Dalcetrapib 125 items
Neutral in 2012, revived genotype-first, still being tested.
Trials, agents, guidance
- Trial DalCor genotype-defined trial (NCT05918861)
- Trial dal-GenE
- Agent Dalcetrapib
- Trial dal-OUTCOMES
Studies
- Dalcetrapib raised HDL-C by up to 40% but did not reduce cardiovascular events in dal-OUTCOMES (N Engl J Med 2012)
- dal-GenE: dalcetrapib misses its primary endpoint in ADCY9 AA-genotype patients (HR 0.88), even after a genetically pre-selected retest of dal-OUTCOMES (Eur Heart J 2022)
- Discovery study links the ADCY9 rs1967309 polymorphism to a 39% cardiovascular benefit from dalcetrapib (Circ Cardiovasc Genet 2015)
- JTT-705, a disulfide-forming CETP inhibitor, raises HDL cholesterol and slows atherosclerosis in rabbits, the original discovery paper reports (Nature 2000)
- REVEAL, the largest ADCY9 pharmacogenetic study yet, finds no genotype interaction with the benefit of anacetrapib, unlike the dalcetrapib hypothesis (Circulation 2019)
- ADCY9 and CETP show signs of having coevolved under sex-specific selection, offering a biological explanation for the pharmacogenomic signal of dalcetrapib (eLife 2021)
- Genotype-dependent dalcetrapib effects on cholesterol efflux and inflammation confirm the ADCY9 pharmacogenomic signal (Circ Cardiovasc Genet 2016)
- Dal-VESSEL trial finds dalcetrapib cut CETP activity 56% without harming endothelial function or blood pressure (Eur Heart J 2012)
- The dal-PLAQUE imaging trial finds no evidence dalcetrapib harms the arterial wall after the failure of torcetrapib (Lancet 2011)
- The first human trial of JTT-705 finds 900 mg raises HDL cholesterol by 34 percent while cutting CETP activity by 37 percent (Circulation 2002)
- Bayesian network meta-analysis of 84,134 patients ranks evacetrapib and anacetrapib best for cardiovascular outcomes among CETP inhibitors (Medicine 2026)
- Early-phase MACE signals predicted outcomes-trial results in 6 of 7 cholesterol drugs, dalcetrapib the exception (Am Heart J Plus 2026)
- dal-GenE: the MI benefit of dalcetrapib in ADCY9 AA-genotype patients survives adjustment for an 18-variable risk prediction index (Eur J Prev Cardiol 2025)
- How ADCY9 and CETP might interact inside arterial macrophages to explain the genotype-dependent effect of dalcetrapib, with dal-GenE poised to test it (Circ Genom Precis Med 2021)
- dal-OUTCOMES secondary analysis: dalcetrapib cuts new-onset diabetes by 23% after acute coronary syndrome, NNT of 40 (Diabetes Care 2020)
- ACCELERATE nested case-control study finds no significant ADCY9 genotype interaction with evacetrapib, unlike the dalcetrapib signal (JAMA Cardiol 2018)
- Pharmacogenomics review details how ADCY9 genotype determines the cardiovascular effect of dalcetrapib in dal-OUTCOMES (ATVB 2017)
- CETP inhibitors raise blood pressure through a CETP-independent, redox- and STAT3-dependent vascular contraction pathway (J Pharmacol Exp Ther 2016)
- CETP inhibitors trigger aldosterone-producing enzymes in adipocytes through Nox-driven reactive oxygen species and STAT3 (J Pharmacol Exp Ther 2015)
- The dal-ACUTE trial finds dalcetrapib raises HDL cholesterol by a third after acute coronary syndrome but boosts cholesterol efflux by only a tenth (Eur Heart J 2014)
- Cysteine 13 of CETP is the key residue that lets dalcetrapib decouple cholesteryl ester transfer from HDL remodeling (Biochim Biophys Acta 2013)
- Only dalcetrapib preserves pre-beta HDL formation and boosts fecal sterol excretion, unlike torcetrapib and anacetrapib (J Lipid Res 2010)
