Identification

Name
Pazopanib
Accession Number
DB06589
Type
Small Molecule
Groups
Approved
Description

Pazopanib is a small molecule inhibitor of multiple protein tyrosine kinases with potential antineoplastic activity. It is developed by GlaxoSmithKline and was FDA approved on October 19, 2009.

Structure
Thumb
Synonyms
  • GW 78603
  • pazopanib
  • Pazopanibum
External IDs
GW-786034 / GW786034
Product Ingredients
IngredientUNIICASInChI Key
Pazopanib Hydrochloride33Y9ANM545635702-64-6MQHIQUBXFFAOMK-UHFFFAOYSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
VotrientTablet, film coated200 mg/1OralGlaxosmithkline Inc2009-10-192017-11-30Us
VotrientTablet400 mgOralNovartisNot applicableNot applicableCanada
VotrientTablet, film coated200 mgOralNovartis Europharm Limited2010-06-14Not applicableEu
VotrientTablet, film coated400 mgOralNovartis Europharm Limited2010-06-14Not applicableEu
VotrientTablet, film coated200 mg/1OralNovartis Pharmaceuticals Corporation2016-07-12Not applicableUs
VotrientTablet, film coated200 mgOralNovartis Europharm Limited2010-06-14Not applicableEu
VotrientTablet, film coated400 mgOralNovartis Europharm Limited2010-06-14Not applicableEu
VotrientTablet200 mgOralNovartis2010-08-13Not applicableCanada
Categories
UNII
7RN5DR86CK
CAS number
444731-52-6
Weight
Average: 437.518
Monoisotopic: 437.163393705
Chemical Formula
C21H23N7O2S
InChI Key
CUIHSIWYWATEQL-UHFFFAOYSA-N
InChI
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)
IUPAC Name
5-({4-[(2,3-dimethyl-2H-indazol-6-yl)(methyl)amino]pyrimidin-2-yl}amino)-2-methylbenzene-1-sulfonamide
SMILES
CN(C1=CC2=NN(C)C(C)=C2C=C1)C1=CC=NC(NC2=CC=C(C)C(=C2)S(N)(=O)=O)=N1

Pharmacology

Indication

Treatment of advanced renal cell cancer and advanced soft tissue sarcoma (in patients previously treated with chemotherapy)

Associated Conditions
Pharmacodynamics

Pazopanib is a synthetic indazolylpyrimidine and reaches steady state concentrations of >15 μg/ml. This concentration is high enough to observe maximal inhibition of VEGFR2 phosphorylation and some anti-tumour activity (concentration required to inhibit receptors is 0.01 - 0.084 μmol/L). A reduction in tumour blood flow, increased tumour apoptosis, inhibition of tumour growth, reduction in tumour interstitial fluid pressure, and hypoxia in cancer cells can be observed in patients receiving treatment.

Mechanism of action

Pazopanib is a second-generation multitargeted tyrosine kinase inhibitor against vascular endothelial growth factor receptor-1, -2, and -3, platelet-derived growth factor receptor-alpha, platelet-derived growth factor receptor-beta, and c-kit. These receptor targets are part of the angiogenesis pathway that facilitates the formation of tumour blood vessel for tumour survival and growth.

TargetActionsOrganism
AVascular endothelial growth factor receptor 1
inhibitor
Human
AVascular endothelial growth factor receptor 2
inhibitor
Human
AVascular endothelial growth factor receptor 3Not AvailableHuman
APlatelet-derived growth factor receptor alpha
inhibitor
Human
APlatelet-derived growth factor receptor beta
inhibitor
Human
AMast/stem cell growth factor receptor Kit
inhibitor
Human
UFibroblast growth factor receptor 3
inhibitor
Human
UTyrosine-protein kinase ITK/TSK
inhibitor
Human
UFibroblast growth factor 1
inhibitor
Human
USH2B adapter protein 3
inhibitor
Human
Absorption

Absorption of pazopanib in cancer patients is slow and incomplete. In patients with solid tumour, over a dose range of 50-2000 mg, absorption is nonlinear. Significant accumulation of pazopanib can also be observed in patients receiving 800 mg once daily for 22 days. Crushing tablets may increase exposure (increase in Cmax and AUC, while Tmax decreases by 2 hours). Bioavailability, oral tablet 800 mg, cancer patient = 21%; Bioavailability may be low due to incomplete absorption from the gastrointestinal tract. The major circulating component of the drug in the systemic is pazopanib, and not its metabolites. Mean maximum plasma concentration= 58.1 µg/mL; Mean AUC= 1037 µg · h/mL;

Volume of distribution

Vd steady state, IV administration 5 mg, cancer patient = 11.1 L (range of 9.15 - 13.4)

Protein binding

>99% protein bound, independent of concentrations over a range of 10-100 μg/mL.

Metabolism

Metabolized by CYP3A4 and to a lesser extent by CYP1A2 and CYP2C8. Metabolites are less active than pazopanib (10 to 20-fold less active). Three of its metabolites can be observed in the systemic and account for <10% of plasma radioactivity.

Route of elimination

Primarily excreted via feces (82.2%) and to a negligible extent via urine (<4%) in cancer patients. Most of the administered dose is excreted unchanged. Approximately 10% of dose are oxidative metabolites and are mostly eliminated via the feces.

Half life

35 hours. Oral absorption is not the rate limiting step of elimination from the plasma.

Clearance

CL, cancer patient, IV administration 5 mg = 4mL/min Half of the absorbed dose is cleared via oxidative metabolism.

Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Interacting Gene/EnzymeAllele nameGenotype(s)Defining Change(s)Type(s)DescriptionDetails
UDP-glucuronosyltransferase 1-1UGT1A1*28(TA;TA)TA pair insertionADR Directly StudiedThe presence of this polymorphism in UGT1A1 is associated with an increase in the incidence of hyperbilirubinemia when treated with pazopanib.Details
HLA class I histocompatibility antigen protein P5HLA-B*57:01(G;G)G alleleADR Directly StudiedThe presence of this polymorphism in HCP5 may indicate an increased risk of ALT elevation leading to drug-related hepatotoxicty from pazpanib therapy.Details

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Pazopanib.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Pazopanib.
2-MethoxyethanolThe risk or severity of adverse effects can be increased when 2-Methoxyethanol is combined with Pazopanib.
3-isobutyl-1-methyl-7H-xanthineThe serum concentration of 3-isobutyl-1-methyl-7H-xanthine can be increased when it is combined with Pazopanib.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Pazopanib.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Pazopanib.
4-MethoxyamphetamineThe metabolism of 4-Methoxyamphetamine can be decreased when combined with Pazopanib.
5-androstenedioneThe metabolism of 5-androstenedione can be decreased when combined with Pazopanib.
6-Deoxyerythronolide BThe metabolism of Pazopanib can be decreased when combined with 6-Deoxyerythronolide B.
6-O-benzylguanineThe serum concentration of 6-O-benzylguanine can be increased when it is combined with Pazopanib.
Food Interactions
  • Avoid drinking grapefruit juice as it is a CYP 3A4 inhibitor and will increase exposure of pazopanib
  • Bioavailability increases with food. Take pazopanib on empty stomach.

