Tumor Necrosis factor (TNF) is a pro-inflammatory cytokine, the high levels of which signify inflammation in several disease conditions like autoimmune disorders (e.g. - rheumatoid arthritis, Crohn's disease and ankylosing spondylitis etc.), numerous cancers, skin diseases like psoriasis and refractory asthma. This is often the rationale that TNF-alpha inhibitors are given such importance in medical literature. Starting from natural compounds like curcumin, cannabis and green tea to xanthine derivatives, hallucination inducing compounds and also the best of all monoclonal antibodies, several TNF inhibitors are being studied in several and physiological conditions.As a result of its significance, TNF-alpha inhibition in cancers researchers got abundant attention [1].
One such inhibitor is Lenalidomide TNF-alpha Receptor inhibitor and one can buy Lenalidomide under the brand of Revlimid. Lenalidomide structure shows that it's 4-amino-glutamyl analog of Thalidomide and its discovery and application in the treatment of myeloma was considered to be a therapeutic milestone owing to the association of this specific disease with a dismal prognosis. Lenalidomide price is around $60 for 500mg and Lenalidomide price may vary according to the proportion purity of the preparation and from one Lenalidomide supplier to different ones. Lenalidomide solubility is extremely poor in water and ethanol however it solubilizes in DMSO to allow a 100 mg/mL solution. 

Though Lenalidomide Revlimid mechanism shares some similarities with its analog Thalidomide, there are some variations in the action of 2 compounds [2]. numerous analyses threw light on different aspects of its mechanism and one concluded Lenalidomide potency as a result of its inhibition of the mevalonate pathway in myeloma treatment [3] whereas another report showed the induction of p21WAF-1 pathway and also the involvement of an epigenetic modification cascade upon Lenalidomide co-treatment with another drug, Pomalidomide, for the treatment of multiple myeloma and lymphoma [4]. Another group in an independent study showed its ability to inhibit Gab1 phosphorylation to impede the proliferation of leukemic cells in vitro [5]. Lenalidomide was shown to exert anti-angiogenic responses in vivo and therefore the endothelial cells in an in vitro system showed reduced cell metastasis and Akt phosphorylation [6]. The anti-angiogenic aspect of Lenalidomide mechanism was additionally investigated in hematological malignancies, showing its capability to act as an immunomodulator [7].

There has been an extended list of Lenalidomide clinical trials however it showed most success in the treatment of cancers like Hodgkin's Lymphoma, Chronic Lymphocytic Leukemia (CLL), non-Hodgkin's Lymphoma and numerous solid tumor cancers, e.g. – pancreatic cancers. The mention of Discoid Lupus Erythematosus is added to the current list [8] and a variety of clinical trials are carried out for the treatment of leukemia and lymphoma cancers with Lenalidomide as one agent or as a part of combination therapy. The aforementioned study [8] was followed by a combination regime in an in vitro erythropoiesis model involving human CD34+ progenitor cells with Lenalidomide and Pomalidomide [9].
Soon Lenalidomide entered in phase I studies in patients with solid tumors [10]. The success of its phase I studies saw the employment of Lenalidomide in phase II clinical trials in renal cell carcinoma [11] where it registered  motivating results owing toits efficacy. Numerous combinations of Lenalidomide and other drugs saw their uses in phase II studies on amyloidosis [12] and phase II trials targeting myeloma [13-14] and they were very successful. The Lenalidomide TNF-alpha inhibitor was used for phase II clinical trials in CLL [15] and studies involving phase II trials in myelodysplastic syndromes (MDSs) patients [16]. It showednoteworthy efficacy in phase III trials involving relapsed/refractory multiple myeloma (RRMM) patients [17] and its low toxicity profile saw its approval in the elderly myeloma patients [18].

1. Zidi, I.e.a., TNF-α and its inhibitors in cancer. Medical Oncology, 2010. 27(2): p. 185-198.
2. Anderson, K.C.e.a., Lenalidomide and Thalidomide: Mechanisms of Action-Similarities and Differences. Seminars in Hematology, 2005. 42(4): p. S3-S8.
3. Spek, E.V.e.a., Inhibition of the mevalonate pathway potentiates the effects of lenalidomide in myeloma. Leukemia Research, 2009. 33(1): p. 100-108.
4. Lozach, L.E.e.a., Pomalidomide and Lenalidomide Induce p21WAF-1 Expression in Both Lymphoma and Multiple Myeloma through a LSD1-Mediated Epigenetic Mechanism. Cancer Res, 2009. 69: p. 7347.
5. Gandhi, A.K.e.a., Lenalidomide inhibits proliferation of Namalwa CSN.70 cells and interferes with Gab1 phosphorylation and adaptor protein complex assembly. Leukemia Research, 2006. 30(7): p. 849-858.
6. Dredge, K.e.a., Orally administered lenalidomide (CC-5013) is anti-angiogenic in vivo and inhibits endothelial cell migration and Akt phosphorylation in vitro. Microvascular Research, 2005. 69(1-2): p. 56-63.
7. Kotla, V.e.a., Mechanism of action of lenalidomide in hematological malignancies. J Hematol Oncol., 2009. 2(36).
8. Shah, A.e.a., Lenalidomide for the Treatment of Resistant Discoid Lupus Erythematosus. Arch Dermatol., 2009. 145(3): p. 303-306.
9. Parseval, L.A.M.e.a., Pomalidomide and lenalidomide regulate erythropoiesis and fetal hemoglobin production in human CD34+ cells. J Clin Invest., 2008. 118(1): p. 248-258.
10. Sharma, R.A.e.a., Toxicity profile of the immunomodulatory thalidomide analogue, lenalidomide: Phase I clinical trial of three dosing schedules in patients with solid malignancies. European Journal of Cancer, 2006. 42(14): p. 2318-2325.
11. Choueiri, T.K.e.a., Phase II study of lenalidomide in patients with metastatic renal cell carcinoma. Cancer, 2006. 107(11): p. 2609-2616.
12. Sanchorawala, V.e.a., Lenalidomide and dexamethasone in the treatment of AL amyloidosis: results of a phase 2 trial. Blood, 2007. 109(2): p. 492-496.
13. Rajkumar, S.V.e.a., Combination therapy with lenalidomide plus dexamethasone (Rev/Dex) for newly diagnosed myeloma. Blood, 2005. 106(13): p. 4050-4053.
14. Richardson, P.G.e.a., A randomized phase 2 study of lenalidomide therapy for patients with relapsed or relapsed and refractory multiple myeloma. Blood, 2006   108(10): p. 3458-3464.
15. Khan, A.C.e.a., Clinical Efficacy of Lenalidomide in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia: Results of a Phase II Study. Journal of Clinical Oncology, 2006. 24(34): p. 5343-5349.
16. Raza, A.e.a., Phase 2 study of lenalidomide in transfusion-dependent, low-risk, and intermediate-1-risk myelodysplastic syndromes with karyotypes other than deletion 5q. Blood, 2008 111(1): p. 86-93.
17. Dimopoulos, M.A.e.a., Study of lenalidomide plus dexamethasone versus dexamethasone alone in relapsed or refractory multiple myeloma (MM): results of a phase 3 study (MM-010). Blood, 2005. 106: p. 6-11.
18. Palumbo, A.e.a., Melphalan, Prednisone, and Lenalidomide Treatment for Newly Diagnosed Myeloma: A Report From the GIMEMA-Italian Multiple Myeloma Network. Journal of Clinical Oncology, 2007. 25(28): p. 4459-4465.

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