DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for hypotrichosis — screening already-approved drugs against its 5-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleHypotrichosis maps to a 5-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
approvedBimatoprostApproved drug
Structures already discussed alongside hypotrichosis in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
Crystal structure of prostaglandin F synathase containing bimatoprost — Bimatoprost has a real, experimentally solved structure in complex with this target (PDB 2F38, 2.0 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 15mdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 2F38 · 2.0 Å · ligand Bimatoprost (15M). Experimental structure, not a prediction.
What the evidence adds up to
Autosomal recessive hypotrichosis (ARH) in five Japanese families was traced to two founder mutations in the LIPH gene: c.736T>A (p.Cys246Ser) in all five families, and c.742C>A (p.His248Asn) in four. Both mutations abolished the hydrolytic activity of PA-PLA₁α and its ability to activate the P2Y5 receptor, linking defective 2-acyl lysophosphatidic acid production to the hair loss. A separate 2015 study identified a novel frameshift deletion (c.932delC) in one family and a previously reported 2-bp deletion (c.659_660delTA) in five other families with autosomal recessive hypotrichosis and woolly hair, extending the evidence that LIPH sequence variants cause the phenotype.
A 2020 case study of a single patient with loose anagen hairs found compound heterozygous missense mutations in TKFC (c.574G>C, p.Gly192Arg; c.682C>T, p.Arg228Trp). Recombinant proteins carrying either mutation showed almost no dihydroxyacetone kinase or D-glyceraldehyde kinase activity, and FMN cyclase activity was reduced to 10% of wildtype. The authors proposed that TKFC mutations may predispose to loose anagen hair, but this rests on one affected individual.
In 2025, six patients from five Chinese families with hypotrichosis 14 were reported to carry five novel LSS gene variants (c.919_921del, c.1987C>T, c.982C>T, c.1405_1407del, c.193_200dup). One patient had hypergonadotropic hypogonadism, a rare accompanying feature. The authors noted that treatment for this condition remains elusive.
The only interventional trial identified was a randomised controlled trial of bimatoprost ophthalmic solution 0.03% for eyelash hypotrichosis. In idiopathic hypotrichosis, the responder rate at month 4 was 40.2% for bimatoprost versus 6.8% for vehicle; in chemotherapy-induced hypotrichosis, the responder rate was 37.5% versus 18.2%. Efficacy was maintained or enhanced at 12 months, but effects diminished markedly 4–6 months after cessation. No drug-related serious adverse events were reported. The trial was limited to eyelash growth and did not address scalp hypotrichosis.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Human Mutation · 2010 · 57 citations
Prevalent<i>LIPH</i>founder mutations lead to loss of P2Y5 activation ability of PA-PLA<sub>1</sub>α in autosomal recessive hypotrichosis
AbstractAutosomal recessive hypotrichosis (ARH) is characterized by sparse hair on the scalp without other abnormalities. Three genes, DSG4, LIPH, and LPAR6 (P2RY5), have been reported to underlie ARH. We performed a mutation search for the three candidate genes in five independent Japanese ARH families and identified two LIPH mutations: c.736T>A (p.Cys246Ser) in all five families, and c.742C>A (p.His248Asn) in four of the five families. Out of 200 unrelated control alleles, we detected c.736T>A in three alleles and c.742C>A in one allele. Haplotype analysis revealed each of the two mutant alleles is derived from a respective founder. These results suggest the LIPH mutations are prevalent founder mutations for ARH in the Japanese population. LIPH encodes PA-PLA(1)alpha (LIPH), a membrane-associated phosphatidic acid-preferring phospholipase A(1)alpha. Two residues, altered by these mutations, are conserved among PA-PLA(1)alpha of diverse species. Cys(246) forms intramolecular disulfide bonds on the lid domain, a crucial structure for substrate recognition, and His(248) is one amino acid of the catalytic triad. Both p.Cys246Ser- and p.His248Asn-PA-PLA(1)alpha mutants showed complete abolition of hydrolytic activity and had no P2Y5 activation ability. These results suggest defective activation of P2Y5 due to reduced 2-acyl lysophosphatidic acid production by the mutant PA-PLA(1)alpha is involved in the pathogenesis of ARH.
