DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for ulnar-mammary syndrome — screening already-approved drugs against its 2-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleUlnar-mammary syndrome maps to a 2-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 ulnar-mammary syndrome 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
T-box transcription factor 3 (TBX3) — TBX3 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 apo structuredrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 1H6F · 1.7 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
Ulnar-mammary syndrome is an autosomal dominant disorder caused by mutations in the TBX3 gene, which was mapped to chromosome 12q23-24.1 in 1995 with a lod score of 6.21 at theta = 0.00 for marker D12S79. A 2025 report describes a 5.5-year-old Chinese boy with a novel TBX3 variant (c.1142_1146) who presented with a hypoplastic left fifth finger, absent interphalangeal creases, a wide space between fourth and fifth fingers, inability to bend the fifth finger, absent nipples, high palate, flat nasal bridge, micropenis, microtestes, short stature, and reduced axillary sweating. Pituitary MRI showed pituitary gland hypoplasia with a thin stalk and loss of posterior pituitary bright signal. After six months of human chorionic gonadotropin treatment the micropenis improved, and after 3.5 years of recombinant human growth hormone body height improved substantially.
The 1995 linkage study noted that the UMS gene region on 12q23-24.1 contains a locus for Holt-Oram syndrome, suggesting the two conditions may be allelic or closely linked. No abstracts in this set report any drug that modifies the underlying TBX3 mutation or its developmental consequences. The 2025 case describes hormone treatments for the endocrine consequences of the syndrome — human chorionic gonadotropin for micropenis and growth hormone for short stature — but these address downstream effects, not the primary genetic defect.
The remaining abstracts concern mammary gland development in mice and cats, not ulnar-mammary syndrome. In mice, Socs2 and Elf5 mediate prolactin-driven mammary development; re-expression of Elf5 in prolactin receptor knockout mice restored lobuloalveolar development and milk production. Overexpression of ATF4 in transgenic mice impaired mammary development, reduced proliferation and differentiation, and accelerated involution. In cats with fibroadenomatous changes, a progesterone antagonist (aglepristone) combined with adjuvant therapy led to mammary gland size reduction within 2-3 weeks and complete remission after 4-5 weeks; in two pregnant cats treated without aglepristone, the natural decline of progesterone at the end of pregnancy allowed normal lactation and weaning of kittens. None of these animal studies test treatments for ulnar-mammary syndrome.
What is missing for ulnar-mammary syndrome is any therapy that targets the TBX3 mutation itself. No clinical trials, no drug repurposing screens, no patient stratification beyond single-gene diagnosis. The 2025 case shows that hormone replacement can manage some endocrine features, but there is no evidence for any intervention that restores limb, mammary, or apocrine gland development. Funding for basic research on TBX3 function and for any preclinical drug screening remains absent.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Molecular Endocrinology · 2006 · 155 citations
Socs2 and Elf5 Mediate Prolactin-Induced Mammary Gland Development
AbstractThe proliferative phase of mammary alveolar morphogenesis is initiated during early pregnancy by rising levels of serum prolactin and progesterone, establishing a program of gene expression that is ultimately responsible for the development of the lobuloalveoli and the onset of lactation. To explore this largely unknown genetic program, we constructed transcript profiles derived from transplanted mammary glands formed by recombination of prolactin receptor (Prlr) knockout or wild-type mammary epithelium with wild-type mammary stroma. Comparison with profiles derived from prolactin-treated Scp2 mammary epithelial cells produced a small set of commonly prolactin-regulated genes that included the negative regulator of cytokine signaling, Socs2 (suppressor of cytokine signaling 2), and the ets transcription factor, E74-like factor 5 (Elf5). Homozygous null mutation of Socs2 rescued the failure of lactation and reduction of mammary signal transducer and activator of transcription 5 phosphorylation that characterizes Prlr heterozygous mice, demonstrating that mammary Socs2 is a key regulator of the prolactin-signaling pathway. Reexpression of Elf5 in Prlr nullizygous mammary epithelium restored lobuloalveolar development and milk production, demonstrating that Elf5 is a transcription factor capable of substituting for prolactin signaling. Thus, Socs2 and Elf5 are key members of the set of prolactin-regulated genes that mediate prolactin-driven mammary development.
Journal of Biological Chemistry · 2003 · 46 citations · open access
Activating Transcription Factor 4 Overexpression Inhibits Proliferation and Differentiation of Mammary Epithelium Resulting in Impaired Lactation and Accelerated Involution
AbstractThe basic leucine zipper containing activating transcription factors (ATFs) modulates the expression of growth-regulating genes. In this study, we sought to determine specifically the consequences of ATF4 expression on mammary gland development in transgenic mice. Overexpression of ATF4 severely impaired normal development of the mammary gland, which was associated with reduced proliferation and differentiation of mammary alveolar epithelium and up-regulation of p21(WAF1) and p27(Kip1). In addition, there was also impaired lactation accompanied by decreased expression of alpha-lactoalbumin, whey acidic protein, and beta-casein, possibly because of the down-regulation of STAT5a tyrosine phosphorylation. Mammary gland involution in ATF4-transgenic mice was accelerated, compared with wild type littermates by whole mount analysis. In addition, day 18 of lactation in transgenic mice was phenotypically equivalent to day 3 of involution in wild type mice, as determined by the TUNEL assay and expression of Bax. The concentration of the proapoptotic molecule caspase-3 was increased during lactation in ATF4-transgenic animal. Mammary glands from ATF4-transgenic mice also showed significant nuclear translocation of activated STAT3 and up-regulation of one of its target genes, insulin-like growth factor-binding protein-5, which is thought to facilitate apoptosis by sequestering insulin-like growth factor. Together, these findings suggest that ATF4 may play a role during mammary gland development and that down-regulation of ATF4 may be important for the onset of involution in the mammary gland.
