WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H100500
CAS#: 191732-72-6
Description: Lenalidomide, also known as CC-5013, is the thalidomide analog with potential antineoplastic activity. Lenalidomide inhibits TNF-alpha production, stimulates T cells, reduces serum levels of the cytokines vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), and inhibits angiogenesis. This agent also promotes G1 cell cycle arrest and apoptosis of malignant cells. Lenalidomide is an approved drug.
Hodoodo Cat#: H100500
Name: Lenalidomide
CAS#: 191732-72-6
Chemical Formula: C13H13N3O3
Exact Mass: 259.10
Molecular Weight: 259.260
Elemental Analysis: C, 60.22; H, 5.05; N, 16.21; O, 18.51
Synonym: CC5013; CC-5013; CC 5013; IMiD1; Lenalidomide; US brand name: Revlimid.
IUPAC/Chemical Name: 3-(4-amino-1-oxoisoindolin-2-yl)piperidine-2,6-dione
InChi Key: GOTYRUGSSMKFNF-UHFFFAOYSA-N
InChi Code: InChI=1S/C13H13N3O3/c14-9-3-1-2-7-8(9)6-16(13(7)19)10-4-5-11(17)15-12(10)18/h1-3,10H,4-6,14H2,(H,15,17,18)
SMILES Code: O=C(C(N(CC1=C2C=CC=C1N)C2=O)CC3)NC3=O
Appearance: White solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
More Info: Chemical structures: Chemical structures of Pomalidomide ; Thalidomide and Lenalidomide are very similar: Lenalidomide, initially known as CC-5013 and marketed as Revlimid by Celgene, is a derivative of thalidomide introduced in 2004. It was initially intended as a treatment for multiple myeloma, for which thalidomide is an accepted therapeutic modality, but has also shown efficacy in the class of hematological disorders known as myelodysplastic syndromes (MDS). Revlimid is also known as Revamid in the UK.The exact mechanism of the immunomodulatory drugs (i.e., thalidomide, CC-4047/Actimid and lenalidomide) is not known. Apart from interfering with the immune system, they are also thought to act on angiogenesis. Lenalidomide and bortezomib are considered therapeutic breakthroughs in myeloma, which generally carries a poor prognosis. Lenalidomide is an off-white to pale-yellow solid powder. It is soluble in organic solvent/water mixtures, and buffered aqueous solvents. Lenalidomide is more soluble in organic solvents and low pH solutions. Solubility was significantly lower in less acidic buffers, ranging from about 0.4 to 0.5 mg/ml. Lenalidomide has an asymmetric carbon atom and can exist as the optically active forms S(-) and R(+), and is produced as a racemic mixture with a net optical rotation of zero. REVLIMID® (lenalidomide) is available in 5 mg, 10 mg, 15 mg and 25 mg capsules for oral administration. Each capsule contains lenalidomide as the active ingredient and the following inactive ingredients: lactose anhydrous, microcrystalline cellulose, croscarmellose sodium, and magnesium stearate. The 5 mg and 25 mg capsule shell contains gelatin, titanium dioxide and black ink. The 10 mg capsule shell contains gelatin, FD&C blue #2, yellow iron oxide, titanium dioxide and black ink. The 15 mg capsule shell contains gelatin, FD&C blue #2, titanium dioxide and black ink. The mechanism of action of lenalidomide remains to be fully characterized. Lenalidomide possesses antineoplastic, immunomodulatory and antiangiogenic properties. Lenalidomide inhibited the secretion of pro-inflammatory cytokines and increased the secretion of antiinflammatory cytokines from peripheral blood mononuclear cells. Lenalidomide inhibited cell proliferation with varying effectiveness (IC50s) in some but not all cell lines. Of cell lines tested, lenalidomide was effective in inhibiting growth of Namalwa cells (a human B cell lymphoma cell line with a deletion of one chromosome 5) but was much less effective in inhibiting growth of KG-1 cells (human myeloblastic cell line, also with a deletion of one chromosome 5) and other cell lines without chromosome 5 deletions. Lenalidomide inhibited the growth of multiple myeloma cells from patients, as well as MM.1S cells (a human multiple myeloma cell line), by inducing cell cycle arrest and apoptosis. Lenalidomide inhibited the expression of cyclooxygenase-2 (COX-2) but not COX-1 in vitro.
