Thalidomide-NH-C6-NH-Boc

• CAT Number: I015162
• CAS Number: 2093536-13-9
• Molecular Formula: C24H32N4O6
• Molecular Weight: 472.53
• Purity: ≥95%
• Synonyms: tert-butyl N-[6-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]hexyl]carbamate
• InChI: InChI=1S/C24H32N4O6/c1-24(2,3)34-23(33)26-14-7-5-4-6-13-25-16-10-8-9-15-19(16)22(32)28(21(15)31)17-11-12-18(29)27-20(17)30/h8-10,17,25H,4-7,11-14H2,1-3H3,(H,26,33)(H,27,29,30)
• InChIKey: MYIJXYLTQWCASN-UHFFFAOYSA-N
• SMILES: CC(C)(C)OC(=O)NCCCCCCNC1=CC=CC2=C1C(=O)N(C2=O)C3CCC(=O)NC3=O

Thalidomide-NH-C6-NH-Boc is a synthesized E3 ligase ligand-linker conjugate that incorporates the Thalidomide based cereblon ligand and a linker used for MI-389 (compound 22) synthesis. MI-389 is a potent phthalimide PROTAC degrader based on the multi-targeted receptor tyrosine kinase inhibitor sunitinib (HY-10255A)[1].
MI-389 (0-1 μM; 72 hours) decreases cell growth with an EC50 value of 21.3 nM, which is comparable to the cellular potency of sunitinib (EC50=17.3 nM)[1].MI-389 (0-500 nM; 72 hours) leads to GSPT1 destabilization fastly as a dosepdependent manner. It shows a complete GSPT1 depletion at 100 nM[1].

Reference

[1]. Ishoey M, et al. Translation Termination Factor GSPT1 Is a Phenotypically Relevant Off-Target of Heterobifunctional Phthalimide Degraders. ACS Chem Biol. 2018 Mar 16;13(3):553-560.
 [Content Brief]

[2]. Mette Ishoey, et al. Translation Termination Factor GSPT1 Is a Phenotypically Relevant Off-Target of Heterobifunctional Phthalimide Degraders.ACS Chem Biol. 2018 Mar 16;13(3):553-560.