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Lenalidomide

別名: CC-5013 中文名稱：來那度胺

Lenalidomide是一種TNF-α分泌抑制劑，在PBMCs中IC50為13 nM。Lenalidomide是 ubiquitin E3 ligase cereblon (CRBN) 的配體，它通過CRBN-CRL4泛素連接酶引起兩個淋巴樣轉(zhuǎn)錄因子IKZF1和IKZF3的選擇性泛素化和降解。Lenalidomide 可促進 cleaved caspase-3 的表達、抑制 VEGF 的表達并誘導(dǎo)凋亡。

Lenalidomide Chemical Structure

Lenalidomide Chemical Structure

CAS: 191732-72-6

規(guī)格 價格 庫存 購買數(shù)量
10mM (1mL in DMSO) 794.43 現(xiàn)貨
10mg 573.3 現(xiàn)貨
50mg 1190.39 現(xiàn)貨
500mg 3595.41 現(xiàn)貨
1g 5487.3 現(xiàn)貨
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Lenalidomide相關(guān)產(chǎn)品

細胞實驗數(shù)據(jù)示例

細胞系 實驗類型 給藥濃度 孵育時間 活性描述 文獻信息
DF15 Function assay 0.1 to 10 uM 5 hrs Induction of cereblon-mediated aiolos degradation in human DF15 cells at 0.1 to 10 uM after 5 hrs by immunoblot analysis 28425720
OPM2 Function assay 0.1 to 10 uM 5 hrs Induction of cereblon-mediated aiolos degradation in human OPM2 cells at 0.1 to 10 uM after 5 hrs by immunoblot analysis 28425720
DF15 Function assay 0.1 to 10 uM 5 hrs Induction of cereblon-mediated ikaros degradation in human DF15 cells at 0.1 to 10 uM after 5 hrs by immunoblot analysis 28425720
OPM2 Function assay 0.1 to 10 uM 5 hrs Induction of cereblon-mediated ikaros degradation in human OPM2 cells at 0.1 to 10 uM after 5 hrs by immunoblot analysis 28425720
EC9706 Antiproliferative assay 150 ug/mL 48 hrs Antiproliferative activity against human EC9706 cells at 150 ug/mL after 48 hrs by CCK-8 assay 28757066
DF15 Function assay 4 hrs Induction of CRL4/CRBN ubiquitin ligase-mediated aiolos degradation in human DF15 cells expressing pLOC-ePL-tagged aiolos after 4 hrs by luminescence based beta-galactosidase enzyme fragmentation complementation assay, EC50 = 0.053 μM. 28358507
DF15 Function assay 4 hrs Induction of cereblon-mediated ikaros degradation in human DF15 cells expressing ePL-tagged ikaros after 4 hrs by luminometric analysis, EC50 = 0.067 μM. 28425720
DF15 Function assay 4 hrs Induction of cereblon-mediated aiolos degradation in human DF15 cells expressing ePL-tagged aiolos after 4 hrs by luminometric analysis, EC50 = 0.087 μM. 28425720
T-cells Function assay 2 to 3 days Inhibition of IL-2 production in human T cells measured after 2 to 3 days by ELISA, EC50 = 0.15 μM. 23168019
NAMALWA Antiproliferative assay 72 hrs Antiproliferative activity against human NAMALWA cells assessed as inhibition of [3H]thymidine incorporation after 72 hrs by scintillation counting, IC50 = 0.36 μM. 23168019
CD34+ progenitor cells Function assay 14 days Decrease in erythroid differentiation of CD34+ progenitor cells from myelodysplastic syndrome del(5q) patient assessed as CD36 expression after 14 days 17576924
CD34+ progenitor cells Function assay 14 days Decrease in myeloid differentiation of CD34+ progenitor cells from myelodysplastic syndrome del(5q) patient assessed as CD33 expression after 14 days 17576924
CD34+ progenitor cells Function assay 14 days Decrease in erythroid differentiation of CD34+ progenitor cells from myelodysplastic syndrome del(5q) patient assessed as glycophorin A expression after 14 days 17576924
CD34+ progenitor cells Growth inhibition assay 14 days Inhibition of cell proliferation of CD34+ progenitor cells from myelodysplastic syndrome del(5q) patient after 14 days 17576924
CD34+ progenitor cells Growth inhibition assay 14 days Growth inhibition of CD34+ progenitor cells from non-del(5q) myelodysplastic syndrome patient after 14 days 17576924
A2780 Growth Inhibition Assay IC50=35.3601 μM SANGER
