PTD10 

PTD10 is a selective and potent BTK PROTAC degrader (DC₅₀ = 0.5 nM, K_D = 2.28 nM). PTD10 can recruit cereblon (CRBN) E3 ligase and form a ternary complex with BTK, thereby mediating the ubiquitination and proteasome-dependent degradation of BTK. PTD10 inhibits cancer cells proliferation, and induces cell apoptosis via activation of the caspase-dependent pathway and mitochondrial pathway. PTD10 potently inhibits the BCR, AKT and NF-κB signaling pathway. PTD10 can be used for researches of B-cell malignancies and autoimmune disease^[1]. (Pink: Btk ligand (HY-19834); Blue: Cereblon ligand (HY-14658); Black: linker (HY-Y0966)).

PTD10 (0.15-3000 nM; 17 h) potently degrades BTK via the CRBN-dependent ubiquitin-proteasome pathway in Ramos cells (DC₅₀ = 0.5 nM) and JeKo-1 cells (DC₅₀ = 0.6 nM), with maximal degradation exceeding 95% in both cell lines^[1].
PTD10 binds to purified BTK with a K_d of 2.28 nM^[1].
PTD10 (2 h) engages intracellular BTK (IC₅₀ = 97 nM) and CRBN (IC₅₀ = 107 nM) in HEK293 cells, with positive cooperativity in BTK binding^[1].
PTD10 efficiently promotes ternary complex formation between BTK and CRBN in HEK293 cells, achieving 100% maximal BRET signal^[1].
PTD10 is a highly selective BTK degrader in TMD8 cells, with no significant off-target degradation of other tested kinases, while degrading neo-substrates IKZF1, IKZF3, and ZNF280D without affecting GSPT1^[1].
PTD10 (0.1-10000 nM; 48 h) potently inhibits growth of TMD8 cells (IC₅₀ = 1.4 nM) and Mino cells (IC₅₀ = 2.2 nM)^[1].
PTD10 (0.15-3000 nM; 48 h) induces dose-dependent apoptosis in TMD8 and Mino cells via activation of the caspase-dependent and mitochondrial pathways^[1].
PTD10 (0.15-3000 nM; 48 h) potently inhibits the BCR signaling pathway in TMD8 and Mino cells^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

922.00

C₄₉H₅₁N₁₁O₈

2642231-19-2

Solid

Light yellow to yellow

O=C1N(C=C(C=C1NC2=NC=C(N3CCN(C[C@@H]3C)C(CNC4=CC=CC5=C4C(N(C5=O)C6CCC(NC6=O)=O)=O)=O)C=C2)C7=CC=NC(N8CCN9C(C8=O)=CC%10=C9CC(C)(C%10)C)=C7CO)C

Room temperature in continental US; may vary elsewhere.

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

• [1]. Li YQ, et al. Discovery of Novel Bruton's Tyrosine Kinase PROTACs with Enhanced Selectivity and Cellular Efficacy. J Med Chem. 2023;66(11):7454-7474.  [Content Brief]