[Side effects of Immune Checkpoint Inhibitors : Diagnostics and Management-an Update]. / Nebenwirkungen von Immuncheckpoint-Inhibitoren : Diagnostik und Management ­ ein Update.

Immune checkpoint inhibitors (ICI) represent a breakthrough in cancer therapy. They are effective in various tumor entities and can be used in more and more treatment settings. This leads to an increase in the number and complexity of cases with immune-related adverse events (irAE). The most common irAE are cutaneous, gastrointestinal and endocrine side effects, whereas less common irAE include pneumonitis, nephritis, myocarditis or neurological reactions. IrAE can usually be successfully treated, mainly with corticosteroids or other immunosuppressants, but they can also result in long-term sequelae or death. The optimal management of patients with steroid-refractory or steroid-dependent side effects still remains unclear. Broad awareness of these irAE across specialties is therefore of crucial importance to ensure early diagnosis and to improve irAE management.

Characterization and Biomedical Applications of Green-Synthesized Selenium Nanoparticles Using Tridax procumbens Stem Extract.

Background Selenium nanoparticles (SeNPs) are one of the metal nanoparticles that have been widely utilized for their anti-microbial, anti-oxidant, anti-inflammatory activities, and other biomedical applications. Tridax procumbens (TP) stem extract is a promising herb species rich in flavonoids, tannins, alkaloids, phytosterols, and hydroxycinnamates, which play a major role in wound healing applications.  Aim The study aims to synthesize SeNPs using TP stem extract, characterizations, and its biomedical applications. Materials and methods SeNPs were synthesized using TP stem extract. The green synthesis of SeNPs was confirmed by ultraviolet-visible (UV-vis) spectra analysis. The synthesized SeNPs were characterized using Fourier-transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). The agar well diffusion method was utilized to evaluate the anti-bacterial properties of the green synthesized SeNPs using TP stem extract. The anti-oxidant effect of SeNPs was tested using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, ferric-reducing anti-oxidant power assay (FRAP), and hydroxyl radical scavenging assay (H2O2). The anti-inflammatory effect was investigated using the bovine serum albumin assay and egg albumin denaturation method, and the cytotoxic effect of the green synthesized SeNPs was tested using the brine shrimp lethality (BSL) assay. Results The green synthesis of SeNPs was confirmed using different types of analysis techniques. The characterizations were done by UV-visible spectroscopy analysis, exhibiting a maximum peak at the range of 330 nm. SEM analysis revealed the shape of the nanoparticle to be hexagonal. The agar well diffusion method exhibited the anti-bacterial efficacy of SeNPs against wound microorganisms with a zone of inhibition of 14.6 mm for Escherichia coli (E. coli), 15.8 mm for Staphylococcus aureus (S. aureus), and 15.4 mm for Pseudomonas aeruginosa (P. aeruginosa). The TP stem-mediated SeNPs showed potential effects in anti-oxidant, anti-inflammatory, and cytotoxic activity, which shows very little toxicity. Conclusion Overall, the green synthesis of TP-stem-mediated SeNPs has great potential in biomedical applications. Thus, the synthesized SeNPs exhibit significant anti-bacterial efficacy against wound pathogens. The TP stem-mediated SeNPs showed potential effects in anti-oxidant, anti-inflammatory, and cytotoxic activity, which shows low toxicity. Furthermore, the green-synthesized SeNPs can be utilized in therapeutic management.

Bioactive daphnane diterpenes from the flower buds of Daphne genkwa (Thymelaeaceae).

Four diterpenes of the daphnane type were isolated from a methanol extract of the flower buds of Daphne genkwa, the two of them were new structures named genkwadanes J (1) and K (2). Their structures were determined based on analysis of their 1D- and 2D-NMR, HRESIMS and ECD calculations. Among the isolates, the cytotoxicity was assessed via the MTT method using the K562, MCF-7 and HeLa cancer cell lines, the positive control was taxol. Compounds 1 and 3 exhibited appreciable cytotoxic activity against the K562 cancer cell line with IC50 values between 6.58 and 5.33 µM. Compounds 2 and 4 showed noteworthy inhibitory effects against the MCF-7 cell line with IC50 values of 3.25 and 2.56 µM, respectively. All compounds showed weak cytotoxicities to the Hela cell line with IC50 values in the range of 20.19-55.23 µM.

Cytotoxic, antioxidant, antibacterial activity of phytochemicals from Phragmanthera austroarabica.

