Receptors antitumor activity

Several reports are available on the biological activities of thioamide derivatives. The thioamide derivatives have shown significant activities, such as antituberculosis drug, anti-influenza virus activity, antitumor activity, anthelmintic activity, opioid receptor binding property, etc.94 101... 

Gourdeau H, McAlpine JB, Ranger M, Simard B, Berger F, Beaudry F, Falardeau P. (2008) Identification, characterization and potent antitumor activity of ECO-4601, a novel peripheral benzodiazepine receptor ligand. Cancer Chemother Pharmacol 61 911-921. 

Iressa (ZD 1839) is an orally active tyrosine kinase inhibitor selective for the epidermal growth factor (EGF) receptor tyrosine kinase. Iressa is undergoing clinical trials in the treatment of various solid tumors, including head and neck cancer, breast cancer and non-small cell lung cancer. Its antitumor activity is derived from the fact that the EGF receptor and EGF signaling are... 

Although Gleevec was carefully designed to inhibit the specific tyrosine kinase produced by the Philadelphia chromosome, it also produces unexpected activities. Gleevec blocks c-kit (the receptor for stem cell factor) [40], and the receptor for platelet-derived growth factor [41]. These additional activities could result in a broader array of antitumor activities, in a broader spectrum of toxicities, or both [42]. 

Interferons. The interferons (IFNs),196,197 which were discovered in 1957, are proteins secreted by leukocytes, fibroblasts, and activated lymphocytes. They inhibit replication of viruses as well as the growth of host cells and also have antitumor activity. Interferons are classified as a (from leukocytes), (3 (from fibroblasts), and y (from lymphocytes). According to their affinities for the two types of known interferon receptors, interferons IFN-a, IFN-(3, and the less well known IFN-0) and IFN-t are... 

Mendel DB et al (2003) In vivo antitumor activity of SU11248, a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor and platelet-derived growth factor receptors determination of a pharmacokinetic/pharmacodynamic relationship. Clin Cancer Res 9 327-337... 

Kreitman. R. J., Puri, R. K., and Pastan, I. (1995). Increased antitumor activity of a circularly permuted interleukin 4- toxin in mice with interleukin 4 receptor-bearing human carcinoma. Cancer Res., 55, 3357—3363. 

In summary, sunitinib maleate (1) is a multitargeted receptor tyrosine kinase inhibitor with potent anti-angiogenic and antitumor activity. It is approved for the treatment of advanced renal cell carcinoma and gastrointestinal stromal tumors, and is currently undergoing clinical trials for a number of additional malignancies. The discovery synthesis of 1 along with its process development approaches were described in this chapter. 

The doses of retinol that are protective in animals are in the toxic range (Section 2.5.1) and are unlikely to be useful in cancer therapy or prevention. A number of synthetic retinoids have been developed, in a search for compounds that show anticancer activity, but are metabolized, stored, and transported differently, or bind to different subtypes of retinoid receptor and are less toxic. RXR-selective ligands are less toxic and more active in animal cancer models than RAR ligands (Lippman and Lotan, 2000). Fenretinamide, and possibly other retinoids that have antitumor activity, exerts at least part of its action by induction of apoptosis by a receptor-independent mechanism (Wu et al., 2001). 

The Co2(CO)6(/tT2-RC=CR) complexes themselves can be biologically active some exhibit antitumor activity exceeding that of cis-platin. The first organometallic derivative of 1 Ib-ethynylestradiol has also been synthesized it incorporates the Co2(CO)6(/ti2-RC=CR) moiety and is a potential high-affinity estrogen receptor marker. ... 

There are some serious drawbacks to the use of cis-platin in anticancer therapy. Severe toxicity problems occur, such as failure of the kidneys and bone marrow (nephrotoxicity and hematoxicity), nausea, intractable vomiting (emesis), peripheral neuropathy, deafness (ototoxicity), and seizures. These toxic side effects of cisplatin limit the dose that can be administered to patients typical doses are 100 mg day for up to five consecutive days. The nephrotoxicity can be reduced by hydration and diuresis. 5-HT3-receptor blockers control nausea and emesis. Much effort has been devoted to the development of chemopro-tective agents, which alleviate the side effects on normal tissues without compromising antitumor activity - mainly sulfur-containing agents such as sodium dithiocarbamate (Naddtc), 2-mercaptoethanesulphonate (mesna), and amifos-tine (WR-2721). Amifostine has recently been approved for coadministration with cisplatin, which reduces nephro- and neurotoxicity. ... 

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