Molecular and therapeutic insights of rapamycin: a multi-faceted drug from Streptomyces hygroscopicus

Abstract

The advancement in pharmaceutical research has led to the discovery and development of new combinatorial life-saving drugs. Rapamycin is a macrolide compound produced from Streptomyces hygroscopicus. Rapamycin and its derivatives are one of the promising sources of drug with broad spectrum applications in the medical field. In recent times, rapamycin has gained significant attention as of its activity against cytokine storm in COVID-19 patients. Rapamycin and its derivatives have more potency when compared to other prevailing drugs. Initially, it has been used exclusively as an anti-fungal drug. Currently rapamycin has been widely used as an immunosuppressant. Rapamycin is a multifaceted drug; it has anti-cancer, anti-viral and anti-aging potentials. Rapamycin has its specific action on mTOR signaling pathway. mTOR has been identified as a key regulator of different pathways. There will be an increased demand for rapamycin, because it has lesser adverse effects when compared to steroids. Currently researchers are focused on the production of effective rapamycin derivatives to combat the growing demand of this wonder drug. The main focus of the current review is to explore the origin, development, molecular mechanistic action, and the current therapeutic aspects of rapamycin. Also, this review article revealed the potential of rapamycin and the progress of rapamycin research. This helps in understanding the exact potency of the drug and could facilitate further studies that could fill in the existing knowledge gaps. The study also gathers significant data pertaining to the gene clusters and biosynthetic pathways involved in the synthesis and production of this multi-faceted drug. In addition, an insight into the mechanism of action of the drug and important derivatives of rapamycin has been expounded. The fillings of the current review, aids in understanding the underlying molecular mechanism, strain improvement, optimization and production of rapamycin derivatives. Graphical abstract

Coronary stent implantation links to the occurrence of eosinophilia and interstitial pneumonia: a case report and systematic review

“…Rapamycin has been proven to suppress the immune system and inhibit cell growth by targeting mammalian rapamycin targets (mTOR). Clinically, it has been utilized to prevent organ transplant rejection [ 19 ], lymphatic leiomyomatosis [ 20 ], and avert coronary artery stent restenosis. It has been difficult to accurately estimate the rate of interstitial pneumonia caused by rapamycin due to the absence of initial symptoms.…”

Rapamycin increases murine lifespan but does not reduce mineral volume in the Matrix GLA Protein (MGP) knockout mouse model of medial arterial calcification

“…In mice, rapamycin has been shown to increase maximum lifespan and delay the onset of cancer as hyperactivity of the mTOR pathway, frequently found in cancers, leads to the expression and activation of many oncogenes like PI3K, Akt, and eIF4E. Hence, rapamycin can slow the proliferation of tumor cells by causing cell arrest, promoting apoptosis, and blocking angiogenesis in tumor growths (43). However, our data show that the increase in lifespan observed in Mgp -/mice following rapamycin treatment is not associated with improvements in SMC contractile protein expression or enhanced autophagy flux.…”

Formulation of cost-effective medium and optimization studies for enhanced production of rapamycin

“…In the present study, medium A exhibited higher rapamycin production due to its diverse carbon and nitrogen sources. Additionally, in medium A, trace elements acted as cofactors, enhancing metabolic activity and increasing rapamycin production [19]. Media B and C had limited substrates, resulting in lower yields.…”