- |||||||||| Entresto (sacubitril/valsartan) / Novartis, ROVI Pharmaceuticals Laboratories
Biomarker, Journal: Aptamer Proteomics for Biomarker Discovery in Heart Failure With Preserved Ejection Fraction: The PARAGON-HF Proteomic Substudy. (Pubmed Central) - Jun 21, 2024
P3
Numerous serum proteins linked to metabolic, coagulation, and extracellular matrix regulatory pathways were associated with worse HFpEF prognosis in the PARAGON-HF proteomic substudy. Our results demonstrate substantial similarities among serum proteomic risk markers for heart failure hospitalization and cardiovascular death when comparing clinical trial participants with heart failure across the ejection fraction spectrum.
- |||||||||| Review, Journal: Drugs for hypertension. (Pubmed Central) - May 21, 2024
These insights will aid in the development of effective therapies to break the vicious cycle of high blood pressure during hypertension, ultimately addressing the expanding global heart failure pandemic. No abstract available
- |||||||||| Tekturna (aliskiren) / PDL, Invokana (canagliflozin) / J&J, Daiichi Sankyo, Mitsubishi Tanabe
Journal: Prediction of new-onset heart failure in patients with type 2 diabetes derived from ALTITUDE and CANVAS. (Pubmed Central) - Apr 8, 2024
In patients with T2D, higher NT-proBNP level, TnT level and BMI are independent and externally validated predictors of new-onset HF, including patients using an SGLT2 inhibitor. This newly developed model may identify patients at high risk of new-onset HF, contributing to early recognition and possibly prevention.
- |||||||||| Tekturna (aliskiren) / PDL
Machine learning does not improve risk prediction in heart failure in comparison to the PREDICT-HF model: derivation and validation in PARADIGM-HF and ATMOSPHERE (Moderated ePosters 3) - Mar 4, 2024 - Abstract #HEARTFAILURE2024HEART_FAILURE_723;
We used the two trials that were used to develop the PREDICT-HF risk model, Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure trial (PARADIGM-HF), the training set, and Aliskiren Trial to Minimize OutcomeS in Patients with HEart FailuRE trial (ATMOSPHERE), the testing set... Although ML based models improved risk prediction when derived in PARADIGM-HF, when tested in ATMOSPHERE their performance fell and did not substantially improve the prediction obtained from the previously validated, and more consistent Cox model in PREDICT-HF.
- |||||||||| ombitasvir (ABT-267) / AbbVie, Tekturna (aliskiren) / PDL
Journal: Identification of novel compounds and repurposing of FDA drugs for 1-deoxy-D-xylulose 5-phosphate reductoisomerase enzyme of Plasmodium falciparum to combat malaria resistance. (Pubmed Central) - Jan 29, 2024
Although ML based models improved risk prediction when derived in PARADIGM-HF, when tested in ATMOSPHERE their performance fell and did not substantially improve the prediction obtained from the previously validated, and more consistent Cox model in PREDICT-HF. Following our computational pipeline, we found five novel ZINC20 compounds (Z-2, Z-3, Z-10, Z-13, and Z-14) and three FDA drugs (Aliskiren, Ceftolozane, and Ombitasvir) that showed striking docking energy (ranging from -8.405 to -10.834
- |||||||||| Tekturna (aliskiren) / PDL
Journal: Renin and renin blockade have no role in complement activity. (Pubmed Central) - Jan 22, 2024
Third, aliskiren, a renin inhibitor, does not block abnormal complement activity introduced by nephritic factors in the fluid phase...And seventh, molecular modeling and docking place C3 in the active site of renin in a position that is not consistent with a productive ground state complex for catalytic hydrolysis. Thus, our study does not support a role for renin in the activation of complement.
- |||||||||| Tekturna (aliskiren) / PDL
Review, Journal: Therapeutic Implications of Renin-Angiotensin System Modulators in Alzheimer's Dementia. (Pubmed Central) - Sep 28, 2023
Clinical trials on RAS modulators in AD are limited, but with promising results, ARBs being more effective that ACEIs in reducing cognitive decline. The varied roles of ACEIs, ARBs, and renin inhibitors in RAS modulation present a promising avenue for AD therapeutic intervention, requiring further research to potentially transform AD treatment strategies.