| Biological target: | Lenalidomide (CC-5013) is a TNF-α secretion inhibitor with IC50 of 13nM. |
| In vitro activity: | Natural killer T (NKT) cells are CD1d-restricted glycolipid reactive innate lymphocytes that play an important role in protection from pathogens and tumors. Antitumor properties of NKT cells are linked to their ability to secrete interferon-γ. NKT cells expanded in the presence of lenalidomide (LEN) had greater ability to secrete IFN-γ (Figure 2A). LEN also led to an increase in ligand-dependent induction of interferon-γ production by freshly isolated NKT cells in human peripheral blood mononuclear cells (PBMCs) (Figure 2D). Therefore, LEN leads to an increase in ligand-reactive interferon-γ secretion by human NKT cells in vitro. Reference: Blood. 2006;108(2):618-621. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1895497/ |
| In vivo activity: | As shown in Fig. 5A, lenalidomide therapy achieved a significant mantle cell lymphoma (MCL) tumor regression (*, P < 0.05), when compared with vehicle groups. Tumors isolated from control and drug-treated MCL-bearing mice revealed a 40% reduction in tumor burden in the lenalidomide-receiving group (Fig. 5B). As exemplified in Fig. 5B and C, a remarkable decrease in the mitotic index, together with the activation of caspase-3 and the tightening of blood vessels, was observed in tumors from lenalidomide-receiving mice. Lenalidomide treatment induced a substantial decrease of cyclin D1 and p27KIP1, which was associated with the phosphorylation of the CDK inhibitor at threonine 198 (Fig. 5B and C). Taken together, these data confirm the in vitro observation that lenalidomide is able to impede the growth of MCL tumors with high cyclin D1 and p27KIP1 contents, its antitumor effect being related to the cytosolic redistribution p27KIP1, and subsequent apoptosis induction. Reference: Clin Cancer Res. 2014 Jan 15;20(2):393-403. https://clincancerres.aacrjournals.org/content/20/2/393.long |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 51.5 | 198.64 | |
| DMF | 16.0 | 61.71 | |
| DMF:PBS (pH 7.2) (1:1) | 0.5 | 1.93 |
The following data is based on the product molecular weight 259.26 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. Moros A, Bustany S, Cahu J, Saborit-Villarroya I, Martínez A, Colomer D, Sola B, Roué G. Antitumoral activity of lenalidomide in in vitro and in vivo models of mantle cell lymphoma involves the destabilization of cyclin D1/p27KIP1 complexes. Clin Cancer Res. 2014 Jan 15;20(2):393-403. doi: 10.1158/1078-0432.CCR-13-1569. Epub 2013 Oct 31. PMID: 24178620. 2. Jian W, Levitt JM, Lerner SP, Sonpavde G. The preclinical activity of lenalidomide in indolent urothelial carcinoma. Anticancer Res. 2014 Jul;34(7):3383-9. PMID: 24982344. |
| In vitro protocol: | 1. Moros A, Bustany S, Cahu J, Saborit-Villarroya I, Martínez A, Colomer D, Sola B, Roué G. Antitumoral activity of lenalidomide in in vitro and in vivo models of mantle cell lymphoma involves the destabilization of cyclin D1/p27KIP1 complexes. Clin Cancer Res. 2014 Jan 15;20(2):393-403. doi: 10.1158/1078-0432.CCR-13-1569. Epub 2013 Oct 31. PMID: 24178620. 2. Jian W, Levitt JM, Lerner SP, Sonpavde G. The preclinical activity of lenalidomide in indolent urothelial carcinoma. Anticancer Res. 2014 Jul;34(7):3383-9. PMID: 24982344. |
| In vivo protocol: | 1. Moros A, Bustany S, Cahu J, Saborit-Villarroya I, Martínez A, Colomer D, Sola B, Roué G. Antitumoral activity of lenalidomide in in vitro and in vivo models of mantle cell lymphoma involves the destabilization of cyclin D1/p27KIP1 complexes. Clin Cancer Res. 2014 Jan 15;20(2):393-403. doi: 10.1158/1078-0432.CCR-13-1569. Epub 2013 Oct 31. PMID: 24178620. 2. Jian W, Levitt JM, Lerner SP, Sonpavde G. The preclinical activity of lenalidomide in indolent urothelial carcinoma. Anticancer Res. 2014 Jul;34(7):3383-9. PMID: 24982344. |
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8: Kunimasa K, Ueda T, Arita M, Maeda T, Hotta M, Ishida T. Drug-induced interstitial pneumonitis due to low-dose lenalidomide. Intern Med. 2012;51(9):1081-5. Epub 2012 Apr 29. Review. PubMed PMID: 22576392.
9: Komrokji RS, List AF. Lenalidomide for treatment of myelodysplastic syndromes. Curr Pharm Des. 2012;18(22):3198-203. Review. PubMed PMID: 22571699.
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