Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P42345 (mTOR)
 26,049 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The association of a birth defect and a segmental hemangioma is well established, a consensus concerning evaluation and monitoring of infants with PHACE or LUMBAR syndromes has been published. The efficacy of propranolol in infantile hemangioma is proven; however there were still unresolved issues concerning the safety in children; after 8 years of use on thousands of children safety data collection did not show any unexpected side effects. Topical treatment of infantile hemangiomas with beta-blockers, such as timolol, is very popular, but recent publications revealed a significant systemic absorption that could be responsible for severe side effects, such as bradycardia, in low birthweight infants. As a consequence, this therapeutic option should be considered with caution. In the last 2 years mTOR inhibitors have been tested in low-flow vascular malformations with varying success, but progress remains to be done in the treatment of vascular abnormalities. Today, genetics has led to advances in the understanding of the pathophysiology and in the future targeted therapies could probably be feasible. Skin barrier deficiency is responsible for the development of allergic phenomena in atopic patients, since it has been shown that sensibilisation, even to food, could probably be induced by skin contact. Unfortunately, the topical treatment with crisaborole, a phosphodiesterase 4 inhibitor, does not look like a revolution in children atopic dermatitis, its efficacy seems equivalent to emollient application. In the field of infectious diseases, changes in viral outbreaks are the most reported. Furthermore epidemic Zika virus, enteroviruses are responsible for expanded dermatological manifestations and also severe meningoencephalitis. Paraviral character of various eruptions, such as gloves and socks syndrome or eruptive pseudoangiomatosis is challenged.
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PMID:[What's new in pediatric dermatology?] 2942 7

The free-living amebae Naegleria, Acanthamoeba, and Balamuthia cause rare but life-threatening infections. All three parasites can cause meningoencephalitis. Acanthamoeba can also cause chronic keratitis and both Balamuthia and Acanthamoeba can cause skin and systemic infections. There are minimal drug development pipelines for these pathogens despite a lack of available treatment regimens and high fatality rates. To identify anti-amebic drugs, we screened 159 compounds from a high-value repurposed library against trophozoites of the three amebae. Our efforts identified 38 compounds with activity against at least one ameba. Multiple drugs that bind the ATP-binding pocket of mTOR and PI3K are active, highlighting these compounds as important inhibitors of these parasites. Importantly, 24 active compounds have progressed at least to phase II clinical studies and overall 15 compounds were active against all three amebae. Based on central nervous system (CNS) penetration or exceptional potency against one amebic species, we identified sixteen priority compounds for the treatment of meningoencephalitis caused by these pathogens. The top five compounds are (i) plicamycin, active against all three free-living amebae and previously U.S. Food and Drug Administration (FDA) approved, (ii) TG02, active against all three amebae, (iii and iv) FDA-approved panobinostat and FDA orphan drug lestaurtinib, both highly potent against Naegleria, and (v) GDC-0084, a CNS penetrant mTOR inhibitor, active against at least two of the three amebae. These results set the stage for further investigation of these clinically advanced compounds for treatment of infections caused by the free-living amebae, including treatment of the highly fatal meningoencephalitis.
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PMID:Identification of plicamycin, TG02, panobinostat, lestaurtinib, and GDC-0084 as promising compounds for the treatment of central nervous system infections caused by the free-living amebae Naegleria, Acanthamoeba and Balamuthia. 3170 63