Lenalidomide (CC-5013)

For research use only.

Catalog No.S1029

102 publications

Lenalidomide (CC-5013) Chemical Structure

CAS No. 191732-72-6

Lenalidomide (CC-5013) is a TNF-α secretion inhibitor with IC50 of 13 nM in PBMCs. Lenalidomide (CC-5013) is a ligand of ubiquitin E3 ligase cereblon (CRBN), and it causes selective ubiquitination and degradation of two lymphoid transcription factors, IKZF1 and IKZF3, by the CRBN-CRL4 ubiquitin ligase. Lenalidomide promotes cleaved caspase-3 expression and inhibit VEGF expression and induces apoptosis.

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Selleck's Lenalidomide (CC-5013) has been cited by 102 publications

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Biological Activity

Description Lenalidomide (CC-5013) is a TNF-α secretion inhibitor with IC50 of 13 nM in PBMCs. Lenalidomide (CC-5013) is a ligand of ubiquitin E3 ligase cereblon (CRBN), and it causes selective ubiquitination and degradation of two lymphoid transcription factors, IKZF1 and IKZF3, by the CRBN-CRL4 ubiquitin ligase. Lenalidomide promotes cleaved caspase-3 expression and inhibit VEGF expression and induces apoptosis.
Targets
CRBN [3]
()
VEGF [1]
()
TNF-α [1]
(PBMCs)
13 nM
In vitro

Lenalidomide strongly induces IL-2 and sIL-2R production. Lenalidomide-induced tyrosine phosphorylation of CD28 on T cells is followed by a down-stream activation of NF-κB. [2] Lenalidomide and pomalidomide inhibits autoubiquitination of CRBN in HEK293 T cells expressing thalidomide-binding competent wild-type CRBN, but not thalidomide-binding defective CRBN(YW/AA). Overexpression of CRBN wild-type protein, but not CRBN(YW/AA) mutant protein, in KMS12 myeloma cells, amplifies pomalidomide-mediated reductions in c-myc and IRF4 expression and increases in p21(WAF-1) expression. Long-term selection for Lenalidomide resistance in H929 myeloma cell lines is accompanied by a reduction in CRBN, while in DF15R myeloma cells resistant to both pomalidomide and Lenalidomide, CRBN protein is undetectable. [3] Lenalidomide prevents induction of defects by down-regulating tumor cell inhibitory molecule expression. Lenalidomide prevents induction of tumor-induced T cell lytic synapse dysfunction. Lenalidomide treatment blocks CLL cell-induced T cell actin synapse dysfunction, mimicks antibody blockade, and down-regulates expression of CLL inhibitory ligands and their receptors on T cells. Lenalidomide treatment prevents tumor-induced immune suppression in FL, DLBCL, HL, MM, SCC, and OC and down-regulates immunosuppressive ligand expression on all tumor cells examined. CTL killing function significantly increases following antibody blockade of CLL inhibitory ligands or Lenalidomide treatment compared to control treatments. Treatment of autologous CLL-T cell co-cultures with Lenalidomide reverses impaired CD8+ T cell lytic synapse formation and granzyme B trafficking. [4]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
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CD34+ progenitor cells NHvVXY9HfW6ldHnvckBie3OjeR?= M2mxd|E1KGSjeYO= MXnE[YNz\WG|ZTDpckBmenm2aILvbYQh\GmoZnXy[Y51cWG2aX;uJI9nKEOGM{SrJJBzd2enbnn0c5Ih[2WubIOg[pJwdSCveXXsc4R6e3CuYYP0bYMhe3mwZILvcYUh\GWuKEXxLUBx[XSrZX70JIF{e2W|c3XkJIF{KEOGM{[g[ZhxemW|c3nvckBi\nSncjCxOEBl[Xm| MmTCQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTd3N{[5NlQoRjF5NUe2PVI1RC:jPh?=
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CD34+ progenitor cells MXzGeY5kfGmxbjDhd5NigQ>? MoPXNVQh\GG7cx?= MX\E[YNz\WG|ZTDpckBmenm2aILvbYQh\GmoZnXy[Y51cWG2aX;uJI9nKEOGM{SrJJBzd2enbnn0c5Ih[2WubIOg[pJwdSCveXXsc4R6e3CuYYP0bYMhe3mwZILvcYUh\GWuKEXxLUBx[XSrZX70JIF{e2W|c3XkJIF{KGeueXPvdIhwemmwIFGg[ZhxemW|c3nvckBi\nSncjCxOEBl[Xm| NGO4bJM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zN{W3OlkzPCd-MUe1O|Y6OjR:L3G+
CD34+ progenitor cells MnT6S5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? M3Xke|E1KGSjeYO= MkXmTY5pcWKrdHnvckBw\iClZXzsJJBzd2yrZnXyZZRqd25ib3[gR2Q{PCticILv[4VvcXSxcjDj[YxteyCocn;tJI16\WyxZInzdIxie3SrYzDzfY5lem:vZTDk[YwpPXFrIIDheIlmdnRiYX\0[ZIhOTRiZHH5dy=> M2W3fVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF5NUe2PVI1Lz5zN{W3OlkzPDxxYU6=
CD34+ progenitor cells NF35XJRIem:5dHigbY5pcWKrdHnvckBie3OjeR?= NGfBNXQyPCCmYYnz NYezWXhzT3Kxd4ToJIlvcGmkaYTpc44hd2ZiQ1SzOEsheHKxZ3XubZRweiClZXzsd{Bnem:vIH7vck1l\WxqNYGpJI16\WyxZInzdIxie3SrYzDzfY5lem:vZTDwZZRq\W62IHHmeIVzKDF2IHThfZM> MkXOQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTd3N{[5NlQoRjF5NUe2PVI1RC:jPh?=
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EC9706 MXHBcpRqeHKxbHnm[ZJifGm4ZTDhd5NigQ>? M1PEUFE2OCC3Zz;tUC=> MUe0PEBpenN? Mo\rRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6|dDDoeY1idiCHQ{m3NFYh[2WubIOgZZQhOTVyIIXnM41NKGGodHXyJFQ5KGi{czDifUBES0tvODDhd5NigQ>? NXfr[Jc4RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMki3OVcxPjZpPkK4O|U4ODZ4PD;hQi=>