- L-type calcium channels explain how torcetrapib raises aldosterone and blood pressure, an effect dalcetrapib does not share (J Hypertens 2010)
- Anacetrapib binds CETP reversibly while dalcetrapib binds covalently, explaining their different inhibitory kinetics (J Lipid Res 2010)
- Structure-activity studies identify JTT-705 as the optimum CETP inhibitor among a series of disulfide and thioester compounds (J Med Chem 2000)
- Dalcetrapib reduces red blood cell sickling in sickle cell disease and boosts the effect of voxelotor when combined (Clin Hemorheol Microcirc 2026)
- Adcy9 gene inactivation shrinks infarct size and preserves cardiac function after MI, but mainly when CETP is absent (Can J Cardiol 2023)
- Dalcetrapib and anacetrapib generate large apoE-containing HDL particles that can bind the hepatic LDL receptor (J Lipid Res 2023)
- Beyond failed HDL trials: a review argues the dal-GenE genomic-test approach to dalcetrapib and ADCY9 is the key to actionable HDL therapy (J Cardiovasc Pharmacol 2021)
- dal-GenE trial design: only patients with the ADCY9 AA genotype will be enrolled, testing whether the benefit of dalcetrapib is genetically confined (Am Heart J 2020)
- Meta-analysis of 62,431 patients across 11 RCTs finds CETP inhibitors do not reduce major adverse cardiovascular events (RR 0.97) (Cardiology 2020)
- Even NMR-measured HDL particle concentration, not just HDL-C, failed to predict cardiovascular risk in dal-Outcomes (Am Heart J 2020)
- ADCY9 inactivation cuts atherosclerosis by 65 percent in mice, but only when CETP is absent (Circulation 2018)
- What the cetrapib trials taught us: torcetrapib, evacetrapib and anacetrapib all raised atherogenic apoproteins, muddying the HDL-raising story (Curr Opin Lipidol 2018)
- Pharmacogenetics of HDL-targeting and statin therapies: dal-OUTCOMES and dal-PLAQUE-2 gave concordant results for dalcetrapib in the favourable genotype (Curr Atheroscler Rep 2017)
- No benefit with evacetrapib despite raising HDL 130% and cutting LDL 37%: is this the end of the road for the cetrapibs? (Expert Opin Pharmacother 2017)
- Same drug, opposite effect: dalcetrapib raised HDL in rabbits but cut it 48% in monkeys, while anacetrapib behaved consistently across species (J Lipid Res 2017)
- In vivo, anacetrapib promotes rather than blocks cholesteryl ester flux into large HDL, contradicting in vitro homotypic-transfer predictions (Eur J Pharmacol 2015)
- Dalcetrapib raises plasma campesterol only in patients with intact ABCA1 and ApoA1, a crossover trial finds (Lipids 2014)
- At matched CETP inhibition, only anacetrapib boosts macrophage-to-feces cholesterol excretion in dyslipidemic hamsters (Eur J Pharmacol 2014)
- In hamsters, anacetrapib raises preβ HDL and reverse cholesterol transport without affecting cholesterol absorption, unlike dalcetrapib (J Lipid Res 2013)
- A distinct HDL-like particle seen in complete genetic CETP deficiency is absent in dalcetrapib-treated volunteers (Curr Vasc Pharmacol 2012)
- Update captures dal-OUTCOMES futility and the decision by Roche to end the dalcetrapib program in May 2012 (Future Cardiol 2012)
- Adding dalcetrapib to pravastatin reshapes HDL composition and boosts two cholesterol efflux pathways in a phase IIb dose-ranging study (Am Heart J 2012)
- Review recounts the termination of dalcetrapib and the broader questions it raises for CETP inhibition and the HDL hypothesis (Drug Des Devel Ther 2012)
- A new reverse-phase-array lipoprotein-profiling method shows dalcetrapib, unlike torcetrapib and anacetrapib, spares pre-beta HDL formation (J Lipid Res 2011)
