Aminotadalafil: An Evidence Ledger

One substitution away from an approved drug

Tadalafil carries a methyl group on one nitrogen of its diketopiperazine ring. Aminotadalafil carries an amino group in that position. The exchange removes a carbon and adds a nitrogen: C22H19N3O4 at 389.4 g/mol becomes C21H18N4O4 at 390.4 g/mol, a difference of one mass unit. Identity was checked this session against three registries that maintain their records independently. PubChem CID 10178467, ChEMBL1774619 and the FDA Global Substance Registration System agree on formula and mass, and GSRS carries CAS 385769-84-6 with UNII FY501QO030 and an average weight of 390.3928.

Stereochemistry is where the registries become more interesting than the formula. The primary entries describe the (6R,12aR) configuration, matching tadalafil. GSRS separately registers a (6S,12aR) diastereomer under its own identifier, UNII 501VYL2GEG and CAS 1093940-70-5, and PubChem holds it as CID 25273568. Two registered diastereomers share a molecular formula, a nominal mass and, in most published methods, a retention window. Lee and colleagues used circular dichroism when they characterised a related analogue in 2013, which is the technique that settles the question; target-screening papers generally do not report whether their separation resolves the pair.

Legal position is unambiguous and worth stating plainly. Aminotadalafil is not an approved medicine in any jurisdiction. ChEMBL records no development phase for it. It appears in no approval register located this session, and the regulatory documents that name it treat its presence in a consumer product as an undeclared drug ingredient rather than as an ingredient with a permitted use.

The literature is analytical chemistry

PubMed returns nine records for aminotadalafil, searched 18 August 2026. Every one of the nine is an analytical paper: structure elucidation of material isolated from a product, or a chromatographic method for finding the compound in a matrix. A full-text search of Europe PMC returns nineteen, and the additional ten are reviews and surveys that mention the name in passing. No record in either set measures what the molecule does.

Origins of the assignment sit with the FDA Forensic Chemistry Center. Gratz, Gamble and Flurer published accurate-mass work in 2006 using Fourier transform ion cyclotron resonance mass spectrometry, reporting a measurement error of 0.1 ppm on the protonated molecule of aminotadalafil and assigning elemental compositions to its fragment ions. What followed is a distributed public-health literature rather than a research programme: Osaka Prefectural Institute of Public Health in 2008, Swissmedic in 2010, the FDA Division of Pharmaceutical Analysis in 2010, the Korea Food and Drug Administration in 2013, a Buenos Aires university group in 2015, the California Department of Public Health in 2020, the National Institute for Food Control in Hanoi in 2021, and the National Institute for Food and Drug Control in Beijing in 2024.

Shape of that record matters more than its size. The compound is thoroughly characterised as an analyte and not characterised at all as a pharmacological agent: there is a validated way to find it in a capsule, a wine and an aerosol cartridge, and no published account of what it does to an enzyme, a cell or an animal. Publication types and correction links were checked on every PMID cited here. None carries a retraction, a notice of concern or an erratum.

The only measured biology is a malaria screen

Beghyn and colleagues published a paper in the Journal of Medicinal Chemistry in 2011 built on an unusual premise: both humans and Plasmodium falciparum possess cyclic nucleotide phosphodiesterases, so analogues of a human PDE5 inhibitor might kill the parasite. Forty tadalafil analogues were synthesised and tested directly on the parasite in culture. Aminotadalafil was one of the compounds in the set.

Results for it are two numbers, both ceilings. Against the chloroquine-susceptible GHA strain of P. falciparum in human erythrocytes at 72 hours, the reported IC50 was greater than 64 micromolar. In the counter-screen for cytotoxicity against human MRC5 SV2 cells at 72 hours, the reported IC50 was also greater than 64 micromolar. A greater-than qualifier at the top of the tested range means the compound did nothing measurable at the highest concentration used. Both records are curated in ChEMBL under CHEMBL1774619 and mirrored in PubChem BioAssay as AIDs 597188 and 597189.

Those two rows are the entire measured-biology file for this molecule. ChEMBL holds two activity records for it and PubChem BioAssay holds the same two. The 2011 paper also ran phosphodiesterase inhibition assays on plasmodial PDE at 20 micromolar, and aminotadalafil has no record in either of them. Neither database holds an assay of this compound against human PDE5. A PubMed search pairing the name with PDE5 or phosphodiesterase returns seven records, all of them method papers that use the phrase to name a class of analytes.

Where it has been found

FDA maintains a Health Fraud Product Database of products found to contain undeclared drug ingredients. Retrieved on 18 August 2026, it held 2,194 dated product entries, of which eleven name undeclared aminotadalafil. The earliest is dated 16 March 2007 and the most recent 3 March 2017: five public notifications, five recalls and one safety alert, with nothing added in the nine years since. Five of the eleven list aminotadalafil alongside at least one undeclared sildenafil analogue. The hazard described in those notifications is interaction with nitrates and a fall in blood pressure, and the text reaches that hazard by identifying the compound as an analogue of tadalafil rather than by citing a measurement made on the analogue.

