Torcetrapib 149 items
ILLUMINATE, the off-target pressor effect, and what the field learned from it.
Trials, agents, guidance
- Agent Torcetrapib
- Trial ILLUMINATE
Studies
- A 34-year genetic study finds CETP-lowering variants cut ischemic heart disease risk by 24 percent with no adverse effects seen with torcetrapib (J Am Coll Cardiol 2012)
- Mendelian randomization shows the hypertensive effect of torcetrapib is not caused by CETP inhibition (Circulation 2010)
- The ILLUMINATE trial halts torcetrapib development after finding a 58 percent rise in death from any cause despite a 72 percent HDL cholesterol increase (N Engl J Med 2007)
- Why raising HDL with CETP inhibitors did not help: evacetrapib and torcetrapib both boosted the harmful apoC3-containing HDL subspecies most (Arterioscler Thromb Vasc Biol 2022)
- The ILLUSTRATE trial finds coronary atheroma regression on torcetrapib only in patients reaching the highest quartile of HDL-C rise (Circulation 2008)
- Pooled RADIANCE trial data link the carotid-thickening harm of torcetrapib to a mineralocorticoid effect, not to its HDL-raising action (Circulation 2008)
- The RADIANCE 2 trial finds torcetrapib raises blood pressure and HDL but does not slow carotid thickening in mixed dyslipidaemia (Lancet 2007)
- The ILLUSTRATE trial finds no significant slowing of coronary atheroma progression from torcetrapib despite reaching an LDL-to-HDL ratio below 1.0 (N Engl J Med 2007)
- The RADIANCE 1 trial finds torcetrapib worsens common carotid thickening in familial hypercholesterolemia despite raising HDL to 81.5 mg per dL (N Engl J Med 2007)
- Twice-daily torcetrapib doubles HDL cholesterol in the first published proof-of-concept trial of a CETP inhibitor (N Engl J Med 2004)
- The first human trial of torcetrapib raises HDL cholesterol by up to 91 percent while producing a lipid profile resembling partial CETP deficiency (Arterioscler Thromb Vasc Biol 2004)
- A proteomic risk score could have flagged harm from torcetrapib within 3 months of ILLUMINATE, revealing unexpected immune and inflammatory effects (Circulation 2018)
- 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 excess mortality and cardiovascular harm of torcetrapib were confined to the low-dose atorvastatin subgroup in ILLUMINATE (J Lipid Res 2012)
- Torcetrapib improved glycemic control in 6,661 diabetic ILLUMINATE participants despite the overall harm of the trial (Circulation 2011)
- 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)
- People with genetically reduced CETP levels have lower, not higher, blood pressure, arguing against a CETP class effect behind the hypertension seen with torcetrapib (Mayo Clin Proc 2010)
- Anacetrapib binds CETP reversibly while dalcetrapib binds covalently, explaining their different inhibitory kinetics (J Lipid Res 2010)
- Torcetrapib impairs blood vessel dilation through a mechanism unrelated to CETP inhibition or HDL elevation, unlike a structurally different CETP inhibitor (J Cardiovasc Pharmacol 2010)
- Torcetrapib induces adrenal aldosterone and cortisol via intracellular calcium signaling, unrelated to CETP inhibition (Endocrinology 2009)
- CETP gene variants that raise HDL cholesterol actually lower diastolic blood pressure, arguing the hypertension seen with torcetrapib is compound specific (Pharmacogenet Genomics 2008)
- Adrenalectomy prevents the torcetrapib blood pressure rise, proving CETP inhibition itself is not the culprit (Br J Pharmacol 2008)
- Torcetrapib binds CETP roughly 5-fold tighter to HDL, locking it into a nonproductive complex that blocks all major lipid transfer (J Lipid Res 2006)
- Proteomics plus Mendelian randomisation could have flagged the blood-pressure toxicity of torcetrapib before ILLUMINATE, a proof-of-concept analysis argues (medRxiv preprint 2025)
- 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)
- Torcetrapib raised HDL ApoC-III and LpA-I subclasses without altering ApoB particles in ILLUMINATE (Am J Cardiol 2017)
- Torcetrapib cuts insulin levels by 49 percent and improves glucose uptake across tissues in insulin-resistant hamsters (Atherosclerosis 2014)
- Network pharmacology points to PDGFR, HGFR, and IL-2 receptor as possible off-target drivers of the cardiovascular harm from torcetrapib (BMC Syst Biol 2012)
