CK1 Degrader

FPFT-2216 is an orally active Molecular glue degrader targeting IKZF1, IKZF3, CK-1α, and PDE6D, with a DC₅₀ of 8 nM against PDE6D. FPFT-2216 mediates ubiquitin-proteasome degradation via the CRL4^CRBN E3 ubiquitin ligase complex and interacts with the non-isoprenoid-binding region of PDE6D. FPFT-2216 activates the p53 signaling pathway, inhibits the CBM complex/NF-κB pathway, upregulates IL-2, suppresses IL-1β and IL-6, and induces tumor cell Apoptosis. FPFT-2216 exhibits anticancer activity against multiple myeloma and lymphoma. FPFT-2216 can be used in research related to multiple myeloma, lymphoma, acute lymphoblastic leukemia, acute myeloid leukemia, pancreatic ductal adenocarcinoma, non-small cell lung cancer, and gastric adenocarcinoma.

DEG-77 is a molecular glue targeting IKZF2 and CK1α, with DC₅₀ values of 15.3 nM and 10 nM, respectively. DEG-77 exhibits significant anti-tumor activity, inducing increased transcriptional levels of the pro-apoptotic protein Bax and the cell cycle arrest protein p21. DEG-77 is applicable to the research of acute myeloid leukemia (AmL), diffuse large B-cell lymphoma and ovarian cancer.

MGD-28 is an orally effective cereblon-dependent molecular glue degrader that potently degrades CK1α, IKZF1, IKZF2, and IKZF3, with respective DC₅₀ values of 7.8, 3.8, 56.3, and 7.1 nM. MGD-28 also induces the degradation of multiple novel substrate proteins including ZFP91, DTWD1, ZNFX1, MBD1, and MBD3 via a CRBN/Cullin- and proteasome-dependent mechanism. MGD-28 induces cell apoptosis. MGD-28 is used in the research of multiple myeloma, acute myeloid leukemia, diffuse large B-cell lymphoma, and related malignancies.

WH-10417-099 is a CRBN-based PROTAC multi-kinase degrader that induces the degradation of the maximum number of unique kinases (over 125 unique kinases, such as CSNK1E and PI3Kγ) simultaneously. WH-10417-099 induces protein degradation via the ubiquitin biotinylation (E-STUB) pathway, exhibits synergistic effects with SB-405483 (HY-W1135319). The E3 ligase ligand and linker of WH-10417-099 can form the conjugate Pomalidomide 4'-PEG5-acid (HY-131647).

Pomalidomide-β-D-glucose is an orally active Molecular glue degrader of IKZF1 and CK1α. Pomalidomide-β-D-glucose forms a ternary complex with CRBN and substrate proteins, inducing ubiquitination and proteasomal degradation of IKZF1 and CK1α. Pomalidomide-β-D-glucose undergoes GLUT1-mediated cellular uptake. Pomalidomide-β-D-glucose can be used for research on multiple myeloma.

IBA-11 is a selective CRBN-dependented CK1α molecular glue degrader. IBA-11 binds to the canonical tri-tryptophan pocket of CRBN, forming a ternary complex with CK1α to mediate its degradation. IBA-11 induces CRBN-dependent ubiquitin-proteasome system-mediated degradation of CK1α. IBA-11 exhibits cytotoxicity against cancer cells. IBA-11 demonstrates in vitro metabolic stability in rat liver microsomes and minimal hERG inhibition. IBA-11 can be used for the research of cancer, such as acute myeloid leukemia.