DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for tooth agenesis — screening already-approved drugs against its 30-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleTooth agenesis maps to a 30-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
No approved-drug candidate for tooth agenesis is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
Molecular view
AP2 associated kinase 1 (AAK1) — AAK1 is one of the genes genetically linked to this disease in Open Targets — shown as context, not as a drug target we're pursuing: no approved-drug candidate for this disease is yet corroborated in the literature we found.
Loading structure…
helix sheet 3zdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 5TE0 · 1.9 Å · ligand methyl (3Z)-3-{[(4-{methyl[(4-methylpiperazin-1-yl)acetyl]amino}phenyl)amino](phenyl)methylidene}-2-oxo-2,3-dihydro-1H-indole-6-carboxylate (XIN). Experimental structure, not a prediction.
What the evidence adds up to
Tooth agenesis, the congenital absence of one or more teeth, affects up to 9.6% of individuals, with higher prevalence in permanent dentition. A 2025 retrospective study of 593 patients aged 8–18 in two regions of Turkey found incisor agenesis in 2.4% of patients, premolar agenesis in 3.9%, and third molar agenesis in 19.9%. The mandibular second premolar was the most commonly missing premolar (19 patients). Regional variation was observed: incisor and premolar agenesis were more common in Central Anatolia, while third molar agenesis was more prevalent in the Mediterranean region. The left mandibular premolar and left maxillary third molar were the most frequently missing teeth in their categories across both regions.
The genetic basis of non-syndromic tooth agenesis is only partially understood. As of 2003, the only genes associated with the non-syndromic form were MSX1 and PAX9, which encode transcription factors critical during tooth development. A 2022 literature review of 32 articles from the previous 18 years expanded this list to include AXIN2, WNT10A, EDA, TGF, and SHH, noting that various forms of agenesis arise from genes that involve interacting molecular pathways. The same review stated that tooth agenesis may be present in up to 9.6% of individuals, with predominance in permanent dentition. A 2021 review noted that non-syndromic hypodontia affects up to 8% of the Caucasian population and remains a challenging clinical problem, with further research needed to establish genotype-phenotype correlation and fully understand pathogenesis.
A 2003 report of missing molars in two generations noted that tooth agenesis appears to be becoming more evident, but it is unknown whether this reflects better detection and awareness or a true increase in prevalence. The 2022 review emphasised that absence of one or several teeth disrupts craniofacial and psychosomatic development in children, who require comprehensive treatment from multiple dental specialties. No drug treatment for tooth agenesis is described in any of these abstracts.
What remains missing is any clinical trial testing a pharmacological intervention for tooth agenesis, any funding for such a trial, and any patient stratification strategy that would allow a drug to be tested against a specific genetic subtype. The genetic pathways are increasingly catalogued, but no molecular therapy has been proposed or tested in humans.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
European Journal Of Oral Sciences · 2003 · 115 citations
Molecular basis of non‐syndromic tooth agenesis: mutations of <i>MSX1</i> and <i>PAX9</i> reflect their role in patterning human dentition
AbstractTooth agenesis constitutes the most common anomalies of dental development in man. Despite this, little is known about the genetic defects responsible for this complex condition. To date, the only genes associated with the non-syndromic form of tooth agenesis are MSX1 and PAX9, which encode transcription factors that play a critical role during tooth development. This paper aims to review current literature about the molecular mechanisms responsible for selective tooth agenesis in humans.
International Journal of Paediatric Dentistry · 2003 · 14 citations
Tooth agenesis: a report of missing molars in two generations
AbstractA recent review has suggested that tooth agenesis is becoming more evident in society, though it is not known whether this observation is related to better detection methods and patient awareness or whether there is a real trend towards an increase in prevalence. In this paper we report developmental absence of permanent molars in two generations, and discuss the possible clinical implications of this pattern of tooth agenesis.
