CC-5013 (Lenalidomide)

카탈로그 번호S1029 배치:S102907

인쇄

기술 자료

화학식

C13H13N3O3
분자량 259.26 CAS 번호 191732-72-6
용해도 (25°C)* 시험관 내(In vitro) DMSO 51 mg/mL (196.71 mM)
Water Insoluble
Ethanol Insoluble
생체 내(In Vivo) (개별적으로 순서대로 용매를 제품에 첨가하십시오.)
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.
Clear solution
5%DMSO 40%PEG300 5%Tween80 50%ddH2O

Selleck 연구소에서 검증했습니다. 이 제형에 대한 조정이 필요한 경우 맞춤형 테스트를 위해 당사 영업팀에 문의하십시오.

 10.000mg/ml (38.57mM) Taking the 1 mL working solution as an example, add 50 μL of 200 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to make it clear; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 
* <1 mg/ml은 약간 용해되거나 불용해됨을 의미합니다.
* Selleck은 모든 화합물의 용해도를 자체적으로 테스트하며, 실제 용해도는 게시된 값과 약간 다를 수 있습니다. 이는 정상적인 현상이며, 약간의 배치 간 변동으로 인해 발생합니다.
* 실온 배송 (안정성 테스트 결과 이 제품은 냉각 조치 없이 배송될 수 있음을 보여줍니다.)

원액 준비

생물학적 활성

설명 Lenalidomide는 PBMC에서 13 nM의 IC50을 갖는 TNF-alpha 분비 억제제입니다. Lenalidomide(CC-5013)는 ubiquitin E3 ligase cereblon(CRBN)의 리간드이며, CRBN-CRL4 ubiquitin ligase에 의해 두 가지 림프구 전사 인자인 IKZF1 및 IKZF3의 선택적 유비퀴틴화 및 분해를 유발합니다. Lenalidomide는 cleaved caspase-3 발현을 촉진하고 VEGF 발현을 억제하며 apoptosis를 유도합니다.
표적
CRBN VEGF TNF-α
(PBMCs)
13 nM
시험관 내(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.

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.

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.

생체 내(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.

프로토콜 (참조)

키나아제 분석:

[1]
  • 인간 PBMC에 의한 TNF-alpha 합성 억제 분석

    정상 공여자의 인간 PBMC는 Ficoll−Hypaque 밀도 구배 원심분리법을 통해 얻습니다. 세포(106 cells/mL)는 10% AB+ 혈청, 2 mM l-글루타민, 100 U/mL 페니실린 및 100 μg/mL 스트렙토마이신이 보충된 RPMI에서 배양됩니다. CC-5013 (Lenalidomide)는 DMSO에 20 mg/mL 농도로 용해하며, 추가 희석은 배양 배지를 사용하여 수행합니다. 대조군을 포함한 모든 분석에서 최종 DMSO 농도는 0.25%입니다. 이 화합물은 LPS를 첨가하기 1시간 전에 세포에 추가됩니다. PBMC(106 cells/mL)는 Salmonella minnesota R595 유래 1 μg/mL의 LPS로 자극합니다. 3중으로 준비된 세포는 5% CO2 환경의 37 °C에서 18−20시간 동안 LPS와 함께 배양됩니다. 이후 상층액을 수확하여 사이토카인 수치를 분석합니다. 일부 실험에서는 상층액을 사용하기 전까지 −70 °C에서 냉동 보관합니다. 세포 생존력은 Trypan blue 배제 염색법으로 분석합니다. 배양 상층액 내 TNF-alpha의 농도는 ELISA를 통해 결정합니다. 이 화학 물질은 최소 3회의 독립적인 실험에서 분석됩니다. 억제율은 100 × [1 − (사이토카인(실험군)/사이토카인(대조군))]으로 결정합니다.
동물 연구:

[5]
  • 동물 모델

    Adult male Sprague-Dawley rats bearing HUVECs cells

  • 용량

    50 mg/kg and 250 mg/kg

  • 투여

    Administered via i.p.

참조

  • 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

고객 제품 검증

<p> </p><p>Effect of lenalidomide treatment (50 mg/kg/day, p.o. for 3 days) on expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), Fas, Fas ligand (FasL), and cleaved caspase-3 in myocardium from lean and ob/ob mice. (a) Representative gel blots of TNF-α, IL-6, Fas, FasL, cleaved caspase-3 and α-Tubulin (as loading control) using specific antibodies. (b) TNF-α.</p>

데이터 출처 [ Obesity , 2012 , 20, 2174-85 ]

<p>MM1S were treated with AT9283 (0.125 μM), lenalidomide (2 μM) or combined therapy for 72 hours. Annexin/PI staining show increased apoptosis associated with caspase 8 and PARP cleavage after 18 and 36 hours of exposure. B) MM.1S cells were treated with AT9283 (0.125 μM), lenalidomide (2 μM) or combined therapy for 4 hours. Whole lysates were immunoblotted with indicated antibodies</p><div><div> </div></div><p> </p>

, , Harvard Medical School

<p>MM.1S cells were cultured for 48 hours in the presence or absence of BMSCs with control media, AT9283, lenalidomide or  AT9283 plus lenalidomide. Cell proliferation was assessed by 3H-TdR uptake (left). MM.1S cells were cultured in the absence or presence of BMSCs and treated for 4 hours with drugs alone or in combination. Whole lysates were immunoblotted with indicated antibodies.</p><div><div> </div></div><p> </p>

, , Harvard Medical School

MM1S were treated with AT9283 (0.125 μM), lenalidomide (2 μM) or combined therapy for 72 hours. Annexin/PI staining show increased apoptosis associated with caspase 8 and PARP cleavage after 18 and 36 hours of exposure.

데이터 출처 [ , , Clin Cancer Res, 2011, 17(10): 3259–71 ]

Selleck's CC-5013 (Lenalidomide) 인용됨 190 출판물

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 Wild-Type p53 to Exert the Dominant-Negative Effect [ Cancer Research, 2025, 1978-1996] PubMed: 40163352
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

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