DeCure for Cholesterol-ester transfer protein deficiency
DeCure's autonomous Metabolic AI scientist is researching a drug-repurposing hypothesis for cholesterol-ester transfer protein deficiency — screening already-approved drugs against its 3-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleCholesterol-ester transfer protein deficiency maps to a 3-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 cholesterol-ester transfer protein deficiency 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
cholesteryl ester transfer protein (CETP) — CETP 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 2obdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 2OBD · 2.1 Å · ligand CHOLESTERYL OLEATE (2OB). Experimental structure, not a prediction.
What the evidence adds up to
In a 1994 report, a 43-year-old man with a plasma HDL cholesterol of 151 mg/dl was found to have complete deficiency of cholesteryl ester transfer protein (CETP) activity; his sister also had complete deficiency, while his mother and daughter had partial deficiency. The genetic cause was a G to A splicing defect in intron 14 of the CETP gene. Individuals with this genetic deficiency have higher HDL cholesterol and lower LDL cholesterol, and may have a reduced risk for cardiovascular disease, according to a 2005 review. That review also states that small molecule inhibitors of CETP are being developed to mimic this beneficial lipoprotein profile, but that randomised clinical trials are required to determine whether CETP inhibition actually reduces cardiovascular events.
A 2007 article notes that plasma HDL cholesterol levels are inversely related to the incidence of coronary heart disease and stroke, and that statin therapy reduces LDL cholesterol but cuts cardiovascular risk by only about one third. On the basis of the high-HDL phenotype seen in human CETP deficiency, a new class of CETP inhibitors was developed. The article states that the CETP inhibitor torcetrapib is effective at raising HDL cholesterol levels, but the abstract cuts off before reporting any clinical outcome. A 2012 review discusses CETP as a potential key to longevity, but again provides no trial data showing that CETP inhibition reduces cardiovascular events or extends life.
No completed randomised trial has yet demonstrated that any CETP inhibitor reduces cardiovascular events or improves survival in humans. The missing elements are large, long-term, event-driven randomised controlled trials, adequate funding for such trials, and patient stratification by baseline HDL and LDL levels or by CETP genotype.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
New England Journal of Medicine · 2007 · 132 citations
CETP Inhibitors to Increase HDL Cholesterol Levels
AbstractPlasma levels of high-density lipoprotein (HDL) cholesterol are inversely related to the incidence of coronary heart disease and stroke. The lowering of low-density lipoprotein (LDL) cholesterol with statin therapy reduces the risk of atherosclerotic cardiovascular disease but only by about one third. These findings have led to the idea that raising HDL cholesterol might be a treatment for atherosclerosis. On the basis of the high-HDL phenotype of a human genetic deficiency of cholesteryl ester transfer protein (CETP),1 a new class of drugs that inhibit CETP was developed.2 Although the CETP inhibitor torcetrapib is effective at raising HDL cholesterol levels, it . . .
Current Topics in Medicinal Chemistry · 2005 · 24 citations
Cholesteryl Ester Transfer Protein: Pharmacological Inhibition for the Modulation of Plasma Cholesterol Levels and Promising Target for the Prevention of Atherosclerosis.
AbstractCholesteryl ester transfer protein (CETP) facilitates the exchange of neutral lipids (such as cholesteryl esters and triglycerides) between anti-atherogenic HDL particles and pro-atherogenic VLDL and LDL particles in human plasma. Individuals possessing a genetic deficiency for CETP have higher HDL cholesterol and lower LDL cholesterol and may have a reduced risk for developing cardiovascular disease. Small molecule inhibitors of CETP are being developed that would appear to provide a beneficial change in lipoprotein profile. However, randomized clinical trials are ultimately required to determine whether CETP inhibition will afford a reduction in cardiovascular events. Keywords: low-density lipoprotein cholesterol (ldl-c), coronary heart disease (chd), reverse cholesterol transport(rct), inflammatory processes, vascular endothelial cells, glycopeptide, phospholipids
Internal Medicine · 1994 · 5 citations · open access
A Family with Complete Deficiency of Plasma Cholesteryl Ester Transfer Protein Activities.
AbstractA 43-year-old male with a high value of high density lipoprotein cholesterol (151 mg/dl) was found among subjects receiving annual health checks. We investigated the cholesteryl ester transfer protein (CETP) activity and conducted a family study. There was complete deficiency of CETP activities in the proband and his sister, and partial deficiency of CETP activities in his mother and daughter. Genetic analysis revealed a splicing defect (G to A point mutation) in intron 14 of the CETP gene.
Cholesteryl Ester Transfer Protein: The Key to Longevity?
AbstractThe negative attributes of cholesterol receive much attention in the media and scientific literature, with good reason. However, there are aspects of cholesterol metabolism that actually reduce the risk of developing cardiovascular disease. Furthermore, variations in the gene for an important cholesterol transport protein may yield significant health benefits. This critical review outlines the basic physiology of cholesterol, discusses cholesteryl ester transfer protein and potential variations in its gene, and identifies the implications of current research in this field for the pharmaceutical industry.
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.