... Click to View More Cell Line Experimental Data

Assay
Methods Test Index PMID
Western blot
phospho-IKKβ / IKKβ ; 

PubMed: 22698399     


Western blot analysis of the indicated proteins following treatment of OCI-Ly10 cells with lenalidomide (10μM) for the indicated times. 

MDM2 / p-MDM2 / p-p53 / p53 ; 

PubMed: 22525275     


(a) Treatment with lenalidomide (Len) increases phosphorylation of ser46 and thr55 of p53. Namalwa cells were treated with lenalidomide at various concentrations for 48 hours, the cell lysates were prepared and analyzed by Western blotting with antibodies to MDM2, phospho-ser46 of p53, phospho-thr55 of p53 and total p53. (b) Treatment with lenalidomide increases phosphorylation of MDM2 at ser166 and ser186. Namalwa cells were treated with lenalidomide at various concentrations for 48 hours, the cell lysates were immunoprecipitated using anti-MDM2 antibody. The samples were separated by SDS PAGE and then Western blotted with either anti-MDM2 or antibodies specific to phospho-ser166, phospho-ser186, total phospho-serine or total phospho-threonine of MDM2 as indicated. 

22698399 22525275
Growth inhibition assay
Cell viability; 

PubMed: 22698399     


Viability (MTS assay) of ABC and GCB DLBCL cell lines treated with lenalidomide for 4 days. Error bars show the standard error of the mean (SEM) of triplicates.

