Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chemokine receptors have evolved as attractive targets for disease conditions which arise due to immunomodulation involving host-defense mechanisms. CCR2, a chemokine receptor, is targeted for diseases like arthritis, multiple sclerosis, vascular disease, obesity, and type 2 diabetes. This study provides a new strategy of a ligand based technique which exploits fingerprint led fragment features in conjunction with structure-guided design for identifying new scaffolds for CCR2. A fragment based mining (FBM) technique was employed on a chemical database to identify novel scaffold hops. The hits were subjected to 3-point pharmacophore fingerprint procedures with Tanimoto similarity metric to compare pharmacophoric fingerprints. The final 66 hits generated by these exercises were predicted by the validated HQSAR model, and the top predicted were suggested as probable scaffolds for CCR2 antagonism. The identified scaffolds were validated through molecular docking studies. The ligands were docked by providing receptor flexibility in the extra cellular domain (1 and 3), N terminal domain, and in the transmembrane (TM1 & TM7) helix region with IFD approach. Some of the scaffolds showed H-bonding potential which was not explored by the data set molecules. All identified scaffolds highlighted a key hydrogen bonding interaction with Thr292 as supported by mutational studies. The observed pi stacking interaction with Tyr188 in data set molecules was also produced by the new scaffolds. Taking the advantage of receptor flexibility the scaffolds explored the hydrophobic binding cleft between helix 1 and 7 occupied by residues Leu44, Leu45, Leu48 and Ile300, Ile303, Ile304, respectively. Two of the identified molecules have promising outcomes and can be considered as novel scaffolds for CCR2 binding.
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PMID:Fingerprint directed scaffold hopping for identification of CCR2 antagonists. 1876 38

W.H.O. predicts that there will be some 438 million diabetic patients in 2030, most of them living in developing countries. The IFD estimates that the prevalence of diabetes will rise by 98% in Africa during the next 20 years, with dramatic implications for public health and national budgets of the poorest countries. Type 2 diabetes is the most common form in Africa; type 1 is rarer than in western countries and tends to occur later. Two other forms seem specific to black Africans: ketosis-prone atypical diabetes, and tropical malnutrition-related diabetes. An increasing prevalence of obesity, diabetes and impaired glucose tolerance is observed in all parts of Africa. Several factors contribute to this situation, including aging, dietary transitions and lack of physical activity, all of which are related to rapid urbanization. In Africa, diabetes is associated with a high mortality rate, especially among insulin-dependent patients. Poor metabolic control can lead to severe ketosis and hypoglycemic accidents that carry a poor prognosis. Microvascular complications include retinopathy and nephropathy, and most patients cannot afford hemodialysis. Foot ulcers are frequent, due to trauma and neuropathies. Macrovascular complications are also increasing, with a high prevalence of hypertension. The poor prognosis of diabetes in Africa is related to late diagnosis, poor education, inadequate access to insulin, antidiabetic drugs and glycemia self-monitoring devices, absence of controlled diets, and difficult access to medical care in rural areas. Patient empowerment, knowledge and self-care must be improved. African governments must develop national prevention programs. Special attention must be paid to the prevention of obesity and diabetes. The urban environment, infrastructure, education, exercise and safe nutrition must be part of an overall policy designed to reduce the burden of chronic non transmissible diseases.
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PMID:[The burden of diabetes in Africa: a major public health problem]. 2253 May 17