DeCure for Familial male-limited precocious puberty
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for familial male-limited precocious puberty — screening already-approved drugs against its 1-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleFamilial male-limited precocious puberty maps to a 1-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 familial male-limited precocious puberty 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
luteinizing hormone/choriogonadotropin receptor (LHCGR) — LHCGR 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 2-morpholin-4-ylethanoylaminodrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 7FIH · 3.2 Å · ligand 5-azanyl-N-tert-butyl-2-methylsulfanyl-4-[3-(2-morpholin-4-ylethanoylamino)phenyl]thieno[2,3-d]pyrimidine-6-carboxamide (55Z). Experimental structure, not a prediction.
What the evidence adds up to
In a 1997 series of five new cases of male-limited precocious puberty, one patient was untreated, two received cyproterone acetate (2.0–3.6 mg/kg/day) without clinical effects, and two were treated with ketoconazole (600 mg/day). In one of those two, a GnRH analogue (Buserelin, 1600 µg/day) was added after six months of effective ketoconazole because central precocious puberty developed; the other did not develop central puberty and his predicted adult height improved from 172.4 to 181.1 cm. Four patients reached final height: one on cyproterone acetate (−2.0 SDS at age 22), one untreated (−1.7 SDS at age 15.5), one on cyproterone acetate (−1.6 SDS at age 19.5), and one on ketoconazole plus GnRH analogue (−2.2 SDS at age 21.3). Three had reduced testicular volume, and one showed oligospermia. The authors concluded that cyproterone acetate did not improve final height, that ketoconazole reduced testosterone but its effect on final height could not be determined, and that testicular impairment may be present in young adulthood.
A 2020 case report describes a boy with familial male-limited precocious puberty (FMPP) caused by a novel LHCGR mutation who was treated with bicalutamide and anastrozole and was responding well. A 2024 Korean case report describes a 16-month-old boy with a family history through three generations, a bone age of 4 years, serum testosterone 5.74 ng/mL (normal <0.05 ng/mL), suppressed LH (<0.07 mIU/mL), and a pathogenic LHCGR variant (c.1730 C>T, p.Thr577Ileu). Bicalutamide and anastrozole were administered, and pubertal progression was sufficiently suppressed without specific side effects. A 2000 study of a Japanese family with an M398T mutation found that two affected males had elevated testosterone and prepubertal gonadotropins, but the father who carried the same mutation had no history of precocious puberty, indicating phenotypic variability even within a family.
The 1997 series shows that cyproterone acetate was ineffective for height, and ketoconazole’s long-term benefit remains uncertain. The 2020 and 2024 reports describe bicalutamide plus anastrozole as promising and well tolerated in individual cases, but these are single-patient observations with no controlled data, no long-term height outcomes, and no information on testicular function in adulthood. The disorder is rare, and what is still missing are prospective trials with sufficient sample size, standardised outcome measures for adult height and fertility, and longer follow-up to determine whether combination therapy consistently improves final height or preserves testicular function.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Hormone Research · 1997 · 30 citations
Long-Term Outcome of Male-Limited Gonadotropin-Independent Precocious Puberty
AbstractLong-term outcome of five new cases of male-limited precocious puberty (MPP) is reported. Three patients had positive family history. One patient was untreated; 2 boys received cyproterone acetate (2.0-3.6 mg/kg/daily) without clinical effects. Two patients were treated with ketoconazole (600 mg/daily); in 1, GnRH analogue therapy (Buserelin, 1,600 microg/day) was added after 6 months of effective ketoconazole treatment for development of central precocious puberty. The other patient did not develop central puberty under ketoconazole treatment and improved his predicted adult height from 172.4 to 181.1 cm. Four patients reached final height [B.A. (therapy cyproterone acetate): age 22.0 years, -2.0 SDS; B.G. (untreated): age 15.5 years, -1.7 SDS; M.M. (therapy cyproterone acetate): age 19.5 years, -1.6 SDS; M.F. (therapy ketoconazole plus GnRH analogue): age 21.3 years, -2.2 SDS]; three had reduced testicular volume (B.A.: -1.6/-1.6 SDS; B.G.: -2.1/-2.1 SDS; M.F.: -2.4/-1.9 SDS); one (M.F.) showed oligospermia. We concluded that in MPP cyproterone acetate treatment did not improve final height; ketoconazole was effective in reducing testosterone secretion, but its real effect on final height cannot be determined; the timing of central puberty may be precocious, suggesting that an adjunctive GnRH analogue treatment may be needed. In some patients, testicular impairment may be present in young adulthood.