The cytotoxic, antioxidant, anticancer, and antibacterial properties of ethanolic extracts from Phragmanthera austroarabica is of interest. Plants of P. austroarabica were gathered from the southern Saudi Arabian region of Albaha. P. austroarabica extract was assessed using DPPH (2, 2-diphenyl-1-picrylhydrazyl). The German Collection of Microorganisms and Cell Cultures (DSMZ) cancer cell lines used in this investigation. The cytotoxic activity of P. austroarabica extract was explored against MCF-7 breast and A549 lung cancer cell lines, along with doxorubicin as a positive control. In both treated cells, P. austroarabica showed a remarkable activity via suppressing the cell's survival. In terms of IC50 (concentration equivalent to a survival rate of 50%), MCF-7 breast cancer cells were more sensitive to P. austroarabica extract.) DPPH colorimetric assay was employed to assess the antioxidant properties of P. austroarabica extract, the antioxidant activity was increased along with increment of extract concentrations. The leaves aqueous extract of P. austroarabica inhibited the growth of S. aureus by 6.3±0.12 mm and 24±0.43 mm and 15±0.56 mm respectively for seed, leaf and stem at concentrations 50 µl. However, the same concentrations inhibited the growth of E. coli by 25±0.75, 0.00 mm and 24±0.18 mm, following the same order. Different superscript letters indicate means that are significantly different at level (p<0.05). Minimal inhibitory concentrations (MIC) of P. austroarabica ethanolic extracts against the tested microorganisms were 1.5, 1.6 and 1.5, respectively for seed, leaf and stem against Staph. Aureus and were 1.2, 0.00 and 1.2, respectively for seed, leaf and stem against E. coli.

Kopsileuconines A-D: bisindole alkaloids with cytotoxic activity from Kopsia hainanensis.

Kopsileuconines A-D (1-4), four monoterpenoid bisindole alkaloids with unprecedented skeletons, along with their biosynthetically related precursors (5-8) were isolated from the roots of Kopsia hainanensis. Compound 1 possessed an undescribed C-6-C-5' dimerization pattern of aspidofractinine-type alkaloids. Compounds 2-4 were rhazinilam-kopsine (2) and rhazinilam-aspidofractinine type (3 and 4) bisindole alkaloids with undescribed skeletons, respectively. Their structures with absolute configurations were fully accomplished by extensive spectroscopic analysis, quantum-chemical calculations, and X-ray crystallography. A plausible biosynthetic pathway for 1-4 was proposed. Compound 2 exhibited a significant inhibitory effect against human lung cancer cell lines PC9 (EGFR mutant), with an IC50 value of 15.07 ± 1.19 µM.

Natural-source Payloads used in the conjugated drugs architecture for cancer therapy: Recent advances and future directions.

Drug conjugates are obtained from tumor-located vectors connected to cytotoxic agents via linkers, which are designed to deliver hyper-toxic payloads directly to targeted cancer cells. These drug conjugates include antibody-drug conjugates (ADCs), peptide-drug conjugates (PDCs), small molecule-drug conjugates (SMDCs), nucleic acid aptamer-drug conjugates (ApDCs), and virus-like drug conjugate (VDCs), which show great therapeutic value in the clinic. Drug conjugates consist of a targeting carrier, a linker, and a payload. Payloads are key therapy components. Cytotoxic molecules and their derivatives derived from natural products are commonly used in the payload portion of conjugates. The ideal payload should have sufficient toxicity, stability, coupling sites, and the ability to be released under specific conditions to kill tumor cells. Microtubule protein inhibitors, DNA damage agents, and RNA inhibitors are common cytotoxic molecules. Among these conjugates, cytotoxic molecules of natural origin are summarized based on their mechanism of action, conformational relationships, and the discovery of new derivatives. This paper also mentions some cytotoxic molecules that have the potential to be payloads. It also summarizes the latest technologies and novel conjugates developed in recent years to overcome the shortcomings of ADCs, PDCs, SMDCs, ApDCs, and VDCs. In addition, this paper summarizes the clinical trials conducted on conjugates of these cytotoxic molecules over the last five years. It provides a reference for designing and developing safer and more efficient conjugates.

1,3-Disubstituted Thiourea Derivatives: Promising Candidates for Medicinal Applications with Enhanced Cytotoxic Effects on Cancer Cells.