- CETP inhibition alone fails to boost reverse cholesterol transport in hamsters unless paired with the LDL-lowering drug berberine (Arterioscler Thromb Vasc Biol 2013)
- Crystal structures show torcetrapib and a second inhibitor block the lipid-transfer tunnel of CETP at its narrow neck (J Biol Chem 2012)
- Torcetrapib cuts apoB-48 production by nearly half, but the effect vanishes in patients already on atorvastatin (J Lipid Res 2012)
- Review argues the off-target harm of torcetrapib is not a class effect shared by dalcetrapib, anacetrapib, and evacetrapib (Drugs 2012)
- CETP inhibition boosts the cholesterol-removing power of large HDL2b particles after a meal, but not their delivery to the liver (Atherosclerosis 2012)
- Torcetrapib boosts reverse cholesterol transport by 118 percent in obese, insulin-resistant transgenic mice (Clin Transl Sci 2011)
- A new reverse-phase-array lipoprotein-profiling method shows dalcetrapib, unlike torcetrapib and anacetrapib, spares pre-beta HDL formation (J Lipid Res 2011)
- Torcetrapib impairs endothelial function and raises vascular oxidative stress in hypertensive rats, reversed by endothelin blockade (Eur Heart J 2012)
- CETP actually boosts the ability of HDL to block LDL oxidation, a finding that may help explain why torcetrapib failed to slow vascular disease (IUBMB Life 2011)
- Review distinguishes CETP inhibitors from the CETP modulator dalcetrapib by their opposite effects on HDL2-to-HDL3 transfer (Curr Opin Lipidol 2011)
- Torcetrapib raises blood pressure in dogs through systemic and pulmonary vasoconstriction that also strains the heart (J Cardiovasc Pharmacol 2009)
- Torcetrapib raises blood pressure and RAAS gene expression in rats, but dalcetrapib does neither (Br J Pharmacol 2009)
- HDL from patients on high-dose torcetrapib removes more cholesterol from macrophages, correlating with the atheroma regression seen on the drug (Am J Cardiol 2009)
- Barter reflects on ILLUMINATE: the harm caused by torcetrapib likely reflects off-target effects, not CETP inhibition itself (Am J Cardiol 2009)
- Torcetrapib and CP-532,623 raise blood pressure via a chemotype-specific mechanism dissociated from CETP inhibition timing (J Cardiovasc Pharmacol 2009)
- Genome-wide protein-ligand network analysis maps the off-target pathways behind the hypertensive side effect of torcetrapib (PLoS Comput Biol 2009)
- A mathematical model shows torcetrapib and JTT-705 inhibit CETP more potently than classic competitive inhibition would predict (J Lipid Res 2009)
- Torcetrapib raises apolipoprotein A-II levels by slowing its clearance and shifting it into a different HDL subpopulation (J Lipid Res 2009)
- Torcetrapib partly restores healthy HDL2 and HDL3 function in type IIB hyperlipidemia, boosting cholesterol efflux by up to 38 percent (Arterioscler Thromb Vasc Biol 2009)
- A review notes a meta-analysis linking CETP-lowering alleles to reduced coronary heart disease, distinct from the off-target failure of torcetrapib (J Lipid Res 2009)
- Natural variation in plasma CETP levels does not affect RAAS responsiveness or blood pressure reactivity in healthy men (Expert Opin Ther Targets 2008)
- Torcetrapib produces smaller but more inflamed, less stable plaques than atorvastatin in humanized transgenic mice (Circulation 2008)
- A Nature Reviews Drug Discovery analysis asks whether the torcetrapib failure means functional quality of HDL matters more than its circulating quantity (Nat Rev Drug Discov 2008)
- Both raising and lowering CETP activity can enhance reverse cholesterol transport, depending on the species and pathway studied (Cardiovasc Res 2008)
- A review proposes that the now-known crystal structure of CETP could guide the design of inhibitors that avoid the nonproductive HDL complex formed by torcetrapib (Am J Cardiol 2007)
- Torcetrapib reduces VLDL apolipoprotein E levels alone, but on background atorvastatin instead boosts its content and speeds VLDL clearance (J Lipid Res 2008)
- Torcetrapib cuts postprandial VLDL-1 by 40 percent and reduces its atherogenic cholesteryl-ester content in type IIB hyperlipidemia (Arterioscler Thromb Vasc Biol 2008)