- |||||||||| Tekturna (aliskiren) / PDL
Review, Journal: First-line diuretics versus other classes of antihypertensive drugs for hypertension. (Pubmed Central) - Jul 17, 2023
The varied roles of ACEIs, ARBs, and renin inhibitors in RAS modulation present a promising avenue for AD therapeutic intervention, requiring further research to potentially transform AD treatment strategies. When used as first-line agents for the treatment of hypertension, thiazides and thiazide-like drugs likely do not change total mortality and likely decrease some morbidity outcomes such as cardiovascular events and withdrawals due to adverse effects, when compared to beta-blockers, calcium channel blockers, ACE inhibitors, and alpha-blockers.
- |||||||||| Tekturna (aliskiren) / PDL
Journal: Investigation renin inhibitor activity from flavonoids derivates by in silico study. (Pubmed Central) - May 31, 2023
Hesperitin, kaempferol, and naringenin had similarities with aliskiren on the amino-acid residues in the renin-binding pocket. However, based on pharmacokinetic analysis, the three compounds had an oral pharmacokinetic profile that could have been better than aliskiren.
- |||||||||| Tekturna (aliskiren) / PDL
Review, Journal: Renin-angiotensin-aldosterone pathway modulators in chronic kidney disease: A comparative review. (Pubmed Central) - Mar 3, 2023
In this review, a comparison has been drawn between the direct renin inhibitor (aliskiren), angiotensin-converting enzyme inhibitors, and angiotensin II receptor blockers. This can be of significance for healthcare providers and researchers to find the particular loci of interest, either in structure or mechanism, and to intervene as per the case presentation to obtain the best possible treatment option.
- |||||||||| telmisartan / Generic mfg.
Preclinical, Journal: Exploring the repurposing potential of telmisartan drug in breast cancer: an in-silico and in-vitro approach. (Pubmed Central) - Feb 27, 2023
All the compounds (enalapril, atenolol, acebutolol, propranolol, amlodipine, verapamil, doxazosin, prazosin, hydralazine, irbesartan, telmisartan, candesartan, and aliskiren) showed remarkable affinity towards the target receptor proteins. IC50 of the drug was calculated to be 7.75?
- |||||||||| Tekturna (aliskiren) / PDL
Journal: A systems biology approach identifies the role of dysregulated PRDM6 in the development of hypertension. (Pubmed Central) - Jan 6, 2023
The het-erozygous SMC-specific Prdm6 knockout mice (Prdm6fl/+ Sm22Cre) exhibited a markedly high-er number of renin-producing cells in the kidneys at embryonic day 18.5 compared to wild-type littermates and developed salt-induced systemic hypertension that was completely responsive to the renin inhibitor aliskiren...Fate mapping and histological studies also showed increased numbers of neural crest-derived cells accompanied by increased collagen deposition in the kidneys of Prdm6fl/+ Wnt1Cre-ZsGreen1Cre compared to wild-type mice. These findings establish the role of PRDM6 as a regulator of renin-producing cells and an attractive target for the development of antihypertensive drugs.
- |||||||||| Tekturna (aliskiren) / PDL
Journal: Mathematical modeling of antihypertensive therapy. (Pubmed Central) - Jan 3, 2023
The extended model paves the way for the next step in personalized medicine that is adapting the model parameters to a real patient and predicting his response to antihypertensive therapy. The model is implemented in the BioUML software and is available at https://gitlab.sirius-web.org/virtual-patient/antihypertensive-treatment-modeling.
