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The FDA granted orphan drug designation to darovasertib, a first-in-class oral, small molecular inhibitor of protein kinase C (PKC), for the treatment of uveal melanoma, on 2 May 2022. Primary uveal melanoma has a high risk of progressing to metastatic uveal melanoma, with a poor prognosis. The activation of the PKC and mitogen-activated protein kinase pathways play an essential role in the pathogenesis of uveal melanoma, and mutations in the G protein subunit alpha q (GNAQ), and G protein subunit alpha11 (GNA11) genes are considered early events in the development of uveal melanoma. Compared to other PKC inhibitors, such as sotrastaurin and enzastaurin, darovasertib is significantly more potent in inhibiting conventional (α, β) and novel (δ, ϵ, η, θ) PKC proteins and has a better tolerability and safety profile. Current Phase I/II clinical trials indicated that darovasertib, combined with the Mitogen-activated protein kinase/Extracellular (MEK) inhibitors, binimetinib or crizotinib, produced a synergistic effect of uveal melanoma. In this article, we summarize the development of drugs for treating uveal melanomas and discuss problems associated with current treatments. We also discuss the mechanism of action, pharmacokinetic profile, adverse effects, and clinical trial for darovasertib, and future research directions for treating uveal melanoma.

A burning sensation on eating spicy foods purportedly supports the role of capsaicin, an active component of chili peppers, in the etiology of oral submucous fibrosis (OSF). Although the mast cell mediators and activated P2X receptors induce a constant burning sensation through an ATP-dependent mechanism, it is the activation of the transient receptor potential vanilloid 1 (TRPV-1) receptor by capsaicin that aggravates it. The molecular basis for the burning pain in OSF is thus attributable to the activation of TRPV1. There is overwhelming evidence that confirms capsaicin has more of a protective role in attenuating fibrosis and is potentially therapeutic in reversing conditions linked to collagen accumulation. The activation of TRPV-1 by capsaicin increases intracellular calcium ([Ca2+]i), upregulates AMP-activated protein kinase (AMPK) and Sirtuin-1 (SIRT-1), to enrich endothelium-dependent vasodilation via endothelial nitric oxide synthase (eNOS). The induction of vasodilation induces antifibrotic effects by alleviating hypoxia. The antifibrotic effects of capsaicin are mediated through the upregulation of antioxidant enzymes, downregulation of inflammatory genes and suppression of new collagen fibril formation. Capsaicin also demonstrates an anticarcinogenic effect by upregulating the cytotoxic T cells and downregulating regulatory T cells through the inhibition of angiogenesis and promotion of apoptosis. Judicious administration of capsaicin with an appropriate delivery mechanism may have therapeutic benefits in reducing pain sensation, rendering antifibrotic effects, and preventing the malignant transformation of OSF. This paper provides an overview of the molecular basis of capsaicin and its therapeutic application as an antifibrotic and anticarcinogenic agent for the treatment of OSF.

Originating in ancient India, Ayurveda is an alternative medicinal approach that provides substantial evidence for a theoretical-level analysis of all aspects of life. Unlike modern medicine, Ayurveda is based upon tridoshas (Vata, pitta, and Kapha) and Prakriti. On the other hand, the research of all the genes involved at the proteomics, metabolomics, and transcriptome levels are referred to as genomics. Geoclimatic regions (deshanupatini), familial characteristics (kulanupatini), and ethnicity (jatiprasakta) have all been shown to affect phenotypic variability. The combination of genomics with Ayurveda known as ayurgenomics provided new insights into tridosha that may pave the way for precision medicine (personalized medicine). Through successful coordination of “omics,” Prakriti-based treatments can help change the existing situation in health care. Prakriti refers to an individual’s behavioral trait, which is established at the moment of birth and cannot be fully altered during one’s existence. Ayurvedic methodologies are based on three Prakriti aspects: aushadhi (medication), vihara (lifestyle), and ahara (diet). A foundation of Prakriti-based medicine, preventative medicine, and improvement of life quality with longevity can be accomplished through these ayurvedic characteristics. In this perspective, we try to understand prakriti’s use in personalized medicine, and how to integrate it with programs for drug development and discovery.

Treatment choices for the “severe acute respiratory syndrome‐related coronavirus‐2 (SARS‐CoV‐2)” are inadequate, having no clarity on efficacy and safety profiles. Currently, no established intervention has lowered the mortality rate in the “coronavirus disease 2019 (COVID‐19)” patients. Recently, 2-deoxy-D-glucose (2-DG) has evaluated as a polypharmacological agent for COVID-19 therapy owing to its influence on the glycolytic pathway, interaction with viral proteins, and anti-inflammatory action. In May 2020, the Indian drug regulatory authority approved 2-DG as an emergency adjunct therapy in mild to severe COVID-19 patients. Clinical studies of 2-DG corroborate that it aids in faster recovery of hospitalized patients and decreases supplemental oxygen. Herein, we describe the development process, synthesis, mechanism of viral eradication, and preclinical and clinical development of 2-DG and its derivatives as molecularly targeted therapeutics for COVID-19 treatment.