British Journal of Dermatology · 2014 · 49 citations · open access
Long‐term safety and efficacy of bimatoprost solution 0·03% application to the eyelid margin for the treatment of idiopathic and chemotherapy‐induced eyelash hypotrichosis: a randomized controlled trial
AbstractBACKGROUND: Bimatoprost ophthalmic solution 0·03% is approved in several countries for the treatment of eyelash hypotrichosis. Previous trials were limited to 4 months of treatment and primarily idiopathic hypotrichosis. OBJECTIVES: To evaluate the long-term safety and efficacy of bimatoprost in patients with idiopathic or chemotherapy-induced hypotrichosis. METHODS: This multicentre, double-masked, randomized, parallel-group study included two 6-month treatment periods [treatment period 1 (TP1) and treatment period 2 (TP2)]. Patients with idiopathic hypotrichosis were randomized to three treatment groups: (i) bimatoprost (TP1 and TP2); (ii) bimatoprost (TP1) and vehicle (TP2); and (iii) vehicle (TP1) and bimatoprost (TP2). Patients with chemotherapy-induced hypotrichosis were randomized to two treatment groups: (i) bimatoprost or vehicle (TP1) and (ii) bimatoprost (TP2). Primary end point was a composite of at least a one-grade improvement in investigator-assessed Global Eyelash Assessment and at least a three-point improvement in patient-reported Eyelash Satisfaction Questionnaire Domain 2 at month 4. Secondary measures included digitally assessed eyelash characteristics. RESULTS: The primary efficacy end point was met in both populations (idiopathic responder rate was 40·2% for bimatoprost vs. 6·8% for vehicle; postchemotherapy responder rate was 37·5% for bimatoprost vs. 18·2% for vehicle). Efficacy by month 6 was maintained (idiopathic) or enhanced (postchemotherapy) at 12 months. Treatment effects were maintained for approximately 2 months but markedly diminished 4-6 months following treatment cessation in patients with idiopathic hypotrichosis. No drug-related serious adverse events were reported. CONCLUSIONS: Daily treatment with bimatoprost ophthalmic solution 0·03% for 1 year was effective and well tolerated in patients with idiopathic and chemotherapy-induced hypotrichosis.
British Journal of Dermatology · 2020 · 13 citations · open access
Autosomal recessive hypotrichosis with loose anagen hairs associated with <i>TKFC</i> mutations*
AbstractBACKGROUND: Loose anagen hair is a rare form of impaired hair anchorage in which anagen hairs that lack inner and outer root sheaths can be gently and painlessly plucked from the scalp. This condition usually occurs in children and is often self-limiting. A genetic basis for the disorder has been suggested but not proven. A better understanding the aetiology of loose anagen hair may improve prevention and treatment strategies. OBJECTIVES: To identify a possible genetic basis of loose anagen hair using next-generation DNA sequencing and functional analysis of variants identified. METHODS: In this case study, whole-exome sequencing analysis of a pedigree with one affected individual with features of loose anagen hair was performed. RESULTS: The patient was found to be compound heterozygous for two single-nucleotide substitutions in TKFC resulting in the following missense mutations: c.574G> C (p.Gly192Arg) and c.682C> T (p.Arg228Trp). Structural analysis of human TKFC showed that both mutations are located near the active site cavity. Kinetic assays of recombinant proteins bearing either of these amino acid substitutions showed almost no dihydroxyacetone kinase or D-glyceraldehyde kinase activity, and FMN cyclase activity reduced to just 10% of wildtype catalytic activity. CONCLUSIONS: TKFC missense mutations may predispose to the development of loose anagen hairs. Identification of this new biochemical pathobiology expands the metabolic and genetic basis of hypotrichosis.
Pediatric Dermatology · 2015 · 5 citations · open access
Frameshift Sequence Variants in the Human Lipase‐H Gene Causing Hypotrichosis
AbstractHypotrichosis is a condition of abnormal hair pattern characterized by sparse to absent hair on different parts of the body, including the scalp. The condition is often characterized by tightly curled woolly hairs, discoloration of hair, and development of multiple keratin filled cysts or papules on the body. Sequence analysis of the lipase H (LIPH) gene, mapped on chromosome 3q27.3, led to the identification of a novel frameshift deletion variant (c.932delC, p.Pro311Leufs*3) in one family and previously reported 2-bp deletion (c.659_660delTA) in five other families, inherited hypotrichosis, and woolly hair in an autosomal recessive pattern. The study further extends the body of evidence that sequence variants in the LIPH gene result in hypotrichosis and woolly hair phenotype.
Hypotrichosis 14: novel variants of the LSS gene in five Chinese families and insights from literature review
AbstractBACKGROUND: Congenital hypotrichosis 14 is a nonsyndromic form of alopecia associated with pathogenic variants in the lanosterol synthase (LSS) gene. Recent studies have expanded the spectrum of LSS-related phenotypes, including congenital cataracts, alopecia-intellectual disability syndrome, and palmoplantar keratoderma. Currently, investigations into this disease are still limited, and its treatment remains elusive. METHODS: In this study, we aimed to report six Chinese patients who were diagnosed with hypotrichosis 14, whose conditions were attributed to five novel and recurrent variants in the LSS gene identified via whole exome sequencing. Moreover, the reported LSS gene has also been summarized. RESULTS: We described six patients in five Chinese families with hair loss, and one of whom had a rare accompanying phenotype of hypergonadotropic hypogonadism, which has rarely been reported. Five novel variants were discovered in the LSS gene, including c.919_921del (p.His307del), c.1987 C > T (p.Arg663Trp), c.982 C > T (p.Arg328*), c.1405_1407del (p.Glu469del) and c.193_200dup (p.Pro68Argfs*14). CONCLUSIONS: Our comprehensive summary of phenotypes caused by LSS gene variants not only enriches the existing knowledge on congenital hypotrichosis 14 but also provides crucial guidance for more accurate genetic counseling and potentially new directions for future research in understanding the disease mechanism and developing targeted therapies.
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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