Table 3 Pharmaceuticals for which PharmacoDB analysis reveals a drug response predictive association with miRNA gene targets.

From: MicroRNA-mRNA networks define translatable molecular outcome phenotypes in osteosarcoma

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*

  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”.
  2. *The drug class includes a chemical replicate corresponding to a reference pharmaceutical.
  3. Experimental drug response (IC50) data is only available for a limited number (≤3) of osteosarcoma cell lines.