GlaxoSmithKline Carcinoma, Renal Cell December 2010
    NCT02450136 Samsung Medical Center Refractory Solid Tumors October 8, 2015
    NCT02180867 National Cancer Institute (NCI) Adult Fibrosarcoma|Alveolar Soft Part Sarcoma|Angiomatoid Fibrous Histiocytoma|Atypical Fibroxanthoma|Clear Cell Sarcoma of Soft Tissue|Epithelioid Malignant Peripheral Nerve Sheath Tumor|Epithelioid Sarcoma|Extraskeletal Myxoid Chondrosarcoma|Extraskeletal Osteosarcoma|Fibrohistiocytic Neoplasm|Glomus Tumor of the Skin|Inflammatory Myofibroblastic Tumor|Intimal Sarcoma|Leiomyosarcoma|Liposarcoma|Low Grade Fibromyxoid Sarcoma|Low Grade Myofibroblastic Sarcoma|Malignant Cutaneous Granular Cell Tu July 11, 2014 Phase 2|Phase 3
    NCT01719302 University of Vermont|Novartis Stage III Adult Soft Tissue Sarcoma October 2012 Phase 1|Phase 2
    NCT00775307 Intergroupe Francophone de Cancerologie Thoracique Carcinoma, Non-Small-Cell Lung November 2008 Phase 2|Phase 3
    NCT00388076 GlaxoSmithKline Solid Tumor Cancer|Neoplasms, Breast April 2006 Phase 1
    NCT00459862 National Cancer Institute (NCI) Advanced Malignant Mesothelioma|Localized Malignant Mesothelioma|Recurrent Malignant Mesothelioma March 2007 Phase 2
    NCT01644825 National Cancer Institute, Naples Ovarian Cancer December 2010 Phase 2
    NCT01362348 GlaxoSmithKline Macular Degeneration July 2011 Phase 2
    NCT00992121 GlaxoSmithKline Carcinoma, Renal Cell November 2009 Phase 1
    NCT00615524 GlaxoSmithKline Hormone-receptor Positive Breast Cancer April 2008 Phase 2
    NCT01931098 National Cancer Institute (NCI)|National Institutes of Health Clinical Center (CC) Glioblastoma|Glioblastoma Multiforme|Gliosarcoma|Brain Neoplasms|Central Nervous System Neoplasms December 10, 2015 Phase 2
    NCT01221506 Abramson Cancer Center of the University of Pennsylvania Carcinoma, Renal Cell October 2010 Early Phase 1
    NCT00788580 Southwest Oncology Group|National Cancer Institute (NCI) Unspecified Adult Solid Tumor, Protocol Specific Phase 1
    NCT02570789 Jean-Pascal Machiels|Cliniques universitaires Saint-Luc- Université Catholique de Louvain Clear-cell Metastatic Renal Cell Carcinoma December 2012 Phase 4
    NCT01031875 Fondazione IRCCS Istituto Nazionale dei Tumori, Milano|National Cancer Institute (NCI) Bladder Cancer|Transitional Cell Cancer of the Renal Pelvis and Ureter|Urethral Cancer December 2009 Phase 2
    NCT00733304 GlaxoSmithKline Macular Degeneration June 2008 Phase 2
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    NCT01208064 European Organisation for Research and Treatment of Cancer - EORTC Lung Cancer July 2011 Phase 2|Phase 3
    NCT01861951 Hannover Medical School Soft Tissue Sarcoma October 2012 Phase 2
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    NCT01666418 University of Zurich Melanoma August 2012 Phase 2
    NCT01408004 Netherlands Working Group on Immunotherapy of Oncology Clear Cell Renal Carcinoma November 2011 Phase 2
    NCT00060151 Case Comprehensive Cancer Center|National Cancer Institute (NCI) Unspecified Adult Solid Tumor, Protocol Specific December 2002 Phase 1
    NCT01202032 Centre Leon Berard Metastatic Renal Cell Carcinoma|Advanced Refractory Solid Tumors Histologically or Cytologically Confirmed July 2010 Phase 1
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    NCT02406521 Dana-Farber Cancer Institute|Bayer Metastatic Renal Cell Carcinoma April 2015 Phase 1
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    NCT01217931 M.D. Anderson Cancer Center|Novartis Kidney Cancer January 2011 Phase 2
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    NCT02049905 CytRx Metastatic, Locally Advanced or Unresectable Soft Tissue Sarcoma January 2014 Phase 3
    NCT02560012 The University of Texas Health Science Center, Houston Carcinoma, Renal Cell December 2015 Phase 2
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    References
    Preparing Stock Solutions
    Concentration Volume (DMSO) Mass 1 mg 5 mg 10 mg
    1 mM 2.2856 mL 11.4280 mL 22.8561 mL
    5 mM 0.4571 mL 2.2856 mL 4.5712 mL
    10 mM 0.2286 mL 1.1428 mL 2.2856 mL
    Kinase Assay
    [1]

