Extensive research into the therapeutics of asthma has yielded numerous effective interventions over the past few decades. However, adverse effects and ineffectiveness of most of these medications especially in the management of steroid resistant severe asthma necessitate the development of better medications. Numerous drug targets with inherent airway smooth muscle tone modulatory role have been identified for asthma therapy. This article reviews the latest understanding of underlying molecular aetiology of asthma towards design and development of better antiasthma drugs. New drug candidates with their putative targets that have shown promising results in the preclinical and/or clinical trials are summarised. Examples of these interventions include restoration of Th1/Th2 balance by the use of newly developed immunomodulators such as toll-like receptor-9 activators (CYT003-QbG10 and QAX-935). Clinical trials revealed the safety and effectiveness of chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) antagonists such as OC0000459, BI-671800 and ARRY-502 in the restoration of Th1/Th2 balance. Regulation of cytokine activity by the use of newly developed biologics such as benralizumab, reslizumab, mepolizumab, lebrikizumab, tralokinumab, dupilumab and brodalumab are at the stage of clinical development. Transcription factors are potential targets for asthma therapy, for example SB010, a GATA-3 DNAzyme is at its early stage of clinical trial. Other candidates such as inhibitors of Rho kinases (Fasudil and Y-27632), phosphodiesterase inhibitors (GSK256066, CHF 6001, roflumilast, RPL 554) and proteinase of activated receptor-2 (ENMD-1068) are also discussed. Preclinical results of blockade of calcium sensing receptor by the use of calcilytics such as calcitriol abrogates cardinal signs of asthma. Nevertheless, successful translation of promising preclinical data into clinically viable interventions remains a major challenge to the development of novel anti-asthmatics.
Andrographolide (AGP), a naturally occurring bioactive compound, has been investigated as a lead compound in cancer drug development. Its multidimensional therapeutic effects have raised interest among medicinal chemists, which has led to extensive structural modification of the compound, resulting in analogues with improved pharmacological and pharmaceutical properties. Nevertheless, the analogues with the improved properties need to be rigorously studied to identify drug-like lead compounds. We scrutinised articles published from 2012 to 2018, to objectively provide opinions on the mechanisms of action of AGP and its analogues, as well as their potential as viable anticancer drugs. Preclinical and clinical data, along with the extensive medicinal chemistry efforts, indicate the compounds are potential anticancer agents with specific value in treating recalcitrant cancers such as pancreatic and lung cancers.