- |||||||||| Tekturna (aliskiren) / PDL
Aliskiren as an Adjunct Treatment for Recurrent C3 Glomerulonephritis (C3GN) in a Transplant Patient (Exhibit Hall, Orange County Convention Center, West Building) - Oct 13, 2022 - Abstract #KIDNEYWEEK2022KIDNEY_WEEK_3250;
She received induction with anti-thymocyte globulin, and maintenance immunosuppression was tacrolimus, mycophenolate mofetil (MMF) and prednisone...She developed 1.5 g/d proteinuria 3 years post-transplant while on losartan...Comparison of pre- and post-biopsy data showed a statistical reduction (p<0.01) in the mean (SD,standard deviation) size of deposits [2201 nanometer (SD 1102) vs 884 nm (SD 255)] as well as the density of deposits [3.8 per capillary loop (SD 2.5) vs 2.5 per capillary loop (SD 2.8)] Discussion Traditionally management of C3GN has included immunosuppressive agents including steroids, MMF and a possible role of complement pathway blocker, eculizumab...In this first report we describe achievement of complete remission in a patient with recurrent C3GN after kidney transplant with Aliskiren and MMF intensification. These data support further trials for this relatively cheap therapy in this rare disease space.
- |||||||||| Tekturna (aliskiren) / PDL
Retrospective data, Review, Journal: Efficacy of Direct Renin Inhibitors in Slowing Down the Progression of Diabetic Kidney Disease: A Meta-Analysis. (Pubmed Central) - Oct 8, 2022
The odds of remission from microalbuminuria to macroalbuminuria were 20% lower in patients receiving direct renin inhibitors compared to patients in the control group (OR: 0.80, 95% CI: 0.69-0.93, p-value=0.003). The use of aliskiren is associated with a significant reduction in UACR, increased remission from microalbuminuria to normal albuminuria and decreased progression from microalbuminuria to macroalbuminuria.
- |||||||||| Tekturna (aliskiren) / PDL
Preclinical, Journal: Soluble (Pro)Renin Receptor Levels Are Regulated by Plasma Renin Activity and Correlated with Edema in Mice and Humans with HFrEF. (Pubmed Central) - Aug 27, 2022
In female DCM mice with elevated PRA levels and plasma s(P)RR levels, a randomized, blinded trial comparing the direct renin inhibitor, aliskiren vs. vehicle control, showed that direct renin inhibition normalized PRA, lowered s(P)RR, and prevented symptomatic HFrEF. Considered in light of previous findings, these data suggest that, in HFrEF, in the absence of renal dysfunction, elevation of plasma s(P)RR levels is caused by increased PRA and associated with the development of systemic edema.
- |||||||||| SPH3127 / Shanghai Pharma
Journal: Discovery of SPH3127: A Novel, Highly Potent, and Orally Active Direct Renin Inhibitor. (Pubmed Central) - Aug 27, 2022
Therefore, we tried to find nonpeptidomimetic DRIs with a MW of < 500 and discovered the promising 2-carbamoyl morpholine derivative 4. In our efforts to improve the pharmacokinetic profile of 4 without a significant increase in the MW, we discovered compound 18 (SPH3127), which demonstrated higher bioavailability and a more potent antihypertensive effect in preclinical models than aliskiren and has completed a phase II clinical trial for essential hypertension.
- |||||||||| Tekturna (aliskiren) / PDL
Journal: Discovery of Novel 2-Carbamoyl Morpholine Derivatives as Highly Potent and Orally Active Direct Renin Inhibitors. (Pubmed Central) - Aug 22, 2022
Therefore, various direct renin inhibitors (DRIs) have been researched over recent decades; however, most exhibited poor pharmacokinetics and oral bioavailability due to the peptidomimetic or nonpeptidomimetic structures with a molecular weight (MW) of >600, and only aliskiren is approved...These compounds have a nonpeptidomimetic structure and a MW of <500. The representative compound 26 was highly potent despite not occupying S1'-S2' sites or the opened flap region used by other DRIs and exerted a significant antihypertensive efficacy via oral administration on double transgenic mice carrying both the human angiotensinogen and the human renin genes.
- |||||||||| Tekturna (aliskiren) / PDL
Journal: Pharmacophore modelling, docking and molecular dynamic simulation studies in the discovery of potential human renin inhibitors. (Pubmed Central) - Aug 17, 2022
The crystal structure of renin-aliskiren complex was explored and receptor-ligand pharmacophore model was developed and validated using pharmit...The result of MD simulation indicated the stable binding of ZINC426421106 and ZINC5481346 with the active site of renin. According to this in-silico study these two compounds are drug-like, nontoxic, and have a high potential for inhibiting renin and could serve as appropriate lead molecules for the development of renin inhibitors as antihypertensive agents.
