- |||||||||| Taltorvic (ridaforolimus) / Takeda, Merck (MSD)
Review, Journal: Clinical research progress of ridaforolimus (AP23573, MK8668) over the past decade: a systemic review. (Pubmed Central) - Apr 8, 2024
Rapamycin, an established mTOR inhibitor in clinical practice, is widely recognized for its therapeutic efficacy...These trials employed diverse drug combinations, incorporating agents such as ponatinib, bicalutamide, dalotuzumab, MK-2206, MK-0752, and taxanes...Our review encompassed analyses of signaling pathways, ridaforolimus as a single therapeutic agent, its compatibility in combination with other drugs, and an assessment of adverse events (AEs). We conclude by recommending further research to advance our understanding of ridaforolimus's clinical applications.
- |||||||||| Taltorvic (ridaforolimus) / Takeda, Merck (MSD)
Journal, Gene Signature: Gene signatures to therapeutics: Assessing the potential of ivermectin against t(4;14) multiple myeloma. (Pubmed Central) - Jan 31, 2024
We conclude by recommending further research to advance our understanding of ridaforolimus's clinical applications. Collectively, the findings offer valuable molecular insights for biomarker validation and potential drug development in t(4;14) MM diagnosis and treatment, with ivermectin emerging as a potential therapeutic alternative.
- |||||||||| NN1213 / Novo Nordisk
Phase classification: BIONICS: Study of BioNIR Drug Eluting Stent System in Coronary Stenosis (clinicaltrials.gov) - Oct 16, 2023
P=N/A, N=1919, Completed,
These effects are maintained even when challenged with FGF19, suggesting that dual inhibition of FGFR4 and HER2 could prevent pathway activation from external stimuli. Phase classification: P2 --> P=N/A
- |||||||||| sirolimus / Generic mfg.
Review, Journal: Three Layers of Personalized Medicine in the Use of Sirolimus and Its Derivatives for the Treatment of Cancer. (Pubmed Central) - May 27, 2023
Current evidence suggests that tumors with mutations in the mTOR signal transduction pathway are sensitive to rapalogue treatment; the rapalogues are metabolized by cytochromes such as CYP3A4, CYP3A5, and CYP2C8 and transported by ABC transporters that are known to vary in activity in individuals; and that tumors can express these transporters and detoxifying enzymes. This results in three levels of genetic analysis that could impact the effectiveness of the mTOR inhibitors.
- |||||||||| Taltorvic (ridaforolimus) / Takeda, Merck (MSD), Torisel (temsirolimus) / Pfizer
Journal: The mTOR Signaling Pathway and mTOR Inhibitors in Cancer: Next-generation Inhibitors and Approaches. (Pubmed Central) - May 11, 2023
Since mTOR resistance mechanisms prevent the effects of mTOR inhibitors used in cancer treatments, new inhibition strategies should be developed. Inhibition approaches are created using nanoparticles, and one of them offers a promising treatment option with evidence supporting its effectiveness.
- |||||||||| Taltorvic (ridaforolimus) / Takeda, Merck (MSD), Torisel (temsirolimus) / Pfizer
Journal: Why is rapamycin not a rapalog? (Pubmed Central) - Jan 9, 2023
Analogs of rapamycin were developed to improve its pharmacological properties, such as low oral bioavailability and a long half-life. The analogs of rapamycin are referred to as 'rapalogs.' Rapamycin is the parent compound and should there with not be called a 'rapalog.'
- |||||||||| Taltorvic (ridaforolimus) / Takeda, Merck (MSD), Torisel (temsirolimus) / Pfizer
Journal: Rapalogs downmodulate intrinsic immunity and promote cell entry of SARS-CoV-2. (Pubmed Central) - Oct 21, 2022
In rodent models of infection, injection of rapamycin prior to and after virus exposure resulted in elevated SARS-CoV-2 replication and exacerbated viral disease, while ridaforolimus had milder effects. Overall, our findings indicate that preexisting use of certain rapalogs may elevate host susceptibility to SARS-CoV-2 infection and disease by activating lysosome-mediated suppression of intrinsic immunity.
- |||||||||| Biomarker, Journal: CDH6 as a prognostic indicator and marker for chemotherapy in gliomas. (Pubmed Central) - Aug 9, 2022
Potential drugs associated with high CDH6 expression were also predicted, including AMG-22, rutin, CCT128930, deforolimus, bis(maltolato)oxovanadium, anagrelide, vemurafenib, CHIR-98014, and AZD5582. Thus, this study showed that CDH6 correlates with glioma immune infiltration, it is expressed mainly in AC-like malignant cells, and it may act as a new target for glioma therapy.