ECC10 Growth Inhibition Assay IC50=34.7443 μM SANGER
NKM-1 Growth Inhibition Assay IC50=32.9568 μM SANGER
NCI-H526 Growth Inhibition Assay IC50=32.683 μM SANGER
SK-OV-3 Growth Inhibition Assay IC50=31.6755 μM SANGER
C8166 Growth Inhibition Assay IC50=31.2274 μM SANGER
JEG-3 Growth Inhibition Assay IC50=31.1614 μM SANGER
KYSE-520 Growth Inhibition Assay IC50=30.8839 μM SANGER
HCC70 Growth Inhibition Assay IC50=30.7346 μM SANGER
SW1990 Growth Inhibition Assay IC50=30.33 μM SANGER
WM-115 Growth Inhibition Assay IC50=30.3099 μM SANGER
MV-4-11 Growth Inhibition Assay IC50=29.7317 μM SANGER
ABC-1 Growth Inhibition Assay IC50=29.6974 μM SANGER
HDLM-2 Growth Inhibition Assay IC50=28.2026 μM SANGER
HCC2218 Growth Inhibition Assay IC50=25.5407 μM SANGER
HuP-T3 Growth Inhibition Assay IC50=25.4009 μM SANGER
CTV-1 Growth Inhibition Assay IC50=25.0149 μM SANGER
SBC-1 Growth Inhibition Assay IC50=23.8696 μM SANGER
ES3 Growth Inhibition Assay IC50=22.6963 μM SANGER
RS4-11 Growth Inhibition Assay IC50=22.1563 μM SANGER
MOLT-4 Growth Inhibition Assay IC50=20.5759 μM SANGER
MSTO-211H Growth Inhibition Assay IC50=20.3573 μM SANGER
LN-405 Growth Inhibition Assay IC50=19.9076 μM SANGER
TE-1 Growth Inhibition Assay IC50=17.9968 μM SANGER
IGROV-1 Growth Inhibition Assay IC50=17.783 μM SANGER
HSC-4 Growth Inhibition Assay IC50=17.6601 μM SANGER
EM-2 Growth Inhibition Assay IC50=17.143 μM SANGER
H9 Growth Inhibition Assay IC50=16.626 μM SANGER
ACN Growth Inhibition Assay IC50=16.5297 μM SANGER
SK-MEL-24 Growth Inhibition Assay IC50=16.4652 μM SANGER
K5 Growth Inhibition Assay IC50=16.1486 μM SANGER
DEL Growth Inhibition Assay IC50=15.499 μM SANGER
COLO-684 Growth Inhibition Assay IC50=15.3979 μM SANGER
PANC-08-13 Growth Inhibition Assay IC50=14.9108 μM SANGER
HAL-01 Growth Inhibition Assay IC50=14.5796 μM SANGER
LCLC-103H Growth Inhibition Assay IC50=14.4892 μM SANGER
SW620 Growth Inhibition Assay IC50=14.2473 μM SANGER
A2058 Growth Inhibition Assay IC50=13.8199 μM SANGER
HOP-62 Growth Inhibition Assay IC50=13.48 μM SANGER
T47D Growth Inhibition Assay IC50=13.2099 μM SANGER
RPMI-8226 Growth Inhibition Assay IC50=12.6241 μM SANGER
SK-MEL-28 Growth Inhibition Assay IC50=11.9764 μM SANGER
KASUMI-1 Growth Inhibition Assay IC50=11.571 μM SANGER
HCC1806 Growth Inhibition Assay IC50=11.4467 μM SANGER
HMV-II Growth Inhibition Assay IC50=10.0172 μM SANGER
BV-173 Growth Inhibition Assay IC50=8.67585 μM SANGER
SK-NEP-1 Growth Inhibition Assay IC50=7.89512 μM SANGER
BT-549 Growth Inhibition Assay IC50=6.21849 μM SANGER
EoL-1-cell Growth Inhibition Assay IC50=4.10515 μM SANGER
JAR Growth Inhibition Assay IC50=2.97001 μM SANGER
L-363 Growth Inhibition Assay IC50=2.92212 μM SANGER
LB771-HNC Growth Inhibition Assay IC50=2.15038 μM SANGER
KY821 Growth Inhibition Assay IC50=35.7681 μM SANGER
MKN1 Growth Inhibition Assay IC50=36.2137 μM SANGER
EKVX Growth Inhibition Assay IC50=37.4212 μM SANGER
EW-16 Growth Inhibition Assay IC50=38.3885 μM SANGER
CTB-1 Growth Inhibition Assay IC50=39.7789 μM SANGER
COR-L105 Growth Inhibition Assay IC50=40.4746 μM SANGER
NCI-SNU-5 Growth Inhibition Assay IC50=41.2069 μM SANGER
Mewo Growth Inhibition Assay IC50=41.9871 μM SANGER
BCPAP Growth Inhibition Assay IC50=43.7917 μM SANGER
KARPAS-45 Growth Inhibition Assay IC50=44.2776 μM SANGER
NCI-H1693 Growth Inhibition Assay IC50=46.6986 μM SANGER
H-EMC-SS Growth Inhibition Assay IC50=48.3224 μM SANGER
697 Growth Inhibition Assay IC50=50.3545 μM SANGER
KP-N-YS Growth Inhibition Assay IC50=52.3142 μM SANGER