The distinct chemical structure of thiourea derivatives provides them with an advantage in selectively targeting cancer cells. In our previous study, we selected the most potent compounds, 2 and 8, with 3,4-dichloro- and 3-trifluoromethylphenyl substituents, respectively, across colorectal (SW480 and SW620), prostate (PC3), and leukemia (K-562) cancer cell lines, as well as non-tumor HaCaT cells. Our research has demonstrated their anticancer potential by targeting key molecular pathways involved in cancer progression, including caspase 3/7 activation, NF-κB (Nuclear Factor Kappa-light-chain-enhancer of activated B cells) activation decrease, VEGF (Vascular Endothelial Growth Factor) secretion, ROS (Reactive Oxygen Species) production, and metabolite profile alterations. Notably, these processes exhibited no significant alterations in HaCaT cells. The effectiveness of the studied compounds was also tested on spheroids (3D culture). Both derivatives 2 and 8 increased caspase activity, decreased ROS production and NF-κB activation, and suppressed the release of VEGF in cancer cells. Metabolomic analysis revealed intriguing shifts in cancer cell metabolic profiles, particularly in lipids and pyrimidines metabolism. Assessment of cell viability in 3D spheroids showed that SW620 cells exhibited better sensitivity to compound 2 than 8. In summary, structural modifications of the thiourea terminal components, particularly dihalogenophenyl derivative 2 and para-substituted analog 8, demonstrate their potential as anticancer agents while preserving safety for normal cells.

Cytosolic protein translation regulates cell asymmetry and function in early TCR activation of human CD8+ T lymphocytes.

Introduction: CD8+ cytotoxic T lymphocytes (CTLs) are highly effective in defending against viral infections and tumours. They are activated through the recognition of peptide-MHC-I complex by the T-cell receptor (TCR) and co-stimulation. This cognate interaction promotes the organisation of intimate cell-cell connections that involve cytoskeleton rearrangement to enable effector function and clearance of the target cell. This is key for the asymmetric transport and mobilisation of lytic granules to the cell-cell contact, promoting directed secretion of lytic mediators such as granzymes and perforin. Mitochondria play a role in regulating CTL function by controlling processes such as calcium flux, providing the necessary energy through oxidative phosphorylation, and its own protein translation on 70S ribosomes. However, the effect of acute inhibition of cytosolic translation in the rapid response after TCR has not been studied in mature CTLs. Methods: Here, we investigated the importance of cytosolic protein synthesis in human CTLs after early TCR activation and CD28 co-stimulation for the dynamic reorganisation of the cytoskeleton, mitochondria, and lytic granules through short-term chemical inhibition of 80S ribosomes by cycloheximide and 80S and 70S by puromycin. Results: We observed that eukaryotic ribosome function is required to allow proper asymmetric reorganisation of the tubulin cytoskeleton and mitochondria and mTOR pathway activation early upon TCR activation in human primary CTLs. Discussion: Cytosolic protein translation is required to increase glucose metabolism and degranulation capacity upon TCR activation and thus to regulate the full effector function of human CTLs.

History of Hemophagocytic Lymphohistiocytosis.

Hemophagocytic lymphohistiocytosis (HLH) is a severe cytokine storm syndrome (CSS), which until the turn of the century, was barely known but is now receiving increased attention. The history of HLH dates back to 1939 when it was first described in adults, to be followed in 1952 by the first description of its primary, familial form in children. Secondary forms of HLH are far more frequent and occur with infections, malignancies, metabolic diseases, iatrogenic immune suppression, and autoinflammatory/autoimmune diseases. Identification of the genetic defects leading to the defective function of natural killer (NK) cells and cytotoxic T cells as well as the corresponding mouse models have revolutionized our understanding of HLH and of immune function. Diagnosis relies on clinical and laboratory criteria; functional and genetic tests can help separate primary from secondary forms. Treatment with immunochemotherapy and hematopoietic stem cell transplantation has considerably improved survival in children with primary HLH, a formerly uniformly fatal disease.

Newly developed humanized anti-CKAP4 antibody suppresses pancreatic cancer growth by inhibiting DKK1-CKAP4 signaling.