References

General References
  1. Sonpavde G, Hutson TE, Sternberg CN: Pazopanib, a potent orally administered small-molecule multitargeted tyrosine kinase inhibitor for renal cell carcinoma. Expert Opin Investig Drugs. 2008 Feb;17(2):253-61. doi: 10.1517/13543784.17.2.253. [PubMed:18230058]
  2. Verweij J, Sleijfer S: Pazopanib, a new therapy for metastatic soft tissue sarcoma. Expert Opin Pharmacother. 2013 May;14(7):929-35. doi: 10.1517/14656566.2013.780030. Epub 2013 Mar 14. [PubMed:23488774]
  3. Deng Y, Sychterz C, Suttle AB, Dar MM, Bershas D, Negash K, Qian Y, Chen EP, Gorycki PD, Ho MY: Bioavailability, metabolism and disposition of oral pazopanib in patients with advanced cancer. Xenobiotica. 2013 May;43(5):443-53. doi: 10.3109/00498254.2012.734642. Epub 2012 Nov 16. [PubMed:23548165]
  4. Deeks ED: Pazopanib: in advanced soft tissue sarcoma. Drugs. 2012 Nov 12;72(16):2129-40. doi: 10.2165/11209950-000000000-00000. [PubMed:23072642]
External Links
KEGG Drug
D05380
PubChem Compound
10113978
PubChem Substance
175427074
ChemSpider
8289501
BindingDB
26474
ChEBI
71219
ChEMBL
CHEMBL477772
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Pazopanib
ATC Codes
L01XE11 — Pazopanib
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
FDA label
Download (593 KB)
MSDS
Download (70.4 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0Active Not RecruitingTreatmentRenal Cell Adenocarcinoma1
0CompletedTreatmentRenal Cell Adenocarcinoma1
1Active Not RecruitingTreatmentAdvanced Cancers1
1Active Not RecruitingTreatmentAdvanced Cancers / Tumors, Solid1
1Active Not RecruitingTreatmentBreast Cancer - Female / Unspecified Adult Solid Tumor - Protocol Specific1
1Active Not RecruitingTreatmentCancer of the Ovary / Cancer, Breast / Carcinoma, Colorectal / Carcinoma, Pancreatic / Melanoma / Non-Small Cell Lung Carcinoma (NSCLC) / Prostate Cancer / Renal Cell Adenocarcinoma / Tumors, Solid1
1Active Not RecruitingTreatmentClear-cell Metastatic Renal Cell Carcinoma / Renal Cell Adenocarcinoma1
1Active Not RecruitingTreatmentMetastatic Disease / Renal Cell Adenocarcinoma / Soft Tissue Sarcoma (STS)1
1Active Not RecruitingTreatmentMetastatic Renal Cell Carcinoma1
1Active Not RecruitingTreatmentMetastatic Solid Tumors1
1Active Not RecruitingTreatmentSolid Neoplasms1
1Active Not RecruitingTreatmentSquamous Cell Carcinoma of the Head and Neck (SCCHN)1
1Active Not RecruitingTreatmentUnspecified Adult Solid Tumor, Protocol Specific1
1CompletedOtherCholangiocarcinomas / Soft-Tissue Sarcoma / Thyroid Cancers / Tumors, Solid1
1CompletedOtherTumors, Solid1
1CompletedScreeningTumors, Solid1
1CompletedSupportive CareAge Related Macular Degeneration (ARMD) / Macular Degeneration1
1CompletedTreatmentAdvanced Cancers1
1CompletedTreatmentAdvanced Solid Tumours / Lung Cancer Non-Small Cell Cancer (NSCLC) / Malignancies1
1CompletedTreatmentCancer, Advanced1
1CompletedTreatmentCarcinoma, Hepatic Cell / Hepatocellular,Carcinoma / Liver Cancer1
1CompletedTreatmentCentral nervous system neoplasms malignant NEC / Genitourinary Neoplasms Malignancy and Gender Unspecified / Malignant Neoplasm of Breast / Malignant Neoplasm of Gastrointestinal Tract / Malignant Neoplasm of Thorax / Melanoma / Neoplasms, Head and Neck1
1CompletedTreatmentChildhood 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 Tissue Sarcoma / Recurrent Childhood Visual Pathway Glioma / Unspecified Childhood Solid Tumor, Protocol Specific1
1CompletedTreatmentColorectal Cancers / Neoplasms, Colorectal2
1CompletedTreatmentGynecologic Tumors1
1CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)2
1CompletedTreatmentMacular Degeneration2
1CompletedTreatmentMalignancies / Renal Cell Adenocarcinoma3
1CompletedTreatmentMalignant Lymphomas / Neoplasms1
1CompletedTreatmentMetastatic Cancers / Tumors, Solid1
1CompletedTreatmentNeoplasms, Breast1
1CompletedTreatmentNeoplasms, Breast / Solid Tumor Cancers1
1CompletedTreatmentNeoplasms, Ovarian1
1CompletedTreatmentNeoplasms / Sarcomas / Stomach Neoplasms1
1CompletedTreatmentProstate Cancer1
1CompletedTreatmentPsoriasis / Psoriasis Vulgaris (Plaque Psoriasis)1
1CompletedTreatmentRecurrent 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 Cancer1
1CompletedTreatmentRenal Cancers / Tumors, Solid1
1CompletedTreatmentRenal Cell Adenocarcinoma2
1CompletedTreatmentRenal Cell Adenocarcinoma / Solid Tumor Cancers1
1CompletedTreatmentRenal Cell Adenocarcinoma / Tumors, Solid1
1CompletedTreatmentSoft Tissue Sarcoma (STS)1
1CompletedTreatmentTumors, Solid1
1CompletedTreatmentUnspecified Adult Solid Tumor, Protocol Specific1
1RecruitingOtherMalignancies1
1RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC) / Non-Small Cell Lung Carcinoma (NSCLC)1
1RecruitingTreatmentSarcomas1
1TerminatedTreatmentCancer, Breast / Head and Neck Carcinoma / Hepatocellular Cancer / Lung Cancers / Malignant Neoplasm of Colon / Malignant Neoplasm of Pancreas / Renal Cancers / Sarcomas1
1TerminatedTreatmentMale Breast Carcinoma / Recurrent Breast Carcinoma / Stage IA Breast Cancer / Stage IB Breast Cancer / Stage IIA Breast Cancer / Stage IIB Breast Cancer / Stage IIIA Breast Cancer1
1TerminatedTreatmentMetastatic Breast Cancer (MBC) / Metastatic Non Small Cell Lung Cancer1
1TerminatedTreatmentMetastatic Cancer (Different Solid Tumour Types)1
1TerminatedTreatmentMetastatic Cancers1
1WithdrawnTreatmentAnaplastic Gliomas / Gliosarcoma / Recurrent Glioblastoma1
1WithdrawnTreatmentNeoplasms, Brain / Neuroblastomas / Sarcoma, Osteogenic / Sarcomas / Wilms' tumor1