- |||||||||| Torisel (temsirolimus) / Pfizer
Journal: Evidence for Bell-Shaped Dose-Response Emetic Effects of Temsirolimus and Analogs: The Broad-Spectrum Antiemetic Efficacy of a Large Dose of Temsirolimus Against Diverse Emetogens in the Least Shrew (Cryptotis parva). (Pubmed Central) - Apr 22, 2022
With its analogs (everolimus, ridaforolimus, and rapamycin), it forms a group of anticancer agents that block the activity of one of the two mammalian targets of rapamycin (mTOR) complexes, mTORC1...We then determined the broad-spectrum antiemetic potential of a 20 mg/kg (i.p.) dose of temsirolimus against diverse emetogens, including selective and nonselective agonists of 1) dopaminergic D receptors (apomorphine and quinpirole); 2) serotonergic 5-HT receptors [5-HT (serotonin) and 2-methyl-5-HT]; 3) cholinergic M receptors (pilocarpine and McN-A-343); 4) substance P neurokinin NK receptors (GR73632); 5) the L-type calcium (Ca) channel (LTCC) (FPL64176); 6) the sarcoplasmic endoplasmic reticulum Ca ATPase inhibitor, thapsigargin; 7) the CB receptor inverse agonist/antagonist, SR141716A; and 8) the chemotherapeutic cisplatin...The mechanisms underlying the pro- and antiemetic effects of temsirolimus evaluated by immunochemistry for c-fos expression demonstrated a c-fos induction in the AP and NTS, but not DMNX with the 10 mg/kg emetic dose of temsirolimus, whereas its larger antiemetic dose (20 mg/kg) had no significant effect. Our study is the first to provide preclinical evidence demonstrating the promising antiemetic potential of high doses of temsirolimus and possibly its analogs in least shrews.
- |||||||||| Taltorvic (ridaforolimus) / Takeda, Merck (MSD), Torisel (temsirolimus) / Pfizer
Select Rapamycin Analogs Promote VSV-G-Mediated Cell Entry by Activating TFEB-Dependent Microautophagy (Poster Board Number: W-265; Hall D) - Apr 20, 2022 - Abstract #ASGCT2022ASGCT_1039;
Our findings suggest that they act at the level of cell-intrinsic immunity to undermine the cell's first line of antiviral defenses. The development of rapamycin analogs that lack this activity may reduce unintended immunosuppression in human subjects.
- |||||||||| Taltorvic (ridaforolimus) / Takeda, Merck (MSD), gedatolisib (PF-05212384) / Celcuity, Torisel (temsirolimus) / Pfizer
Journal: Structural Aspects of mTOR Inhibitors: In Progress to Search Potential Compounds. (Pubmed Central) - Apr 13, 2022
The mTOR inhibitors bearing heterocyclic moieties such as quinazoline, thiophene, morpholine, imidazole, pyrazine, furan, quinoline are under investigation against various cancer cell lines (U87MG, PC-3, MCF-7, A549, MDA-231). In this review, we summarized updated research related to mTOR inhibitors, their structure-activity relationship which may help scientists for the development of potent inhibitors against cancer.
- |||||||||| Taltorvic (ridaforolimus) / Takeda, Merck (MSD)
RAPALOGS DOWNMODULATE INTRINSIC IMMUNITY AND PROMOTE CELL ENTRY OF SARS-CoV-2 ([VIRTUAL]) - Feb 7, 2022 - Abstract #CROI2022CROI_254;
In the hamster model of SARS-CoV-2 infection, injection of rapamycin four hours prior to virus exposure resulted in elevated virus titers in lungs, accelerated weight loss, and decreased survival. Our findings indicate that preexisting use of certain rapalogs may elevate host susceptibility to SARS-CoV-2 infection and disease by activating a lysosome-mediated suppression of intrinsic immunity.
- |||||||||| Taltorvic (ridaforolimus) / Takeda, Merck (MSD), Nexavar (sorafenib) / Bayer, Amgen
Review, Journal: Advances in targeted therapy for osteosarcoma based on molecular classification. (Pubmed Central) - Feb 5, 2022
Therefore, we indicated the importance of molecular classification on the targeted therapy for osteosarcoma. And the stratification of patients based on the genetic characteristics of osteosarcoma will help to obtain a better therapeutic response to targeted therapies, bringing us closer to the era of personalized medicine.