22698399
In vivo The induction of angiogenesis by bFGF is significantly inhibited by oral treatment of Lenalidomide in a dose-dependent manner. Lenalidomide significantly decreases the percentage of vascularized area from 5.16% (control group) to 2.58% (50 mg/kg). Lenalidomide significantly reduces the calculated total MVL from 21.07 (control) to 8.11 (50 mg/kg). Lenalidomide significantly inhibites HUVEC migration through the fibronectin-coated membranes towards 0.1 ng/mL of bFGF at 100 μM, 1 ng/mL of VEGF at concentrations of 10 μM and 100 μM. [5]

Protocol

Animal Research:

[5]

- Collapse
  • Animal Models: Adult male Sprague-Dawley rats bearing HUVECs cells
  • Dosages: 50 mg/kg and 250 mg/kg
  • Administration: Administered via i.p.
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 52 mg/mL (200.57 mM)
Water Insoluble
Ethanol Insoluble
In vivo Add solvents to the product individually and in order(Data is from Selleck tests instead of citations):
5% DMSO+40%PEG 300+5%Tween80+ddH2O
For best results, use promptly after mixing.
10mg/mL

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 259.26
Formula

C13H13N3O3

CAS No. 191732-72-6
Storage powder
in solvent
Synonyms N/A
Smiles C1CC(=O)NC(=O)C1N2CC3=C(C2=O)C=CC=C3N

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
Dosage mg/kg Average weight of animals g Dosing volume per animal ul Number of animals
Step 2: Enter the in vivo formulation ()
% DMSO % % Tween 80 % ddH2O
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Bio Calculators

Molarity Calculator

Molarity Calculator

Calculate the mass, volume or concentration required for a solution. The Selleck molarity calculator is based on the following equation:

Mass (mg) = Concentration (mM) × Volume (mL) × Molecular Weight (g/mol)

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*When preparing stock solutions, please always use the batch-specific molecular weight of the product found on the via label and MSDS / COA (available on product pages).

Dilution Calculator

Dilution Calculator

Calculate the dilution required to prepare a stock solution. The Selleck dilution calculator is based on the following equation:

Concentration (start) x Volume (start) = Concentration (final) x Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2 ( Input Output )

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* When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and MSDS / COA (available online).

The Serial Dilution Calculator Equation

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  • Computed Result

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    C2=C1/X C2: LOG(C2):
    C3=C2/X C3: LOG(C3):
    C4=C3/X C4: LOG(C4):
    C5=C4/X C5: LOG(C5):
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    C8=C7/X C8: LOG(C8):
Molecular Weight Calculator

Molecular Weight Calculator

Enter the chemical formula of a compound to calculate its molar mass and elemental composition:

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Tip: Chemical formula is case sensitive. C10H16N2O2 c10h16n2o2

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Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molecular mass (molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

Molarity Calculator

Mass Concentration Volume Molecular Weight

Clinical Trial Information

NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT04669171 Not yet recruiting Biological: EO2463|Drug: lenalidomide|Biological: rituximab Follicular Lymphoma|Marginal Zone Lymphoma Enterome April 15 2021 Phase 1|Phase 2
NCT03660072 Not yet recruiting Other: Non-Interventional Multiple Myeloma Bristol-Myers Squibb January 31 2021 --
NCT04191616 Recruiting Drug: Carfilzomib|Drug: Dexamethasone|Drug: Pomalidomide Relapsed or Refractory Multiple Myeloma Amgen August 6 2020 Phase 2
NCT04467281 Recruiting Drug: 89Zr-DFO-daratumumab|Diagnostic Test: PET/CT Multiple Myeloma Memorial Sloan Kettering Cancer Center June 30 2020 Phase 2

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

Tel: +1-832-582-8158 Ext:3

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Frequently Asked Questions

  • Question 1:

    What is the formulation for mouse injection(i.p.)?

  • Answer:

    This paper has the information you need: http://link.springer.com/article/10.1208/s12248-012-9401-2. Add lenalidomide to the appropriate volume of sterile phosphate-buffered saline (PBS) containing 1% hydrochloric acid (HCl). the pH of this preparation was adjusted to 7.0–7.6 using sodium hydroxide and sterile filtered using a 0.22 μm Steriflip filter.

  • Question 2:

    what is the procedure to resuspend this compound?

  • Answer:

    You can resuspend this compund by DMSO, the solubility is about 52 mg/mL (200.57 mM). For in vivo study, you can prepare the working solution with the vehicle of: 30% PEG400/0.5% Tween80/5% propylene glycol for oral administration.

E3 ligase Ligand Inhibitors with Unique Features

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID