Scoping review of anticancer drug utilization in lung cancer patients at the end of life.

PURPOSE: This scoping review aims to deepen the understanding of end-of-life anticancer drug use in lung cancer patients, a disease marked by high mortality and symptom burden. Insight into unique end-of-life treatment patterns is crucial for improving the appropriateness of cancer care for these patients. METHODS: Comprehensive searches were carried out in Medline and Embase to find articles on the utilization of anticancer drugs in the end of life of lung cancer patients. RESULTS: We identified 68 publications, highlighting the methodological characteristics of studies including the timing of the research, disease condition, treatment regimen, type of treatment, and features of the treatment. We outlined the frequency of anticancer drug use throughout different end-of-life periods. CONCLUSION: This review provides a comprehensive overview of primary studies exploring end-of-life treatments in lung cancer patients. Methodological inconsistencies pose many challenges, revealing a notable proportion of patients experiencing potential overtreatment, warranting more standardized research methods for robust evaluations.

Harnessing the potency of scorpion venom-derived proteins: applications in cancer therapy.

Despite breakthroughs in the development of cancer diagnosis and therapy, most current therapeutic approaches lack precise specificity and sensitivity, resulting in damage to healthy cells. Selective delivery of anti-cancer agents is thus an important goal of cancer therapy. Scorpion venom (SV) and/or body parts have been used since early civilizations for medicinal purposes, and in cultures, SV is still applied to the treatment of several diseases including cancer. SV contains numerous active micro and macromolecules with diverse pharmacological effects. These include potent anti-microbial, anti-viral, anti-inflammatory, and anti-cancer properties. This review focuses on the recent advances of SV-derived peptides as promising anti-cancer agents and their diagnostic and therapeutic potential applications in cancers such as glioma, breast cancer, prostate cancer, and colon cancer. Well-characterized SV-derived peptides are thus needed to serve as potent and selective adjuvant therapy for cancer, to significantly enhance the patients' survival and wellbeing.

Computer-Aided Design of VEGFR-2 Inhibitors as Anticancer Agents: A Review.

Due to its intricate molecular and structural characteristics, vascular endothelial growth factor receptor 2 (VEGFR-2) is essential for the development of new blood vessels in various pathological processes and conditions, especially in cancers. VEGFR-2 inhibitors have demonstrated significant anticancer effects by blocking many signaling pathways linked to tumor growth, metastasis, and angiogenesis. Several small compounds, including the well-tolerated sunitinib and sorafenib, have been approved as VEGFR-2 inhibitors. However, the widespread side effects linked to these VEGFR-2 inhibitors-hypertension, epistaxis, proteinuria, and upper respiratory infection-motivate researchers to search for new VEGFR-2 inhibitors with better pharmacokinetic profiles. The key molecular interactions required for the interaction of the small molecules with the protein target to produce the desired pharmacological effects are identified using computer-aided drug design (CADD) methods such as pharmacophore and QSAR modeling, structure-based virtual screening, molecular docking, molecular dynamics (MD) simulation coupled with MM/PB(GB)SA, and other computational strategies. This review discusses the applications of these methods for VEGFR-2 inhibitor design. Future VEGFR-2 inhibitor designs may be influenced by this review, which focuses on the current trends of using multiple screening layers to design better inhibitors.

A Dual Action Platinum(IV) Complex with Self-assembly Property Inhibits Prostate Cancer through Mitochondrial Stress Pathway.

Platinum(IV) prodrugs are highly promising anticancer agents because they can selectively target tumors and minimize the adverse effects associated with their PtII congeners. In this study, we synthesized dual action PtIV complexes by linking oxoplatin with lithocholic acid. The synthesized compounds, designated as PL-I, PL-II, and PL-III, can spontaneously self-assemble in water, resulting in the formation of spherical shape nanoparticles. Among the developed complexes, PL-III appeared to be the most potent compound against all the tested cancer cell lines, with 10 fold higher cytotoxicity compared to cisplatin in PC3 cells. The complex arrests the cell cycle in the S and G2 phases and induces DNA damage. Additional mechanistic investigations demonstrate that PL-III predominantly localizes within the mitochondria and cytoplasm. Consequently, PL-III disrupts mitochondrial membrane potential, increases ROS production, and perturbs mitochondrial bioenergetics in PC3 cells. The complex induces apoptosis through the mitochondrial pathway by upregulating pro-apoptotic protein expression and downregulating anti-apoptotic protein expression from the BCl-2 protein family. These results demonstrate that higher cellular uptake and reduction of PL-III by biological reductants in PC3 cells resulted in a synergistic effect of lithocholic acid and cisplatin, which can be easily observed due to its unique cytotoxic mechanism. This further underscores the significance of dual-action PtIV complexes in enhancing the efficacy of cancer therapy.

