CRBN-DDB1 Protein, Human (sf9, His, Avi)

CRBN-DDB1, CUL4, and Rbx1 form an E3 ubiquitin ligase complex. CRBN-DDB1 is necessary for lenalidomide (HY-A0003) and pomalidomide (HY-10984) to exert T cell immunomodulatory functions and upregulate IL-2 and TNF-α. CRBN-DDB1 mediates the anti-proliferative and cell cycle arrest effects of both classes of drugs in myeloma cells and regulates p21WAF1 expression. CRBN-DDB1 can serve as a molecular glue platform to recruit novel small molecule degraders and target kinases such as WEE1 and CK1α. CRBN-DDB1 protein, Human (sf9, His, Avi) is a recombinant CRBN-DDB1 protein expressed from Sf9 insect cells with N-His, N-Avi tags^[1][2][3].

CRBN-DDB1 constitutes a functional CUL4-Rbx1 E3 ubiquitin ligase complex and represents the direct protein target of thalidomide, lenalidomide and pomalidomide. CRBN-DDB1 binds lenalidomide and pomalidomide with significantly higher affinity than thalidomide and exhibits no binding to phthalimide. CRBN-DDB1 acts as a drug-dependent substrate adaptor that promotes the ubiquitination and proteasomal degradation of IKZF1 and IKZF3 upon lenalidomide treatment. CRBN-DDB1 is essential for the immunomodulatory effects of lenalidomide and pomalidomide in T cells, including the upregulation of IL-2 and TNF-α. CRBN-DDB1 mediates the antiproliferative and cell cycle inhibitory activities of lenalidomide and pomalidomide in multiple myeloma cells through induction of p21WAF1. CRBN-DDB1 expression level directly determines myeloma cell sensitivity and resistance to immunomodulatory imide drugs. CRBN-DDB1 serves as a universal molecular glue platform capable of recruiting novel small-molecule degraders targeting kinases such as WEE1 and CK1α^[1][2][3].

CRBN-DDB1 Protein, Human (2 μg) combines with lenalidomide, pomalidomide and thalidomide in fluorescence thermal melt assay. The IC₅₀ values of Lenalidomide (HY-A0003), Pomalidomide (HY-10984) and Thalidomide (HY-14658) are approximately 3 μM, 3 μM and 30 μM respectively^[3].

Fluorescence polarization (FP) assay determined the dissociation constant (Kd) of CRBN/DDB1 with thalidomide to be approximately 82 nM.

Human

Sf9 insect cells

N-His;N-Avi

Q96SW2-1 (M1-L442)&Q16531-1 (M1-H1140)

51185&1642

Approximately 55 kDa (CRBN) & 120 kDa (DDB1), based on SDS-PAGE under reducing conditions.

≥ 90%, as determined by reducing SDS-PAGE.

Solution

Supplied as a 0.22 μm filtered solution of 50 mM HEPES, pH 7.5, 200 mM NaCl, 10% glycerol.

<1 EU/μg, determined by LAL method.

Please use rapid thawing with running water to thaw the protein.

Stored at -80°C for 1 year from date of receipt. It is stable at -20°C for 3 months after opening. It is recommended to freeze aliquots at -80°C for extended storage. Avoid repeated freeze-thaw cycles.

Shipping with dry ice.

• [1]. Lopez-Girona A, et al. Direct Binding with Cereblon Mediates the Antiproliferative and Immunomodulatory Action of Lenalidomide and Pomalidomide. Blood. 2011 Nov 18;118(21):738.

  [2]. Krönke J, et al. Lenalidomide Promotes CRBN-Mediated Ubiquitination and Degradation of IKZF1 and IKZF3. Blood. 2013 Nov 15;122(21):LBA-5.

  [3]. Razumkov H, et al. Discovery of CRBN-Dependent WEE1 Molecular Glue Degraders from a Multicomponent Combinatorial Library. Journal of the American Chemical Society, 2024, 146(46): 31433-31443.