1WithdrawnTreatmentUnspecified Adult Solid Tumor, Protocol Specific1
1, 2Active Not RecruitingTreatmentAdvanced Renal Cell Carcinoma1
1, 2Active Not RecruitingTreatmentAdvanced Soft Tissue Sarcoma1
1, 2Active Not RecruitingTreatmentHigh 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 / Stage III Uterine Corpus Leiomyosarcoma AJCC v8 / Stage IIIA Uterine Corpus Leiomyosarcoma AJCC v8 / Stage IIIB Uterine Corpus Leiomyosarcoma AJCC v8 / Stage IIIC Uterine Corpus Leiomyosarcoma AJCC v8 / Stage IV Uterine Corpus Leiomyosarcoma AJCC v8 / Stage IVA Uterine Corpus Leiomyosarcoma AJCC v8 / Stage IVB Uterine Corpus Leiomyosarcoma AJCC v8 / Uterine Corpus Leiomyosarcoma1
1, 2Active Not RecruitingTreatmentRenal Cell Adenocarcinoma1
1, 2CompletedTreatmentAdvanced Urothelial Cancer of Bladder After Failure of Platinum-containing Therapy1
1, 2CompletedTreatmentCorneal Neovascularization1
1, 2CompletedTreatmentOperable Soft Tissue Sarcoma / Stage III Adult Soft Tissue Sarcoma1
1, 2CompletedTreatmentOvarian Epithelial Cancer1
1, 2Enrolling by InvitationTreatmentTumors, Solid1
1, 2Not Yet RecruitingTreatmentRefractory Pediatric Solid Tumors / Relapsed Pediatric Solid Tumors1
1, 2Not Yet RecruitingTreatmentSoft Tissue Sarcoma (STS)1
1, 2RecruitingTreatmentCancer of the Ovary / Fallopian Tube Cancer / Primary Peritoneal Cavity Cancer1
1, 2RecruitingTreatmentClear Cell Renal Cell Carcinoma / Stage IV Renal Cell Cancer1
1, 2RecruitingTreatmentGlioblastoma Multiforme (GBM)1
1, 2RecruitingTreatmentPancreatic Alpha Cell Carcinoma / Pancreatic Beta Islet Cell Carcinoma / Pancreatic Delta Cell Carcinoma / Pancreatic G-cell Carcinoma / Recurrent Islet Cell Carcinoma1
1, 2RecruitingTreatmentTumors, Central Nervous System / Tumors, Solid1
1, 2TerminatedTreatmentCancer of the Ovary / Fallopian Tube Cancer / Primary Peritoneal Cancer1
1, 2TerminatedTreatmentCancer of the Ovary / Neoplasms, Ovarian1
1, 2TerminatedTreatmentMalignant Neoplasm of Stomach1
2Active Not RecruitingTreatmentAtypical Carcinoid Tumor / Foregut Carcinoid Tumor / Hindgut Carcinoid Tumor / Lung Carcinoid Tumor / Metastatic Carcinoid Tumors / Metastatic Digestive System Neuroendocrine Tumor G1 / Midgut Carcinoid Tumor / Recurrent Digestive System Neuroendocrine Tumor G1 / Regional Digestive System Neuroendocrine Tumor G11
2Active Not RecruitingTreatmentCancer of the Ovary / Fallopian Tube Cancer / Malignant Peritoneal Neoplasm1
2Active Not RecruitingTreatmentCancer, Breast / Neoplasms, Breast1
2Active Not RecruitingTreatmentCarcinoma of the Collecting Ducts of Bellini / Chromophobe Renal Cell Carcinoma / Kidney Medullary Carcinoma / Kidney Oncocytoma / Metastatic Renal Cell Cancer / Papillary Renal Cell Carcinoma / Renal Cell Carcinoma Recurrent / Sarcomatoid Renal Cell Carcinoma / Stage IV Renal Cell Cancer / Type 1 Papillary Renal Cell Carcinoma / Type 2 Papillary Renal Cell Carcinoma1
2Active Not RecruitingTreatmentCentral Nervous System Neoplasms / Glioblastoma Multiforme (GBM) / Glioblastomas / Gliosarcoma / Neoplasms, Brain1
2Active Not RecruitingTreatmentClear Cell Renal Cell Carcinoma / Renal Cell Cancer, Recurrent / Stage IV Renal Cell Cancer1
2Active Not RecruitingTreatmentHormone-Resistant Prostate Cancer / Recurrent Prostate Carcinoma1
2Active Not RecruitingTreatmentLung Cancer Small Cell Lung Cancer (SCLC)1
2Active Not RecruitingTreatmentMetastatic Renal Cell Carcinoma1
2Active Not RecruitingTreatmentRecurrent Thyroid Gland Carcinoma / Stage III Differentiated Thyroid Gland Carcinoma / Stage III Differentiated Thyroid Gland Carcinoma AJCC v7 / Stage III Thyroid Gland Medullary Carcinoma / Stage III Thyroid Gland Medullary Carcinoma AJCC v7 / Stage IVA Differentiated Thyroid Gland Carcinoma / Stage IVA Differentiated Thyroid Gland Carcinoma AJCC v7 / Stage IVA Thyroid Gland Medullary Carcinoma / Stage IVA Thyroid Gland Medullary Carcinoma AJCC v7 / Stage IVA Thyroid Gland Undifferentiated (Anaplastic) Carcinoma / Stage IVA Thyroid Gland Undifferentiated (Anaplastic) Carcinoma AJCC v7 / Stage IVB Differentiated Thyroid Gland Carcinoma / Stage IVB Differentiated Thyroid Gland Carcinoma AJCC v7 / Stage IVB Thyroid Gland Medullary Carcinoma / Stage IVB Thyroid Gland Medullary Carcinoma AJCC v7 / Stage IVB Thyroid Gland Undifferentiated (Anaplastic) Carcinoma / Stage IVB Thyroid Gland Undifferentiated (Anaplastic) Carcinoma AJCC v7 / Stage IVC Differentiated Thyroid Gland Carcinoma / Stage IVC Differentiated Thyroid Gland Carcinoma AJCC v7 / Stage IVC Thyroid Gland Medullary Carcinoma / Stage IVC Thyroid Gland Medullary Carcinoma AJCC v7 / Stage IVC Thyroid Gland Undifferentiated (Anaplastic) Carcinoma / Stage IVC Thyroid Gland Undifferentiated (Anaplastic) Carcinoma AJCC v7 / Thyroglobulin Antibody Negative / Thyroid Gland Undifferentiated (Anaplastic) Carcinoma1
2Active Not RecruitingTreatmentRenal Cancers2
2Active Not RecruitingTreatmentRenal Cell Adenocarcinoma2
2Active Not RecruitingTreatmentRenal Cell Carcinoma Recurrent / Stage III Renal Cell Cancer / Stage III Renal Cell Cancer AJCC v7 / Stage IV Renal Cell Cancer / Stage IV Renal Cell Cancer AJCC V71
2Active Not RecruitingTreatmentSalivary Gland Carcinoma1
2Active Not RecruitingTreatmentSarcomas1
2Active Not RecruitingTreatmentSoft Tissue Sarcoma (STS)1
2Active Not RecruitingTreatmentStage III Melanoma / Stage IV Melanoma / Unresectable Melanoma1
2Active Not RecruitingTreatmentThyroid Gland Undifferentiated (Anaplastic) Carcinoma1
2Active Not RecruitingTreatmentVon Hippel-Lindau Syndrome1
2CompletedSupportive CareLymphedema of the extremities1
