Supplemental Methods; Supplemental Tables S1-S7; and Supplemental Figures S1-S6 from Synthetic Lethal Strategy Identifies a Potent and Selective TTK and CLK1/2 Inhibitor for Treatment of Triple-Negative Breast Cancer with a Compromised G1–S Checkpoint

Autor: John F. Boylan, Jennifer R. Riggs, Heather K. Raymon, Ning Jiang, Tao Shi, Yuhong Ning, David Mikolon, Tam Tran, Rama Krishna Narla, Leo A. Barnes, Sophie X. Peng, Gordafaried Deyanat-Yazdi, Shuichan Xu, Dan Zhu
Rok vydání: 2023
Popis: SUPPLEMENTAL METHODS • Correlative analysis of CC-671 sensitivity data with genomic features in the 240 Oncopanel • Correlative analysis of CC-671 sensitivity data with genomic features or tumor subtypes in 49 breast cancer cell lines • Molecular of action studies • Xenograft efficacy studies SUPPLEMENTAL DATA • Table S1. Primer sequences for PCR • Table S2. Invitrogen kinase panel data • Table S3. Growth inhibition (IC50 and AUCR Values) of CC-671 in breast cancer panel • Table S4. CC-671 effects on cancer cell proliferation, apoptosis, and cell cycle • Table S5. Cell lines in Oncopanel with mutations in CTNNB1 exon 3 • Table S6. Correlation between CC-671 IC50 values and mutations in CTNNB1 exon 3 in cancer cell lines • Table S7. Correlation of CDKN2A and TP53 mutations with sensitivity or resistance to CC-671 in lung and melanoma cell lines from the Oncopanel • Figure S1. CLK2 knockdown by siRNA reduced phosphorylation of SRp75 in CAL51 cells • Figure S2. Induction of apoptosis in vivo with a single dose of CC-671 in MDA-MB-231 tumors • Figure S3. Antitumor activity of CC-671 in CAL51 and MDA-MB-231 TNBC xenograft models • Figure S4. CC-671 potently and selectively inhibits proliferation and induces apoptosis in cancer cell lines from different anatomic origins • Figure S5. Cancer cell lines with CTNNB1 exon 3 mutations tend to be more sensitive to CC-671 in Oncopanel, but the correlation does not reach statistical significance • Figure S6. TTK expression and CC-671 potency correlate with the growth rates (t0) of cell lines in both breast cancer panel and Oncopanel
Databáze: OpenAIRE