- |||||||||| Taltorvic (ridaforolimus) / Takeda, Merck (MSD)
Retrospective data, Review, Journal: mTOR inhibitors and risk of ovarian cysts: a systematic review and meta-analysis. (Pubmed Central) - Nov 4, 2021
Ovarian cyst development is a common adverse event during immunosuppression treatment with mTORi. These cysts are benign conditions, but they require pelvic ultrasound follow-up and in some cases hospital admission and surgery.
- |||||||||| NN1213 / Novo Nordisk
Trial completion, Trial completion date: BIONICS: Study of BioNIR Drug Eluting Stent System in Coronary Stenosis (clinicaltrials.gov) - Mar 23, 2021
P2, N=1919, Completed,
These cysts are benign conditions, but they require pelvic ultrasound follow-up and in some cases hospital admission and surgery. Active, not recruiting --> Completed | Trial completion date: Nov 2021 --> Nov 2020
- |||||||||| Taltorvic (ridaforolimus) / Takeda, Merck (MSD)
Trial completion: Angiography Study of BioNIR Drug Eluting Stent System (NIREUS) (clinicaltrials.gov) - Feb 21, 2021
P2, N=300, Completed,
Active, not recruiting --> Completed | Trial completion date: Nov 2021 --> Nov 2020 Active, not recruiting --> Completed
- |||||||||| Taltorvic (ridaforolimus) / Takeda, Merck (MSD)
Journal: Short-Term Environmental Conditioning Enhances Tumorigenic Potential of Triple-Negative Breast Cancer Cells. (Pubmed Central) - Aug 27, 2020
Epidermal growth factor and the mTORC1 inhibitor ridaforolimus produced similar but relatively reduced effects on tumorigenic potential...Conditioning regimens failed to alter proliferation or adhesion of cancer cells in vitro or kinase signaling through Akt and ERK measured by multiphoton microscopy in vivo, suggesting that other mechanisms enhanced tumorigenesis. Given the dynamic nature of the tumor environment and time-varying concentrations of small-molecule drugs, this work highlights how variable conditions in tumor environments shape tumor formation, metastasis, and response to therapy.
- |||||||||| Taltorvic (ridaforolimus) / Takeda, Merck (MSD)
Journal, Head-to-Head: Looking for a Hidden Superiority in Noninferiority DES Studies. (Pubmed Central) - Jun 19, 2020
Given the dynamic nature of the tumor environment and time-varying concentrations of small-molecule drugs, this work highlights how variable conditions in tumor environments shape tumor formation, metastasis, and response to therapy. No abstract available
- |||||||||| Afinitor (everolimus) / Novartis, sirolimus / Generic mfg., sapanisertib (TAK-228) / Takeda
[VIRTUAL] Phase II study of TAK228 in patients with advanced non-small cell lung cancer (NSCLC) harboring NFE2L2 and KEAP1 mutations. (Poster Board 373) - Apr 29, 2020 - Abstract #ASCO2020ASCO_2460;
P2
TAK228 is tolerable with differential activity in NFE2L2 (primary endpoint met) and KEAP1 mutant LUSC. A randomized phase 2 trial of TAK228 + docetaxel vs. SoC chemotherapy in advanced LUSC pts with NFE2L2/KEAP1 mut is in development (LungMAP S1900D) as is an NCI CTEP phase 1/1b trial of TAK228 + CB-839 in advanced NSCLC patients with NFE2L2/KEAP1 mut (NCI #10327).
- |||||||||| Taltorvic (ridaforolimus) / Takeda, Merck (MSD)
Review, Journal: Newer-generation Metallic Stents: Design, Performance Characteristics, and Outcomes. (Pubmed Central) - Jan 8, 2020
These stents incorporate certain characteristics, such as polymer-free drug coatings, ultrathin stent struts, bioresorbable polymers, and composite materials, that address currently unmet clinical needs to enhance acute stent performance, improve longer-term clinical outcomes, and obviate obligatory prolonged dual antiplatelet therapy. This article reviews the key and novel features of these stents.
- |||||||||| Journal: Autophagy as a molecular target for cancer treatment. (Pubmed Central) - Dec 20, 2019
In this sense, we also review the shared regulatory pathways that play a role in autophagy and malignant transformation. Finally, anti-cancer therapeutic agents used as either inhibitors or inducers of autophagy have been discussed.