2CompletedTreatmentAdenocarcinoma of the Prostate1
2CompletedTreatmentAdult Giant Cell Glioblastoma / Adult Glioblastoma / Adult Gliosarcoma / Recurrent Adult Brain Tumor1
2CompletedTreatmentAdvanced Malignant Mesothelioma / Localized Malignant Mesothelioma / Recurrent Malignant Mesothelioma1
2CompletedTreatmentAdvanced and / or Metastatic Liposarcoma1
2CompletedTreatmentAdvanced/Metastatic Neuroendocrine Tumors1
2CompletedTreatmentBladder Cancers / Transitional Cell Cancer of the Renal Pelvis and Ureter / Urethral Cancer1
2CompletedTreatmentCancer of the Ovary1
2CompletedTreatmentCancer of the Ovary / Fallopian Tube Cancer / Malignant Peritoneal Neoplasm / Malignant Tumor of Peritoneum / Neoplasms, Ovarian1
2CompletedTreatmentCancer, Breast / Male Breast Cancer / Recurrent Breast Cancer / Stage IV Breast Cancer1
2CompletedTreatmentCervix Diseases / Malignancies / Neoplasms, Ovarian / Ovarian Epithelial Cancer / Primary Peritoneal Carcinoma / Tumors / Uterine Diseases1
2CompletedTreatmentChondrosarcomas / Metastatic Chondrosarcoma1
2CompletedTreatmentClear Cell Renal Cell Carcinoma1
2CompletedTreatmentClear Cell Renal Cell Carcinoma / Stage I Renal Cell Cancer / Stage II Renal Cell Cancer / Stage III Renal Cell Cancer1
2CompletedTreatmentDistal Urethral Cancer / Metastatic Bladder Cancer / Proximal Urethral Cancer / Recurrent Bladder Cancer / Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter / Recurrent Urethral Cancer / Transitional Cell Carcinoma of the Bladder / Urethral Cancer Associated With Invasive Bladder Cancer1
2CompletedTreatmentGIST1
2CompletedTreatmentGastrin-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 Tumor1
2CompletedTreatmentGastrointestinal Stromal Tumors1
2CompletedTreatmentGliomas1
2CompletedTreatmentLeukemia Acute Myeloid Leukemia (AML)1
2CompletedTreatmentLiposarcoma / Metastatic Liposarcoma / Surgically Unresectable Liposarcoma1
2CompletedTreatmentLocally Advanced or Metastatic Non-clear Cell Type Renal Cell Carcinoma1
2CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)3
2CompletedTreatmentLung Cancer Small Cell Lung Cancer (SCLC)1
2CompletedTreatmentLung Cancer Small Cell Lung Cancer (SCLC) / Lung Cancers1
2CompletedTreatmentLung Cancers1
2CompletedTreatmentMacular Degeneration2
2CompletedTreatmentMalignant Neoplasm of Stomach1
2CompletedTreatmentMelanoma1
2CompletedTreatmentMultiple Myeloma (MM) / Renal Cell Adenocarcinoma1
2CompletedTreatmentNeoplasms, Breast3
2CompletedTreatmentNeoplasms, Ovarian1
2CompletedTreatmentNeoplasms, Uterine Cervix / Recurrent, IV-B Cervical cancer1
2CompletedTreatmentNeuroendocrine Tumors1
2CompletedTreatmentPlatinum-resistant Advanced Ovarian Cancer1
2CompletedTreatmentRecurrent Fallopian Tube Carcinoma / Recurrent Ovarian Carcinoma / Recurrent Primary Peritoneal Carcinoma1
2CompletedTreatmentRecurrent Lymphoepithelioma of the Nasopharynx / Recurrent Squamous Cell Carcinoma of the Nasopharynx / Stage IV Lymphoepithelioma of the Nasopharynx / Stage IV Squamous Cell Carcinoma of the Nasopharynx1
2CompletedTreatmentRecurrent Melanoma / Stage IV Cutaneous Melanoma AJCC v6 and v7 / Stage IV Skin Melanoma1
2CompletedTreatmentRecurrent Prostate Cancer1
2CompletedTreatmentRecurrent Uterine Corpus Sarcoma / Uterine Carcinosarcoma1
2CompletedTreatmentRenal Cell Adenocarcinoma3
2CompletedTreatmentSoft Tissue Sarcoma (STS)1
2Not Yet RecruitingTreatmentSoft Tissue Sarcoma (STS)1
2RecruitingTreatmentAdult 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 Adult Soft Tissue Sarcoma / Stage III Adult Soft Tissue Sarcoma / Stage IV Adult Soft Tissue Sarcoma1
2RecruitingTreatmentAdult Angiosarcoma / Recurrent Adult Soft Tissue Sarcoma / Stage III Adult Soft Tissue Sarcoma / Stage IV Adult Soft Tissue Sarcoma1
2RecruitingTreatmentAdult Liposarcoma / Metastatic Bone Sarcomas / Metastatic Liposarcoma / Recurrent Adult Soft Tissue Sarcoma / Recurrent Liposarcoma / Recurrent Osteosarcoma / Stage IV Adult Soft Tissue Sarcoma1
2RecruitingTreatmentAdvanced Renal Cell Carcinoma / Metastatic Renal Cell Carcinoma1
2RecruitingTreatmentBiliary Carcinoma / Carcinoma of Gallbladder / Cholangiocarcinomas1
2RecruitingTreatmentCancer of the Ovary1
2RecruitingTreatmentClear Cell Metastatic Renal Cell Carcinoma1
2RecruitingTreatmentClear Cell Renal Cell Carcinoma / Stage III Renal Cell Cancer AJCC v8 / Stage IV Renal Cell Cancer / Stage IV Renal Cell Cancer AJCC V71
2RecruitingTreatmentExtraskeletal Myxoid Chondrosarcoma / Solitary Fibrous Tumor1
2RecruitingTreatmentHemangiosarcoma1
2RecruitingTreatmentLeiomyosarcomas1
2RecruitingTreatmentMalignant Solid Neoplasms1
2RecruitingTreatmentProgressive Desmoids Tumors1
2RecruitingTreatmentRefractory Pediatric AML / Refractory Pediatric Solid Tumors / Relapsed Pediatric AML / Relapsed Pediatric Solid Tumors1
2RecruitingTreatmentSarcomas / Soft Tissue Sarcoma (STS)1
2RecruitingTreatmentSoft Tissue Sarcoma (STS)1
2RecruitingTreatmentSoft-Tissue Sarcoma1
2RecruitingTreatmentThyroid Carcinoma1
2RecruitingTreatmentTumors, Solid1
2TerminatedBasic ScienceCancer of the Ovary / Cancer, Breast / Cervical Cancers / Gastrointestinal Cancers / Glioblastomas / Lung Cancer Non-Small Cell Cancer (NSCLC) / Lung Cancer Small Cell Lung Cancer (SCLC) / Malignant Neoplasm of Pancreas / Melanoma / Renal Cell Adenocarcinoma / Soft Tissue Sarcoma (STS)1
2TerminatedTreatmentBladder Cancers1
2TerminatedTreatmentDermatofibrosarcomas of DARIER FERRAND(DFSP)1
2TerminatedTreatmentEstrogen 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 Cancer1
