- |||||||||| lepodisiran (LY3819469) / Eli Lilly
Journal: Lepodisiran for Elevated Lipoprotein(a). (Pubmed Central) - Mar 27, 2024 In HPV-negative HNSCC, CDK4/6 inhibitor shows promising anti-tumor effects, which exhibits a synergistic effect when combined with EGFR inhibitor only in specific drug concentration and mouse model. No abstract available
- |||||||||| Olumiant (baricitinib) / Incyte, Eli Lilly
Clinical, PK/PD data, Journal: A population pharmacokinetic model using allometric scaling for baricitinib in patients with juvenile idiopathic arthritis. (Pubmed Central) - Mar 27, 2024 The PK modeling suggested the optimal dosing regimen based on weight for pediatric patients as: 2-mg QD for patients 10 to <30?kg and 4-mg QD for patients ?30?kg. The use of a population PK model of baricitinib treatment in adult patients with RA, with the addition of allometric scaling for weight on clearance and volume terms, was useful to predict exposures and identify weight-based dosing in pediatric patients with JIA.
- |||||||||| tirbanibulin oral (KX2-391 oral) / Hanmi, Athenex, Retevmo (selpercatinib) / Eli Lilly, Braftovi (encorafenib) / Ono Pharma, Pierre Fabre, Pfizer
Preclinical, Journal, Machine learning: Prediction of cytochrome P450-mediated bioactivation using machine learning models and in vitro validation. (Pubmed Central) - Mar 27, 2024 Encorafenib and tirbanibulin were observed of bioactivation potential with shifts of 3-6 folds or so. Overall, this study provided a reliable and robust strategy to predict the P450-mediated bioactivation, which will be helpful to the assessment of adverse drug reactions (ADRs) in clinic and the design of new candidates with lower toxicities.
- |||||||||| metformin / Generic mfg.
Journal: Anti-ENO1 antibody combined with metformin against tumor resistance: a novel antibody-based platform. (Pubmed Central) - Mar 26, 2024 The study preliminarily revealed anti-ENO1 antibody combined with metformin could overcome drug resistance against CSCs by inhibiting the Wnt//?-catenin pathway and might serve as a potential precursor platform for screening ADC. More importantly, it is reasonably believed that antibody-based drug combination therapy might function as an encouraging tool for oncotherapy.
- |||||||||| Opdivo (nivolumab) / Ono Pharma, BMS, Yervoy (ipilimumab) / Ono Pharma, BMS
Journal, HEOR, PD(L)-1 Biomarker, IO biomarker, Cost-effectiveness, Cost effectiveness, Metastases: Nivolumab plus ipilimumab versus the EXTREME regimen in recurrent/metastatic squamous cell carcinoma of the head and neck: a cost-effectiveness analysis. (Pubmed Central) - Mar 26, 2024 Importantly, there was heterogeneity in the cost-effectiveness probabilities, based on primary sites and expression levels of PD-L1. Therefore, tailored treatment based on individual patient and clinical characteristics, remains important, and may impact the cost-effectiveness of the regimens under study.
- |||||||||| Review, Journal: GLP-1 receptor agonists: A review of glycemic benefits and beyond. (Pubmed Central) - Mar 26, 2024
In addition to improving glycemic control, GLP-1 RAs have been shown to lower total body weight, BP, and cholesterol as well as to improve renal function and beta-cell proliferation. These agents should be considered in every patient with T2DM due to their substantial clinical benefits and potential to help reduce disease burden.
- |||||||||| rifampicin / Generic mfg.
PK/PD data, Preclinical, Journal: Rifampin- and Silymarin-Mediated Pharmacokinetic Interactions of Exogenous and Endogenous Substrates in a Transgenic OATP1B Mouse Model. (Pubmed Central) - Mar 26, 2024 Silymarin increased the Cmax of pitavastatin 2.7-fold and pravastatin 1.9-fold in the OATP1B mice. The data of the OATP1B mice were similar to those of the pitavastatin and pravastatin clinical data; however, the FVB mice data more closely recapitulated pitavastatin clinical data than the data of the OATP1B mice, suggesting that the OATP1B mice are a reasonable, though costly, preclinical strain for predicting pharmacokinetic interactions when doses are optimized to achieve clinically relevant plasma concentrations.
