Mal-PEG1-Val-Cit-PABC-diphosphate-BTK degrader-1 

Mal-PEG1-Val-Cit-PABC-diphosphate-BTK degrader-1 is a cleavable linker-payload conjugate and cereblon-binding BTK bifunctional degrader. Mal-PEG1-Val-Cit-PABC-diphosphate-BTK degrader-1 induces BTK degradation and exerts cytotoxic effects when delivered via CD79b monoclonal antibody. Mal-PEG1-Val-Cit-PABC-diphosphate-BTK degrader-1, when formulated as a CD79b antibody-drug conjugate, achieves sustained in vivo BTK degradation in tumor-bearing mice with reduced systemic payload exposure. Mal-PEG1-Val-Cit-PABC-diphosphate-BTK degrader-1 can be used for the research of activated b-cell-like diffuse large b-cell lymphoma (ADC linker: (HY-130944); PROTAC: (HY-163295))^[1].

Mal-PEG1-Val-Cit-PABC-diphosphate-BTK degrader-1 (compound 3) as part of a CD79b-3 ADC enables sustained, 6-day full BTK degradation in TMD8 tumor-bearing mice with minimal systemic payload exposure, using a molar dose of the payload that is ~30-fold lower than the free parent degrader dose^[1].

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

1671.63

C₈₀H₉₄F₂N₁₄O₂₀P₂

Solid

White to off-white

COC1=C(N2CCC(N(COP(O)(OP(O)(OCC3=CC=C(NC([C@H](CCCNC(N)=O)NC([C@@H](NC(CCOCCN4C(C=CC4=O)=O)=O)C(C)C)=O)=O)C=C3)=O)=O)C2=O)=O)C=C(C(N5CCC6(CCN(CCC7=CC=C(C8=CC9=C(N=CN=C9C%10=CC(F)=CC(NC(C%11=CC=C(C(O)(C)C)C=C%11F)=O)=C%10C)N8)C=C7)CC6)CC5)=O)C=C1

Room temperature in continental US; may vary elsewhere.

-20°C, protect from light, stored under nitrogen

*In solvent : -80°C, 6 months; -20°C, 1 month (protect from light, stored under nitrogen)

• [1]. Zhang A, et al. Design, Synthesis, and In Vitro and In Vivo Evaluation of Cereblon Binding Bruton's Tyrosine Kinase (BTK) Degrader CD79b Targeted Antibody-Drug Conjugates. Bioconjug Chem. 2024;35(2):140-146.  [Content Brief]