2TerminatedTreatmentExtra-Adrenal Paraganglioma / Metastatic Adrenal Gland Pheochromocytoma / Paraganglioma / Recurrent Adrenal Gland Pheochromocytoma1
2TerminatedTreatmentHereditary Haemorrhagic Telangiectasia (HHT)1
2TerminatedTreatmentLocally Advanced Renal Cell Carcinoma / Metastatic Renal Cell Carcinoma1
2TerminatedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)2
2TerminatedTreatmentLung Cancer Small Cell Lung Cancer (SCLC)1
2TerminatedTreatmentMalignant Neoplasm of Pancreas1
2TerminatedTreatmentMetastatic Alveolar Soft Part Sarcoma1
2TerminatedTreatmentMetastatic Bone Sarcomas / Sarcoma, Osteogenic1
2TerminatedTreatmentPenile Squamous Cell Carcinoma Stage IV1
2TerminatedTreatmentProstate Cancer1
2TerminatedTreatmentRenal Cell Adenocarcinoma1
2TerminatedTreatmentSarcomas1
2Unknown StatusTreatmentAdvanced Gastric Cancer1
2Unknown StatusTreatmentAdverse Drug Events / Renal Cell Adenocarcinoma / Self Efficacy1
2Unknown StatusTreatmentBladder (Urothelial, Transitional Cell) Cancer / Bladder (Urothelial, Transitional Cell) Cancer Metastatic or Unresectable / Bladder (Urothelial, Transitional Cell) Cancer Resectable (Pre-Cystectomy) / Bladder (Urothelial, Transitional Cell) Cancer Superficial (Non-Invasive) / Bladder Cancers1
2Unknown StatusTreatmentGastrointestinal Stromal Tumors (GISTs)1
2Unknown StatusTreatmentGerm Cell Tumors / Measurable Disease / Relapse or Progression After 2 or 3 Chemotherapy Regimens / Relapse or Progression After High-dose Chemotherapy1
2Unknown StatusTreatmentHead and Neck Squamous Cell Carcinoma (HNSCC)1
2Unknown StatusTreatmentMetastatic Renal Cell Carcinoma1
2Unknown StatusTreatmentRelapsed or Metastatic Uterine Leiomyosarcomas or Carcinosarcomas1
2WithdrawnTreatmentCervical Cancers1
2WithdrawnTreatmentGastrointestinal Stromal Tumors1
2WithdrawnTreatmentHormone-receptors Positive Breast Cancer1
2WithdrawnTreatmentSoft Tissue Sarcoma (STS)1
2WithdrawnTreatmentUterine Leiomyosarcoma1
2, 3CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
2, 3SuspendedTreatmentAdult Fibrosarcoma / Alveolar Soft Part Sarcoma (ASPS) / Angiomatoid Fibrous Histiocytoma / Atypical Fibroxanthoma / Chondrosarcoma, Mesenchymal / Clear Cell Sarcoma of Soft Tissue / Epithelioid Malignant Peripheral Nerve Sheath Tumor / Epithelioid Sarcoma / Extraskeletal Myxoid Chondrosarcoma / Extraskeletal osteosarcomas / Fibrohistiocytic Neoplasm / Glomus Tumor of the Skin / Inflammatory Myofibroblastic Tumors / Intimal Sarcoma / Leiomyosarcomas / Liposarcoma / Low Grade Fibromyxoid Sarcoma / Low Grade Myofibroblastic Sarcoma / Malignant Cutaneous Granular Cell Tumor / Malignant Peripheral Nerve Sheath Tumour (MPNST) / Malignant Triton Tumor / Myxofibrosarcoma / Myxoid Chondrosarcoma / Myxoinflammatory Fibroblastic Sarcoma / Nerve Sheath Neoplasm / PEComa / Pericytic Neoplasm / Plexiform Fibrohistiocytic Tumor / Sclerosing Epithelioid Fibrosarcoma / Stage IB Soft Tissue Sarcoma / Stage IB Soft Tissue Sarcoma AJCC v7 / Stage IIB Soft Tissue Sarcoma / Stage IIB Soft Tissue Sarcoma AJCC v7 / Stage III Soft Tissue Sarcoma / Stage III Soft Tissue Sarcoma AJCC v7 / Stage IV Soft Tissue Sarcoma / Stage IV Soft Tissue Sarcoma AJCC v7 / Synovial Sarcoma / Undifferentiated (Embryonal) Sarcoma / Undifferentiated High Grade Pleomorphic Sarcoma of Bone1
2, 3TerminatedTreatmentLung Cancers1
3Active Not RecruitingTreatmentClear Cell Renal Cell Carcinoma / No Evidence of Disease / Renal Cell Carcinoma Recurrent / Stage IV Renal Cell Cancer / Stage IV Renal Cell Cancer AJCC V71
3Active Not RecruitingTreatmentLocally Advanced or Metastatic Renal Cell Carcinoma / Renal Cell Adenocarcinoma1
3Active Not RecruitingTreatmentMalignancies1
3Active Not RecruitingTreatmentRenal Cell Adenocarcinoma1
3CompletedTreatmentCancer of the Ovary / Neoplasms, Ovarian1
3CompletedTreatmentMetastatic, Locally Advanced or Unresectable Soft Tissue Sarcoma1
3CompletedTreatmentRenal Cell Adenocarcinoma4
3CompletedTreatmentSoft Tissue Sarcoma (STS)1
3RecruitingTreatmentAdvanced Angiosarcoma1
3RecruitingTreatmentRenal Cell Adenocarcinoma1
4CompletedTreatmentClear-cell Metastatic Renal Cell Carcinoma / Locally Advanced and/or Metastatic Renal Cell Carcinoma / Renal Cell Adenocarcinoma1
4CompletedTreatmentMalignancies1
4RecruitingOtherMetastatic Renal Cell Cancer1
Not AvailableActive Not RecruitingNot AvailableMetastatic Renal Cell Carcinoma1
Not AvailableActive Not RecruitingDiagnosticAdvanced Solid Tumors / Malignancies1
Not AvailableActive Not RecruitingTreatmentStage IIA Adult Soft Tissue Sarcoma / Stage III Adult Soft Tissue Sarcoma / Stage IV Adult Soft Tissue Sarcoma1
Not AvailableCompletedNot AvailableMetastatic Renal Cell Carcinoma1
Not AvailableCompletedNot AvailableRenal Cell Adenocarcinoma3
Not AvailableCompletedNot AvailableSoft Tissue Sarcoma (STS)1
Not AvailableCompletedDiagnosticClear Cell Renal Cell Carcinoma / Renal Cell Cancer, Recurrent / Stage IV Renal Cell Cancer1
Not AvailableNot Yet RecruitingTreatmentRefractory Solid Tumors1
Not AvailableRecruitingTreatmentRefractory Solid Tumors1
Not AvailableRecruitingTreatmentRenal Cancers1
Not AvailableWithdrawnTreatmentClear Cell Renal Cell Carcinoma / Renal Cell Adenocarcinoma1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
TabletOral200 mg
TabletOral400 mg
Tablet, film coatedOral200 mg
Tablet, film coatedOral200 mg/1
Tablet, film coatedOral400 mg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US7262203No2007-08-282021-12-19Us
US8114885No2012-02-142021-12-19Us
US7105530No2006-09-122023-10-19Us