- |||||||||| Avastin (bevacizumab) / Roche, paclitaxel / Generic Mfg.
Review, Journal: PI3K/AKT/mTOR inhibitors for advanced or recurrent endometrial cancer. (Pubmed Central) - Oct 8, 2019
In a recurrent disease setting, mTOR inhibitors may result in improved progression-free survival, but we found no clear benefit in overall survival or tumour response rate. We await the publication of at least five ongoing studies investigating the role of PI3K/AKT/mTOR inhibitors in advanced or recurrent endometrial cancer before any conclusions can be drawn on their use.
- |||||||||| paclitaxel / Generic Mfg.
DrugCell: A visible neural network to guide precision medicine (Board 6: Level 2 - Hall D) - Sep 18, 2019 - Abstract #AACRNCIEORTC2019AACR_NCI_EORTC_434;
Accordingly, combination of paclitaxel with the mTOR inhibitor, MK8669, was highly synergistic across multiple cell lines...In support of these mechanisms, combination of etoposide, a topoisomerase II inhibitor, with AKT or MEK inhibitors (downstream of the cholinergic receptor) or the HDAC inhibitor vorinostat were highly synergistic across multiple cell lines...Finally, we used DrugCell to predict effective therapeutic combinations for acute myeloid leukemia patients, leading to identification of drug combinations currently in clinical trials including lenalidomide + DNMT inhibitors and tandutinib + PI3K/MTOR inhibitors. Armed with interpretability and generalizability, DrugCell serves as an important step towards a next generation of intelligent systems in drug discovery and precision medicine.
- |||||||||| Taltorvic (ridaforolimus) / Takeda, Merck (MSD), Afinitor (everolimus) / Novartis
Journal: The EluNIR Ridaforolimus Eluting Coronary Stent System. (Pubmed Central) - Jun 9, 2019
The stent has thin struts with variable widths and a delivery catheter with a spring tip. These characteristics may explain the good angiographic and clinical results of this stent, which were non-inferior to the FDA approved Medtronic Resolute stent DES.
- |||||||||| Taltorvic (ridaforolimus) / Takeda, Merck (MSD), dalotuzumab (MK 0646) / Merck (MSD), Pierre Fabre
Trial completion: A Phase II Trial of Ridaforolimus and Exemestane, Compared to Ridaforolimus, Dalotuzumab and Exemestane in Participants With Breast Cancer (MK-8669-064) (clinicaltrials.gov) - Apr 20, 2019
P2, N=80, Completed,
These characteristics may explain the good angiographic and clinical results of this stent, which were non-inferior to the FDA approved Medtronic Resolute stent DES. Terminated --> Completed
- |||||||||| Taltorvic (ridaforolimus) / Takeda, Merck (MSD)
Trial termination, Metastases: A Study of Ridaforolimus in Pediatric Participants With Advanced Solid Tumors (MK-8669-056) (clinicaltrials.gov) - Jun 8, 2018
P1, N=21, Terminated,
Because the PFS reported for R/E was similar to that reported for everolimus plus exemestane in patients with advanced breast cancer, it is possible that lower-dose ridaforolimus in the R/D/E arm (from overlapping toxicities with IGF1R inhibitor) contributed to lack of improved PFS. Active, not recruiting --> Terminated
- |||||||||| Taltorvic (ridaforolimus) / Takeda, Merck (MSD), dalotuzumab (MK 0646) / Merck (MSD), Pierre Fabre
Trial termination: A Phase II Trial of Ridaforolimus and Exemestane, Compared to Ridaforolimus, Dalotuzumab and Exemestane in Participants With Breast Cancer (MK-8669-064) (clinicaltrials.gov) - Apr 19, 2018
P2, N=80, Terminated,
Active, not recruiting --> Terminated Active, not recruiting --> Terminated
- |||||||||| Taltorvic (ridaforolimus) / Takeda, Merck (MSD)
Trial completion: BIONICS Israel Trial (clinicaltrials.gov) - Mar 27, 2018
P=N/A, N=58, Completed,
The recommended phase II dose and schedule is ridaforolimus 30 mg (days 1-5 and 8-12) plus day 1 paclitaxel (175 mg/m) and carboplatin (AUC 5 mg/mL/min) on a 21-day cycle. Recruiting --> Completed
|