- Unlike torcetrapib, dalcetrapib shifts cholesterol homeostasis toward absorption markers rather than synthesis markers (Atherosclerosis 2011)
- Review distinguishes CETP inhibitors from the CETP modulator dalcetrapib by their opposite effects on HDL2-to-HDL3 transfer (Curr Opin Lipidol 2011)
- Doses of dalcetrapib up to 4500 mg, far above the therapeutic dose, are well tolerated in a phase I ascending-dose study (Clin Drug Investig 2011)
- Review of phase II dalcetrapib data flags its unique CETP-binding mechanism ahead of dal-OUTCOMES (Expert Opin Investig Drugs 2010)
- A 48-week trial finds dalcetrapib raises HDL cholesterol by a third with no measurable effect on lymph node size (Eur Heart J 2010)
- Torcetrapib raises blood pressure and RAAS gene expression in rats, but dalcetrapib does neither (Br J Pharmacol 2009)
- Dal-OUTCOMES trial design targets 15,600 recent-ACS patients to test whether dalcetrapib reduces cardiovascular events (Am Heart J 2009)
- Pooled phase II data show dalcetrapib raises HDL cholesterol up to 36 percent without the blood pressure or aldosterone effects seen with torcetrapib (Am J Cardiol 2009)
- A mathematical model shows torcetrapib and JTT-705 inhibit CETP more potently than classic competitive inhibition would predict (J Lipid Res 2009)
- A critical appraisal argues high CETP may actually lower cardiovascular risk when triglycerides are low, complicating the case for CETP inhibition (Eur J Clin Invest 2007)
- Torcetrapib raises large alpha-1 HDL particles by more than 50 percent in humans, mainly by slowing ApoA-I breakdown (Curr Opin Lipidol 2006)
- CETP is shown to directly drive formation of cholesterol-rich remnant lipoprotein particles, and JTT-705 blocks the effect (Clin Chim Acta 2007)
- Adding JTT-705 to pravastatin raises HDL cholesterol by 28 percent after just 4 weeks in a placebo-controlled trial (Am J Cardiol 2005)
- JTT-705 blocks vascular smooth muscle cell proliferation and angiogenesis through a mechanism independent of CETP inhibition (Atherosclerosis 2005)
- JTT-705 (dalcetrapib) inhibits CETP and raises HDL-C across five animal species, mimicking CETP-deficient humans in marmosets (Eur J Pharmacol 2003)
- JTT-705 raises HDL cholesterol but fails to reduce aortic atherosclerosis in rabbits with severe hypercholesterolaemia (Clin Sci 2002)
- The same cysteine-binding chemistry that makes dalcetrapib a CETP inhibitor also lets it block the SARS-CoV-2 3CL protease (ACS Omega 2021)
- Dalcetrapib (JTT-705) blocks SARS-CoV-2 cell fusion by disrupting spike protein disulfide bonds (FASEB J 2021)
- Repeated dosing shows dalcetrapib does not accumulate in rats despite forming covalent disulfide bonds with tissue thiols (Xenobiotica 2021)
- A PBPK model correctly predicts higher exposure to the active thiol form of dalcetrapib in chronic kidney disease (Xenobiotica 2021)
- A review of dalcetrapib pharmacokinetics finds no clinically significant drug interactions across over 13,000 patients and volunteers (Clin Pharmacokinet 2018)
- In dal-Outcomes, Lp(a) after acute coronary syndrome did not predict recurrent ischaemic events on background statin therapy (JAMA Cardiol 2018)
- Metabolite profiling identifies more than 80 breakdown products of dalcetrapib in human plasma, none of them major (J Pharm Biomed Anal 2018)
- CETP inhibitors, challenges and perspectives: off-target failure for torcetrapib, futility for dalcetrapib and evacetrapib, early promise for anacetrapib and TA-8995 (Expert Rev Cardiovasc Ther 2016)