Concentrations appear once. Nguyen and colleagues screened 92 herbal supplements and ingredients on the Vietnamese market in 2021 and found PDE-5 inhibitors in twenty. One sample carried aminotadalafil at 0.52 plus or minus 0.05 mg/g, alongside sildenafil at 5.25, tadalafil at 4.77 and sildenafil N-oxide at 0.56 mg/g. The authors read the pattern as intentional addition of the high-concentration compounds with the trace-level ones arriving as by-products of their manufacture. One internal inconsistency belongs on the record: aminotadalafil is quantified in the paper's concentration table but absent from the preceding table listing the fourteen compounds the screen detected.

Matrices vary more than the product category suggests. FDA analysts identified amino-tadalafil in electronic cigarette cartridges in 2010. Swissmedic chemists isolated an unknown from an illegal health-food product the same year and characterised it as a condensation product of aminotadalafil and hydroxymethylfurfural, attributing it to drug-excipient incompatibility. Korean investigators found an acetylated derivative, acetaminotadalafil at C23H20N4O5, in a bulk powder being sold as a supplement ingredient. A 2008 Japanese paper reported aminotadalafil in one product together with hydroxyhomosildenafil and a chloroacetyl tadalafil analogue.

What the detection record does not settle

Detection papers report presence, not amount. Of the primary studies naming aminotadalafil, exactly one publishes a concentration in a real sample. The rest are method development, structure elucidation, or screening summaries that record a compound as found without saying how much. Any statement about the quantity a consumer of an adulterated product would have encountered rests on a single measurement in a single sample.

Negative results carry more weight here than usual, because at least one is quantified. Jin and colleagues at the National Institute for Food and Drug Control in Beijing built a 90-compound UPLC-MS/MS panel that includes aminotadalafil, with limits of detection for it of 45 to 79 ng/g across tablets, capsules and protein powder and 36 to 46 ng/mL in wine and beverages. Of 286 batches screened, eight were positive: sildenafil in six tablet batches, 2-hydroxypropyl nortadalafil in a wine, N-ethyltadalafil in a capsule. Aminotadalafil was looked for at those limits and not found.

Immunoassay work adds a detection figure that is frequently repurposed. Yang and colleagues designed haptens for a group-screening ELISA covering tadalafil, amino tadalafil, acetamino tadalafil, nortadalafil and N-desmethyl ent-tadalafil, and reported 50 percent inhibition concentrations across those five compounds spanning 0.89 to 4.27 ng/mL. That number describes how tightly a compound binds an antibody raised against a hapten. It is not an enzyme inhibition constant, and it does not become one when it is reprinted under a heading about PDE5.

The human record is empty

ClinicalTrials.gov returns zero studies for aminotadalafil, searched 18 August 2026. Splitting the term into two words returns eleven, and all eleven are tadalafil studies matched on separate tokens: oncology combinations with checkpoint inhibitors, pre-clinical heart failure, erectile dysfunction, overactive bladder. None of them involves the analogue, and the registry holds no interventional or observational study in which aminotadalafil is administered, measured, or named as a comparator.

Nothing sits behind the registry gap either. A PubMed search pairing aminotadalafil with pharmacokinetics returns zero records; with metabolism or metabolite, zero; with impurity, zero. No study in any animal species was located. No published toxicology exists for the compound. The single PubMed record returned by pairing the name with case-report and adverse-event terms is the 2015 Argentine chemistry paper, which contains no patient.

Distinction between what has been measured and what has been inferred is the whole of this record. What has been measured: a molecular formula, an exact mass, a set of fragment ions, a retention time, a detection limit, one concentration in one product, and inactivity against a malaria parasite at 64 micromolar. What has been inferred: that a compound built on the tadalafil scaffold behaves like tadalafil in a human body. Regulators state that inference openly and act on it, which is a defensible way to run a public-health programme and is not the same thing as data.

What is not known

Almost everything about aminotadalafil's behaviour in a living organism is unknown. There is no pharmacokinetic study in any species, no metabolism or excretion work, no dose-response relationship, no exposure data, no toxicology and no genotoxicity assessment. No animal has been given the compound in any published experiment located this session. The single measured biological endpoint is inactivity in a malaria growth assay and its cytotoxicity counter-screen, both capped at 64 micromolar, which establishes only that the compound did nothing detectable in those two systems at that concentration. Its activity against human PDE5, the property that the entire commercial and regulatory framing assumes, has never been measured and published: no such assay exists in ChEMBL or PubChem BioAssay, and no PubMed record reports one. Human data of any kind are absent, ClinicalTrials.gov holds no study naming the compound, and no clinical case report attributes an outcome to it. On the analytical side the gaps are narrower but real: only one paper publishes a concentration in a real product, so the distribution of amounts present in adulterated goods is uncharacterised; the stereochemical identity of material found in products is confirmed only where circular dichroism was used, and two diastereomers are separately registered; and no stability or degradation study exists beyond the single Swissmedic isolation of a hydroxymethylfurfural condensation product, which demonstrates that the molecule reacts with excipient degradation products without characterising how fast or under what conditions.

Questions