- A review says the CETP crystal structure could enable inhibitors that avoid the nonproductive HDL-binding complex formed by torcetrapib (Curr Opin Cardiol 2007)
- Torcetrapib cuts aortic atherosclerosis by 60 percent in rabbits fed an atherogenic diet, tracking the ratio of total cholesterol to HDL (J Lipid Res 2007)
- Doubling the dose of torcetrapib from 60 to 120 mg turns a modest boost in macrophage cholesterol efflux into a dramatic one (Arterioscler Thromb Vasc Biol 2007)
- 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 alone raises HDL cholesterol by up to 54.5 percent, with less LDL benefit in patients with high triglycerides (J Am Coll Cardiol 2006)
- Adding torcetrapib to atorvastatin raises HDL cholesterol by up to 40 percent with no dose-related rise in adverse events (J Am Coll Cardiol 2006)
- Torcetrapib raises large alpha-1 HDL particles by more than 50 percent in humans, mainly by slowing ApoA-I breakdown (Curr Opin Lipidol 2006)
- Torcetrapib alone clears apoB100 faster, but added to atorvastatin it instead cuts LDL and IDL production (Arterioscler Thromb Vasc Biol 2006)
- Two novel CETP gene variants are found in humans, and torcetrapib inhibits both variant and normal CETP equally (Biochim Biophys Acta 2005)
- CETP directly delivers HDL cholesteryl ester to the liver through a receptor-independent pathway that torcetrapib only partly blocks (Arterioscler Thromb Vasc Biol 2005)
- Torcetrapib raises apolipoprotein A-I in alpha1-migrating HDL by up to 382 percent at twice-daily dosing, without changing fecal sterol excretion (Arterioscler Thromb Vasc Biol 2005)
- Torcetrapib inhibits every common CETP genetic variant equally, even the two that are naturally more stable in the body (J Biol Chem 2005)
- A turmeric compound, calebin A, binds CETP nearly as tightly as torcetrapib in a computational drug-discovery screen (Res Pharm Sci 2026)
- How CETP moves cholesterol between lipoproteins: a structural review of the mechanism behind torcetrapib, anacetrapib and obicetrapib (Curr Atheroscler Rep 2023)
- Adding torcetrapib to atorvastatin lowers lipoprotein(a) by 11 percent while modestly raising PCSK9, an ILLUMINATE biomarker substudy finds (J Clin Lipidol 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)
- BMS-795311 matches torcetrapib for raising HDL in hamsters without raising blood pressure or aldosterone synthase (J Med Chem 2015)
- Lipid-based drug delivery greatly improves oral exposure to two CETP inhibitors, torcetrapib and CP-532,623, in beagle dogs (Eur J Pharm Biopharm 2014)
- Novel non-THQ torcetrapib analog PF-04445597 avoids the aldosterone-inducing effect linked to torcetrapib toxicity (Xenobiotica 2014)
- Torcetrapib raises blood pressure across four independent cardiovascular models, validating them as predictive lead-optimization tools (J Cardiovasc Pharmacol 2012)
- A review of biomarker and imaging trials shows the favorable lipid effects of torcetrapib failed to predict a 58 percent rise in mortality (Can J Cardiol 2012)
- A structural-and-metabolic-network computational model predicts off-target causes of the hypertensive side effect of torcetrapib in kidney tissue (PLoS Comput Biol 2010)
- Review traces the ILLUMINATE mortality signal of torcetrapib to adrenal aldosterone secretion, not receptor blockade (Hypertens Res 2010)
- Noninvasive high-definition oscillometry matches implanted telemetry for tracking torcetrapib-induced blood pressure rises in dogs (J Am Assoc Lab Anim Sci 2010)
- A review of CETP molecular mechanisms notes the negative phase III torcetrapib trials challenged the future of the drug class (Cell Mol Life Sci 2010)
- A humanized transgenic mouse model shows torcetrapib raises HDL cholesterol by 53 percent, less than a potent PPAR-alpha agonist (J Cardiovasc Pharmacol Ther 2010)
- A review argues that after the torcetrapib failure, HDL functionality biomarkers are needed since HDL cholesterol alone is not a functional measure (Expert Rev Cardiovasc Ther 2010)
- A review argues that the harms of torcetrapib trace to its own tight CETP binding and an aldosterone-like effect, not to CETP inhibition itself (Rom J Intern Med 2010)