Cytoskeleton-associated protein 4 (CKAP4) is a cell surface receptor for Dickkopf 1 (DKK1), a secreted protein. The DKK1-CKAP4 pathway is activated in various malignant tumors, including pancreatic, lung, esophageal, and liver cancers, to promote tumor growth. Thus, CKAP4 has been expected to represent a novel molecular target of cancer therapy. Recombinant mouse anti-CKAP4 antibodies were generated based on an original mouse antibody (3F11-2B10) and inhibited DKK1-CKAP4 signaling and xenograft tumor formation induced by pancreatic cancer cells, which was comparable with 3F11-2B10. From the 3F11-2B10 nucleotide sequence, humanized anti-CKAP4 antibody (Hv1Lt1) was subsequently developed. The binding affinity of Hv1Lt1 for CKAP4 was superior to that of 3F11-2B10. Hv1Lt1 inhibited DKK1 binding to CKAP4, AKT activity, and sphere formation of pancreatic cancer cells, which was comparable with 3F11-2B10. Hv1Lt1 also suppressed xenograft tumor formation induced by human pancreatic cancer cells and tumor growth in murine cancer models, in which murine pancreatic cancer organoids were orthotopically transplanted into the pancreas. In resected tumor samples from mice treated with Hv1Lt1, anti-tumor immune reactions were modulated and cytotoxic T cells were highly infiltrated in the tumor microenvironment. Additionally, combination of Hv1Lt1 and other chemotherapy drugs exhibited stronger effects compared with monotherapy. These results suggest that Hv1Lt1 represents a promising anti-cancer therapy.

Cosmetic Preservative Potential and Chemical Composition of Lafoensia replicata Pohl. Leaves.

The study evaluated the preservative potential of Lafoensia replicata Pohl. leaf extracts in cosmetics, highlighting their antioxidant, antimicrobial, and in vitro cytotoxic activities for ethanolic extract prepared by the maceration and tincture method. Total phenol content showed a higher phenol concentration in ethanolic extract and tinctures, and by LC-MS/MS-ESI-QTOF analysis, flavonoids, hydrolyzed tannins, and phenolic acids were identified. The ethanolic extract and tincture showed high antimicrobial activity against Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans (MIC < 50 µg mL-1), high antioxidant activity (EC50 < 50 µg mL-1 in the DPPH method, and results > 450 µmol trolox equivalent in the ABTS and FRAP method), and low cytotoxicity in human keratinocytes (IC50 > 350 µg mL-1). The results suggest these extracts could be an alternative to synthetic preservatives in the cosmetic industry.

Comparative Analysis of Polyphenolic Profile and Chemopreventive Potential of Hemp Sprouts, Leaves, and Flowers of the Sofia Variety.

This study investigates the phytochemical composition and biological activities of hemp (Cannabis sativa L.) leaves, flowers' methanolic extracts from the Sofia variety, and its sprouts cultivated under different light conditions (natural light, darkness, blue, and white LED light for 5, 7, and 9 days). Phytochemical analysis using HPLC identified four key polyphenolic compounds in sprouts' extracts: chlorogenic, caffeic, and gallic acids, and myricetin, with a predomination of the chlorogenic acid. In contrast, leaves and flowers' extracts contained cannflavins A and B and chlorogenic, p-coumaric, and ferulic acids, with a significant presence of isochlorogenic acid. Antioxidant capacity, assessed by FRAP method, revealed higher antioxidant potential in leaves compared to flowers and sprouts, with sprouts grown under blue and white LED lights exhibiting the highest activity. Cytotoxic activity was evaluated on human colon cancer cell lines (HT29, HCT116, DLD-1) and normal colon epithelial cells (CCD 841 CoN). Results demonstrated significant and selective cytotoxicity against cancer cell lines, with leaves showing more pronounced effects than flowers, and sprouts only moderate activity. All samples revealed an anti-inflammatory effect in vitro. To conclude, sprouts, leaves, and flowers of the Sofia hemp may be considered promising products for chemoprevention in the future.

Establishment of a protocol for rapidly expanding Epstein-Barr-virus-specific cytotoxic T cells with enhanced cytotoxicity.

BACKGROUND: Lytic Epstein-Barr virus (EBV) infection plays a major role in the pathogenesis of nasopharyngeal carcinoma (NPC). For patients with recurrent or metastatic NPC and resistant to conventional therapies, adoptive cell therapy using EBV-specific cytotoxic T cells (EBV-CTLs) is a promising option. However, the long production period (around 3 to 4 weeks) and low EBV-CTL purity (approximately 40% of total CD8 T cells) in the cell product limits the application of EBV-CTLs in clinics. Thus, this study aimed to establish a protocol for the rapid production of EBV-CTLs. METHODS: By culturing peripheral blood mononuclear cells (PBMCs) from EBV-seropositive donors with EBV-specific peptides and interleukin (IL)-2, IL-15, and interferon α (IFN-α) for 9 days, we identified that IL-15 can enhance IL-2-mediated CTL activation and significantly increase the yield of CTLs. RESULTS: When IFN-α was used in IL-2/IL-15-mediated CTL production from days 0 to 6, the productivity of EBV-CTLs and EBV-specific cytotoxicity significantly were reinforced relative to EBV-CTLs from IL-2/IL-15 treatment. Additionally, IFN-α-induced production improvement of virus-specific CTLs was not only the case for EBV-CTLs but also for cytomegalovirus-specific CTLs. CONCLUSION: We established a novel protocol to rapidly expand highly pure EBV-CTLs from PBMCs, which can produce EBV-CTLs in 9 days and does not require feeder cells during cultivation.