Journal of Clinical Research in Pediatric Endocrinology · 2020 · 10 citations · open access
A Case of Familial Male-limited Precocious Puberty with a Novel Mutation
AbstractFamilial male-limited precocious puberty (FMPP), also known as testotoxicosis, is a rare cause of precocious puberty in males. It is caused by a mutation in the luteinizing hormone/chorionic gonadotropin receptor (LHCGR) gene, resulting in the receptor being constitutively activated. This causes excessive production of testosterone, leading to precocious puberty in males. Generally, boys present with signs of puberty, such as pubic hair growth, acne, and increased height velocity around the age of 2-4 years old. Like any other cause of precocious puberty, the goal of treatment is to prevent virilization and also delay closure of the epiphyseal plates to maintain adult height potential. Treatment, therefore, is aimed at decreasing the effects of testosterone, as well as stopping the conversion of testosterone to estrogen. Little is known about the long-term effects of treatment because the disorder is so rare. However, studies using bicalutamide and anastrozole have been promising. In this report, we present a boy with FMPP with a novel mutation in the LHCGR gene, who has been responding well to therapy using both drugs.
Endocrine Journal · 2000 · 6 citations · open access
Japanese Familial Patients with Male-Limited Precocious Puberty.
AbstractFamilial male-limited precocious puberty (FMPP) is a rare disease caused by constitutively activating mutations in the luteinizing hormone receptor (LH-R) gene. In the present study, we analyzed the LH-R gene in members of a Japanese FMPP family. Two males of the family were affected and had a heterozygous M398T mutation; one patient developed pubertal signs as early as 2 years of age, and the other at 6 years of age. Both patients had elevated serum testosterone levels and prepubertal gonadotropin secretions. The father of the latter patient carried the M398T mutation, but lacked history of precocious puberty. Thus, phenotypic differences were observed in the three males with the same LH-R mutation belonging to the same family. In summary, we have described a Japanese family with FMPP.
Annals of Pediatric Endocrinology & Metabolism · 2024 · 0 citations · open access
Familial male-limited precocious puberty due to an activating mutation of the LHCGR: a case report and literature review
AbstractFamilial male-limited precocious puberty (FMPP) is a rare form of gonadotropin-independent precocious puberty that is caused by an activating mutation of the LHCGR gene. Herein, we report a case of FMPP with a mutation of the LHCGR gene in a Korean boy with familial history of precocious puberty through 3 generations. A 16-month-old boy presented with signs of precocious puberty, including pubic hair, acne, and increased growth velocity. The patient's grandfather and father had a history of precocious puberty and profound short stature. On physical examination, the patient had prepubertal testes with pubic hair development appropriate for Tanner stage II. The stretched penile length was 7 cm (>2 standard deviation score), and observed bone age was that of a 4-year-old boy. Laboratory findings showed high serum testosterone (5.74 ng/mL [appropriate for Tanner IV-V]; normal range, <0.05 ng/mL) with suppressed luteinizing hormone (<0.07 mIU/mL) and normal serum level of follicular stimulating hormone (0.56 mIU/mL; normal range, 0.38-1.11 mIU/mL). Genetic testing revealed a pathogenic variant of LHCGR (c.1730 C>T (p.Thr577Ileu)), confirming FMPP. Bicalutamide and anastrozole were administered, and pubertal progression was sufficiently suppressed without any specific side effects. To our knowledge, this is the first case of genetically confirmed FMPP in Korea.
International Journal of Homoeopathic Sciences · 2023 · 0 citations · open access
Precocious puberty: An emerging concern and exploring homoeopathic perspective
AbstractPrecocious puberty denotes the early initiation of puberty and the emergence of secondary sexual characteristics in children. This leads to lot of concern among parents and children. Diagnosing this condition presents significant challenges due to wide range of potential causes, including benign variations and more serious conditions like malignancies. This discussion aims to emphasize the importance of early detection, assessment, treatment and management of precocious puberty, underscoring role of Homoeopathic medicine for comprehensive management to prevent potential complications.
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.