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0433 mg/mLALOGPS
logP3.59ALOGPS
logP3.55ChemAxon
logS-4ALOGPS
pKa (Strongest Acidic)10.41ChemAxon
pKa (Strongest Basic)5.07ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area119.03 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity132.18 m3·mol-1ChemAxon
Polarizability45.41 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.8788
Caco-2 permeable+0.5
P-glycoprotein substrateNon-substrate0.8307
P-glycoprotein inhibitor INon-inhibitor0.8126
P-glycoprotein inhibitor IIInhibitor0.5
Renal organic cation transporterNon-inhibitor0.8152
CYP450 2C9 substrateNon-substrate0.7797
CYP450 2D6 substrateNon-substrate0.8008
CYP450 3A4 substrateNon-substrate0.6024
CYP450 1A2 substrateNon-inhibitor0.5
CYP450 2C9 inhibitorNon-inhibitor0.5065
CYP450 2D6 inhibitorNon-inhibitor0.7779
CYP450 2C19 inhibitorNon-inhibitor0.6811
CYP450 3A4 inhibitorNon-inhibitor0.5385
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.5668
Ames testNon AMES toxic0.6543
CarcinogenicityNon-carcinogens0.8567
BiodegradationNot ready biodegradable0.9935
Rat acute toxicity2.3961 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9219
hERG inhibition (predictor II)Non-inhibitor0.7129
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-052r-0118900000-097bcfa914e959e3d51a
MS/MS Spectrum - , positiveLC-MS/MSsplash10-004i-0910000000-fd84ad14c383d8fa623f

