BDBM65454 CC-5013 US11530219, Compound Lenalidomide Lenalidomide US9694015, 6.1 191732-72-6 Revimid Revlimid
- Lopez-Girona, A; Mendy, D; Ito, T; Miller, K; Gandhi, AK; Kang, J; Karasawa, S; Carmel, G; Jackson, P; Abbasian, M; Mahmoudi, A; Cathers, B; Rychak, E; Gaidarova, S; Chen, R; Schafer, PH; Handa, H; Daniel, TO; Evans, JF; Chopra, R Cereblon is a direct protein target for immunomodulatory and antiproliferative activities of lenalidomide and pomalidomide. Leukemia 26: 2326-35 (2012)
- Zhang, F; Wu, Z; Chen, P; Zhang, J; Wang, T; Zhou, J; Zhang, H Discovery of a new class of PROTAC BRD4 degraders based on a dihydroquinazolinone derivative and lenalidomide/pomalidomide. Bioorg Med Chem 28: (2020)
- ChEMBL_1985380 (CHEMBL4618786) Binding affinity to CBRN (unknown origin) incubated for 60 mins by lenalidomide displacement assay
- ChEMBL_2364122 Displacement of BODIPY-lenalidomide from human N-terminal NanoLuc-fused CRBN expressed in HEK293T cells incubated for 2 hrs by NanoBRET assay
- ChEMBL_1823466 (CHEMBL4323230) Binding affinity to cereblon in human MDA-MB-231 cells assessed as reduction in cell growth inhibition measured after 4 days in presence of 10 uM of lenalidomide
- ChEMBL_1823467 (CHEMBL4323231) Binding affinity to cereblon in human MDA-MB-231 cells assessed as reduction in cell growth inhibition measured after 4 days in presence of 30 uM of lenalidomide
- ChEMBL_1823468 (CHEMBL4323232) Binding affinity to cereblon in human MDA-MB-231 cells assessed as reduction in cell growth inhibition measured after 4 days in presence of 100 uM of lenalidomide
- ChEMBL_1823469 (CHEMBL4323233) Binding affinity to cereblon in human MDA-MB-468 cells assessed as reduction in cell growth inhibition measured after 4 days in presence of 10 uM lenalidomide
- ChEMBL_1823470 (CHEMBL4323234) Binding affinity to cereblon in human MDA-MB-468 cells assessed as reduction in cell growth inhibition measured after 4 days in presence of 30 uM lenalidomide
- ChEMBL_1823471 (CHEMBL4323235) Binding affinity to cereblon in human MDA-MB-468 cells assessed as reduction in cell growth inhibition measured after 4 days in presence of 100 uM lenalidomide
- ChEMBL_1823460 (CHEMBL4323224) Binding affinity to cereblon in human RV4:11 cells expressing wild type p53 assessed as reduction in cell growth inhibition measured after 4 days in presence of 10 uM lenalidomide
- ChEMBL_1823461 (CHEMBL4323225) Binding affinity to cereblon in human RV4:11 cells expressing wild type p53 assessed as reduction in cell growth inhibition measured after 4 days in presence of 30 uM lenalidomide
- ChEMBL_1823462 (CHEMBL4323226) Binding affinity to cereblon in human RV4:11 cells expressing wild type p53 assessed as reduction in cell growth inhibition measured after 4 days in presence of 100 uM lenalidomide
- Lenalidomide Assay Compounds in Atto565-Lenalidomide displacement assay were dispensed in a 384-well microplate (Corning, 4514) using D300e Digital Dispenser (HP) normalized to 1% DMSO into 10 nM Atto565-Leanlidomide, 100 nM DDB1deltaB-CRBN, 50 mM Tris pH 7.5, 200 mM NaCl, 0.1% Pluronic F-68 solution (Sigma). Compound titrations were incubated for 60 min at RT. The change in fluorescence polarization was monitored using a PHERAstar FS microplate reader (BMG Labtech) for 1 h in 120 s cycles. Data from three independent replicates (n=3) was used to estimate IC50 values using variable slope equation in GraphPad Prism 7. Compounds 9, 10, and 11 are potent binders of CRBN with IC50 comparable to FDA approved lenalidomide, while being inactive in degradation of IKZF1
- ChEMBL_1823463 (CHEMBL4323227) Binding affinity to cereblon in human RV4:11/IRMI-2 cells harboring p53 hotspot mutation Y236H/R249G assessed as reduction in cell growth inhibition measured after 4 days in presence of 10 uM lenalidomide
- ChEMBL_1823464 (CHEMBL4323228) Binding affinity to cereblon in human RV4:11/IRMI-2 cells harboring p53 hotspot mutation Y236H/R249G assessed as reduction in cell growth inhibition measured after 4 days in presence of 30 uM lenalidomide
- ChEMBL_1823465 (CHEMBL4323229) Binding affinity to cereblon in human RV4:11/IRMI-2 cells harboring p53 hotspot mutation Y236H/R249G assessed as reduction in cell growth inhibition measured after 4 days in presence of 100 uM lenalidomide
- Fluorescence thermal melt assay Thermal stabilities of CRBN-DDB1 in the presence or absence of phthalimide, thalidomide, lenalidomide and pomalidomide were done in the presence of Sypro Orange in a microplate format according to Pantoliano et al. Two ug of protein in 20 ul of assay buffer (25mM Tris HCl, pH 8.0, 150mM NaCl, 2 uM Sypro Orange) were subjected to stepwise increase of temperature from 20 to 70 °C and the fluorescence was read at every 1 °C on an ABIPrism 7900HT (Applied Biosystems, Carlsbad, CA, USA). Compounds were dissolved in DMSO (1% final in assay) and tested in quadruplicate at a concentration range between 30 nM to 1000 uM; controls contained 1% DMSO only.
- CRBN Fluorescence Polarization Assay In this competitive fluorescent polarization assay Cy5 conjugated lenalidomide analog (Cy5-O-Len)13 was used as a fluorescent probe. 6×His-CRBN-DDB1 protein (200 nM) and Cy5-O-Len probe (30 nM) were combined in 20 mM HEPES pH 7, 150 mM NaCl, 0.005% Tween-20 assay buffer. 20 μL of this assay cocktail was dispensed into wells of Corning 3821 black 384-well plates. Compounds were transferred to the assay plate from a dose-response plate using a Pintool on a Biomek FXP Laboratory Automation Workstation (Beckman Coulter). The plates were incubated in the dark for 1 hour at room temperature and then read on an Envision plate reader (PerkinElmer, Massachusetts, USA). IC50 values were determined using a proprietary software RISE (Robust Investigation of Screening Experiments), developed in house on the Pipeline Pilot platform (Biovia, v. 17.2.0). Data represent the mean of three independent determinations.