PROTAC PD-1/PD-L1 degrader-1

• CAT Number: I015140
• CAS Number: 2447066-37-5
• Molecular Formula: C59H58ClN7O11
• Molecular Weight: 1076.59
• Purity: ≥95%
• Synonyms: 5-[4-[1-[[5-chloro-2-[(3-cyanophenyl)methoxy]-4-[[3-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-methylphenyl]methoxy]phenyl]methyl]piperidine-2-carbonyl]piperazin-1-yl]-N-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]-5-oxopentanamide
• InChI: InChI=1S/C59H58ClN7O11/c1-36-40(10-5-11-42(36)39-17-19-48-51(30-39)76-27-26-75-48)35-78-50-31-49(77-34-38-9-4-8-37(28-38)32-61)41(29-44(50)60)33-66-21-3-2-14-47(66)58(73)65-24-22-64(23-25-65)54(70)16-7-15-52(68)62-45-13-6-12-43-55(45)59(74)67(57(43)72)46-18-20-53(69)63-56(46)71/h4-6,8-13,17,19,28-31,46-47H,2-3,7,14-16,18,20-27,33-35H2,1H3,(H,62,68)(H,63,69,71)
• InChIKey: CJIXMPCTSMEQPG-UHFFFAOYSA-N
• SMILES: CC1=C(C=CC=C1C2=CC3=C(C=C2)OCCO3)COC4=C(C=C(C(=C4)OCC5=CC(=CC=C5)C#N)CN6CCCCC6C(=O)N7CCN(CC7)C(=O)CCCC(=O)NC8=CC=CC9=C8C(=O)N(C9=O)C1CCC(=O)NC1=O)Cl

PROTAC PD-1/PD-L1 degrader-1, a PD-1/PD-L1 PROTAC based on Cereblon E3 ligand, inhibits PD-1/PD-L1 interaction with an IC50 of 39.2 nM. PROTAC PD-1/PD-L1 degrader-1 significantly restores the immunity repressed in a co-culture model of Hep3B/OS-8/hPD-L1 and CD3 T cells. PROTAC PD-1/PD-L1 degrader-1 moderately reduces the protein levels of PD-L1 in a lysosome-dependent manner[1].
PROTAC PD-1/PD-L1 degrader-1 (compound p22) reduces cell surface PD-L1 expression for more than 14%[1].
PROTAC PD-1/PD-L1 degrader-1 (1-10 μM; 24 hours) reduces PD-L1 expression in a dose-dependent manner by 21% and 35% at 1 μM and 10 μM, respectively[1].

Reference

[1]. Cheng B, Ren Y, Cao H, Chen J. Discovery of novel resorcinol diphenyl ether-based PROTAC-like molecules as dual inhibitors and degraders of PD-L1. Eur J Med Chem. 2020;199:112377.
 [Content Brief]