- A review argues the mortality signal from torcetrapib traces to off-target toxicity, not to CETP inhibition itself (Am J Cardiol 2009)
- Torcetrapib does not block CETP or LPS-binding-protein interactions, ruling out a direct sepsis-mortality mechanism (J Lipid Res 2010)
- A conformationally constrained CETP inhibitor matches the HDL-raising efficacy of torcetrapib across hamsters, transgenic mice, and monkeys (J Med Chem 2009)
- A translational-medicine commentary argues the failure of 4 large torcetrapib trials calls for biomarker-driven drug development, not abandonment of CETP as a target (Biochem Pharmacol 2009)
- A review draws lessons from ILLUMINATE on the hypertension risk of CETP inhibitors despite raising HDL cholesterol by up to 100 percent (Curr Hypertens Rep 2009)
- A review weighs four possible explanations for why torcetrapib raised cardiovascular risk despite raising HDL cholesterol (Ann Med 2009)
- A review links the B1B1 CETP genotype to higher CETP activity, lower HDL cholesterol, and more pronounced postprandial lipemia (Curr Med Chem 2009)
- A review argues the off-target effects of torcetrapib, not the CETP-inhibition mechanism itself, likely overrode any cardiovascular benefit (Cardiol Clin 2008)
- Biosensor mapping places the torcetrapib binding site at Cys-13 in the CETP lipid-binding pocket (Bioconjug Chem 2008)
- A review argues ABCA1 and ABCG1 transporters, not raw HDL cholesterol level, drive HDL's atheroprotective effect after the torcetrapib failure (Cell Metab 2008)
- 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 argues four disappointing torcetrapib trials require refining the HDL hypothesis, since HDL may be more carrier protein than cholesterol transporter (Ann Med 2008)
- A review questions whether CETP inhibitors can ultimately reduce cardiovascular events after torcetrapib raised blood pressure without slowing coronary atherosclerosis (Am J Cardiol 2007)
- 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)
- A meta-analysis of 23 trials finds HDL-raising tracks with reduced atherosclerosis progression for every drug class except the torcetrapib-atorvastatin combination (J Clin Lipidol 2007)
- Review asks whether torcetrapib will become the next big advance in coronary heart disease prevention (Curr Atheroscler Rep 2007)
- A review previews a large-scale CETP-inhibitor imaging and outcomes program as the next frontier after statin-driven atherosclerosis regression (Can J Cardiol 2006)
- Torcetrapib can double HDL cholesterol while lowering LDL cholesterol by up to 42 percent, a review of CETP inhibitors reports (Curr Opin Pharmacol 2006)
- Doubling torcetrapib to its maximum tolerated dose more than doubles HDL cholesterol when combined with atorvastatin (Drugs Today 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)
- A review of torcetrapib/atorvastatin combination therapy covers the chemistry, mechanism, and pharmacokinetics behind their complementary lipid effects (Expert Rev Cardiovasc Ther 2005)
- Prospective cohort data link elevated CETP concentration to higher cardiovascular risk only when triglycerides are also high (Curr Opin Lipidol 2004)
- Machine learning and molecular dynamics show why obicetrapib binds the CETP hydrophobic tunnel more tightly than the failed torcetrapib (ChemMedChem 2025)
- An acoustic-fusion formulation of torcetrapib boosts drug exposure roughly 8-fold over a crystalline suspension in rats (Int J Pharm 2021)
- Torcetrapib increases large HDL particles more than a novel FXR antagonist in a hamster model of dyslipidemia (Pharmacol Res Perspect 2018)
- A review appraises whether newer CETP inhibitors can avoid the off-target effects that undid torcetrapib (Curr Cardiol Rep 2016)
- Torcetrapib raises HDL cholesterol in primates without touching non-HDL cholesterol, distinguishing it from an FXR antagonist tested alongside it (Life Sci 2014)
- A review argues the torcetrapib setback shifted focus from HDL cholesterol quantity to HDL particle functionality (Am J Ther 2014)
- Review collates the bioanalytical methods developed to quantify anacetrapib, dalcetrapib, and torcetrapib in biological samples (Biomed Chromatogr 2013)
- A review questions whether CETP inhibition can reduce cardiovascular events given the complex link between CETP loss-of-function and coronary risk (Curr Cardiol Rep 2011)
