Table 3.

Pharmaceuticals for which PharmacoDB analysis reveals a drug response predictive association with miRNA gene targets.

Name	Drug Class	Median IC50 (µM)	Median Regression Coefficient	Chemical Replicates
thapsigargin	SERCA inhibitor	0.003	0.273	1
daporinad	NAPRT inhibitor	0.004	0.323	1
paclitaxel	microtubule stabilizing agent	0.016	0.552	1
dinaciclib†	CDK inhibitor	0.016	0.288	3
CGP-60474†	CDK inhibitor	0.028	0.266	3
panobinostat	HDAC inhibitor	0.112	0.291	1
WH-4-023†	Src inhibitor	0.156	0.268	2
methotrexate	DHFR inhibitor	0.160	—	1*
alvocidib†	CDK inhibitor	0.221	0.283	3
irinotecan	topoisomerase inhibitor	0.444	0.265	4*
doxorubicin	topoisomerase inhibitor	0.521	0.260	4*
topotecan	topoisomerase inhibitor	0.698	0.273	4*
trametinib	MEK inhibitor	0.897	0.270	2
AZ628†	RAF inhibitor	0.966	0.256	1
TAE684	ALK inhibitor	1.143	0.266	1
dasatinib	Abl/Src inhibitor	2.846	0.304	2
pictilisib	PI3K inhibitor	3.359	0.452	1
etoposide	topoisomerase inhibitor	3.678	—	4*
tozasertib	aurora kinase inhibitor	4.504	0.377	1
PD-0325901	MEK inhibitor	5.199	0.292	2
nilotinib	Abl inhibitor	5.703	0.278	1
cisplatin	alkylating agent	8.414	—	1*

Methotrexate, etoposide, and cisplatin are included for comparative purposes. Median IC50 values are obtained across all osteosarcoma cell lines. The median regression coefficient is calculated from the significant gene – drug interactions used to identify the drugs. The nine bolded drugs act through pathways enriched in target genes of the miRNA profile (shown and bolded in Table S5). Specifically, dinaciclib, CGP060474, and alvocidib inhibit the “cell cycle pathway”, trametinib, AZ628, and PD-0325901 inhibit the “MAPK pathway”, dasatinib and nilotinib act through the “Inhibition of Cellular Proliferation” by Gleevec pathway, and pictilisib inhibits the “PI3K pathway”.

*The drug class includes a chemical replicate corresponding to a reference pharmaceutical.

^†Experimental drug response (IC50) data is only available for a limited number (≤3) of osteosarcoma cell lines.