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The arrival of comprehensive genome sequencing has accelerated the understanding of genetically aberrant advanced cancers and target identification for possible cancer treatment. Fibroblast growth factor receptor (FGFR) gene alterations are frequent findings in various rare and advanced cancers refractive to mainstay chemo-therapy or surgical interventions. Several FGFR inhibitors have been developed for addressing these genetically altered FGFR-harboring malignancies, and some have performed well in clinical trials. In contrast, others are still being investigated in different phases of clinical trials. FDA has approved four anticancer agents such as erdafitinib, pemigatinib, infigratinib, and futibatinib, for clinical use in oncogenic FGFR-driven malignancies. These include cholangiocarcinoma, urothelial carcinoma, and myeloid/lymphoid malignancies. Pemigatinib is the only FGFR inhibitor globally approved (USA, EU, and Japan) and available as a targeted therapy for two types of cancer, including FGFR2 fusion or other rearrangements harboring cholangiocarcinoma and relapsed/refractory myeloid/lymphoid neoplasms with FGFR1 rearrangements. Myeloid/lymphoid neoplasm is the latest area of application added to the therapeutic armamentarium of FGFR inhibitors. Furthermore, futibatinib is the first-in-class covalent or irreversible pan-FGFR inhibitor that has received FDA approval for locally advanced or metastatic intrahepatic cholangiocarcinoma harboring FGFR2 gene aberrations. This review highlights the current clinical progress concerning the safety and efficacy of all the approved FGFR-TKIs (tyrosine kinase inhibitors) and their ongoing investigations in clinical trials for other oncogenic FGFR-driven malignancies.

Advancement in nanotechnology and its intervention into the medical field has led to significant development in the field of oral health. Also, the combination of nanomaterial science and biotechnology in dental nanorobotics has enthralled us by adding momentum to contemporary dental practices. The progressive nature of dental afflictions often requires an umbrella approach for their prevention, diagnosis, and complete treatment. Furthermore, the complex nature of dental diseases entails customized treatment modalities, which provides the development of various nanotechnology armamentariums. Furthermore, with the objective of controlled drug delivery, researchers have done a plethora of work to apply nanomaterials such as nanospheres, nanotubes, and nanocomposites for dental infections. However, the fundamental concern with nanotechnology is cost involvement and scaleup hurdles which limits its commercialization. Nevertheless, we hope that optimal utilization of the available nanotechnological interventions for modern dental practice will shortly improve oral health. Hence, this review primarily focuses on the types of nanotechnological interventions explored for various dental afflictions. Also, the authors have attempted to enlighten the readers about the practical aspects of nanotherapeutics for dental disease, that is, a journey from laboratory to product commercialization.

The objective of this study is to create a nanoemulgel formulation of Ribociclib (RIBO), a highly selective inhibitor of CDK4/6 through the utilization of spontaneous emulsification method. An experimental investigation was conducted to construct pseudo-ternary phase diagram for the most favourable formulation utilizing rice bran oil, which is known for its diverse anticancer properties. The formulation consisted of varying combination of the surfactant and as the co-surfactant (Tween 80 and Transcutol, respectively) referred to as Smix and the trials were optimized to get the desired outcome. The nanoemulsion (NE) formulations that were developed exhibited a droplet size of 179.39 nm, accompanied with a PDI of 0.211. According to the data released by Opt-RIBO-NE, it can be inferred that the Higuchi model had the most favourable fit among many kinetics models considered. The results indicate that the use of nanogel preparations for the topical delivery of RIBO in breast cancer therapy, specifically RIBO-NE-G, is viable. This is supported by the extended release of the RIBO, and the appropriate level of drug permeation observed in Opt-RIBO-NE-G. Due to RIBO and Rice Bran oil, RIBO-NE-G had greater antioxidant activity, indicating its effectiveness as antioxidants. The stability of the RIBO-NE-G was observed over a period of three months, indicating a favourable shelf life. Therefore, this study proposes the utilization of an optimized formulation of RIBO-NE-G may enhance the efficacy of anticancer treatment and mitigate the occurrence of systemic side effects in breast cancer patients, as compared to the use of suspension preparation of RIBO. [ABSTRACT FROM AUTHOR]

Background: Epilepsy is a neurological disorder characterized by anomalous brain activity, convulsions and odd behaviour. Ten pyrrole carbohydrate based analogues (Va-Vj) were synthesized with amide as intermediate in the current research with the goal of reducing convulsions and seizures. Materials and Methods: The newly developed compounds were synthesized. Numerous methods (IR, NMR, mass, elemental analysis, etc.,) were used to characterize these substances. Several models were used to test each of these molecules for anticonvulsant activity. By using the rotarod and ethanol potentiation techniques, neurotoxicity was also evaluated. The study meticulously examined each parameter and showed ADME predictions for each of the 10 congeners that were produced. In addition, studies on molecular docking employed the GABA-A target protein. Results: Anticonvulsant screening results identified compounds Ve, Vd, Vc and Va as the most efficacious of the series. All synthesized equivalents largely passed the neurotoxicity test. The results of molecular docking revealed significant interactions at the active site of GABA-A with Ile C:242, Asp C:424, Phe D:307, Arg C:250 Trp C:241 and Phe C:240 and the outcomes were good and in agreement with in vivo findings. Conclusion: The study's findings showed that some substances had promising anticonvulsant properties that were comparable to those of the standard drug. The highly active novel anticonvulsant analogues may therefore represent a possible lead and additional studies may result in a potential new drug candidate. [ABSTRACT FROM AUTHOR]

Aim: The current research was performed for the preparation and optimization of Transniosomes (TN) preparation for the dermic distribution of Ursolic Acid (UA). Materials and Methods: The formulation was optimized by using the "Box-Behnken design" software. Particles size, % EE, and in vitro study was performed for the optimal formulations after they had been optimised. In addition, morphological, CLSM and dermatocokinetic studies were performed in order to complete the evaluation of the optimal formulation of TN. Results: The improved UA-TN formulation showed vesicles in the shape of lamellae that were completely sealed, with particles size, percentage EE and in vitro release of 145.5 ± 2.56 nm, 84.74 ± 2.49% and 86.28 ± 1.74%. respectively. The percentage cumulative drug permeated through skin for UA-CF gel and UA-TN gel was 36.30% and 84.05% respectively. When equated to the Rhodamine B-hydro methanolic liquid, the confocal pictures that were acquired of rat skin evidently demonstrated that the loaded rhodamine B with TN gel formulation allowed for a deeper penetration of the substance. Further, the UA-TN gel applied mice skin disclosed significant changes in CSkin max and AUC0-8 in compare to rat skin applied with UA-CF gel formulation. Conclusion: The successful optimization and characterization of TN of UA using Box-Behnken design and enhanced dermal delivery reflect the novelty of the work. Present research data showed that the developed TN vesicle formulation was found to be effectively useful drug carrier for UA topical delivery. [ABSTRACT FROM AUTHOR]