Targeting Bcl-2 with Indole Scaffolds: Emerging Drug Design Strategies for Cancer Treatment.

The B-cell lymphoma-2 (Bcl-2) protein family plays a crucial role as a regulator in the process of apoptosis. There is a substantial body of evidence indicating that the upregulation of antiapoptotic Bcl-2 proteins is prevalent in several cancer cell lines and original tumour tissue samples. This phenomenon plays a crucial role in enabling tumour cells to avoid apoptosis, hence facilitating the development of resistant cells against chemotherapy. Therefore, the success rate of chemotherapy for cancer can be enhanced by the down-regulation of anti-apoptotic Bcl-2 proteins. Furthermore, the indole structural design is commonly found in a variety of natural substances and biologically active compounds, particularly those that possess anti-cancer properties. Due to its distinctive physicochemical and biological characteristics, it has been highly regarded as a fundamental framework in the development and production of anti-cancer drugs. As a result, a considerable range of indole derivatives, encompassing both naturally occurring and developed compounds, have been identified as potential candidates for the treatment of cancer. Several of these derivatives have advanced to clinical trials, while others are already being used in clinical settings. This emphasizes the significant role of indole in the field of research and development of anti-cancer therapeutics. This study provides an overview of apoptosis and the structural characteristics of Bcl-2 family proteins, and mainly examines the present stage and recent developments in Bcl-2 inhibitors with an indole scaffold embedded in their structure.

Camptothecin and its derivatives: Advancements, mechanisms and clinical potential in cancer therapy.

Camptothecin (CPT), an alkaloid isolated from the Camptotheca tree, has demonstrated significant anticancer properties in a range of malignancies. However, its therapeutic efficacy is limited by its hydrophobicity, poor bioavailability, and systemic toxicity. Derivatives, analogues, and nanoformulations of CPT have been synthesized to overcome these limitations. The aim of this review is to comprehensively analyze existing studies to evaluate the therapeutic efficacy, mechanistic aspects, and clinical potential of CPT and its modified forms, including derivatives, analogues, and nanoformulations, in cancer treatment. A comprehensive literature review was performed using PubMed/Medline, Scopus, and Web of Science databases; articles were selected based on specific inclusion criteria, and data were extracted on the pharmacological profile, clinical studies, and therapeutic efficacy of CPT and its different forms. Current evidence suggests that derivatives and analogues of CPT have improved water solubility, bioavailability, and reduced systemic toxicity compared to CPT. Nanoformulations further enhance targeted delivery and reduce off-target effects. Clinical trials indicate promising outcomes with enhanced survival rates and lower side effects. CPT and its modified forms hold significant promise as potent anticancer agents. Ongoing research and clinical trials are essential for establishing their long-term efficacy and safety; the evidence overwhelmingly supports further development and clinical testing of these compounds.

New rhodol-sulforaphane conjugates as innovative isothiocyanate-based cytotoxic agents for cancer cells.

In search of semisynthetic derivatives with increased antitumor activity, we condensed sulforaphane (SFR) with rhodol, a fluorophore platform capable of modifying the intracellular trafficking and pharmacokinetics of the linked molecules. The two tested derivatives, namely MG28 and MG46, showed a far higher, as compared to SFR, cytotoxicity toward cancer cells. Apoptotic cell death was preceded by the extensive generation of DNA lesions, which were repaired relatively slowly and caused formation of micronuclei. Unlike SFR, rhodol-SFR conjugates' DNA lesions resulted from direct interactions with nuclear DNA. Overall, MG28 and MG46 exhibit a remarkable cytotoxic effect, which is the likely consequence of their direct and intense DNA damaging activity, i.e., a novel and peculiar mechanism arising from the conjugation of the parental rhodol and SFR. Considering that a wide number of clinically used drugs kill cancer cells by inducing DNA damage, MG could represent a new and promising chance in antitumor chemotherapy.

Zn(II)-curcumin complexes-based anticancer agents.

There is a great deal of research interest in the design of alternative metallodrugs to Pt(II)-derivatives for cancer treatment. The low solubility of such drugs in biological mediums leading to poor bioavailability is the major hurdle of several metal-based anticancer agents. These issues have recently been addressed by designing bio-active ligands based on metal-containing anticancer agents. Conjugating with bioactive ligands has significantly improved the bioavailability of the metallodrugs and their cancer cell targeting ability. One such naturally available bioactive ligand is curcumin. Until recently, several curcumin-based anticancer metallodrugs have been developed and successfully demonstrated for their anticancer studies. In this article, we aim to highlight, the synthesis, structure, and anticancer properties of various Zn(II)-curcumin-based coordination complexes. The effect of introducing different functional groups, targeting ligands, and photo-active ligands on the anticancer potential of such complexes has been mentioned in detail. The current status and future perspective on curcumin-based metallodrugs for cancer treatment have also been stated.

Identification of Novel Bromodomain-Containing Protein 4 (BRD4) Binders through 3D Pharmacophore-Based Repositioning Screening Campaign.

A 3D structure-based pharmacophore model built for bromodomain-containing protein 4 (BRD4) is reported here, specifically developed for investigating and identifying the key structural features of the (+)-JQ1 known inhibitor within the BRD4 binding site. Using this pharmacophore model, 273 synthesized and purchased compounds previously considered for other targets but yielding poor results were screened in a drug repositioning campaign. Subsequently, only six compounds showed potential as BRD4 binders and were subjected to further biophysical and biochemical assays. Compounds 2, 5, and 6 showed high affinity for BRD4, with IC50 values of 0.60 ± 0.25 µM, 3.46 ± 1.22 µM, and 4.66 ± 0.52 µM, respectively. Additionally, these compounds were tested against two other bromodomains, BRD3 and BRD9, and two of them showed high selectivity for BRD4. The reported 3D structure-based pharmacophore model proves to be a straightforward and useful tool for selecting novel BRD4 ligands.

Early follow-up of outpatients with oral anticancer therapy in the ONCORAL multidisciplinary community-hospital program.

BACKGROUND: Healthcare professionals are faced with the new challenges of preventing and managing drug-related problems (DRPs) with oral anticancer therapy (OAT): side-effects, drug-drug interactions (DDIs), non-adherence, or medication errors. This study aims to assess the impact of ONCORAL, a real-life multidisciplinary care plan for cancer patients based on community and hospital follow-up, for the first OAT cycle. METHODS: A prospective cohort study was conducted between October 1, 2021 and October 1, 2022 including all outpatients starting OAT treatment. During the first OAT cycle, the program consists of 6 weekly scheduled face-to-face or phone consultations to prevent and manage DRPs. Nurse and pharmacist interventions (NPIs) are realized to optimize treatments (primary outcomes). Secondary outcomes included the relative dose intensity (RDI) of the first cycle. RESULTS: A total of 562 NPIs were performed by the ONCORAL team: that is, 87.1% of the 209 patients included, for a mean of 3.1 ±â€…2.2 NPIs/patient. NPIs-concerned DRPs detected by the nurse and pharmacist (346, 61.6%), symptoms and/or adverse effects reported as PROs by the patient or family (138, 24.6%), or pathway issues (78, 13.9%). Seventy-three DDIs were detected and managed during medication review, in a quarter of patients (n = 54/209), leading to the discontinuation of a daily concomitant medication in 30 cases. The mean RDI at the end of the first cycle, calculated for 209 patients, was 83.1 ±â€…23.9% (17.56-144.23). CONCLUSION: In these ambulatory cancer patients, the interest in tailored monitoring of DRPs as a whole, including the prevention and management of drug interactions in addition to symptoms and adverse effects, is highlighted.

Synthesis and Preliminary Anticancer Evaluation of 4-C Derivatives of Diphyllin.

The natural lignan diphyllin has shown promising antitumor activity, although its clinical advancement has been impeded by challenges such as low solubility, poor metabolic stability, and limited potency. In response, we developed and synthesized two sets of diphyllin 4-C derivatives, comprising six ester derivatives and eight 1, 2, 3-triazole derivatives. Notably, among these derivatives, 1, 2, 3-triazole derivatives 7c and 7e demonstrated the most potent cytotoxic effects, with IC50 values ranging from 0.003 to 0.01 µM. Treatment with 0.2 µM of 7c and 7e resulted in a reduction of V-ATPase activity in HGC-27 cells to 23% and 29%, respectively.

Better in the Near Infrared: Sulfonamide Perfluorinated-Phenyl Photosensitizers for Improved Simultaneous Targeted Photodynamic Therapy and Real-Time Fluorescence Imaging.

Tetraphenyloporphyrin derivatives are a useful scaffold for developing new pharmaceuticals for photodynamic therapy (PDT) and the photodiagnosis (PD) of cancer. We synthesized new sulfonamide fluorinated porphyrin derivatives and investigated their potential as photosensitizers and real-time bioimaging agents for cancer. We found that 5,10,15,20-tetrakis-[2',3',5',6'-tetrafluoro-4'-methanesulfamidyl)phenyl]bacteriochlorin (F4BMet) has intense absorption and fluorescence in the near-infrared, efficiently generates singlet oxygen and hydroxyl radicals, has low toxicity in the dark, and high phototoxicity. We increased its bioavailability with encapsulation in Pluronic-based micelles, which also improved the photodynamic effect. F4BMet exhibits pH-dependent properties (lower pH promoted its aggregation), and a GlyGly buffer was used to effectively solubilize the compound. In vitro findings with 2D cell culture were complemented with human-induced pluripotent stem cell (hiPSC)-derived organoids. F4BMet in P123 micelles showed enhanced efficacy compared to F4BMet in the GlyGly formulation. F4BMet was further evaluated in real-time bioimaging and PDT of BALB/c mice bearing CT26 tumors. After i.v. injection, the photosensitizer was visible in the tumor area 3 h after injection. The most successful therapeutic approach proved to be tumor-targeted PDT using P123-encapsulated F4BMet illuminated 24 h after administration with a light dose of 42 J/cm2, which led to a 30% long-term cure rate.

Enhancing Anti-Cancer Immune Response by Acidosis-Sensitive Nanobody Display.

One of the main challenges with many cancer immunotherapies is that biomarkers are needed for targeting. These biomarkers are often associated with tumors but are not specific to a particular tumor and can lead to damage in healthy tissues, resistance to treatment, or the need for customization for different types of cancer due to variations in targets. A promising alternative approach is to target the acidic microenvironment found in most solid tumor types. This can be achieved using the pH (Low) Insertion Peptide (pHLIP), which inserts selectively into cell membranes under acidic conditions, sparing healthy tissues. pHLIP has shown potential for imaging, drug delivery, and surface display. For instance, we previously used pHLIP to display epitopes on the surfaces of cancer cells, enabling antibody-mediated immune cell recruitment and selective killing of cancer cells. In this study, we further explored this concept by directly fusing an anti-CD16 nanobody, which activates natural killer (NK) cells, to pHLIP, eliminating the need for antibody recruitment. Our results demonstrated the insertion of pH-sensitive agents into cancer cells, activation of the CD16 receptor on effector cells, and successful targeting and destruction of cancer cells by high-affinity CD16+ NK cells in two cancer cell lines.

Recent progress of protein kinase inhibitors derived from marine peptides for developing anticancer agents.

Protein kinases, mediating their biological function via their catalytic activity, play important role in cell development, including cell proliferation, migration, angiogenesis and survival. Over the years, protein kinase inhibitors have been developed as an important class of anticancer agents clinically. However, the off-targeting and drug resistance of protein kinase inhibitors limit their efficiency. Anticancer peptides derived from marine organisms represent a novel class of bioactive substances, and some of the peptides exhibit anticancer effect via inhibiting protein kinases. In this mini review, the recent progress of anticancer peptides targeting protein kinases from marine sources are presented. Marine peptides inhibiting resistant cancer cells by targeting novel domains of protein kinases are highlighted. The challenges and prospects of developing marine peptides as anticancer agents are also discussed.

Molecular docking analysis of imeglimin and its derivatives with estrogen receptor-alpha.

Estrogen receptor-α (ER- α) is a principal endocrine regulatory protein in breast cancer. The progression of ER-α positive breast cancer is slowed by selective estrogen receptor modulators such as Tamoxifen. But, long term therapy with Tamoxifen leads to resistance. Therefore, it is of interest to document the Molecular docking and pharmacokinetic analysis of imeglimin derivatives with ER-alpha. Among the 166 derivatives of Imeglimin, only five derivatives were shortlisted after toxicity testing. The selected derivatives showed good binding affinity with favorable pharmacokinetic profiles. The selected compounds of Imeglimin were found to possess excellent anticancer potential and could be considered as novel, cost-effective anticancer agents effective against ER positive breast cancer for further investigation.

Newly synthesized chitosan nanoparticles loaded with caffeine/moringa leaf extracts Halt Her2, BRCA1, and BRCA2 expressions.

Breast cancer is among the highest morbidity and mortality rates in women around the world. In the present investigation we aimed to synthesis novel nanosystem combining two naturally important anticancer agents with different mechanism of action namely Moringa oleifera and caffeine. Firstly, chemical analysis of Moringa oleifera extract and caffeine was done by gas chromatography-mass spectroscopy (GC-MS) in order to assess the main chemical compounds present and correlate between them and the possible anticancer effect. The novel nanosystem was characterized through dynamic light scattering techniques which revealed the stability and homogeneity of the prepared M. oleifera leaves extract/Caffeine loaded chitosan nanoparticles, while FTIR and transmission electron microscope (TEM) proved the shape and the successful incorporation of M. oleifera leaves extract/Caffeine onto the nanochitosan carrier. Our initial step was to assess the anticancer effect in vitro in cancer cell line MCF-7 which proved the significant enhanced effect of M. oleifera leaves extract/Caffeine nanosystem compared to M. oleifera leaves extract or caffeine loaded nanoparticles. Further studies were conducted in vivo namely tumor biomarkers, tumor volume, bioluminescence imaging, molecular and histopathological investigations. The present study proved the potent anticancer effect of the synthesized M. oleifera leaves extract/Caffeine loaded chitosan nanoparticles. Mo/Caf/CsNPs exhibited a large number of apoptotic cells within the tumor mass while the adipose tissue regeneration was higher compared to the positive control. The prepared nanoparticles downregulated the expression of Her2, BRCA1 and BRCA2 while mTOR expression was upregulated. The aforementioned data demonstrated the successful synergistic impact of Moringa and caffeine in decreasing the carcinoma grade.

Glassy carbon electrodes modified with graphitic carbon nitride nanosheets and CoNiO2 bimetallic oxide nanoparticles as electrochemical sensor for Sunitinib detection in human fluid matrices and pharmaceutical samples.

A sophisticated electrochemical sensor is presented employing a glassy carbon electrode (GCE) modified with a novel composite of synthesized graphitic carbon nitride (g-C3N4) and CoNiO2 bimetallic oxide nanoparticles (g-C3N4/CoNiO2). The sensor's electrocatalytic capabilities for Sunitinib (SUNI) oxidation were demonstrated exceptional performance with a calculated detection limit (LOD) of 52.0 nM. The successful synthesis and integrity of the composite were confirmed through meticulous characterization using various techniques. FT-IR analysis affirmed the successful synthesis of g-C3N4/CoNiO2 by providing insights into its molecular structure. XRD, FE-SEM, SEM-EDX, and BET analyses collectively validated the material's structural integrity, surface morphology, and electrocatalytic performance. Optimization of key analytical parameters, such as loading volume, concentration, electrolyte solution type, and pH, enhanced the electrocatalytic sensing capabilities of g-C3N4/CoNiO2. The synergistic interaction between g-C3N4 and CoNiO2 bimetallic oxide nanoparticles executed the sensor highly effective in the electrical oxidation of SUNI. Across a concentration range of 0.1-83.8 µM SUNI, the anodic peak current exhibited a linear increase with good precision. Application of the newly developed g-C3N4/CoNiO2 system to detect SUNI in a variety of samples, including urine, human serum, and capsule dosage forms, obtained satisfactory recoveries ranging from 97.1 to 103.0%. This methodology offers a novel approach to underscore the potential of the developed sensor for applications in biological and pharmaceutical monitoring.

