DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for cleft lip — screening already-approved drugs against its 32-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleCleft lip maps to a 32-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 cleft lip 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
CREB binding lysine acetyltransferase (CREBBP) — CREBBP 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 1vudrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 9H0K · 1.75 Å · ligand propionyl Coenzyme A (1VU). Experimental structure, not a prediction.
What the evidence adds up to
The abstracts provided contain no drug repurposing studies for cleft lip. Research from 2008, 2015, and 2020 describes genetic and signalling pathway contributions to cleft lip and palate, including IRF6, MSX1, FGF family genes, and Shh signalling, but states that the functional variants and detailed mechanisms linking these pathways to the defect remain undefined. Maternal cigarette smoking is identified as a risk factor, particularly in mothers carrying GSTT1-null variants. No therapeutic intervention is tested or proposed in these papers.
Two systematic reviews of surgical treatment, published in 2014 and 2022, conclude that there is no consensus on the optimal surgical technique, that the severity of the cleft guides the choice of technique, and that surgeon experience is a determining factor. A 2013 paper catalogues unfavourable results after unilateral and bilateral cleft lip repair, including dehiscence, scarring, vermillion notching, lip shortening, white roll malalignment, fistulae, and nasal deformities, and describes management options based on the authors’ experience.
No drug, no compound, no pharmacological agent is mentioned in any of these abstracts. There are no data on survival, response rates, or sample sizes relevant to drug treatment. The research remains at the level of genetic association and surgical technique, with no evidence for any medical therapy that could prevent or treat cleft lip.
What is missing is any clinical trial of a drug for cleft lip, any funding for drug repurposing in this condition, and any patient stratification based on the genetic variants that have been identified but not yet functionally linked to the defect. Without these, no pharmacological approach can be evaluated.
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 Dental Research · 2008 · 238 citations
Unraveling Human Cleft Lip and Palate Research
AbstractThe focus of this work is to highlight the most recent advances in the understanding of cleft lip and palate occurrence. Information regarding research on long-term outcomes, genes and their interactions with other genes, and gene-environment interactions is compiled to provide the reader with a critical and up-to-date overview on the current knowledge of the etiology of cleft lip and palate. Recent epidemiological evidence strongly suggests that individuals born with clefts have a shorter lifespan and may have a higher incidence of cancer and psychological disorders. IRF6 has been shown to be an important contributor to cleft lip and palate, but the functional variant leading to the defect has not yet been defined. Inactivation of MSX1 and genes in the FGF family has also been shown to lead to cleft lip and palate. In addition, missense mutations in several candidate genes may cause cleft lip and palate, but definitive evidence regarding the biological consequences of these mutations is yet to be unraveled. Maternal cigarette smoking increases the risk of a baby born with clefts, in particular when the mother carries the GSTT1-null variants. The latest approaches in cleft research include the analysis of several additional phenotypical features of the population, with the goal of increasing the statistical power of genetics studies.
BioMed Research International · 2015 · 37 citations · open access
The Roles of Hedgehog Signaling in Upper Lip Formation
AbstractCraniofacial development consists of a highly complex sequence of the orchestrated growth and fusion of facial processes. It is also known that craniofacial abnormalities can be detected in 1/3 of all patients with congenital diseases. Within the various craniofacial abnormalities, orofacial clefting is one of the most common phenotypic outcomes associated with retarded facial growth or fusion. Cleft lip is one of the representative and frequently encountered conditions in the spectrum of orofacial clefting. Despite various mechanisms or signaling pathways that have been proposed to be the cause of cleft lip, a detailed mechanism that bridges individual signaling pathways to the cleft lip is still elusive. Shh signaling is indispensable for normal embryonic development, and disruption can result in a wide spectrum of craniofacial disorders, including cleft lip. This review focuses on the current knowledge about the mechanisms of facial development and the etiology of cleft lip that are related to Shh signaling.
Indian Journal of Plastic Surgery · 2013 · 27 citations · open access
Unfavourable results in the repair of the cleft lip
AbstractINTRODUCTION: Unfavorable results in unilateral and bilateral cleft lip repair are often easy to spot but not always easy to prevent as to treat. We have tried to deal with the more common problems and explain possible causes and the best possible management options from our experience. UNILATERAL CLEFT LIP REPAIR: Unfavorable results immediately after repair involve Dehiscence and Scaring. Delayed blemishes include vermillion notching, a short lip, deficiency in the height of the lateral vermillion on the cleft side, white roll malalignment, oro-vestibular fistula, the cleft lip nose deformity, a narrow nostril and a "high-riding" nostril. We analyze the causes of these blemishes and outline our views regarding the treatment of these. BILATERAL CLEFT LIP: Immediate problems again include dehiscence as also loss of prolabium or premaxilla. Delayed unfavorable results are central vermillion deficiency, a lip that is too tight, bilateral cleft lip nose deformity, problems with the premaxilla and maxillary growth disturbances. Here again we discuss the causation of these problems and our preferred methods of treatment. CONCLUSION: We have detailed the significant unfavorable results after unilateral and bilateral cleft lip surgery. The methods of treatment advocated have been layer from our own experience.
Revista do Colégio Brasileiro de Cirurgiões · 2014 · 23 citations · open access
Surgical treatment of cleft lip
AbstractWe performed a systematic review of the literature on the surgical treatment of cleft lip, emphasizing the prevalence, complications associated with the treatment and the points of disagreement between authors. We conducted a literature cross-sectional search that analyzed publications in books, articles and on the databases SciELO - Scientific Electronic Library Online, PubMed, of the National Center for Biotechnology Information. We conclude that: 1) the severity of the cleft will indicate the technique presenting more advantages; 2) the different approaches indicate that there is no consensus on the optimal technique; and 3) the surgeon experience contributes to choosing the best option.
INDIGO (University of Illinois at Chicago) · 2022 · 0 citations · open access
Surgical treatment of cleft lip
AbstractWe performed a systematic review of the literature on the surgical treatment of cleft lip, emphasizing the prevalence, complications associated with the treatment and the points of disagreement between authors. We conducted a literature cross-sectional search that analyzed publications in books, articles and on the databases SciELO - Scientific Electronic Library Online, PubMed, of the National Center for Biotechnology Information. We conclude that: 1) the severity of the cleft will indicate the technique presenting more advantages; 2) the different approaches indicate that there is no consensus on the optimal technique; and 3) the surgeon experience contributes to choosing the best option.
[Key signaling pathways associated with risks forcleft lip and palate].
AbstractThe molecular mechanism of cleft lip and palate has been a hot topic for research in recent years. With the development of genetic technology, more than 100 genes have been associated with cleft lip and palate, though the pathological mechanism of such genes has not been delineated.The information carried by each of these genes may affect the phenotype through signal pathway, and abnormal function of these signal pathways has been found in the formation of cleft lip and palate. A series of signal factors have known to involve in the regulation of gene expression, and may interact with each other to form complex signal regulatory networks which are involved in the guidance of cell activity and tissue formation. This article has summarized several signal pathways related to lip and palate, and the molecular mechanism underlying the development of lip and palate.
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.