NCI-H1304 Growth Inhibition Assay IC50=52.7024 μM SANGER
NOS-1 Growth Inhibition Assay IC50=52.8559 μM SANGER
NCI-H2342 Growth Inhibition Assay IC50=53.0508 μM SANGER
KYSE-270 Growth Inhibition Assay IC50=53.6364 μM SANGER
LU-135 Growth Inhibition Assay IC50=55.1853 μM SANGER
OE33 Growth Inhibition Assay IC50=55.818 μM SANGER
ML-2 Growth Inhibition Assay IC50=55.9489 μM SANGER
KMOE-2 Growth Inhibition Assay IC50=56.2893 μM SANGER
Daoy Growth Inhibition Assay IC50=56.3204 μM SANGER
KNS-62 Growth Inhibition Assay IC50=57.0142 μM SANGER
NBsusSR Growth Inhibition Assay IC50=57.5705 μM SANGER
UACC-257 Growth Inhibition Assay IC50=58.6264 μM SANGER
LU-139 Growth Inhibition Assay IC50=58.826 μM SANGER
CAL-85-1 Growth Inhibition Assay IC50=58.8643 μM SANGER
NCI-H720 Growth Inhibition Assay IC50=58.8942 μM SANGER
MLMA Growth Inhibition Assay IC50=59.091 μM SANGER
A3-KAW Growth Inhibition Assay IC50=59.2809 μM SANGER
Ramos-2G6-4C10 Growth Inhibition Assay IC50=59.6287 μM SANGER
A388 Growth Inhibition Assay IC50=60.449 μM SANGER
LAMA-84 Growth Inhibition Assay IC50=60.9905 μM SANGER
GCT Growth Inhibition Assay IC50=61.0786 μM SANGER
K-562 Growth Inhibition Assay IC50=61.5333 μM SANGER
NCI-H1666 Growth Inhibition Assay IC50=61.875 μM SANGER
NCI-H1993 Growth Inhibition Assay IC50=63.4043 μM SANGER
NCI-H358 Growth Inhibition Assay IC50=65.0121 μM SANGER
NB6 Growth Inhibition Assay IC50=65.988 μM SANGER
HCE-T Growth Inhibition Assay IC50=67.0798 μM SANGER
DOK Growth Inhibition Assay IC50=67.4948 μM SANGER
HT-1376 Growth Inhibition Assay IC50=69.8314 μM SANGER
NEC8 Growth Inhibition Assay IC50=70.1243 μM SANGER
G-402 Growth Inhibition Assay IC50=70.9395 μM SANGER
GR-ST Growth Inhibition Assay IC50=71.172 μM SANGER
QIMR-WIL Growth Inhibition Assay IC50=71.4434 μM SANGER
CHP-212 Growth Inhibition Assay IC50=71.965 μM SANGER
KU812 Growth Inhibition Assay IC50=72.9702 μM SANGER
Becker Growth Inhibition Assay IC50=73.1489 μM SANGER
ChaGo-K-1 Growth Inhibition Assay IC50=74.7486 μM SANGER
A498 Growth Inhibition Assay IC50=74.9308 μM SANGER
NCI-H69 Growth Inhibition Assay IC50=75.7663 μM SANGER
NCI-H209 Growth Inhibition Assay IC50=78.6147 μM SANGER
CAL-33 Growth Inhibition Assay IC50=78.9939 μM SANGER
COLO-680N Growth Inhibition Assay IC50=79.1007 μM SANGER
D-283MED Growth Inhibition Assay IC50=79.812 μM SANGER
ATN-1 Growth Inhibition Assay IC50=81.1187 μM SANGER
NCI-N87 Growth Inhibition Assay IC50=81.7296 μM SANGER
MHH-NB-11 Growth Inhibition Assay IC50=81.8849 μM SANGER
HEL Growth Inhibition Assay IC50=82.4134 μM SANGER
NB69 Growth Inhibition Assay IC50=83.0033 μM SANGER
MPP-89 Growth Inhibition Assay IC50=83.2575 μM SANGER
COLO-829 Growth Inhibition Assay IC50=85.4912 μM SANGER
ONS-76 Growth Inhibition Assay IC50=85.7908 μM SANGER
EW-3 Growth Inhibition Assay IC50=86.2032 μM SANGER
EW-11 Growth Inhibition Assay IC50=86.4336 μM SANGER
SW900 Growth Inhibition Assay IC50=87.2053 μM SANGER
MOLT-13 Growth Inhibition Assay IC50=87.2243 μM SANGER
HuP-T4 Growth Inhibition Assay IC50=91.0405 μM SANGER
HCC1419 Growth Inhibition Assay IC50=91.6374 μM SANGER
CAL-72 Growth Inhibition Assay IC50=92.0219 μM SANGER
Mo-T Growth Inhibition Assay IC50=92.7697 μM SANGER
OC-314 Growth Inhibition Assay IC50=92.8821 μM SANGER
BHT-101 Growth Inhibition Assay IC50=93.1 μM SANGER
EW-18 Growth Inhibition Assay IC50=93.8462 μM SANGER
TE-12 Growth Inhibition Assay IC50=94.3055 μM SANGER
MDA-MB-361 Growth Inhibition Assay IC50=96.0516 μM SANGER
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生物活性