- A review finds niacin remains the most potent HDL-raising therapy while CETP inhibitors stand closest to clinic despite the mortality signal seen with torcetrapib (Curr Treat Options Cardiovasc Med 2010)
- A workaround measures two acyl-glucuronide metabolites of torcetrapib in monkey urine without ever having reference standards for them (Biomed Chromatogr 2010)
- A review of nonstatin add-on therapies finds torcetrapib raised mortality in coronary patients despite a marked rise in HDL cholesterol (Curr Atheroscler Rep 2009)
- Adding a bile correction factor sharpens allometric prediction of human pharmacokinetic parameters for orally dosed torcetrapib (Eur J Drug Metab Pharmacokinet 2009)
- A perspective argues the torcetrapib failure should redirect HDL drug development away from raw cholesterol concentration and toward specific antiatherosclerotic components (Ann Clin Biochem 2009)
- A review argues the torcetrapib failure highlights HDL functionality, not raw HDL cholesterol level, as the real therapeutic target (Curr Opin Investig Drugs 2008)
- Torcetrapib is extensively metabolized in humans with terminal half-lives of 211 to 373 hours (Drug Metab Dispos 2008)
- A review proposes injecting synthetic HDL directly as an alternative after torcetrapib, the furthest-developed HDL-raising pill, was halted for excess mortality (Nutr Metab Cardiovasc Dis 2008)
- A review attributes the excess deaths seen with torcetrapib to an off-target effect, not to CETP inhibition, while low HDL remains an important risk marker (Curr Opin Endocrinol Diabetes Obes 2008)
- A review argues the torcetrapib failure shifted laboratory focus from HDL cholesterol concentration to HDL particle heterogeneity and function (Clin Chem 2008)
- A new LC-MS/MS assay quantifies torcetrapib in hamster and dog plasma down to 1 nanogram per mL (Biomed Chromatogr 2008)
- A post hoc review of the safety monitoring board for the torcetrapib trial warns against over-relying on formal statistical stopping rules (Eur J Clin Pharmacol 2008)
- A regulatory perspective argues the termination of torcetrapib means future HDL therapies will need preapproval proof of effects on actual disease progression (Am J Cardiol 2007)
- A chiral HPLC method separates the two torcetrapib enantiomers in hamster plasma down to 0.1 microgram per mL (J Chromatogr B 2007)
- A review argues the torcetrapib failure highlighted the gap between HDL cholesterol levels and HDL anti-inflammatory function (J Clin Lipidol 2007)
- 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)
- Hypothesis paper proposes that the ILLUMINATE deaths from torcetrapib trace to eNOS inhibition via HDL-SR-BI signaling loss (Med Hypotheses 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)
- Torcetrapib shifts almost entirely into triglyceride-rich lipoproteins in hyperlipidemic human plasma (Pharm Res 2006)
- 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)
- A review argues raising HDL with torcetrapib is a promising new approach to atherosclerosis, pending trials with hard clinical endpoints (Recent Pat Cardiovasc Drug Discov 2006)
- A review of four lipid transfer proteins highlights the early human results of torcetrapib as opening a new era in coronary heart disease prevention (Atherosclerosis 2005)
- 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)
- A review catalogs the chiral and achiral bioanalytical methods developed to measure torcetrapib across six species (Bioanalysis 2009)
- Torcetrapib forms more than 28 species-dependent metabolites in rats, monkeys, and mice (Drug Metab Dispos 2008)
- A diabetes-dyslipidemia review predicts the disappointing torcetrapib results will renew interest in niacin therapy (Curr Opin Endocrinol Diabetes Obes 2008)
- Chiral LC-MS/MS assay separates torcetrapib enantiomers in hamster plasma down to 5 ng/mL (J Chromatogr B 2007)
- Self-emulsifying formulation cuts the food effect of torcetrapib from 5-fold to 3-fold in dogs (Int J Pharm 2008)
- RADIANCE 1 and 2 are designed to compare torcetrapib plus atorvastatin against atorvastatin alone in over 1,650 patients using carotid ultrasound (Curr Med Res Opin 2007)