A Systematic Framework for Drug Repositioning from Integrated Omics and Drug Phenotype Profiles Using Pathway-Drug Network
Table 5
Predicted drugs after pathway-based drug repositioning.
Drug name
Ranking score
-score
p value
Description
Doxorubicin
0.999
8.935
0
It works by intercalating DNA, with the most serious adverse effect being life threatening heart damage.
Exemestane
0.803
6.880
Tyrosine kinase inhibitor which selectively inhibits HER2
Methotrexate
0.708
5.892
blocks the production of steroids derived from cholesterol and is clinically used in the treatment of Cushing’s syndrome and metastatic breast cancer.
Megestrol
0.668
5.464
It binds to and inhibits the enzyme dihydrofolate reductase, resulting in inhibition of purine nucleotide and thymidylate synthesis and, subsequently, inhibition of DNA and RNA syntheses.
Paclitaxel
0.646
5.235
It binds to and stabilizes microtubules, preventing their depolymerization and so inhibiting cellular motility, mitosis, and replication.
Aminoglutethimide
0.637
5.148
It blocks the production of steroids derived from cholesterol and is clinically used in the treatment of Cushing’s syndrome and metastatic breast cancer.
Tamoxifen
0.634
5.113
It is an antagonist of the estrogen receptor in breast tissue via its active metabolite, hydroxytamoxifen. In other tissues such as the endometrium, it behaves as an agonist and thus may be characterized as a mixed agonist/antagonist.
Vinblastine
0.625
5.020
It is an antimicrotubule drug used to treat certain kinds of cancer, including Hodgkin’s lymphoma, non-small cell lung cancer, breast cancer, head and neck cancer, and testicular cancer.
Fulvestrant
0.604
4.802
It is drug treatment of hormone receptor-positive metastatic breast cancer in postmenopausal women with disease progression following antiestrogen therapy. It is an estrogen receptor antagonist with no agonist effects, which works by downregulating the estrogen receptor.
Letrozole
0.579
4.539
It is an oral nonsteroidal aromatase inhibitor for the treatment of hormonally responsive breast cancer.
MS-275
0.530
4.023
Entinostat, also known as SNDX-275 and MS-275, is a benzamide histone deacetylase inhibitor undergoing clinical trials for treatment of various cancers.
GW-8510
0.477
3.467
0.000263332
Cyclin-dependent kinase 5 inhibitors: inhibition of dopamine transporter activity.
Camptothecin
0.475
3.452
0.000278495
It is an alkaloid isolated from the stem wood of the Chinese tree, Camptotheca acuminata. This compound selectively inhibits the nuclear enzyme DNA topoisomerase.
Phenoxybenzamine
0.461
3.303
0.000478379
It is an alpha-adrenergic antagonist with long duration of action. It has been used to treat hypertension and as a peripheral vasodilator.
Tyrphostin_AG-825
0.447
3.159
0.000792504
It is tyrosine kinase inhibitor, which selectively inhibits HER2.
Alsterpaullone
0.447
3.150
0.000815292
CDC2 protein kinase, antiangiogenic potential of small molecular inhibitors of cyclin-dependent kinases in vitro.
Celastrol
0.442
3.100
0.000966191
Celastrol is a remedial ingredient isolated from the root extracts of “Tripterygium wilfordii” (Thunder of God vine) and “Celastrus regelii.” In “in vitro” and “in vivo” animal experiments, celastrol exhibits antioxidant, anti-inflammatory, anticancer, and insecticidal activities.
Known breast cancer drug. Potential drug candidate for repositioning.
