Phosphodiesterase (PDE) 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.

KRAS IN-44 (Compound S2C2M2) is a PDE6D degrader. KRAS IN-44 inhibits PDE6D-dependent KRAS trafficking and KRAS downstream signaling pathways. KRAS IN-44 down-regulates EGF-induced the phosphorylation of PI3K, AKT, and mTOR. KRAS IN-44 increases Apoptosis. KRAS IN-44 has antitumor activity against hepatoblastoma.

PROTAC PDE4 degrader-1 is an orally active CRBN-recruiting PDE4B PROTAC degrader. PROTAC PDE4 degrader-1 shows an IC₅₀ of 1.9 μM against PDE4B, degrades PDE4B via the ubiquitin-proteasome pathway, and shows weak activity against PDE4C. PROTAC PDE4 degrader-1 inhibits the secretion of pro-inflammatory cytokines TNF-α and IL-6, reduces the infiltration of inflammatory cells into lung tissues, protects lung tissues and alleviates acute lung injury. PROTAC PDE4 degrader-1 can be used for the research of acute lung injury.

TM-04-064-02 is a molecular glue degrader. TM-04-064-02 induces proteins (such as IKZF1/3, PPIL4, ETF1 and PDE6D) to bind to CRBN, promoting their ubiquitination and degradation.