Drug Design for Neuropathic Pain Regulation From Traditional Chinese Medicine.
Drug design for neuropathic pain regulation from traditional chinese medicine.
Filed under: Drug and Alcohol Rehabilitation
Sci Rep. 2013; 3: 844
Tou WI, Chang SS, Lee CC, Chen CY
FAAH-like anandamide transporter (FLAT) regulates anandamide transport for hydrolysis and may be an attractive drug target for pain regulation. We aimed to discover potential FLAT antagonists from traditional Chinese medicine (TCM) using virtual screening, ligand-based drug design and molecular dynamics simulation (MD). Guineensine and Retrofractamide A exhibited high Dock Scores in FLAT. Consensus from multiple linear regression (MLR; R(2) = 08973) and support vector machine (SVM; R(2) = 0.7988) showed similar bioactivities for Guineensine and the FAAH-1 inhibitor (9Z)-1-(5-pyridin-2-yl-1,3,4-oxadiazol-2-yl)octadec-9-en-1-one. Contour of Guineensine to CoMFA and CoMSIA features also imply bioactivity. MD revealed shake or vibration in the secondary structure of FLAT complexed with Guineensine and (9Z)-1-(5-pyridin-2-yl-1,3,4-oxadiazol-2-yl)octadec-9-en-1-one. Ligand movement might contribute to protein changes leading to vibration patterns. Violent vibrations leading to an overall decrease in FLAT function could be the underlying mechanism for Guineensine. Here we suggest Guineensine as a drug-like compound with potential application in relieving neuropathic pain by inhibiting FLAT.
HubMed – drug
Drug development for the irritable bowel syndrome: current challenges and future perspectives.
Filed under: Drug and Alcohol Rehabilitation
Front Pharmacol. 2013; 4: 7
De Ponti F
Medications are frequently used for the treatment of patients with the irritable bowel syndrome (IBS), although their actual benefit is often debated. In fact, the recent progress in our understanding of the pathophysiology of IBS, accompanied by a large number of preclinical and clinical studies of new drugs, has not been matched by a significant improvement of the armamentarium of medications available to treat IBS. The aim of this review is to outline the current challenges in drug development for IBS, taking advantage of what we have learnt through the Rome process (Rome I, Rome II, and Rome III). The key questions that will be addressed are: (a) do we still believe in the “magic bullet,” i.e., a very selective drug displaying a single receptor mechanism capable of controlling IBS symptoms? (b) IBS is a “functional disorder” where complex neuroimmune and brain-gut interactions occur and minimal inflammation is often documented: do we need to target gut motility, visceral sensitivity, or minimal inflammation? (c) are there validated biomarkers (accepted by regulatory agencies) for studies of sensation and motility with experimental medications in humans? (d) do animal models have predictive and translational value? (e) in the era of personalized medicine, does pharmacogenomics applied to these medications already play a role? Finally, this review will briefly outline medications currently used or in development for IBS. It is anticipated that a more focused interaction between basic science investigators, pharmacologists, and clinicians will lead to better treatment of IBS.
HubMed – drug
Evaluation of safety and efficacy of tivantinib in the treatment of inoperable or recurrent non-small-cell lung cancer.
Filed under: Drug and Alcohol Rehabilitation
Cancer Manag Res. 2013; 5: 15-20
Broggini M, Garassino MC, Damia G
Tivantinib is a selective, oral, non-ATP-competitive, small molecule inhibitor of the c-Met receptor, tyrosine kinase, which is implicated at different levels of tumor cell migration, invasion, proliferation, and metastasis. Tivantinib has shown antitumor activity in various human tumor cell lines and in xenograft models of human cancers, including non-small-cell lung cancer. Few therapeutic options are available at present for advanced non-small-cell lung cancer, so there is a pressing need for new therapeutic strategies to improve response and survival. Amplification of Met has been reported in more than 20% of lung tumors that have acquired resistance to epidermal growth factor receptor inhibitors, implying that treatment of these tumors with a c-Met inhibitor should overcome resistance. Tivantinib has shown interesting and promising results in advanced non-small-cell lung cancer and appears to be well tolerated, either alone or in combination with other drugs. An interesting additional feature is the ability of the drug to delay development of new metastasis, in agreement with the proposed role of Met in this particular setting.
HubMed – drug
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