A gene for ulnar–mammary syndrome maps to 1 2q23–q24.1
AbstractUlnar-mammary syndrome (UMS) is an autosomal dominant disorder characterized by posterior limb deficiencies or duplications, apocrine/mammary gland hypoplasia and/or dysfunction, abnormal dentition, delayed puberty and genital anomalies. We report the mapping of a gene causing UMS to chromosome 12q23-24.1. Linkage analysis generated a positive lod score of 6.21 at theta = 0.00 with the marker D12S79, and recombinants bracket the UMS gene to a 21 cM region. This region contains a locus for Holt-Oram syndrome (HOS) suggesting that the genes for UMS and HOS may be allelic or closely linked. The identification of the gene causing UMS will be an important step toward understanding the molecular mechanisms that control limb and apocrine gland development.
Open Veterinary Journal · 2021 · 5 citations · open access
Conservative treatments for feline fibroadenomatous changes of the mammary gland
AbstractBACKGROUND: Fibroadenomatous changes (FAC) of the mammary gland in cats represents a benign, progesterone-associated fibroglandular proliferation of one or more mammary glands that may occur in intact female cats at the time of puberty, during pregnancy or pseudopregnancy, or in female and male cats of any age under progestin treatment. Nowadays, the elective treatment of FAC is based on the progesterone antagonist aglepristone. This study aimed to report the treatment of FAC with a combination of drugs designed to preserve mammary gland integrity, even in pregnant cats. CASE DESCRIPTION: emollient gel. If the gland was inflamed or ulcerated, broad-spectrum antimicrobial, and anti-inflammatory treatments were given, and the ulcers were treated topically with a hypericum and neem-based cream. Two of the four pregnant cats were treated with the same therapeutic schedule plus cloprostenol to facilitate uterine emptying. Two pregnant cats underwent the same protocol except for aglepristone, which was not administered to safeguard the litter and see if the adjuvant therapy worked independently. At term, they delivered four and three kittens, respectively, that were normally nursed and weaned after 40 days. In all the studied cases, the mammary gland reduced in size 2-3 weeks after the start of the treatment and completely remitted after 4-5 weeks. CONCLUSION: This case series encourages adjuvant therapy in the course of FAC to preserve mammary gland integrity and functionality. Exploiting the natural decline of progesterone at the end of pregnancy (or pseudopregnancy), the therapy may also be used without aglepristone, when its use has other limitations.
Journal of Animal and Feed Sciences · 2004 · 4 citations · open access
Effect of nutrients on p70S6K activation in the bovinemammary gland
AbstractThe effect of jugular infusions of glucose and amino acids on activation of p70S6K was studied in the bovine mammary gland. Cows were starved for 22 h to quench milk protein synthesis before resupplying EEA+Glc, Glc, Met+Lys, His, Leu or saline. Results implicate glucose as a regulator of global, rather than ribosomal, protein synthesis. EAA appear to play a far greater role in p70S6K regulation than glucose. His and Leu appear to act as metabolic agents in the mammary epithelial cell; Leu through elevating RNA levels thereby contributing to the long-term protein synthesis capacity, and His through stimulating protein translation.
Intractable & Rare Diseases Research · 2025 · 1 citations · open access
Clinical and genetic analysis of ulnar-mammary syndrome caused by a novel <i>TBX3</i> mutation in a Chinese boy
AbstractUlnar-mammary syndrome (UMS) is caused by TBX3 mutation and is a disorder characterized by altered limb, breast, tooth, hair, apocrine gland, and genital development. The clinical and genetic data of a 5.5th boy with UMS were carefully analyzed. Clinical biochemical data, pituitary MRI, and whole exome gene detection were analyzed. The impact of the mutation and stability of TBX3 on the mRNA structure was analyzed by the M-fold program. Three-dimensional protein structures were calculated and analyzed. The patient presented with a hypoplastic left fifth finger, an absence of interphalangeal creases, a large space between the fourth and fifth fingers, no bending ability of the fifth finger, absent nipples, high palates, a flat nasal bridge, a micropenis, micro-testes, short stature and reduced axillary sweating. Pituitary magnetic resonance imaging (MRI) revealed pituitary gland hypoplasia with a thin pituitary stalk and loss of a strong signal in the posterior pituitary. A novel variant (c.1142_1146) in the TBX3 gene was detected in the proband and further verified by DNA sequencing. M-fold results revealed that the variant altered the mRNA structure and stability of the TBX3 gene. Clinical, genetic, and biochemical studies confirmed that the congenital normal idiopathic hypogonadotropic hypogonadism was associated with pituitary hypoplasia. After half a year of treatment with human chorionic gonadotropin (HCG), the micropenis was significantly improved. After 3.5 years of treatment with recombinant human growth hormone, the body height was largely improved. One novel variant of the TBX3 gene was confirmed in an UMS patient, which enriched the spectrum of TBX3 genotypes.
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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