DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for BH4-deficient hyperphenylalaninemia A — screening already-approved drugs against its 6-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleBH4-deficient hyperphenylalaninemia A maps to a 6-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
approvedTetrahydrobiopterinApproved drug
Structures already discussed alongside bh4-deficient hyperphenylalaninemia a in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
BOVINE ENDOTHELIAL NITRIC OXIDE SYNTHASE HEME DOMAIN — Tetrahydrobiopterin has a real, experimentally solved structure in complex with this target (PDB 1D1V, 1.93 Å). This is the drug's own deposited structure, not a prediction, and confirms it is a structurally characterised molecule rather than an untested guess.
Loading structure…
helix sheet h4bdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 1D1V · 1.93 Å · ligand Tetrahydrobiopterin (H4B). Experimental structure, not a prediction.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Journal of Pediatric Endocrinology and Metabolism · 2018 · 20 citations · open access
Molecular genetics of tetrahydrobiopterin deficiency in Chinese patients
AbstractBackground The overall incidence of hyperphenylalaninemia (HPA) in China is 1:11,763, with tetrahydrobiopterin (BH4) deficiency accounting for 8.55% of patients with HPA in the mainland. Much progress has been made in the diagnosis and treatment of BH4 deficiency with the introduction of neonatal screening in China. However, the screening rate is still low and screening is not universally available. Methods A total of 44 BH4-deficient patients were enrolled in this study, of which 39 were diagnosed with BH4 deficiency, while the remaining five showed typical characteristics of BH4 deficiency at a later period. The entire coding regions and adjacent intronic regions of GCH1, PTS, PCBD1 and QDPR genes were analyzed using target sequencing. Results Nineteen (n=19) different mutations in the PTS gene including four novel mutations and one mutation in QDPR were identified. p.P87S, p.D96N, IVS1-291A>G, p.N52S, p.K91R, p.V56M, p.T106M and p.F40GfsX53 in PTS were the prevalent mutations with ≥3% relative frequency. The mutation p.R221X in the QDPR gene was found with relatively lower frequencies (2.27%). The remaining 12 mutations in PTS were found at relative frequencies of 1.14%. Conclusions The results could be of value for genetic counseling and prenatal diagnosis in the patients' families and for the molecular diagnosis of BH4 deficiencies. Furthermore, four novel mutations expand and improve the PTS mutation database.
Ambiance in Life International Scientific Journal in Medicine of Southern Caucasus · 2021 · 0 citations · open access
HYPERPHENYLALANINEMIA: CASE REPORT
AbstractBackground: Hyperphenylalaninemia (HPA) is a group of autosomal recessive diseases caused by impaired metabolism of the essential amino acid phenylalanine (Phe), which enters the human body with protein food [1]. HFA combines several genetically heterogeneous forms of phenylalanine metabolism disorders similar in clinical features: classical phenylketonuria (PKU), caused by phenylalanine-4-hydroxylase (PAH) deficiency and hyperphenylalaninemia (HPA), associated with tetrahydrobiopterin (BH4) metabolic disorders [2]. The pterin-dependent form of hyperphenylalaninemia accounts for about 2% of all cases of HPA. These conditions are caused by a deficiency of enzymes involved in the synthesis or reduction of tetrahydrobiopterin (BH4), which is a PAH cofactor, as well as tyrosine hydroxylase and tryptophan hydroxylase [3, 4]. Currently, several genetically heterogeneous forms of BH4-deficient HPA are known: type A, 6-pyruvoyltetrahydropterine synthase (PTPS) deficiency, type B, guanosine triphosphate cyclohydrolase 1 (GTPCH) deficiency, type C, dihydropterine reductase (DHPR) deficiency, type D, pterin-4a-α-carbinolamine dehydratase (PCBD) deficiency, DOPA-dependent dystonia caused by sepiapterin reductase (SPR) deficiency and HPA without tetrahydrobiopterin deficiency, caused by mutations in the DNAJC12 gene encoding the JDP1 protein [5, 6]. Pterin-dependent forms of HPA have clinical manifestations similar to classical PKU. In these forms, the main role in the pathogenesis is played by a severe deficiency in the neurotransmitters of the catecholamine and serotonin series, which makes isolated diet therapy meaningless and requires different approaches to treatment. The complex of treatment for such patients includes BH4 or its synthetic analogs [3-5].
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
DeCure is a research and publication project, not medical advice and not a treatment. "DeCure for X" describes a research goal, not a claim that a cure exists. Backing a cure is a contribution to fund the research — it is not an investment, and confers no yield, royalty, equity or IP ownership. Papers are published open-access by the DeCure.ai DAO.
