Table 1.
Inhibitors of cardiomyocyte hypertrophy: class I hits.
| Compound | % Inhibition PE
|
% Inhibition PMA
|
Pharmacological class
|
Target
|
||
|---|---|---|---|---|---|---|
| Cell area | ANF | Cell area | ANF | |||
| Bromocriptine | >100 | >100 | >100 | >100 | Central nervous system (CNS) | Dopamine D2 agonist |
| Phenelzine | >100 | >100 | >100 | 94 | CNS | MAOi |
| SKF-83566 | >100 | >100 | 72 | 59 | CNS | Dopamine D1 antagonist |
| Securinine | >100 | 86 | >100 | >100 | CNS, NP | GABA (A) receptor |
| Clozapinea | >100 | 80 | 60 | 61 | CNS/antipsychotic | Multiple GPCRs |
| Perospirone | >100 | >100 | 97 | 73 | CNS/antipsychotic | Multiple GPCRs |
| Loxapine | 90 | 84 | 70 | 52 | CNS/antipsychotic | Multiple GPCRs |
| Imipraminea | >100 | 89 | >100 | 82 | CNS/antidepressant | Multiple GPCRs |
| Doxepina | >100 | 96 | 79 | 51 | CNS/antidepressant | Multiple GPCRs |
| Fluvoxaminea | >100 | 68 | >100 | 86 | CNS/antidepressant | Serotonin transporter, σ1R |
| Escitalopram | 94 | 71 | 71 | 52 | CNS/antidepressant | Serotonin transporter |
| Nortriptyline | >100 | 93 | 93 | 63 | CNS/antidepressant | Multiple GPCRs |
| Atomoxetine | >100 | 56 | >100 | 87 | CNS/ADHD | Norepinephrine transporter |
| Eticlopride | >100 | 66 | >100 | 68 | CNS | Dopamine-D2 receptor |
| Nefazodone | >100 | >100 | >100 | 86 | CNS/antidepressant | Multiple GPCRs |
| Bicalutamide | 80 | 73 | 63 | 62 | Nuclear hormone receptors (NHR) | Androgen receptor |
| RU-486 | >100 | 66 | >100 | >100 | NHR | Progesterone receptor |
| Melengestrol | 62 | 65 | 64 | 71 | NHR | Progesterone receptor? |
| Oxymetholone | 57 | 53 | 62 | 80 | NHR/Anabolic steroid | Androgen receptor? |
| Tretinoin | >100 | 82 | >100 | 83 | NHR? | Retinoic acid receptors? |
| Isotretinoin | 73 | 79 | >100 | 75 | NHR? | Retinoic acid receptors? |
| Tiratricol | >100 | >100 | >100 | >100 | NHR? | Thyroid hormone receptors? |
| Ethopropazine | >100 | 92 | >100 | 68 | Anticholinergic | Multiple GPCRs |
| Mebeverine | >100 | 97 | >100 | 67 | Antimuscarinic | Muscarinic receptors |
| Clemizole | >100 | >100 | >100 | 83 | Antihistamine | Histamine H1 receptor |
| Naftopidilb | >100 | >100 | 82 | 87 | Cardiovascular | α-1 adrenergic receptorb |
| Labetalol | 69 | 69 | 55 | 64 | Cardiovascular | Mixed α/β blocker |
| Cloperastine | >100 | >100 | >100 | 93 | Antitussive | Multiple GPCRs? |
| Candesartan | >100 | 100 | >100 | >100 | Cardiovascular | Angiotensin receptor |
| Penbutolol | 85 | 81 | 60 | 64 | Cardiovascular | β-adrenergic receptors |
| Nicardipine | >100 | 99 | 91 | 83 | Cardiovascular | Calcium channel blocker |
| Verapamil | 74 | 71 | 65 | 67 | Cardiovascular | Calcium channel blocker |
| Propafenonea | >100 | 81 | >100 | 89 | Cardiovascular/anti-arrhythmic | Sodium channel blocker |
| Benoxinate | >100 | 84 | 96 | 56 | CNS | Sodium channel blocker |
| Vorinostat | >100 | 95 | 99 | 95 | Cancer | HDAC inhibitor |
| Atorvastatin | >100 | 80 | 82 | 92 | Cardiovascular/dyslipidemia | HMG-CoA reductase |
| Cerivastatin | >100 | >100 | >100 | >100 | Cardiovascular/dyslipidemia | HMG-CoA reductase |
| Mevastatin | >100 | 60 | >100 | >100 | Cardiovascular/dyslipidemia | HMG-CoA reductase |
| Lovastatina | >100 | 60 | >100 | >100 | Cardiovascular/dyslipidemia | HMG-CoA reductase |
| Ezetimibe | >100 | 62 | 89 | 78 | Dyslipidemia | NPC1L1 |
| Diphenoxylate | >100 | >100 | >100 | >100 | Antidiarrheal | Opioid receptor(s) |
| GR 89696 | 98 | 67 | 69 | 58 | Analgesic? | β-opioid receptor agonist |
| Phenazopyridine | >100 | 70 | 88 | 79 | Analgesic | Unknown |
| Mycophenolate mofetil | 73 | 76 | 79 | 89 | Immune suppressant | IMDH inhibitor |
| Ketoconazole | >100 | 64 | 63 | 64 | Antifungal | 14-α demethylase, PXR |
| Itraconazole | >100 | 78 | >100 | >100 | Antifungal | 14-α demethylase |
| Artesunate | >100 | 86 | >100 | >100 | Antimalarial | Unknown |
| Rifabutin | >100 | 44 | 110 | 107 | Antibiotic | RNA polymerase |
| Irinotecan | 81 | 56 | 71 | 57 | Antineoplastic | Topoisomerase |
| Carmofur | 76 | 51 | 79 | 91 | Antineoplastic | Pyrimidine analog |
| 5-Azacytidine | 85 | 79 | 80 | 67 | Antineoplastic | DNA methyltransferase |
| Dihydrogedunin | 93 | 84 | 98 | 82 | Natural products (NP) | Unknown |
| α-Dihydrogedunol | >100 | 88 | 69 | 71 | NP | Unknown |
| Khayanthone | 93 | 75 | 78 | 68 | NP | Unknown |
| Gangaleoidin | >100 | 82 | >100 | >100 | NP | Unknown |
| 4′-Hydroxychalcone | >100 | 95 | 88 | 99 | NP | Unknown |
| Avocadyne | >100 | 97 | 100 | 74 | NP | Unknown |
| Abietic acid | 94 | 81 | 58 | 73 | NP | Unknown |
Some compounds with structures and/or mechanisms of action that are unlikely to be of therapeutic interest were intentionally omitted from this summary table.
a
Scored as hits in both NIHcc and Spectrum collections.
b
Other α-adrenergic antagonists were not effective against PMA-mediated hypertrophy. Naftopidil has also been reported to inhibit TGF-β signaling.