Taxonomy

Description
This compound belongs to the class of organic compounds known as alkyldiarylamines. These are tertiary alkylarylamines having two aryl and one alkyl groups attached to the amino group.
Kingdom
Organic compounds
Super Class
Organic nitrogen compounds
Class
Organonitrogen compounds
Sub Class
Amines
Direct Parent
Alkyldiarylamines
Alternative Parents
Benzenesulfonamides / Benzenesulfonyl compounds / Indazoles / Aniline and substituted anilines / Toluenes / Aminopyrimidines and derivatives / Organosulfonamides / Imidolactams / Heteroaromatic compounds / Pyrazoles
show 6 more
Substituents
Alkyldiarylamine / Benzenesulfonamide / Benzenesulfonyl group / Benzopyrazole / Indazole / Aniline or substituted anilines / Aminopyrimidine / Toluene / Monocyclic benzene moiety / Pyrimidine
show 19 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
aminopyrimidine, sulfonamide, indazoles (CHEBI:71219)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Vegf-b-activated receptor activity
Specific Function
Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFB and PGF, and plays an essential role in the development of embryonic vasculature, the regulation of angiogenesis, cell ...
Gene Name
FLT1
Uniprot ID
P17948
Uniprot Name
Vascular endothelial growth factor receptor 1
Molecular Weight
150767.185 Da
References
  1. Sonpavde G, Hutson TE: Pazopanib: a novel multitargeted tyrosine kinase inhibitor. Curr Oncol Rep. 2007 Mar;9(2):115-9. [PubMed:17288876]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Vascular endothelial growth factor-activated receptor activity
Specific Function
Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD. Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and ...
Gene Name
KDR
Uniprot ID
P35968
Uniprot Name
Vascular endothelial growth factor receptor 2
Molecular Weight
151525.555 Da
References
  1. Sonpavde G, Hutson TE: Pazopanib: a novel multitargeted tyrosine kinase inhibitor. Curr Oncol Rep. 2007 Mar;9(2):115-9. [PubMed:17288876]
Kind
Protein
Organism
Human
Pharmacological action
Yes
General Function
Vascular endothelial growth factor-activated receptor activity
Specific Function
Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFC and VEGFD, and plays an essential role in adult lymphangiogenesis and in the development of the vascular network and the cardi...
Gene Name
FLT4
Uniprot ID
P35916
Uniprot Name
Vascular endothelial growth factor receptor 3
Molecular Weight
152755.94 Da
References
  1. Sonpavde G, Hutson TE: Pazopanib: a novel multitargeted tyrosine kinase inhibitor. Curr Oncol Rep. 2007 Mar;9(2):115-9. [PubMed:17288876]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Vascular endothelial growth factor-activated receptor activity
Specific Function
Tyrosine-protein kinase that acts as a cell-surface receptor for PDGFA, PDGFB and PDGFC and plays an essential role in the regulation of embryonic development, cell proliferation, survival and chem...
Gene Name
PDGFRA
Uniprot ID
P16234
Uniprot Name
Platelet-derived growth factor receptor alpha
Molecular Weight
122668.46 Da
References
  1. Sonpavde G, Hutson TE: Pazopanib: a novel multitargeted tyrosine kinase inhibitor. Curr Oncol Rep. 2007 Mar;9(2):115-9. [PubMed:17288876]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Vascular endothelial growth factor binding
Specific Function
Tyrosine-protein kinase that acts as cell-surface receptor for homodimeric PDGFB and PDGFD and for heterodimers formed by PDGFA and PDGFB, and plays an essential role in the regulation of embryonic...
Gene Name
PDGFRB
Uniprot ID
P09619
Uniprot Name
Platelet-derived growth factor receptor beta
Molecular Weight
123966.895 Da
References
  1. Sonpavde G, Hutson TE: Pazopanib: a novel multitargeted tyrosine kinase inhibitor. Curr Oncol Rep. 2007 Mar;9(2):115-9. [PubMed:17288876]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Transmembrane receptor protein tyrosine kinase activity
Specific Function
Tyrosine-protein kinase that acts as cell-surface receptor for the cytokine KITLG/SCF and plays an essential role in the regulation of cell survival and proliferation, hematopoiesis, stem cell main...
Gene Name
KIT
Uniprot ID
P10721
Uniprot Name
Mast/stem cell growth factor receptor Kit
Molecular Weight
109863.655 Da
References
  1. Sonpavde G, Hutson TE: Pazopanib: a novel multitargeted tyrosine kinase inhibitor. Curr Oncol Rep. 2007 Mar;9(2):115-9. [PubMed:17288876]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Protein tyrosine kinase activity
Specific Function
Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation and apoptosis. Plays an...
Gene Name
FGFR3
Uniprot ID
P22607
Uniprot Name
Fibroblast growth factor receptor 3
Molecular Weight
87708.905 Da
References
  1. Deeks ED: Pazopanib: in advanced soft tissue sarcoma. Drugs. 2012 Nov 12;72(16):2129-40. doi: 10.2165/11209950-000000000-00000. [PubMed:23072642]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Non-membrane spanning protein tyrosine kinase activity
Specific Function
Tyrosine kinase that plays an essential role in regulation of the adaptive immune response. Regulates the development, function and differentiation of conventional T-cells and nonconventional NKT-c...
Gene Name
ITK
Uniprot ID
Q08881
Uniprot Name
Tyrosine-protein kinase ITK/TSK
Molecular Weight
71830.405 Da
References
  1. Deeks ED: Pazopanib: in advanced soft tissue sarcoma. Drugs. 2012 Nov 12;72(16):2129-40. doi: 10.2165/11209950-000000000-00000. [PubMed:23072642]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
S100 protein binding
Specific Function
Plays an important role in the regulation of cell survival, cell division, angiogenesis, cell differentiation and cell migration. Functions as potent mitogen in vitro.
Gene Name
FGF1
Uniprot ID
P05230
Uniprot Name
Fibroblast growth factor 1
Molecular Weight
17459.58 Da
References
  1. Deeks ED: Pazopanib: in advanced soft tissue sarcoma. Drugs. 2012 Nov 12;72(16):2129-40. doi: 10.2165/11209950-000000000-00000. [PubMed:23072642]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Signaling adaptor activity
Specific Function
Links T-cell receptor activation signal to phospholipase C-gamma-1, GRB2 and phosphatidylinositol 3-kinase.
Gene Name
SH2B3
Uniprot ID
Q9UQQ2
Uniprot Name
SH2B adapter protein 3
Molecular Weight
63224.45 Da
References
  1. Deeks ED: Pazopanib: in advanced soft tissue sarcoma. Drugs. 2012 Nov 12;72(16):2129-40. doi: 10.2165/11209950-000000000-00000. [PubMed:23072642]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Keisner SV, Shah SR: Pazopanib: the newest tyrosine kinase inhibitor for the treatment of advanced or metastatic renal cell carcinoma. Drugs. 2011 Mar 5;71(4):443-54. doi: 10.2165/11588960-000000000-00000. [PubMed:21395357]
  2. Goh BC, Reddy NJ, Dandamudi UB, Laubscher KH, Peckham T, Hodge JP, Suttle AB, Arumugham T, Xu Y, Xu CF, Lager J, Dar MM, Lewis LD: An evaluation of the drug interaction potential of pazopanib, an oral vascular endothelial growth factor receptor tyrosine kinase inhibitor, using a modified Cooperstown 5+1 cocktail in patients with advanced solid tumors. Clin Pharmacol Ther. 2010 Nov;88(5):652-9. doi: 10.1038/clpt.2010.158. Epub 2010 Sep 29. [PubMed:20881954]
  3. Verweij J, Sleijfer S: Pazopanib, a new therapy for metastatic soft tissue sarcoma. Expert Opin Pharmacother. 2013 May;14(7):929-35. doi: 10.1517/14656566.2013.780030. Epub 2013 Mar 14. [PubMed:23488774]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Keisner SV, Shah SR: Pazopanib: the newest tyrosine kinase inhibitor for the treatment of advanced or metastatic renal cell carcinoma. Drugs. 2011 Mar 5;71(4):443-54. doi: 10.2165/11588960-000000000-00000. [PubMed:21395357]
  2. Goh BC, Reddy NJ, Dandamudi UB, Laubscher KH, Peckham T, Hodge JP, Suttle AB, Arumugham T, Xu Y, Xu CF, Lager J, Dar MM, Lewis LD: An evaluation of the drug interaction potential of pazopanib, an oral vascular endothelial growth factor receptor tyrosine kinase inhibitor, using a modified Cooperstown 5+1 cocktail in patients with advanced solid tumors. Clin Pharmacol Ther. 2010 Nov;88(5):652-9. doi: 10.1038/clpt.2010.158. Epub 2010 Sep 29. [PubMed:20881954]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. Keisner SV, Shah SR: Pazopanib: the newest tyrosine kinase inhibitor for the treatment of advanced or metastatic renal cell carcinoma. Drugs. 2011 Mar 5;71(4):443-54. doi: 10.2165/11588960-000000000-00000. [PubMed:21395357]
  2. Verweij J, Sleijfer S: Pazopanib, a new therapy for metastatic soft tissue sarcoma. Expert Opin Pharmacother. 2013 May;14(7):929-35. doi: 10.1517/14656566.2013.780030. Epub 2013 Mar 14. [PubMed:23488774]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. Verweij J, Sleijfer S: Pazopanib, a new therapy for metastatic soft tissue sarcoma. Expert Opin Pharmacother. 2013 May;14(7):929-35. doi: 10.1517/14656566.2013.780030. Epub 2013 Mar 14. [PubMed:23488774]
  2. FDA Label, Pazopanib [File]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Deng Y, Sychterz C, Suttle AB, Dar MM, Bershas D, Negash K, Qian Y, Chen EP, Gorycki PD, Ho MY: Bioavailability, metabolism and disposition of oral pazopanib in patients with advanced cancer. Xenobiotica. 2013 May;43(5):443-53. doi: 10.3109/00498254.2012.734642. Epub 2012 Nov 16. [PubMed:23548165]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Xenobiotic-transporting atpase activity
Specific Function
High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
Gene Name
ABCG2
Uniprot ID
Q9UNQ0
Uniprot Name
ATP-binding cassette sub-family G member 2
Molecular Weight
72313.47 Da
References
  1. Deng Y, Sychterz C, Suttle AB, Dar MM, Bershas D, Negash K, Qian Y, Chen EP, Gorycki PD, Ho MY: Bioavailability, metabolism and disposition of oral pazopanib in patients with advanced cancer. Xenobiotica. 2013 May;43(5):443-53. doi: 10.3109/00498254.2012.734642. Epub 2012 Nov 16. [PubMed:23548165]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
Gene Name
SLCO1B1
Uniprot ID
Q9Y6L6
Uniprot Name
Solute carrier organic anion transporter family member 1B1
Molecular Weight
76447.99 Da
References
  1. Deeks ED: Pazopanib: in advanced soft tissue sarcoma. Drugs. 2012 Nov 12;72(16):2129-40. doi: 10.2165/11209950-000000000-00000. [PubMed:23072642]
  2. Hu S, Mathijssen RH, de Bruijn P, Baker SD, Sparreboom A: Inhibition of OATP1B1 by tyrosine kinase inhibitors: in vitro-in vivo correlations. Br J Cancer. 2014 Feb 18;110(4):894-8. doi: 10.1038/bjc.2013.811. Epub 2014 Jan 7. [PubMed:24398510]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the...
Gene Name
UGT1A1
Uniprot ID
P22309
Uniprot Name
UDP-glucuronosyltransferase 1-1
Molecular Weight
59590.91 Da
References
  1. Deeks ED: Pazopanib: in advanced soft tissue sarcoma. Drugs. 2012 Nov 12;72(16):2129-40. doi: 10.2165/11209950-000000000-00000. [PubMed:23072642]

Drug created on March 19, 2008 10:38 / Updated on December 10, 2018 13:38