Journal of Pre-Clinical and Clinical Research · 2022 · 3 citations · open access
Tooth agenesis: genes and syndromic diseases –literature review
AbstractIntroduction and Objective. Tooth agenesis may be present even in 9.6% of individuals of both genders, with the predominance in permanent dentition. The aim of the study was to present a review of the literature on the etiology of dental agenesis, with particular emphasis on the genetic background and the associated syndromes of congenital abnormalities. Objective and Review Methods. Online databases were searched: Pubmed, GoogleScholar and Scopus. 32 articles from the last 18 years were qualified for the study and used in this review. Inclusion criteria were: children, congenital disorders, syndromic diseases, missing teeth, tooth agenesis. The study takes into account both syndromes common in the population and rare disorders. Brief description of the state of knowledge. Many genes are responsible for both isolated and syndromic tooth agenesis. The most studied and involved in the formation of this anomaly are: MSX1, PAX9, AXIN2, WNT10A, EDA, TGF, SHH. The presented study shows that various forms of agenesis are caused by genes that involve interacting molecular pathways. The course of this phenomenon is very diverse, especially in syndromes of defects accompanied by other craniofacial anomalies. Summary. The absence of one or several teeth seriously disrupts the proper development of a child, as tooth agenesis affects the craniofacial development and psychosomatic development of a patient at developmental age. Children diagnosed with missing tooth buds should receive comprehensive treatment, which includes dentists with such specialties as: maxillofacial surgeon, dental surgeon, orthodontist or prosthodontist.
Retrospective Evaluation of Tooth Agenesis in Different Regions of Turkey with Panoramic Radiography
AbstractObjectives: Dental agenesis refers to the absence of one or more teeth, occurring in both primary and permanent dentitions. It can result in several complications, impacting functional aspects of the dentition, such as chewing and speech. This study aimed to evaluate the prevalence of agenesis of permanent incisors, premolars, and third molars in patients aged 8-18. The prevalences were compared according to age, gender, and the regions they live in. Material and Methods: This study was conducted in the Central Anatolia and Mediterranean regions of Turkey. It included data from 593 patients, 304 females and 289 males. The study involved a retrospective evaluation of the patients' orthopantomographic images. Descriptive statistics were employed for the analysis. Results: In the study, the prevalence of incisor agenesis among all patients was 2.4%. Premolar agenesis was found in 3.9% of patients, with the mandibular second premolar being the most commonly missing premolar (missing in 19 patients). The prevalence of third molar agenesis was 19.9% (118 patients). Incisor and premolar agenesis were more common in the Central Anatolia region than the Mediterranean region, whereas third molar agenesis was more prevalent in the Mediterranean region. In both regions, the left mandibular premolar was the most frequently missing premolar tooth, and the left maxillary third molar was the most frequently missing third molar tooth. Conclusion: This study presents a thorough analysis of the prevalence and distribution of tooth agenesis, with a particular focus on incisors, premolars, and third molars. The results emphasize the necessity of considering gender differences and specific tooth locations in the diagnostic and therapeutic approaches to tooth agenesis.
Genetic Basis of Dental Agenesis: Non-Syndromic Hypodontia
AbstractTooth agenesis or hypodontia is one of the most prevalent developmental anomalies of the human dentition which affects up to 8% of the Caucasian population. It is a quite heterogenous condition which describes the congenital absence of one or more teeth and can occur either with a syndrome (syndromic hypodontia) or without (non-syndromic hypodontia). Hypodontia still constitutes a challenging clinical problem. Our insight on the cause of tooth agenesis is increasing as a result of recent advances in the field of molecular biology and human genetics. Further research is needed to establish a genotype phenotype correlation and to fully understand the pathogenesis of tooth agenesis. This review presents the genes and signaling pathways associated with nonsyndromic hypodontia, based on the most current literature and provides an overview of novel genes that seem to contribute to dental agenesis.
Indonesian Journal of Dental Medicine · 2018 · 0 citations · open access
HYPODONTIA WITH CLASS I MALLOCLUSION AND MAXILLARY DIASTEMA
AbstractBackground: Dental agenesis is a term that refers to the absence of one or more teeth, and hypodontia refers to a severe type of tooth agenesis involving less than six or more than one congenitally missing teeth, excluding the third molars. Purpose: This aimed to report the correction of overbite by using intrusion archwires. Case: A 20-year-old female patient had class I malocclusion and deep overbite, incisor retroclination, mild mandibular crowding and agenesis of 12, 13, 14, 15, and 24. Case management: The case was treated with non-extraction using 0.022 pre-adjusted technique to level and unravel using intrusion archwires to correct the deep overbite. Conclusion: The 17-month treatment resulted in a corrected overbite, good occlusion, and good facial aesthetics.
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.
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