Drug Discovery Today
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miRNAs in PAH: biomarker, therapeutic target or both?
Pulmonary arterial hypertension (PAH) is characterized by progressive increase in pulmonary vascular resistance leading to right ventricular hypertrophy and failure. There is a need to find new biomarkers to detect PAH at its early stages and also for new, more effective treatments for this disease....
Rescuing the BMPR2 signaling axis in pulmonary arterial hypertension.
Pulmonary arterial hypertension (PAH) is a lethal disorder characterized by pulmonary arterial remodeling, increased right ventricular systolic pressure (RVSP), vasoconstriction and inflammation. The heritable form of PAH (HPAH) is usually (>80%) caused by mutations in the bone morphogenic protein r...
Cellular and molecular mechanisms of cartilage damage and repair.
Cartilage breakdown is the disabling outcome of rheumatic diseases, whether prevalently inflammatory such as rheumatoid arthritis or prevalently mechanical such as osteoarthritis (OA). Despite the differences between immune-mediated arthritides and OA, common mechanisms drive cartilage breakdown. In...
Regeneration of stalled immune responses to transformed and infected cells using γδ T cells.
We review how recent findings regarding the biology of γδT cells have revealed that they, surprisingly, could serve as convenient tools for this purpose, in that they combine innate cytotoxic cell and pAPC functions in one cell type, with potential benefits in cancer immunotherapy and infectious dis...
Drug enterohepatic circulation and disposition: constituents of systems pharmacokinetics.
We critically evaluate the existing methods, techniques and animal models used for determining drug distribution, elimination and EHC, and collectively portray characteristics of 43 drugs that undergo EHC. EHC could represent an unexplored way to excrete unwanted substrates out of the body. The inte...
Novel therapeutic strategies for treatment of visceral leishmaniasis.
Leishmaniasis reveals itself in two forms, cutaneous and visceral, but the later exerts serious complications and may lead to death, if untreated. The availability of limited number of antileishmanial chemotherapeutic agents, the high cost of treatment, growing incidences of resistance to first line...
Phenotypic screens as a renewed approach for drug discovery.
The significant reduction in the number of newly approved drugs in the past decade has been partially attributed to failures in discovery and validation of new targets. Evaluation of recently approved new drugs has revealed that the number of approved drugs discovered through phenotypic screens, an...
Current status of liposomal porphyrinoid photosensitizers.
The complete eradication of various targets, such as infectious agents or cancer cells, while leaving healthy host cells untouched, is still a great challenge faced in the field of medicine. Photodynamic therapy (PDT) seems to be a promising approach for anticancer treatment, as well as to combat va...
Is autologous chondrocyte implantation (ACI) an adequate treatment option for repair of cartilage defects in paediatric patients?
Cartilage lesions in the knee of juvenile patients require an effective repair to regain life-long functional activity of the joint. Autologous chondrocyte implantation (ACI) is discussed to be advantageous over other methods for cartilage repair regarding long-term outcome. ACI has successfully bee...
Sclerostin: how human mutations have helped reveal a new target for the treatment of osteoporosis.
In the 1990s there was a tremendous mood of optimism among pharmaceutical scientists that identification of disease-associated variations in the human genome would result in a surge of new drug targets (the 'gene-to-drug' mantra). To date the expected deluge of new drugs has not arrived. However, a...