    VEGFR enzyme assays for VEGGR1, VEGFR2, and VEGFR3 are run in homogeneous time-resolved fluorescence (HTRF) format in 384-well microtiter plates using a purified, baculovirus-expressed glutathione-S-transferase (GST) fusion protein encoding the catalytic c-terminus of human VEGFR receptor kinases 1, 2, or 3. Reactions are initiated by the addition of 10 μL of activated VEGFR2 kinase solution [final concentration, 1 nM enzyme in 0.1 M 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES), pH 7.5, containing 0.1 mg/mL bovine serum albumin (BSA), 300 μM dithiothreitol (DTT)] to 10 μL substrate solution [final concentration, 360 nM peptide, (biotin-aminohexyl-EEEEYFELVAKKKK-NH2), 75 μM ATP, 10 μM MgCl2], and 1 μL of titrated compound in DMSO. Plates are incubated at room temperature for 60 min, and then the reaction is quenched by the addition of 20 μL of 100 mM ethylene diamine tetraacetic acid (EDTA). After quenching, 20 μL HTRF reagents (final concentration, 15 nM Streptavidin-linked allophycocyanin, 1 nM Europium-labeled antiphosphotyrosine antibody diluted in 0.1 mg/mL BSA, 0.1 M HEPES, pH 7.5) is added and the plates incubated for a minimum of 10 min. The fluorescence at 665 nM is measured with a Wallac Victor plate reader using a time delay of 50 μs[1]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Cell Assay
    [1]

    Pazopanib is prepared in DMSO and then diluted to final concentration in medium[1].

    The effect of Pazopanib on cell proliferation is measured using 5-bromo-2-deoxyuridine (BrdU) incorporation method using commercially available kits. HUVEC is seeded in medium containing 5% fetal bovine serum (FBS) in type 1 collagen coated 96-well plates and incubated overnight at 37°C, 5% CO2. The medium is aspirated from the cells, and various concentrations of Pazopanib in serum-free medium are added to each well. After 30 min, either VEGF (10 ng/mL) or bFGF (0.3 ng/mL) is added to the wells. Cells are incubated for an additional 72 h and BrdU (10 μM) is added during the last 18 to 24 h of incubation. At the end of incubation, BrdU incorporation in cells is measured by ELISA. Data are fitted with a curve described by the equation, y=Vmax(1−(x/(K+x))), where K is equal to the IC50[1]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Animal Administration
    [1][2]

    Pazopanib is triturated with sodium carboxymethyl cellulose (0.5 % w/v) using a pestle and mortar and 5 mg/mL suspension is made after adding sufficient quantity of phosphate buffer saline (pH 7.4) (Rat)[2].

    Mice[1]
    Tumors are initiated by injection of tumor cell suspension in 8−12 week old nude mice. When tumors reach a volume of 100−200 mm3, mice are randomized and divided into groups of eight. Pazopanib is administered once or twice daily at 10, 30, or 100 mg/kg. Animals are euthanized by inhalation of CO2 at the completion of the study. Tumor volume is measured twice weekly by calipers, using the equation: tumor volume (mm3)=(length×width2)/2. Results are routinely reported as % inhibition=1−(average growth of the drug treated population/average growth of vehicle treated control population).
    Rat[2]
    Male Brown-Norway (BN; pigmented) rats weighing 200 to 250 g are acclimatized for at least two days prior to any experimental procedure. After overnight fasting for 12-16 h, an intraperitoneal injection of 30 mg/mL solution of Streptozotocin in 10 mM citrate buffer (pH 4.5) is administered (60 mg/kg body weight) to induce diabetes. After 3-4 h of Streptozotocin injection, animals are put on a regular diet and 24 h after Streptozotocin injection, blood sample (5-10 μL) is collected via tail vein. The blood glucose levels in the animals are determined with a glucose monitor. Animals with blood glucose levels greater than 250 mg/dL are considered diabetic. The animals are divided into three groups. Group 1: Healthy (n=12), Group 2: Diabetic (n=12) and Group 3: Diabetic+Treatment (n=12). Treatment is started immediately after diabetes induction. Both eyes are dosed twice daily for 30 days with 0.5 % w/v Pazopanib suspension (10 μL volume in each eye) and animals in all groups are sacrificed on day 31, 16-17 h after last dose on day 30. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    References
    Molecular Weight

    437.52

    Formula

    C₂₁H₂₃N₇O₂S

    CAS No.

    444731-52-6

    Storage
    Powder -20°C 3 years
      4°C 2 years
    In solvent -80°C 6 months
      -20°C 1 month
    Shipping

    Room temperature in continental US; may vary elsewhere

    Solvent & Solubility

    DMSO: ≥ 43 mg/mL

    * "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

    Purity: 99.44%

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    Product Name:
    Pazopanib
    Cat. No.:
    HY-10208
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