- A review proposes that HDL regulates the beta2-adrenergic receptor pathway through the same ADCY9 signaling axis linked to dalcetrapib response (Arch Med Res 2015)
- Simvastatin blunts the boost that dalcetrapib gives to cholesterol efflux from macrophages in vitro (Cardiovasc Drugs Ther 2015)
- Dalcetrapib is rapidly hydrolyzed to its active thiol and excreted largely unchanged in rats and monkeys (Xenobiotica 2014)
- Hepatic and renal impairment increase dalcetrapib active-thiol exposure by up to 81% (Clin Pharmacokinet 2013)
- The weight-loss drug orlistat cuts exposure to active dalcetrapib by more than half by blocking its ester hydrolysis (J Cardiovasc Pharmacol 2012)
- Review details the mode of action and clinical profile of dalcetrapib as dal-OUTCOMES interim results end its development (Expert Opin Investig Drugs 2012)
- Liver tumors seen in a 2-year mouse study of dalcetrapib trace to a rodent-specific pathway not relevant to humans (Toxicol Appl Pharmacol 2012)
- Dalcetrapib cut CETP activity up to 58% and raised HDL-C up to 34% regardless of diabetes or metabolic syndrome status (Diabetes Obes Metab 2012)
- A high-fat meal raises exposure to dalcetrapib by up to 44 percent across three phase I crossover studies (Clin Ther 2011)
- Intestinal and hepatic first-pass metabolism strips more than 90 percent of active dalcetrapib-thiol in monkeys (Xenobiotica 2011)
- Review finds anacetrapib and dalcetrapib safely raise HDL-C without the off-target effects that doomed torcetrapib (Ann Pharmacother 2011)
- Ezetimibe does not blunt the HDL-raising effect of dalcetrapib, and each drug leaves the other pharmacokinetics largely unchanged (Br J Clin Pharmacol 2010)
- Atorvastatin reduces exposure to dalcetrapib without diminishing its cardiovascular benefit, two crossover studies find (Expert Opin Investig Drugs 2010)
- Even at more than 6 times the therapeutic dose, dalcetrapib does not prolong the QT interval in healthy subjects (Eur J Clin Pharmacol 2010)
- Rosuvastatin raises its own peak concentration by 26 percent when combined with dalcetrapib, but the LDL benefit of the combination still exceeds statin alone (J Clin Pharmacol 2010)
- The rodent-specific scavenger receptor MARCO drives the off-target lipid uptake seen with dalcetrapib in mouse macrophages (Toxicol In Vitro 2010)
- JTT-705, the dalcetrapib precursor compound, blocks LPS-triggered TNF-alpha production in mice by targeting a cysteine on MD-2 (J Biol Chem 2009)
- Dalcetrapib inhibits CYP enzymes in vitro but has no clinically relevant drug interaction with a five-probe drug cocktail (Curr Med Res Opin 2009)
- Ketoconazole unexpectedly lowers exposure to dalcetrapib rather than raising it, contrary to typical CYP3A4-inhibitor interactions (Clin Ther 2009)
- A review links the B1B1 CETP genotype to higher CETP activity, lower HDL cholesterol, and more pronounced postprandial lipemia (Curr Med Chem 2009)
- Review asks whether JTT-705 (dalcetrapib) or anacetrapib can still succeed after the collapse of torcetrapib (Expert Opin Investig Drugs 2008)
- JTT-705 (dalcetrapib) raised HDL-C 26% and improved endothelial function only in low-baseline-HDL patients (Thromb Res 2009)
- A review concludes the mineralocorticoid-driven hypertension seen with torcetrapib is not a CETP-inhibitor class effect, since JTT-705 and MK-825 do not raise blood pressure (Nat Clin Pract Cardiovasc Med 2008)
- A review of CETP inhibition in dyslipidemia finds that the benefit of raising HDL depends heavily on triglyceride-rich lipoprotein levels (Curr Atheroscler Rep 2007)
