Lenalidomide (CC-5013)

製品コードS1029 バッチS102905

印刷

化学情報

Synonyms

CC-5013

Storage
(From the date of receipt)

3 years -20°C powder
1 years -80°C in solvent

化学式

C₁₃H₁₃N₃O₃

分子量

259.26

CAS No.

191732-72-6

Solubility (25°C)*

体外

DMSO

51 mg/mL (196.71 mM)

Water

Insoluble

Ethanol

Insoluble

体内（毎回新しく調製した物を用意してください）

Homogeneous suspension

CMC-NA

≥5mg/ml

Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

* <1 mg/ml means slightly soluble or insoluble.
* 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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明	Lenalidomide 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.
in vitro	Lenalidomide strongly induces IL-2 and sIL-2R production. This compound-induced tyrosine phosphorylation of CD28 on T cells is followed by a down-stream activation of NF-κB. ^[2] This compound 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 this compound resistance in H929 myeloma cell lines is accompanied by a reduction in CRBN, while in DF15R myeloma cells resistant to both pomalidomide and this chemical, CRBN protein is undetectable. ^[3] This chemical prevents induction of defects by down-regulating tumor cell inhibitory molecule expression. It prevents induction of tumor-induced T cell lytic synapse dysfunction. This compound 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. This 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 this chemical treatment compared to control treatments. Treatment of autologous CLL-T cell co-cultures with this agent reverses impaired CD8⁺ T cell lytic synapse formation and granzyme B trafficking. ^[4]
in vivo	The induction of angiogenesis by bFGF is significantly inhibited by oral treatment of Lenalidomide in a dose-dependent manner. This compound significantly decreases the percentage of vascularized area from 5.16% (control group) to 2.58% (50 mg/kg). It significantly reduces the calculated total MVL from 21.07 (control) to 8.11 (50 mg/kg). This chemical 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]

製品説明

Lenalidomide 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.

in vitro

Lenalidomide strongly induces IL-2 and sIL-2R production. This compound-induced tyrosine phosphorylation of CD28 on T cells is followed by a down-stream activation of NF-κB. ^[2]

This compound 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 this compound resistance in H929 myeloma cell lines is accompanied by a reduction in CRBN, while in DF15R myeloma cells resistant to both pomalidomide and this chemical, CRBN protein is undetectable. ^[3]

This chemical prevents induction of defects by down-regulating tumor cell inhibitory molecule expression. It prevents induction of tumor-induced T cell lytic synapse dysfunction. This compound 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. This 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 this chemical treatment compared to control treatments. Treatment of autologous CLL-T cell co-cultures with this agent reverses impaired CD8⁺ T cell lytic synapse formation and granzyme B trafficking. ^[4]

in vivo

The induction of angiogenesis by bFGF is significantly inhibited by oral treatment of Lenalidomide in a dose-dependent manner. This compound significantly decreases the percentage of vascularized area from 5.16% (control group) to 2.58% (50 mg/kg). It significantly reduces the calculated total MVL from 21.07 (control) to 8.11 (50 mg/kg). This chemical 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]

プロトコル(参考用のみ)

キナーゼアッセイ	Assay for inhibition of TNF synthesis by human PBMCs
キナーゼアッセイ	Human PBMCs from normal donors are obtained by Ficoll−Hypaque density centrifugation. Cells (10⁶ cells/mL) are cultured in RPMI supplemented with 10 AB+ serum, 2 mM l-glutamine, 100 U/mL penicillin, and 100 μg/mL streptomycin. Lenalidomide is dissolved in DMSO at 20 mg/mL; further dilution is done with culture medium. The final DMSO concentration in all assays including the controls is 0.25%. This compound is added to cells 1 hour prior to the addition of LPS. PBMCs (10⁶ cells/mL) are stimulated with 1 μg/mL of LPS from Salmonella minnesota R595. Cells, in triplicate, are incubated with LPS for 18−20 hours at 37 °C in 5% CO₂. Supernatants are then harvested and assayed for cytokine levels. In some experiments, supernatants are kept frozen at −70 °C until use. Cell viability is assayed by Trypan blue exclusion dye method. The concentration of TNFα in the culture supernatants is determined by ELISA. This chemical is assayed in a minimum of three separate experiments. Percent inhibition is determined as 100 × [1 − (cytokine(experimental)/cytokine(control))].
細胞アッセイ	細胞株	PBMCs
	濃度	13 nM
	反応時間
	実験の流れ	Cells were treated with various concentrations of this compound (5a).
動物実験	動物モデル	Adult male Sprague-Dawley rats bearing HUVECs cells
	投薬量	50 mg/kg and 250 mg/kg
	投与方法	Administered via i.p.

参考

https://pubmed.ncbi.nlm.nih.gov/10386948/
https://pubmed.ncbi.nlm.nih.gov/16255679/
https://pubmed.ncbi.nlm.nih.gov/22552008/

https://pubmed.ncbi.nlm.nih.gov/22547582/
https://pubmed.ncbi.nlm.nih.gov/15797261/
https://pubmed.ncbi.nlm.nih.gov/21968939/
https://pubmed.ncbi.nlm.nih.gov/19951978/
http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=74&abstractID=50171
http://cancerres.aacrjournals.org/cgi/content/short/72/8_MeetingAbstracts/1942?rss=1

+ 展开

カスタマーフィードバック

: Data from [Obesity , 2012, 20, 2174-85]

: , , Harvard Medical School

: , , Harvard Medical School

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Dual targeting PD-L1 and 4-1BB to overcome dendritic cell-mediated lenalidomide resistance in follicular lymphoma [ Signal Transduct Target Ther, 2025, 10(1):29]	PubMed: 39828715
IKAROS levels are associated with antigen escape in CD19- and CD22-targeted therapies for B-cell malignancies [ Nat Commun, 2025, 16(1):3800]	PubMed: 40268897
A patient-derived T cell lymphoma biorepository uncovers pathogenetic mechanisms and host-related therapeutic vulnerabilities [ Cell Rep Med, 2025, S2666-3791(25)00102-8]	PubMed: 40147445
Haploinsufficiency of miR-143 and miR-145 reveal targetable dependencies in resistant del(5q) myelodysplastic neoplasm [ Leukemia, 2025, 39(4):917-928]	PubMed: 40000845
The Prolonged Half-Life of the p53 Missense Variant R248Q Promotes Accumulation and Heterotetramer Formation with Wildtype p53 to Exert the Dominant-Negative Effect [ Cancer Res, 2025, 10.1158/0008-5472.CAN-24-1136]	PubMed: 40163352
Enhancing T cell cytotoxicity in multiple myeloma with bispecific αPD-L1 × αCD3 T cell engager-armed T cells and low-dose bortezomib therapy [ Biomed Pharmacother, 2025, 184:117878]	PubMed: 39891948
Rapid and high-throughput screening of proteolysis targeting chimeras using a dual-reporter system expressing fluorescence protein and luciferase [ BMC Biol, 2025, 23(1):51]	PubMed: 39985000
KAT/3BP: A Metabolism-Targeting Agent with Single and Combination Activity in Aggressive B-Cell Lymphomas [ Cancers (Basel), 2025, 17(12)2034]	PubMed: 40563683
Reposition of lenalidomide as a radiation protector based on LINCS gene expression signatures and its preclinical validation [ Sci Rep, 2025, 15(1):12955]	PubMed: 40234645
Lenalidomide regulates the CCL21/CCR7/ERK1/2 axis to inhibit migration and proliferation in diffuse large B-cell lymphoma [ Oncol Res, 2025, 33(1):199-212]	PubMed: 39735670

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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