Repositioning Candidate Details
| Candidate ID: | R0951 |
| Source ID: | DB06237 |
| Source Type: | approved |
| Compound Type: | small molecule |
| Compound Name: | Avanafil |
| Synonyms: | (S)-4-(3-Chloro-4-methoxybenzylamino)-2-(2-hydroxymethylpyrrolidin-1-yl)-N-pyrimidin-2-ylmethyl-5-pyrimidinecarboxamide; Avanafil |
| Molecular Formula: | C23H26ClN7O3 |
| SMILES: | COC1=C(Cl)C=C(CNC2=C(C=NC(=N2)N2CCC[C@H]2CO)C(=O)NCC2=NC=CC=N2)C=C1 |
| Structure: |
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| DrugBank Description: | Avanafil is a phosphodiesterase-5 (PDE5) inhibitor used in the treatment of erectile dysfunction. In comparison with other drugs of the same class, it shows greater selectivity for PDE5 over PDE6 than both and but less selectivity than , suggesting a relatively lower risk of visual disturbances associated with off-target PDE6 inhibition. It first received FDA approval on April 27, 2012, with subsequent EMA approval in June 2013. |
| CAS Number: | 330784-47-9 |
| Molecular Weight: | 483.951 |
| DrugBank Indication: | Avanafil is indicated for the treatment of erectile dysfunction. |
| DrugBank Pharmacology: | Avanafil is a strong competitive inhibitor of phosphodiesterase 5 (PDE5) with a demonstrated _in vitro_ IC<sub>50</sub> of 5.2 nM. Its inhibitory effects on PDE5 are 100-fold more potent than on PDE6 and >1000-fold more potent than on other PDE enzymes, meaning it is less likely to cause visual disturbances and cardiovascular adverse effects when compared with less selective PDE5 inhibitors such as and . It has a relatively quick onset of action allowing for administration as early as 15 minutes prior to sexual activity. PDE5 inhibitors like avanafil can cause significant drug interactions when administered alongside certain antihypertensive agents (e.g. alpha blockers, substantial amounts of alcohol). PDE5 inhibitors have also been associated with the development of non-arteritic anterior ischemic optic neuropathy (NAION), a rare condition that typically presents as sudden loss of vision in one or both eyes and appears to be more common in patients with a "crowded" optic disc. Patients presenting with any degree of vision loss should immediately discontinue use of all PDE5 inhibitors and seek medical attention. In some jurisdictions, a history of NAION or other degenerative retinal disorders is considered a contraindication to avanafil therapy. |
| DrugBank MoA: | Avanafil inhibits the cGMP-specific phosphodiesterase type 5 (PDE5) which is responsible for the degradation of cGMP in the corpus cavernosum located around the penis. Sexual arousal results in the local release of nitric oxide, which in turn stimulates the enzyme guanylate cyclase to produce cGMP. Elevated levels of cGMP result in local smooth muscle relaxation and increased blood flow to the penis (i.e. an erection). As PDE5 inhibitors like avanafil require the endogenous release of nitric oxide in order to exert their pharmacologic effect, they have no effect on the user in the absence of sexual stimulation/arousal. |
| Targets: | cGMP-specific 3',5'-cyclic phosphodiesterase inhibitor |
| Inclusion Criteria: | Therapeutic strategy associated |
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