產(chǎn)品描述 Lenalidomide是一種TNF-α分泌抑制劑，在PBMCs中IC50為13 nM。Lenalidomide是 ubiquitin E3 ligase cereblon (CRBN) 的配體，它通過CRBN-CRL4泛素連接酶引起兩個淋巴樣轉(zhuǎn)錄因子IKZF1和IKZF3的選擇性泛素化和降解。Lenalidomide 可促進 cleaved caspase-3 的表達、抑制 VEGF 的表達并誘導(dǎo)凋亡。
靶點
CRBN [3] VEGF [1] TNF-α [1]
(PBMCs)
13 nM
體外研究(In Vitro)
體外研究活性

CC-5013強誘導(dǎo)IL-2和sIL-2R產(chǎn)量。CC-5013作用于T細胞，誘導(dǎo)CD28的酪氨酸磷酸化，隨后下調(diào)NF-κB的激活。[2]

Lenalidomide和Pomalidomide作用于表達與Thalidomide結(jié)合野生型CRBN的，而不是Thalidomide結(jié)合缺陷型CRBN(YW/AA)的HEK293 T細胞，抑制CRBN自體泛素化。KMS12多發(fā)性骨髓瘤細胞中，CRBN野生型蛋白而不是CRBN(YW/AA) 突變型蛋白的過表達, 放大Pomalidomide調(diào)節(jié)的c-myc和IRF4表達降低和p21(WAF-1) 表達增高。H929 多發(fā)性骨髓瘤細胞系中長期抗Lenalidomide 的選擇性與CRBN降低相關(guān),然而抗Pomalidomide和 Lenalidomide的DF15R多發(fā)性骨髓瘤 中, 檢測不到CRBN蛋白。[3]

Lenalidomide通過下調(diào)腫瘤細胞抑制性分子表達而抑制缺陷發(fā)生。Lenalidomide防止腫瘤誘導(dǎo)的T細胞裂解功能障礙發(fā)生。Lenalidomide 作用于T細胞，抑制慢性淋巴細胞性白血病（CLL）細胞誘導(dǎo)的T細胞肌動蛋白突觸功能受損, 且下調(diào)CLL抑制配體及其他受體的表達。Lenalidomide 作用于FL, DLBCL, HL, MM, SCC,和 OC，抑制腫瘤誘導(dǎo)的免疫抑制，且作用于所有檢測的腫瘤細胞時,下調(diào)免疫抑制配體表達。[4]
細胞實驗 細胞系 良性或惡性 B (CLL)細胞, RPMI8226 MM 細胞
濃度 1 μM或5 nM
孵育時間 24小時
方法

