FINGOLIMOD – AN IMMUNOMODULATOR

by Selleckchem | Apr 02 2012

PROPERTIES AND ORIGIN:
Fingolimod (FTY720) derivative of a metabolite of a fungal strain Isaria sinclairii,and is known to be the 1st oral medicine which recently get approval for using against the multiple Sclerosis. Multiple seclerosis is an auto immune disease hence Fingolimod offers a glimmering hope against this debilitating disease. Fingolimod got approval in 2010-11 and after its approval Novartis (manufacturers) ensured its continous availability in market for patients. structure of Fingolimod SIP receptor inhibitor is chemically very different from ISP-1 (parent metabolite) and in order to enhance its efficacy and phamacokinetic properties, this sphingosine analog molecule is rationally modified. This drug is marketed by name Fingolimod Gilenya. This drug is an immunomodulating one and was used as an anti-rejection drug after the transplantation processes [1] in clinical trials of phase I and phase II [2]. Fingolimod is an oral medicine and gives good solubility in ethanol and DMSO upto a 100mg/ml solution. It is supplied as an HCl salt. One can buy Fingolimod from supplier Fingolimod. Its price is almost around $40 for a 100 mg vial.

FINGOLIMOD: LYMPHOCYTE REGULATOR
The mode of action of the drug Fingolimod FTY720 involves its capability to have lymphocytes in the lymph nodes making their circulation unable to CNS [3] where these lymphocytes can cause exasperation of Multiple Sclerosis by producing an an auto-immune response [4-5]. This agonist of SIP receptor reverses the activity of BCR/ABL kinase enzymes by getting phophorylate by the sphingosine kinase-2 forms FTY720-phosphate which binds to 4 of the 5 subtypes of G-protein coupled SIP receptor. IC50 for fingolimod is found to be 0.15 nM. Despite of its efficiency as an anti-rejection drug in auto-immune disease (Multiple Sclerosis) and transplantations, it was still been found to used as a valuable treatment regime for some cancer types [6] and viral infections also [7].

FINGOLIMOD AGAINST MULTIPLE SCLEROSIS:
According to a study of healthy controls, Fingolimod is easy to biotransformed into various easily discardable metabolites hence got approval in clinical trials [8]. It scored better than the other immunoregulatory drugs due to its specificity and efficiency towards lymphocytes and as a result other immune cells remain spare from its effect and restore the immune system. This novel drug is also checked to study how it acts directly on neuronal system and was observed to get attack by immune cells keeping the neurons spare [9]. Different preclinical trials were also conducted to reveal its toxicity profiling and efficacy before its entry into clinical analysis [10].
A Magnetic Resonance Imaging analysis was conducted on Multiple Sclerosis relapsing patients and it showed very remarkable in relapse rate of these patients experiencing Fingolimod as compared to the placebo medicated patients [11], though there were some side effects also associated with it. The same group of researchers extended this study which showed a consistent overall improvement in maximum of the patients treated with Fingolimod. It was a well-tolerated treatment with Fingolimod in spite of an increase in its dose from 0.5 mg/Kg of body mass to 1.25 mg/Kg per body mass over a prolonged time period [12], hence validating its valuability in Multiple Sclerosis. It showed remarkable results as compared to traditonal treatment of Multiple Sclerosis which comprises of an intra muscular injection of interferon -1a (IFN-1a) in clinical studies [13]. The great success of this Fingolimod Src-bcr-Abl inhibitor in treating Multiple Sclerosis has sub stained its value as a most efficient drug available in niche [14]. Further more attempts are being made to produce its analogs to achieve a side effect free and less toxic profile.

REFERENCES:
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