WBC100 (14-D-Valine-TPL) is a potent, selective, orally active c-Myc glue degrader targeting the ubiquitin E3 ligase CHIP-mediated 26S proteasome pathway, primarily used in research for c-Myc overexpressing tumors [1].

WBC100 selectively targets and eradicates cancer cell lines overexpressing c-Myc, such as Mia-paca2, H9, and MOLM-13, as well as non-cancerous cell lines with low c-Myc expression, including L02, MRC-5, and WI38 cells. The half-maximal inhibitory concentrations (IC50) for the overexpressing cancer cells were determined to be 61×10^-9 M, 17×10^-9 M, and 16×10^-9 M, respectively. In contrast, the IC50 values for the normal cell lines were significantly higher, at 2205×10^-9 M, 151×10^-9 M, and 570×10^-9 M [1]. Treatment with WBC100 (0-320 nM; 24 hours) resulted in a dose-dependent reduction of c-Myc protein levels in MOLM-13 and Mia-paca2 cells without significantly affecting the levels of XPB, Rpb1, and STAT3 proteins. Furthermore, the decrease in c-Myc protein levels induced by WBC100 could be rescued by MG132 [1].

WBC100, administered orally at a dosage of 0.1-0.4 mg/kg twice daily for 21 days, demonstrated dose-dependent antitumor activity in vivo. Higher (0.4/0.2 mg/kg) doses of WBC100 resulted in the eradication of MOLM-13-luciferase cells in vivo, with all mice remaining disease-free by day 35. Moreover, at a lower dose of 0.1 mg/kg, WBC100 significantly inhibited leukemia tumor growth in mice and extended survival [1]. When given orally at a dosage of 0.4-0.8 mg/kg once daily for 14 days, WBC100 eliminated refractory MOLM-13-luciferase cells in vivo, whereas (+)-JQ1 administered at 50 mg/kg by intraperitoneal injection once daily for the same duration was ineffective in suppressing tumor growth. WBC100 exhibited stronger antitumor activity than the c-Myc transcription inhibitor (+)-JQ1 [1].