Dual perspective on autophagy in glioma: Detangling the dichotomous mechanisms of signaling pathways for therapeutic insights.

Autophagy is a normal physiological process that aids the recycling of cellular nutrients, assisting the cells to cope with stressed conditions. However, autophagy's effect on cancer, including glioma, is uncertain and involves complicated molecular mechanisms. Several contradictory reports indicate that autophagy may promote or suppress glioma growth and progression. Autophagy inhibitors potentiate the efficacy of chemotherapy or radiation therapy in glioma. Numerous compounds stimulate autophagy to cause glioma cell death. Autophagy is also involved in the therapeutic resistance of glioma. This review article aims to detangle the complicated molecular mechanism of autophagy to provide a better perception of the two-sided role of autophagy in glioma and its therapeutic implications. The protein and epigenetic modulators of the cytoprotective and cytotoxic role of autophagy are described in this article. Moreover, several signaling pathways are associated with autophagy and its effects on glioma. We have reviewed the molecular pathways and highlighted the signaling axis involved in cytoprotective and cytotoxic autophagy. Additionally, this article discusses the role of autophagy in therapeutic resistance, including glioma stem cell maintenance and tumor microenvironment regulation. It also summarizes several investigations on the anti-glioma effects of autophagy modulators to understand the associated mechanisms and provide insights regarding its therapeutic implications.

An automated assay platform for the evaluation of antiviral compounds against polioviruses.

High-throughput screening requires assays that have flexibility to test large numbers of specimens while being accurate to ensure reproducibility across all specimens and variables tested. Previously, we used a low-throughput, cell-based assay to identify compounds with antiviral activity against polioviruses. In this report, we report the development and implementation of a high-throughput automation platform for the identification of compounds with antiviral activity against polioviruses. The platform uses off-the-shelf automated equipment combined with a modified assay, with minimal changes to existing laboratory space. We evaluated automation systems from Hudson Robotics Inc., Agilent Technologies, and a microplate reader from PerkinElmer during the platform design. Optimization for high throughput was focused on bulk reagent additions, serial dilutions, microplate washing and measuring results from the tens-to-hundreds of microplates. We evaluated the automated cell-based assay for selectivity, sensitivity, accuracy, precision, and reproducibility. This platform can be applied to screen novel antivirals against polioviruses and non-polio enteroviruses.

Targeting the MHC-I endosomal-lysosomal trafficking pathway in cancer: From mechanism to immunotherapy.

Immune checkpoint blockade (ICB) therapy has achieved broad applicability and durable clinical responses across cancer types. However, the overall response rate remains suboptimal because some patients do not respond or develop drug resistance. The low infiltration of CD8+ cytotoxic T cells (CTLs) in the tumor microenvironment due to insufficient antigen presentation is closely related to the innate resistance to ICB. The duration and spatial distribution of major histocompatibility complex class I (MHC-I) expression on the cell surface is critical for the efficient presentation of endogenous tumor antigens and subsequent recognition and clearance by CTLs. Tumor cells reduce the surface expression of MHC-I via multiple mechanisms to impair antigen presentation pathways and evade immunity and/or develop resistance to ICB therapy. As an increasing number of studies have focused on membrane MHC-I trafficking and degradation in tumor cells, which may impact the effectiveness of tumor immunotherapy. It is necessary to summarize the mechanism regulating membrane MHC-I translocation into the cytoplasm and degradation via the lysosome. We reviewed recent advances in the understanding of endosomal-lysosomal MHC-I transport and highlighted the means exploited by tumor cells to evade detection and clearance by CTLs. We also summarized new therapeutic strategies targeting these pathways to enhance classical ICB treatment and provide new avenues for optimizing cancer immunotherapy.

