Appendix Table A2.
A Selection of “Target-Action Pairs,” Each with MAF_W >0.001 and <5% Genotype Missingness for at Least One Single-Nucleotide Polymorphism/Single Nucleotide Variant from the ExomeChip
| Target | Mechanism of action | Small molecule | Current indication(s) | Marketing start date |
|---|---|---|---|---|
| Muscarinic acetylcholine receptor M1 | Antagonist | Dicyclomine | IBS, colicky abdominal pain, diverticulitis | November 5, 1950 |
| Antagonist | Cyclopentolate | Mydriasis and cycloplegia (for diagnostic purposes) | June 30, 1958 | |
| Antagonist | Glycopyrronium | Salivary, tracheobronchial, and pharyngeal secretions, acid reflux, cardiac vagal inhibitory reflexes during induction of anesthesia and intubation, COPD | March 28, 1961 | |
| Antagonist | Scopolamine | Colicky abdominal pain, bradycardia, sialorrhea, diverticulitis, IBS, motion sickness | January 1, 1966 | |
| Antagonist | Clidinium | Peptic ulcer disease, colicky abdominal pain, diverticulitis, IBS | September 1, 1966 | |
| Antagonist | Propantheline | Enuresis, hyperhidrosis, abdominal spasm, bladder spasm | December 14, 1981 | |
| Antagonist | Pirenzepine | Peptic ulcer, gastric ulcer, and duodenal ulcer. | December 31, 1984 | |
| Antagonist | Trihexyphenidyl | Parkinson's disease, extrapyramidal reactions | November 1, 1987 | |
| Tyrosine-protein kinase BTK | Inhibitor | Acalabrutinib | Mantle cell lymphoma | October 31, 2017 |
| Inhibitor | Ibrutinib | Mantle cell lymphoma, chronic lymphocytic leukemia, Waldenstrom's macroglobulinemia | November 7, 2013 | |
| Prostaglandin F2-alpha receptor | Agonist | Tafluprost | Elevated intraocular pressure | February 10, 2012 |
| Agonist | Travoprost | October 20, 2006 | ||
| Agonist | Latanoprost | March 20, 1995 | ||
| Agonist | Dinoprost tromethamine | Abortion of second-trimester pregnancy, induction of labor, vasodilation (for diagnostic purposes) | December 31, 1974 | |
| Alpha-1A adrenergic receptor | Agonist | Tetryzoline | Minor eye irritation | November 30, 1979 |
| Agonist | Methoxamine | Hypotension | December 31, 1950 | |
| Agonist | Ergonovine | Postpartum hemorrhage, postabortion hemorrhage | December 31, 1939 | |
| Alpha-1A adrenergic receptor | Antagonist | Silodosin | BPH | March 23, 2009 |
| Antagonist | Tamsulosin | September 12, 1997 | ||
| Heat-stable enterotoxin receptor | Agonist | Linaclotide | IBS with constipation, chronic idiopathic constipation | August 30, 2012 |
| Toll-like receptor 7 | Agonist | Imiquimod | Facial actinic keratosis, genital and perianal warts | February 25, 2010 |
| P2Y purinoceptor 12 | Antagonist | Prasugrel | Atherothrombosis, MI | July 10, 2009 |
| Antagonist | Ticlopidine | Thrombotic stroke | July 1, 1999 | |
| Antagonist | Clopidogrel | Atherosclerosis | January 1, 1900 | |
| Substance-P receptor | Antagonist | Netupitant | Iatrogenic emesis | October 13, 2014 |
| Antagonist | Aprepitant | March 26, 2003 | ||
| Estrogen receptor alpha | Ligand | Synthetic conjugated estrogens, A | Postmenopausal vulvar and vaginal atrophy, vasomotor atonia | May 12, 1999 |
| Ligand | Synthetic conjugated estrogens, B | Postmenopausal vulvar and vaginal atrophy, vasomotor atonia, vaginal dryness | April 24, 2006 |
Each row gives one “target-action” pair from the 227 “pairs” available for genomic drug repurposing, with its currently associated indications.A4
BPH, benign prostatic hyperplasia; BTK, Bruton's tyrosine kinase; COPD, chronic obstructive pulmonary disease; IBS, irritable bowel syndrome; MI, myocardial infarction.