A Systematic Framework for Drug Repositioning from Integrated Omics and Drug Phenotype Profiles Using Pathway-Drug Network
Table 8
The neighbors of candidate drug “camptothecin” on the validation network.
Nodes
Description
Weight
TOP1
Topoisomerase (DNA) I: the reaction catalyzed by topoisomerases leads to the conversion of one topological isomer of DNA to another.
0.999
CASP3
Caspase 3: apoptosis-related cysteine peptidase: it is involved in the activation cascade of caspases responsible for apoptosis execution.
0.965
TP53
Tumor protein p53: it acts as a tumor suppressor in many tumor types and induces growth arrest or apoptosis depending on the physiological circumstances and cell type.
0.965
Doxorubicin
It is a drug used in cancer chemotherapy; it works by intercalating DNA, with the most serious adverse effect being life threatening heart damage.
0.890
ABCG2
ATP-binding cassette, subfamily G (WHITE), member 2; xenobiotic transporter that may play an important role in the exclusion of xenobiotics from the brain. It may be involved in brain-to-blood efflux. It appears to play a major role in the multidrug resistance phenotype of several cancer cell lines.
0.873
CDK1
Cyclin-dependent kinase 1: it plays a key role in the control of the eukaryotic cell cycle. It is required in higher cells for entry into S phase and mitosis. p34 is a component of the kinase complex that phosphorylates the repetitive C-terminus of RNA polymerase II.
0.846
ABCB1
ATP-binding cassette, subfamily B (MDR/TAP), member 1; energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
0.843
BCL2
B-cell CLL/lymphoma 2: it suppresses apoptosis in a variety of cell systems including factor-dependent lymphohematopoietic and neural cells. It regulates cell death by controlling the mitochondrial membrane permeability. It appears to function in a feedback loop system with caspases. It inhibits caspase activity either by preventing the release of cytochrome c from the mitochondria and/or by binding to the apoptosis-activating factor (APAF-1).
0.820
Paclitaxel
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.
0.812
CDK2
Cyclin-dependent kinase 2; involved in the control of the cell cycle; interacting with cyclins A, B1, B3, D, or E. Activity of CDK2 is maximal during S phase and G2.
0.754
Vinblastine
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.
0.560
Methotrexate
It blocks the production of steroids derived from cholesterol and is clinically used in the treatment of Cushing’s syndrome and metastatic breast cancer.
0.554
TOP2A
Topoisomerase (DNA) II alpha 170 kDa; control of topological states of DNA by transient breakage and subsequent rejoining of DNA strands.