Cystatin F Depletion in Mycobacterium tuberculosis-Infected Macrophages Improves Cathepsin C/Granzyme B-Driven Cytotoxic Effects on HIV-Infected Cells during Coinfection.

Cystatin F (CstF) is a protease inhibitor of cysteine cathepsins, including those involved in activating the perforin/granzyme cytotoxic pathways. It is targeted at the endolysosomal pathway but can also be secreted to the extracellular milieu or endocytosed by bystander cells. CstF was shown to be significantly increased in tuberculous pleurisy, and during HIV coinfection, pleural fluids display high viral loads. In human macrophages, our previous results revealed a strong upregulation of CstF in phagocytes activated by interferon γ or after infection with Mycobacterium tuberculosis (Mtb). CstF manipulation using RNA silencing led to increased proteolytic activity of lysosomal cathepsins, improving Mtb intracellular killing. In the present work, we investigate the impact of CstF depletion in macrophages during the coinfection of Mtb-infected phagocytes with lymphocytes infected with HIV. The results indicate that decreasing the CstF released by phagocytes increases the major pro-granzyme convertase cathepsin C of cytotoxic immune cells from peripheral blood-derived lymphocytes. Consequently, an observed augmentation of the granzyme B cytolytic activity leads to a significant reduction in viral replication in HIV-infected CD4+ T-lymphocytes. Ultimately, this knowledge can be crucial for developing new therapeutic approaches to control both pathogens based on manipulating CstF.

A new isoprenyl-phenol-type meroterpenoid from mangrove endophytic fungus Aspergillus sp. GXNU-Y65.

Asperphenol A (1), a new isoprenyl-phenol-type meroterpenoid, was isolated from the mangrove endophytic fungus Aspergillus sp. GXNU-Y65 together with five known compounds (2-6). All structures were assigned using extensive NMR spectroscopic data and electronic circular dichroism (ECD) calculations. Compounds 1-6 were evaluated for their cytotoxic activity against A549 and T24 human cancer cell lines. Among them, compounds 1 and 5 exhibited moderate inhibitory activities against T24 cancer cell lines with the IC50 values of 26.71 and 43.50 µM, respectively.

Four new homoisoflavonoids from Caesalpinia pulcherrima.

Four new homoisoflavonoids, 7-hydroxy-3-[hydroxy(4'-methoxyphenyl)methyl]-benzopyran-4-one (1), (3R)-7, 8-dihydroxy-3-(4'-methoxybenzyl)-chroman-4-one (2), 7-hydroxy-3-(2'-hydroxy-4'-methoxybenzyl)-chroman-4-one (3), and 7-hydroxy-3-(2'-hydroxy-4'-methoxybenzyl)-benzopyran-4-one (4), were isolated from the seeds of Caesalpinia pulcherrima. The structures of new compounds were elucidated by MS and NMR spectra. Their absolute configurations were assigned using electronic circular dichroism spectrum. Compounds 2 and 4 exhibited cytotoxic effects on MCF-7/TAM cells with the IC50 values of 101.4 ± 0.03 and 93.02 ± 0.03 µM, respectively.

A novel selective FAK inhibitor E2 inhibits ovarian cancer metastasis and growth by inducing cytotoxic autophagy.

Ovarian cancer (OC) is the deadliest form of the gynecologic malignancies and effective therapeutic drugs are urgently needed. Focal adhesion kinase (FAK) is overexpressed in various solid tumors, and could serve as a potential biomarker of ovarian cancer. However, there are no launched drugs targeting FAK. Hence, the development of the novel FAK inhibitors is an emerging approach for the treatment of ovarian cancer. In this work, we characterized a selective FAK inhibitor E2, with a high inhibitory potency toward FAK. Moreover, E2 had cytotoxic, anti-invasion and anti-migration activity on ovarian cancer cells. Mechanistically, after treatment with E2, FAK downstream signaling cascades (e.g., Src and AKT) were suppressed, thus resulting in the ovarian cancer cell arrest at G0/G1 phase and the induction of cytotoxic autophagy. In addition, E2 attenuated the tumor growth of PA-1 and ES-2 ovarian cancer subcutaneous xenografts, as well as suppressed peritoneal metastasis of OVCAR3-luc. Furthermore, E2 exhibited favorable pharmacokinetic properties. Altogether, these findings demonstrate that E2 is a selective FAK inhibitor with potent anti-ovarian cancer activities both in vivo and in vitro, offering new possibilities for OC treatment strategies.