William (Bill) Kemp’s Post

Excited to share our latest research on "Discovery of Novel Pyrazolo[1,5-a]pyrimidine Derivatives as Potent Reversal Agents Against ABCB1-Mediated Multidrug Resistance." In this study, we've identified a promising compound, 16q, that significantly enhances the sensitivity of multidrug-resistant cancer cells to chemotherapy. By effectively binding and stabilizing the ABCB1 protein, 16q restores the efficacy of paclitaxel, paving the way for more effective cancer treatments. Check out the full abstract below! #CancerResearch #DrugResistance #Chemotherapy #MolecularBiology #PharmaceuticalSciences #Cancer

Check out our new review on Orally Bioavailable Proteolysis-Targeting Chimeras: An Innovative Approach in the Golden Era of Discovering Small-Molecule Cancer Drugs. This review encapsulates the latest advancements in orally delivered PROTACs that have entered clinical evaluation as well as developments highlighted in recent scholarly articles. The insights and methodologies elaborated upon in this review could be instrumental in supporting the discovery and refinement of novel PROTAC degraders aimed at the treatment of various human cancers."

Abstract: Cancer poses a significant threat to human health. Therefore, it is urgent to develop potent anti-cancer drugs with excellent inhibitory activity and no toxic side effects. Pyrrole and its derivatives are privileged heterocyclic compounds with significant diverse pharmacological effects. These compounds can target various aspects of cancer cells and have been applied in clinical settings or are undergoing clinical trials. As a result, pyrrole has emerged as a promising drug scaffold and has been further probed to get novel entities for the treatment of cancer. This article reviews recent research progress on anti-cancer drugs containing pyrrole. It focuses on the mechanism of action, biological activity, and structure-activity relationships of pyrrole derivatives, aiming to assist in designing and synthesizing innovative pyrrole-based anti-cancer compounds. https://lnkd.in/ggFvtbNz - #drugdevelopment #science #medicinalchemistry #drugdiscovery #medicine #drugspharmaceuticals #oncology #drug

A recent study highlighted the growing importance of personalized medicine in cancer treatment. It found that drugs tested in personalized trials for NSCLC showed a greater improvement in progression-free survival (PFS). However, the impact on overall survival (OS) is more complex, and the authors rightly point out that newer drug mechanisms might require longer follow-up to see a benefit in OS. This emphasizes the need for ongoing research alongside personalized treatment approaches.  Further studies exploring biomarkers beyond just tumor mutations, like tumor microenvironment or immune cell infiltration, could be key to unlocking even greater benefits for patients. Read more from Nature Portfolio here: https://lnkd.in/eiiU4AVx #CancerResearch #PrecisionMedicine

GOING BEYOND GSK3368715 - PRMT1 INHIBITOR GSK3368715 has been the first PRMT1 (targeting the protein arginine methyltransferase 1) inhibitor to enter in a clinic trial (Phase 1) but terminated early due to a lack of clinical efficacy, extensive side effects, and dose-limiting toxicities. A new article just accepted in ChemMedChem (Chemistry Europe) addresses this issue by synthesizing PROTACs containing the same pharmacophore as GSK3368715, combined with a motif that recruits the VHL or CRBN E3-ligase. #GSK3368715 #PRMT1

NAMPT-targeting PROTAC and nicotinic acid co-administration elicit safe and robust anti-tumor efficacy in NAPRT-deficient pan-cancers 1. NAD+ = rechargeable battery of biological systems. 2. There are three pathways of NAD+ biosynthesis. 1) Kynureine pathway: de novo synthesis of NAD+ from Tryptophan 2) Preiss-Handler pathway: NAPRT has a main role to make NAD+ from nicotinic acid. 3) Salvage pathway: NAMPT is a key enzyme to make NAD+ from nicotinamide. 3. Cancer cells utilize all pathways to meet their energy demand. 4. Therefore, NAMPT has been considered as a promising target for cancer therapy. 5. Fan groups of ShanghaiTech University have developed a next-generation PROTAC to degrade NAMPT. 6. Treatment with the lead PROTAC and nicotinic acid is efficacious against NAPRT-deficient pan-cancers. Because normal cells retain NAPRT activity and can utilize nicotinic acid, the toxicity of NAMPT-targeting PROTACs is mitigated. https://lnkd.in/ghGQGCr3

The precision of LC-MS/MS is a game-changer in the development of antibody-drug conjugates (ADCs), essential for advancing oncology. By providing a detailed analysis of ADC components, LC-MS/MS ensures that new treatments are effective and safe for patients. Explore how this powerful analytical tool is paving the way for better cancer treatment outcomes. #CancerResearch #LCMS #ADCs #Biotechnology https://hubs.li/Q02GcX2r0

Our collaborative effort to characterize novel resistance mechanisms to #KRAS inhibitors is out in #NatureCommunications - Nature Portfolio. In this study led by 💫 Chiara Ambrogio w/ Matteo Cereda, Eng, PhD David Santamaria and others, we demonstrate that adaptive mechanisms and increased KRAS-GTP loading contribute to the development of resistance to KRAS G12C (OFF) inhibitors. 💊 Using the preclinical tool tri-complex KRASG12C-selective covalent inhibitor, RMC-4998 (also known as RM-029), that targets the active GTP-bound (ON) state of the oncogene, we provide a proof-of-concept that the clinical stage KRASG12C(ON) inhibitor RMC-6291 alone or in combination with KRAS G12C(OFF) drugs can be an alternative potential therapeutic strategy to overcome resistance due to increased KRAS-GTP loading. Dana-Farber Cancer Institute, University of Turin Institut Bergonié Harvard Medical School KRAS Kickers Terri Conneran Link: https://lnkd.in/eJizjzzw

🔬 Skye Montoya, a graduate student in Dr. Taylor lab, is first author on a new publication, co-led by Justin Taylor, physician-scientist at Sylvester. The study introduces a new therapy for chronic lymphocytic leukemia (CLL). Currently, patients are often prescribed BTK inhibitors, which can become less effective as some patients develop resistance. The innovative approach? A next-gen BTK-targeting therapy that inactivates and destroys BTK molecules. The current study went from clinical findings to laboratory research, and then back to the clinical setting, within two years. "That’s record time," said Dr. Taylor, who attributed the speed to the commitment of his team and the breadth of resources available at Sylvester. The study, published in Science Magazine and co-led with Memorial Sloan Kettering Cancer Center researchers and the biotechnology company Nurix Therapeutics, demonstrates NX-2127's potential not only for CLL but possibly other B-cell malignancies and autoimmune conditions. #CancerResearch #Leukemia https://lnkd.in/ewK4-aBj

#cancerresearch #oncology #cancertreatment https://lnkd.in/e6T6wBk6 Among the antidiabetic drugs, #metformin may possess #anticancer properties, potentially reducing cancer cell proliferation, inducing #apoptosis, and enhancing cancer cell sensitivity to chemotherapy. However, other antidiabetic drugs have revealed heterogeneous responses. Sulfonylureas and TZDs have not demonstrated consistent anti-cancer activity, while SGLT2 inhibitors and DPP-4 inhibitors have shown some potential benefits. GLP-1RAs have raised concerns due to possible associations with an increased risk of certain cancers. This review highlights that further research is warranted to elucidate the mechanisms underlying the potential anti-cancer effects of these drugs and to establish their efficacy and safety in clinical settings.