- |||||||||| Tekturna (aliskiren) / PDL, Crixivan (indinavir sulfate) / Merck (MSD)
Regio- and diastereoselective rhodium-catalyzed allylic substitution with unstabilized benzyl nucleophiles (Virtual-only (Zoom)) - Aug 9, 2022 - Abstract #ACSFall2022ACS_Fall_2771;
This seminar will also outline the development of a diastereoselective variant, which permits both acyclic and cyclic allylic carbonates bearing a homoallylic stereocenter to undergo benzylation with high levels of diastereocontrol. Hence, this approach provides a rare example of 1,2-stereoinduction in transition metal-catalyzed allylic substitution.
- |||||||||| Entresto (sacubitril/valsartan) / Novartis, ROVI Pharmaceuticals Laboratories, Tekturna (aliskiren) / PDL
Clinical data, Journal: Clinical Outcomes Related to Background Diuretic Use and New Diuretic Initiation in Patients With HFrEF. (Pubmed Central) - Jun 10, 2022
Hence, this approach provides a rare example of 1,2-stereoinduction in transition metal-catalyzed allylic substitution. Patients with HFrEF not taking diuretic medications and those who remained off them had better outcomes than patients treated with diuretic agents or who commenced them.
- |||||||||| Tekturna (aliskiren) / PDL
Preclinical, Journal: Cardiac and pulmonary expression of renin, prorenin, mast cells and macrophages in a rat model of fat embolism syndrome. (Pubmed Central) - May 14, 2022
This difference is not only related to the number of the inflammatory cells but also to their location in different organs as evidenced by the difference in the distribution and location of R/P cells in hearts and lungs. Future studies will investigate the underlying mechanisms that lead to pulmonary susceptibility while preserving cardiac integrity in response to a FE induced inflammatory response in order to better design a therapeutic intervention for the fat embolism syndrome.
- |||||||||| Tekturna (aliskiren) / PDL
Journal: The effects of the renin inhibitor aliskiren on neuronal toxic damage. (Pubmed Central) - Apr 9, 2022
In conclusion, aliskiren upregulates cell viability, reduces inflammatory damage and apoptosis induced by Aβ accumulation in AD via inhibiting PDE4B. These findings have expanded the scope of future application of aliskiren and provided a theoretical basis.
- |||||||||| Tekturna (aliskiren) / PDL, Januvia (sitagliptin) / Merck (MSD)
Retrospective data, Journal: Identifying congeners and transformation products of organic contaminants within complex chemical mixtures in impacted surface waters with a top-down non-targeted screening workflow. (Pubmed Central) - Apr 1, 2022
Reference standards were used to confirm the identification of 53 contaminants among them lesser-known pharmaceuticals (aliskiren, sitagliptin) and consumer product additives (lauramidopropyl betaine, 2,2,4-trimethyl-1,2-dihydroquinoline)...As such, several previously unknown TPs of pesticides (metolachlor) and pharmaceuticals (gliclazide, irbesartan) were identified as tentative candidates or probable structures...Furthermore, it allows elucidating the structure of TPs directly from samples without relying on bottom-up studies under conditions discussed herein. The top-down workflow and the MNC tools show great potential for data mining and retrospective analysis of previous NTS studies.
- |||||||||| Journal: A Fully Automated Online SPE-LC-MS/MS Method for the Determination of 10 Pharmaceuticals in Wastewater Samples. (Pubmed Central) - Mar 25, 2022
Due to the shorter overall run time of 15 min, including sample preparation, and reduced sample volume (0.9 mL), this on-line SPE-LC-MS/MS method was extremely convenient and efficient in comparison to the classical off-line SPE method. The proposed method was also highly sensitive and can be used for ultratrace quantification of the studied pharmaceuticals in wastewaters, providing useful data for effective environmental monitoring.
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