- Torcetrapib can double HDL cholesterol while lowering LDL cholesterol by up to 42 percent, a review of CETP inhibitors reports (Curr Opin Pharmacol 2006)
- A review traces the CETP-inhibitor rationale from CETP-deficient Japanese populations with high HDL to early human trials of torcetrapib and JTT-705 (J Am Coll Cardiol 2006)
- A review finds genetic and plasma CETP-level studies give no clear answer on whether CETP inhibition will reduce atherosclerosis risk (Curr Drug Targets Cardiovasc Haematol Disord 2005)
- Prospective cohort data link elevated CETP concentration to higher cardiovascular risk only when triglycerides are also high (Curr Opin Lipidol 2004)
- JTT-705 reshapes HDL toward larger, apolipoprotein E-rich particles with more antioxidant enzyme activity in rabbits (Arterioscler Thromb Vasc Biol 2004)
- JTT-705 raises HDL cholesterol in rabbits by speeding up apolipoprotein A-I synthesis, not by slowing its breakdown (Atherosclerosis 2004)
- HDL from rabbits treated with JTT-705 removes cholesterol from macrophages just as efficiently as normal HDL, despite higher CETP-inhibited levels (Atherosclerosis 2002)
- Systematic review of 49 cardiovascular calcification trials finds dalcetrapib among the singleton agents showing no benefit (J Am Heart Assoc 2023)
- Review highlights ADCY9 pharmacogenomics as a model for rescuing dalcetrapib and future lipid trials (Curr Opin Lipidol 2016)
- dal-PLAQUE substudy finds dalcetrapib did not affect progression of vascular calcification (J Am Coll Cardiol 2016)
- High-pressure crystallization confirms a predicted, more stable polymorph of dalcetrapib before late-stage development (Nat Commun 2015)
- Dalcetrapib, but not anacetrapib, raises plasma and liver levels of the dietary antioxidants lutein and zeaxanthin (Lipids 2014)
- Review collates the bioanalytical methods developed to quantify anacetrapib, dalcetrapib, and torcetrapib in biological samples (Biomed Chromatogr 2013)
- Probenecid raises exposure to the active thiol form of dalcetrapib by up to 21 percent (Int J Clin Pharmacol Ther 2013)
- Dalcetrapib is hydrolyzed within 20 seconds in human intestinal fluid, but is stable in gastric fluid at low pH (Int J Pharm 2012)
- Dalcetrapib does not affect the pharmacokinetics of a combined oral contraceptive in a crossover trial (Int J Clin Pharmacol Ther 2012)
- Torcetrapib can raise HDL cholesterol by up to 106 percent alone or combined with atorvastatin, a review of emerging HDL-raising therapies notes (Curr Drug Targets 2007)
- A review makes the case for CETP inhibition as a novel strategy to reduce residual atherosclerotic risk beyond statin therapy (Eur Heart J 2007)
- A review of HDL-raising therapy notes that both JTT-705 and torcetrapib attenuate aortic atherosclerosis in cholesterol-fed rabbits (Pharmacol Ther 2006)
- A review outlines early evidence that CETP inhibitors JTT-705 and torcetrapib raise HDL and lower LDL cholesterol in mildly dyslipidaemic patients (Expert Opin Investig Drugs 2006)
- Torcetrapib 120 mg per day raises HDL cholesterol by 46 percent and lowers LDL cholesterol by 8 percent in subjects with low HDL, a review reports (Expert Opin Investig Drugs 2004)
- LC-MS/MS method quantifies dalcetrapib-thiol and its S-methyl and S-glucuronide metabolites down to 5 ng/mL (J Pharm Biomed Anal 2012)
- The dal-PLAQUE study is designed to track dalcetrapib effects on carotid plaque burden and inflammation with MRI and PET/CT (Am Heart J 2011)
- The dal-VESSEL study is designed as the largest trial of brachial flow-mediated dilatation to test dalcetrapib effects on endothelial function (Curr Med Res Opin 2011)