Synthesis and Clinical Development of Palbociclib: An Overview

Abstract

: Breast cancer is the second most commonly identified cancer in women in the United States after skin cancer. The past few years have seen a substantial increase in breast cancer awareness campaigns and active research in fields of diagnosis and targeted therapy. These factors have led to a better mechanistic understanding of the disease, detection at earlier stages and more personalized approach to treatment, ultimately causing a crucial increase in the survival rates after detection. However, with the advances in treatment, cases of patients developing primary resistance and acquired resistance are increasing. Most of the breast cancers which develop resistance to therapy are ER+ and are typically treated with tamoxifen and fulvestrant. These drugs either lower the levels of estrogen or inhibit the receptors for estrogen and prevent the tumor from spreading. Around one third of women treated with these drugs develop resistance to them, lowering their chances of survival. This has directed to the search of newer drug therapies to target advanced breast cancer and resistance. One of these efforts has resulted in the development of Palbociclib, a first in class inhibitor of cyclin dependent kinases 4 and 6 (CDK4 and CDK6), which was granted accelerated approval from FDA for combination therapy in postmenopausal women with ER+, HER2- metastatic breast cancer. This review is focused on the various aspects of “Palbociclib” including its synthesis, molecular modeling studies and efficacy and safety profile with clinical trials data.

Toward Biomass-Based Organic Electronics: Continuous Flow Synthesis and Electropolymerization of N-Substituted Pyrroles

“…The flow was subsequently reduced to 0.25 mL min −1 (t r = 3.14 min), and the temperature was incrementally raised to 220 °C (entries 4−8). The adjustments generated increasingly higher yields at each temperature step, resulting in a 43% crude 1 H NMR yield at 220 °C (see SI for the 1 H NMR yield protocol).…”

Cancer-testis antigen CEP55 serves as a prognostic biomarker and is correlated with immune infiltration and immunotherapy efficacy in pan-cancer

“…We detected possible inhibitors for the regulation of CEP55 expression or the targeting of CEP55-related pathways and confirmed these using molecular docking analyses. Three smallmolecule compounds were identified that had a strong affinity for CEP55: cytochalasin B, which is a G-actin superimposed inhibitor that can suppress the growth of many types of cancer (Croop and Holtzer, 1975); palbociclib, which is a CDK4/6 inhibitor licensed by the FDA for the treatment of ER+, HER2-breast cancer (Konar et al, 2022), and given that CDK4/6 are critical cell cycle regulators, off-target effects of palbociclib on CEP55 may contribute to its efficacy in triggering tumor cell cycle arrest; and bisbenzimide, which is involved in numerous pharmacological actions, including anticancer, antiparasitic, antibacterial, antifungal, antiviral, and chemosensor activities (Verma et al, 2020). However, the exact effects of these three small compounds on CEP55 remain to be further investigated.…”

Synthetic and Medicinal Perspective of 1,2,4‐Triazole as Anticancer Agents

“…1,2,4‐triazole containing molecules played an important role in biological and pharmacological activities. Based on our interest on organic and medicinal chemistry, [86–115] we summarized 1,2,4‐triazoles fused with various other heterocyclic molecules such as pyrimidine, pyridine, piperidine, indole, 1,2,3‐triazole etc. as anticancer agents.…”