- |||||||||| Olumiant (baricitinib) / Incyte, Eli Lilly
Journal: Baricitinib and tofacitinib off-target profile, with a focus on Alzheimer's disease. (Pubmed Central) - Mar 26, 2024 The results suggest a low likelihood of successful repurposing in AD due to low brain permeability, even at the maximum recommended daily dose. While additional research is needed to evaluate the potential impact of the off-target interaction on AD, the combined approach of ML-based target prediction, in vitro confirmation, and PBPK modeling may help prioritize drugs with a high likelihood of being effectively repurposed for AD.
- |||||||||| Mounjaro (tirzepatide) / Eli Lilly
Journal: Effect of tirzepatide on body fat distribution pattern in people with type 2 diabetes. (Pubmed Central) - Mar 26, 2024 While additional research is needed to evaluate the potential impact of the off-target interaction on AD, the combined approach of ML-based target prediction, in vitro confirmation, and PBPK modeling may help prioritize drugs with a high likelihood of being effectively repurposed for AD. In this exploratory analysis, treatment with tirzepatide in people with T2D resulted in a significant reduction of z-VAT and z-LF, while z-aSAT was increased from an initially negative value, suggesting a possible treatment-related shift towards a more balanced fat distribution pattern with prominent VAT and LF loss.
- |||||||||| Olumiant (baricitinib) / Incyte, Eli Lilly, Rinvoq (upadacitinib) / AbbVie, Sotyktu (deucravacitinib) / BMS
Journal: Macrophage re-programming by JAK inhibitors relies on MAFB. (Pubmed Central) - Mar 26, 2024 These outcomes were also shared by macrophages exposed to other JAKi (baricitinib, tofacitinib), but not in the presence of the TYK2 inhibitor deucravacitinib. As a whole, our results indicate that JAKi promote macrophage re-programming towards the acquisition of a more anti-inflammatory/pro-resolution profile, an effect that correlates with the ability of JAKi to enhance MAFB expression.
- |||||||||| Olumiant (baricitinib) / Incyte, Eli Lilly
Trial initiation date, Immunomodulating: REVERSE-LC: REVERSE-Long COVID-19 With Baricitinib Study (clinicaltrials.gov) - Mar 26, 2024 P3, N=550, Not yet recruiting, The identification of VTE in the SNDS is possible with a good PPV. Initiation date: Mar 2024 --> Jun 2024
- |||||||||| 5-fluorouracil / Generic mfg.
Journal: Anthracycline-based hepatic arterial infusion chemotherapy achieved 17 (Pubmed Central) - Mar 25, 2024 This strategy might be expected to concomitantly trigger the crosstalk of adaptive immune response leading to a complementing T cell immune rejection of tumors. A 46-year-old woman with estrogen receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer who had multiple LMs and bone metastases underwent seven lines of systemic therapy (paclitaxel/bevacizumab for 38
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, Verzenio (abemaciclib) / Eli Lilly
Journal: Sustained remission after cord blood transplantation for breast cancer with lung metastases and myelodysplastic syndrome. (Pubmed Central) - Mar 25, 2024 No abstract available A 38-year-old woman treated with fulvestrant and abemaciclib for recurrent breast cancer with multiple lung metastases was diagnosed with myelodysplastic syndrome (MDS) with increased blasts 2...Breast cancer treatment was interrupted and venetoclax and azacitidine therapy was started...Lung metastatic activity on FDG-PET/CT scan also completely disappeared by half a year post-transplantation, and this response has continued as of 1
- |||||||||| Review, Journal: FGFR-targeted therapeutics: clinical activity, mechanisms of resistance and new directions. (Pubmed Central) - Mar 25, 2024
The next generation of small-molecule inhibitors, such as lirafugratinib and LOXO-435, and the FGFR2-specific antibody bemarituzumab are expected to have a reduced risk of hyperphosphataemia and the ability to overcome certain resistance mutations. In this Review, we describe the development and current clinical role of FGFR inhibitors and provide perspective on future research directions including expansion of the therapeutic indications for use of FGFR inhibitors, combination of these agents with immune-checkpoint inhibitors and the application of novel technologies, such as artificial intelligence.
- |||||||||| Journal: Emerging biologic therapies for systemic lupus erythematosus. (Pubmed Central) - Mar 25, 2024
signaling; and (2) they provide cells with a surface coating of 25 While many drug candidates which met the end points in phase II trials have failed phase III trials, the number of target-specific therapies for SLE has continued to expand.
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