使用CellTracker Blue CMAC對良性或惡性B (CLL)細胞(2 × 106)進行染色， 然后使用2 μg/mL金黃色葡萄球菌超抗原(sAg) (SEA 和 SEB) 在37oC下進行脈沖處理30分鐘。B細胞和等量T細胞(從原代共培養(yǎng)中純化的)按200 × g轉(zhuǎn)速離心5分鐘，然后與CD8+ T 細胞在37oC下溫育10分鐘，或者與 CD3+ T細胞溫育20分鐘。使用細胞收集器使細胞轉(zhuǎn)移到顯微鏡載玻片上，然后在室溫下和3% 溶于PBS的甲醛混合15分鐘。在完全培養(yǎng)基中加入終濃度為1 μM的Lenalidomide。對照組則使用DMSO處理細胞。
實驗圖片 檢測方法 檢測指標(biāo) 實驗圖片 PMID
Western blot MDM2 / p-MDM2 / p-p53 / p53 phospho-IKKβ / IKKβ 22525275
Growth inhibition assay Cell viability 22698399
體內(nèi)研究(In Vivo)
體內(nèi)研究活性

口服處理Lenalidomide，顯著抑制bFGF誘導(dǎo)的血管生成，這種作用存在劑量依賴性。Lenalidomide 顯著降低血管面積百分數(shù)，從對照組的5.16%降低到實驗組的2.58（50 mg/kg劑量處理）和 1.69（250 mg/kg 劑量處理）。 Lenalidomide 顯著降低全部MVL，從對照組的21.07降低到實驗組的8.11（50 mg/kg劑量處理）和1.90（250 mg/kg劑量處理）。[5]
動物實驗 Animal Models 攜帶HUVECs細胞的成年雄性Sprague–Dawley大鼠
Dosages 50 mg/kg和250 mg/kg
Administration 腹腔注射
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT06177028 Not yet recruiting
Cognitive Impairment Mild|Cognitive Dysfunction|Amyloid Plaque|Neurodegenerative Disease Hereditary|Inflammation Brain
St. Joseph''s Hospital and Medical Center Phoenix|Texas Tech University
 January 2 2024 Phase 2
NCT06149286 Recruiting
Relapsed/Refractory Follicular Lymphoma|Marginal Zone Lymphoma (MZL)
Regeneron Pharmaceuticals
 December 28 2023 Phase 3
NCT06299553 Recruiting
DLBCL - Diffuse Large B Cell Lymphoma
Incyte Biosciences Italy S.r.l
 December 4 2023 --

化學(xué)信息&溶解度

分子量 259.26 分子式

C13H13N3O3
CAS號 191732-72-6 SDF Download Lenalidomide SDF
Smiles C1CC(=O)NC(=O)C1N2CC3=C(C2=O)C=CC=C3N
儲存條件(自收到貨起)

體外溶解度
批次：

DMSO : 52 mg/mL ( (200.57 mM) ；DMSO吸濕會降低化合物溶解度，請使用新開封DMSO)

Water : Insoluble

Ethanol : Insoluble

摩爾濃度計算器

體內(nèi)溶解度
批次：

現(xiàn)配現(xiàn)用，請按從左到右的順序依次添加，澄清后再加入下一溶劑

 動物體內(nèi)配方計算器

實驗計算

摩爾濃度計算器

質(zhì)量 濃度 體積 分子量

動物體內(nèi)配方計算器（澄清溶液）

第一步：請輸入基本實驗信息（考慮到實驗過程中的損耗，建議多配一只動物的藥量）

mg/kg g μL 只

第二步：請輸入動物體內(nèi)配方組成（配方適用于不溶于水的藥物；不同批次藥物配方比例不同，請聯(lián)系Selleck為您提供正確的澄清溶液配方）

% DMSO % % Tween 80 % ddH2O
%DMSO %

計算結(jié)果：

工作液濃度： mg/ml；

DMSO母液配制方法： mg 藥物溶于μL DMSO溶液（母液濃度mg/mL，注：如該濃度超過該批次藥物DMSO溶解度，請先聯(lián)系Selleck）；

體內(nèi)配方配制方法：取μL DMSO母液，加入μL PEG300，混勻澄清后加入μL Tween 80，混勻澄清后加入μL ddH2O，混勻澄清。

體內(nèi)配方配制方法：取μL DMSO母液，加入μL Corn oil，混勻澄清。

注意：1. 首先保證母液是澄清的；
2.一定要按照順序依次將溶劑加入，進行下一步操作之前必須保證上一步操作得到的是澄清的溶液，可采用渦旋、超聲或水浴加熱等物理方法助溶。

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常見問題及建議解決方法

問題 1:
What is the formulation for mouse injection(i.p.)?

回答：
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.

問題 2:
what is the procedure to resuspend this compound？

回答：
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.

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