The efficacy of the treatment of advanced renal cell carcinoma
In order to investigate the efficacy of molecule targeting drug tyrosine kinase inhibitor pazopanib which inhibist the angiogenesis in patients with advanced renal cell carcinoma, People's Liberation Army General Hospital, in June 2006 to May 2007, the participation of pazopanib in patients with advanced renal cell carcinoma randomized clinical drug trials of outpatient 14 cases, were divided into pazopanib group (n = 10) and placebo group ( 4 cases), were treated with pazopanib 800mg/d and placebo after 12 weeks of treatment duration, according to the results of CT scan before and after medication , efficacy was determined . The results showed that the reduced average ratios of measurable disease focus of pazopanib and placebo patients were 27.6%,-2.8% (P
Adverse reactions
Diarrhea, hypertension, hair color change, nausea, loss of appetite, vomiting, fatigue, weakness, headache, abdominal pain and so on.
Cause serious liver problems, so health care workers should take blood tests to monitor liver function before using the drug in patients and during treatment of patients.
Hazardous to the fetus,people during pregnancy are forbid using this drug.
Pazopanib can also lead to arrhythmias, during treatment patients should have regular electrocardiogram measuring heart rate, and regular blood tests to monitor electrolytes since an electrolyte imbalance will also play a role in arrhythmia.
Clinical Use
Tyrosine kinase inhibitor:
Treatment of metastatic renal cell carcinoma and soft
tissue sarcoma
Drug interactions
Potentially hazardous interactions with other drugs
Antibacterials: avoid with clarithromycin, rifampicin
and telithromycin.
Antifungals: avoid with itraconazole, ketoconazole
and voriconazole.
Antipsychotics: avoid with clozapine (increased risk
of agranulocytosis).
Antivirals: avoid with atazanavir, boceprevir,
indinavir, ritonavir and saquinavir.
Grapefruit juice: avoid concomitant administration.
Avoid concomitant use with other inhibitors or
inducers of CYP3A4. Dose alterations may be
required.
Metabolism
Metabolism primarily by CYP3A4, with minor
contributions from CYP1A2 and CYP2C8. The four
principle pazopanib metabolites account for only 6% of
the exposure in plasma. One of these metabolites inhibits
the proliferation of VEGF-stimulated human umbilical
vein endothelial cells with a similar potency to that
of pazopanib, the others are 10- to 20-fold less active.
Therefore, activity of pazopanib is mainly dependent on
parent pazopanib exposure.
Elimination is mostly via the faeces.
Check Digit Verification of cas no
The CAS Registry Mumber 444731-52-6 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 4,4,4,7,3 and 1 respectively; the second part has 2 digits, 5 and 2 respectively.
Calculate Digit Verification of CAS Registry Number 444731-52:
(8*4)+(7*4)+(6*4)+(5*7)+(4*3)+(3*1)+(2*5)+(1*2)=146
146 % 10 = 6
So 444731-52-6 is a valid CAS Registry Number.
InChI:InChI=1/C21H23N7O2S.ClH/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);1H
444731-52-6Relevant articles and documents
Switching on prodrugs using radiotherapy
Geng, Jin,Zhang, Yichuan,Gao, Quan,Neumann, Kevin,Dong, Hua,Porter, Hamish,Potter, Mark,Ren, Hua,Argyle, David,Bradley, Mark
, p. 805 - 810 (2021/06/14)
Chemotherapy is a powerful tool in the armoury against cancer, but it is fraught with problems due to its global systemic toxicity. Here we report the proof of concept of a chemistry-based strategy, whereby gamma/X-ray irradiation mediates the activation of a cancer prodrug, thereby enabling simultaneous chemo-radiotherapy with radiotherapy locally activating a prodrug. In an initial demonstration, we show the activation of a fluorescent probe using this approach. Expanding on this, we show how sulfonyl azide- and phenyl azide-caged prodrugs of pazopanib and doxorubicin can be liberated using clinically relevant doses of ionizing radiation. This strategy is different to conventional chemo-radiotherapy radiation, where chemo-sensitization of the cancer takes place so that subsequent radiotherapy is more effective. This approach could enable site-directed chemotherapy, rather than systemic chemotherapy, with ‘real time’ drug decaging at the tumour site. As such, it opens up a new era in targeted and directed chemotherapy. [Figure not available: see fulltext.].
Pyrimidineamines as angiogenesis modulators
-
, (2015/11/16)
Pyrimidine derivatives, which are useful as VEGFR2 inhibitors are described herein. The described invention also includes methods of making such pyrimidine derivatives as well as methods of using the same in the treatment of hyperproliferative diseases.
A novel practical synthesis of pazopanib: An anticancer drug
Mei, Yi Cheng,Yang, Bao Wei,Chen, Wei,Huang, Dan Dan,Li, Ying,Deng, Xin,Liu, Bao Ming,Wang, Jing Jie,Qian, Hai,Huang, Wen Long
, p. 276 - 279 (2012/08/27)
Abstract: This paper reports a novel approach to synthesize pazopanib. In our synthetic route, the potently mutagenic alkylating agents such as dimethyl sulfate and methyl iodide are avoided. A novel regioselective methylation of the 2- position of 3-methyl-6-nitro-1H-indazole was reported. This novel route is one step shorter than the previously reported route.
