Text Mining-Based Drug Discovery in Osteoarthritis

Table 3

Candidate drugs targeting genes with OA.

Number	Drug	Description	Gene	Drug-gene interaction	Score	Approved by FDA	Approved use in OA	Clinical trial phase in O A	Reference (PubMed ID)
1	Celecoxib	COX-2	PTGS2	Inhibitor	12	Yes	Yes	4	12093311|12086292
2	Etodolac	Mainly COX-2	PTGS2	Inhibitor	11	Yes	Yes	2	12824918|11009046
3	Oxaprozin	Mainly COX-1	PTGS2	Inhibitor	10	Yes	Yes	2	19338579|9831331
4	Meloxicam	COX-2	PTGS2	Inhibitor	11	Yes	Yes	4	10567199|10220944
5	Icosapent	Eicosanoids	PTGS2	Inhibitor	7	Yes	No	Not available	12573452|16190133
6	Aminosalicylic acid	Antimycobacterial agent	PTGS2	Inhibitor	6	Yes	No	Not available	16855178|12463455
7	Mesalamine	Anti-inflammatory agent	PTGS2	Inhibitor	9	Yes	No	Not available	16855178|12463455
8	Indomethacin	Mainly COX-1	PTGS2	Inhibitor	8	Yes	Yes	4	15668944|15730717
9	Nabumetone	COX-2	PTGS2	Inhibitor	11	Yes	Yes	4	11304699|12047490
10	Tenoxicam	PTG synthetase inhibitor	PTGS2	Inhibitor	10	Yes	Yes	2	11563332|16245223
11	Lenalidomide	Immunomodulatory drug	PTGS2	Modulator	3	Yes	No	Not available	15598423|12720152
12	Rofecoxib	COX-2	PTGS2	Inhibitor	15	Yes	Yes	3	10580458|11398914
13	Piroxicam	COX-1	PTGS2	Inhibitor	10	Yes	Yes	2	11952155|11785774
14	Sulindac	PTG synthetase inhibitor	PTGS2	Inhibitor	9	Yes	Yes	2	11118042|10372826
15	Mefenamic acid	PTG synthetase inhibitor	PTGS2	Inhibitor	11	Yes	Yes	2	10393680|15792781
16	Naproxen	PTG synthetase inhibitor	PTGS2	Inhibitor	11	Yes	Yes	4	17604186|17612049
17	Sulfasalazine	PTG synthetase inhibitor	PTGS2	Inhibitor	7	Yes	No	Not available	16855178|12463455
18	Phenylbutazone	PTG synthetase inhibitor	PTGS2	Inhibitor	9	Yes	No	Not available	15939622|15489888
19	Diflunisal	PTG synthetase inhibitor	PTGS2	Inhibitor	11	Yes	Yes	Not available	11315375|8737748
20	Suprofen	PTG synthetase inhibitor	PTGS2	Inhibitor	7	Yes	No	Not available	11885959|17139284
21	Salicylic acid	PTG synthetase inhibitor	PTGS2	Inhibitor	10	Yes	Yes	Not available	15035793|15348270
22	Aspirin	Mainly COX-1	PTGS2	Inhibitor	12	Yes	Yes	Not available	17522398|17181859
23	Bromfenac	PTG synthetase inhibitor	PTGS2	Inhibitor	6	Yes	No	Not available	16982289|16846546
24	Ketoprofen	COX-2	PTGS2	Inhibitor	11	Yes	Yes	3	14513718|11729362
25	Balsalazide disodium	PTG synthetase inhibitor	PTGS2	Inhibitor	7	Yes	No	Not available	17981262|12950415
26	Lumiracoxib	COX-2	PTGS2	Inhibitor	10	Yes	Yes	3	14965322|15017615
27	Salsalate	PTG synthetase inhibitor	PTGS2	Inhibitor	7	Yes	Yes	Not available	9711054|10452868
28	Ginseng, Asian	Adaptogen	PTGS2	Inhibitor	4	Yes	No	Not available	17436372|15753395
29	Antrafenine	Cyclooxygenase inhibitor	PTGS2	Inhibitor	7	Yes	No	Not available	17604186|17612049
30	Antipyrine	Cyclooxygenase inhibitor	PTGS2	Inhibitor	2	Yes	No	Not available	11695253
31	Tiaprofenic acid	PTG synthetase inhibitor	PTGS2	Inhibitor	8	Yes	Yes	Not available	2277128|11752352
32	Etoricoxib	COX-2	PTGS2	Inhibitor	12	Yes	Yes	4	17573128|17164136
33	Resveratrol	Polyphenolic phytoalexin	PTGS2	Inhibitor	2	Yes	No	3	11752352
34	Nepafenac	COX-1 and COX-2	PTGS2	Inhibitor	5	Yes	No	Not available	10850857
35	Parecoxib	COX-2	PTGS2	Inhibitor	3	Yes	No	Not available	10794682
36	Captopril	Inhibitor of ACE	MMP9	Inhibitor	5	Yes	No	Not available	12381651|19057128
37	Glucosamine	Precursor of lipids	MMP9	Antagonist	6	Yes	Yes	4	12405690|16616490
38	Rilonacept	Interleukin 1 inhibitor	IL1RN	Binder	3	Yes	No	Not available	23319019|12815153
39	Danazol	Gonadotropin inhibitor	CCL2	Inhibitor	3	Yes	No	Not available	11056242|11216879
40	Etanercept	Fusion protein	TNF	Antibody	12	Yes	No	Not available	10375846|10405518
41	Adalimumab	Monoclonal antibody	TNF	Antibody	12	Yes	No	Not available	12044041|15022409
42	Infliximab	TNF-α blocker	TNF	Inhibitor	17	Yes	No	Not available	16456024|16052578
43	Inamrinone	PDE3 inhibitor	TNF	Inhibitor	6	Yes	No	Not available	11805217|1611705
44	Golimumab	Monoclonal antibody	TNF	Antibody	6	Yes	No	Not available	21079302
45	Certolizumab pegol	TNF-α inhibitor	TNF	Neutralizer	6	Yes	No	Not available	23620660
46	Pomalidomide	COX-2	TNF	Inhibitor	2	Yes	No	Not available	22917017
47	Siltuximab	Monoclonal antibody	IL6	Antagonist	4	Yes	No	Not available	8823310
48	Clenbuterol	Beta(2) agonist	NGF	Stimulator	6	Yes	No	Not available	10525174|10403429
49	Aflibercept	Recombinant fusion protein	VEGFA	Inhibitor	7	Yes	No	Not available	22813448
50	Carvedilol	Beta adrenoceptor blocker	VEGFA	Other	5	Yes	No	Not available	15071347|15942707
51	Dalteparin sodium	Anticoagulant	VEGFA	Inhibitor	4	Yes	No	Not available	17692905|21091776
52	Ranibizumab	VEGFA antagonist	VEGFA	Inhibitor	14	Yes	No	Not available	18046235|18054637
53	Bevacizumab	VEG inhibitor	VEGFA	Inhibitor	10	Yes	No	Not available	15705858|11752352

Fifty-three drugs which met the criteria of targeting one of the candidate genes by an appropriate interaction were collected in the final list. Whether the drug has been approved by the FDA and whether it has been approved for OA are documented in the table. ACE: angiotensin-converting enzyme; TNF: tumor necrosis factor; PDE: phosphodiesterase; PTG: prostaglandin; VEGF: vascular endothelial growth factor.