WBC100 (14-D-Valine-TPL) is a potent, selective, and orally active c-Myc molecule glue degrader. WBC100 is a c-Myc degrader and targets ubiquitin E3 ligase CHIP mediated 26S proteasome pathway. WBC100 is used forc-Myc overexpressing tumors research.
WBC100 selectively kills c-Myc overexpressing cancer cells Mia-paca2, H9, and MOLM-13 cell as well as c-Myc-low normal human cell lines L02, MRC-5 and WI38, the IC50 values are 61 × 10-9, 17 × 10-9, and 16 × 10-9M for c-Myc overexpressing cancer cells, respectively. Whereas the IC50 values for normal cell lines are 2205 × 10-9, 151 × 10-9, and 570 × 10-9M, respectively[1].WBC100 (0-320 nM; 24 hour) decreases c-Myc protein levels in MOLM-13 cells and Mia-paca2 cells in a dose-dependent manner, but has no obvious impact on XPB, Rpb1, and STAT3. Additionally, MG132 can rescue the WBC100-induced decline in c-Myc protein[1].
WBC100 (p.o.; 0.1-0.4 mg/kg; twice daily; 21 days) exerts dose-dependent antitumor activity invivo. Higher or medium (0.4/0.2mg/kg) doses of WBC100 eradicates MOLM-13-luciferase cells in vivo and all the mice were disease-free survival on day 35. Additionally, at a low dose (0.1mg/kg), WBC100 also significantly inhibits tumor growth and prolongs survival of leukemia mice[1].WBC100 (p.o.; 0.4-0.8 mg/kg; once daily; 14 days) eliminates refractory MOLM-13-luciferase cells in vivo, but both (+)-JQ1 (50mg/kg, intraperitoneal (i.p.), once a day for 14 d) is ineffective in suppressing tumor growth. WBC100 exhibits stronger antitumor activity than c-Myc transcription inhibitor (+)-JQ1[1].
References:
[1]. Ying Xu, et al. A Selective Small-Molecule c-Myc Degrader Potently Regresses Lethal c-Myc Overexpressing Tumors. Adv Sci (Weinh). 2022 Mar;9(8):e2104344.