Studies on the ameliorative potential of Rheum webbianum rhizome extracts on 1,2-dimethylhydrazine (DMH) induced colorectal cancer and associated hepatic and haematological abnormalities in swiss albino rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Rheum webbianum Royle (RW) holds significant ethnopharmacological importance owing to its 5000-year history of cultivation for medicinal and culinary purposes. Demonstrating therapeutic advantages in traditional and contemporary medical practices, RW exhibits key pharmacological effects including anticancer activity, gastrointestinal control, anti-inflammatory properties, and suppression of fibrosis. Despite its recognized vast bioactivities in ethnopharmacology, its efficacy against the colorectal cancer (CRC) remains incompletely understood. AIM OF THE STUDY: This study for the first time aims to investigate the chemo-preventive capabilities of various extracts derived from RW rhizomes against CRC development. MATERIALS AND METHODS: Four types of RW extracts were prepared by using different solvents viz: Hexane, Ethy-acetate, Ethanol and Methanol. All the four extracts were evaluated for cytotoxicity on HCT-116 human CRC cells. Promising extracts were further investigated in-vivo at varying doses using 1,2-dimethylhydrazine (DMH) induced rat CRC model to assess the anti-oxidant and anticancer properties as well as their effects on the associated hepatic deterioration and hematological alterations. RESULTS: Cell viability: In-vitro assessments demonstrated a dose and time-dependent reduction in HCT-116 cell viability following treatment with methanolic and ethanolic extracts of RW, reducing viability by up to 85% and 90%, respectively, at 200 µg/ml. HISTOPATHOLOGY: Histopathological analyses revealed significant improvements in colon tissue morphology in RW extract-treated groups compared to DMH-only treated animals. RW-treated groups showed reduced structural abnormalities, congestion, inflammatory cell infiltration, crypt abscess formation, and dysplasia. In contrast, the DMH-only group exhibited irregular glandular structure, mucosal destruction, extensive inflammatory cell infiltration, crypt abscess formation, and dysplasia. These results highlight the potential of RW methanolic and ethanolic extracts in mitigating colon cancer-related histopathological alterations. Haematological, and hepatic parameters: In the DMH-induced colorectal cancer rat model, significant hematological imbalances were evident, including a 49.13% decrease in erythrocytes, 32.18% in hemoglobin, and 26.79% in hematocrit, along with a 79.62% increase in white blood cells and 68.96% rise in platelets. Administration of RW rhizome extracts effectively restored these hematological parameters to levels comparable to those in the control group. Furthermore, RW treatment significantly reduced serum ALT and AST levels, which had increased by 36.78% and 33.12%, respectively, due to DMH exposure. RW intervention also mitigated the onset of atherosclerosis, evidenced by notable reductions in serum total cholesterol and triglyceride levels. Comparative analysis indicated that RW-treated DMH groups effectively restored lipid profiles, contrasting with the DMH-only group which exhibited markers indicative of colon cancer. Oxidative stress: The DMH-treated group showed a significant increase in MDA levels by 195.59%, indicative of heightened free radical production, coupled with decreased levels of SOD (33%), CAT (48%), GSH (58%), and GR activity (49%), signifying oxidative stress. Treatment with RW extracts in DMH-treated rats markedly reduced MDA levels and enhanced SOD, CAT, GSH, and GR activities. These results underscore the antioxidant efficacy of RW extracts. CONCLUSION: This study underscores the significant potential of RW rhizome extracts in inhibiting colorectal cancer development. Further investigations are warranted to identify the active constituents responsible for these promising outcomes, positioning RW as a natural and potential agent in combating colon cancer.

Characterization and prediction of OATP1B activity in prostate cancer patients on abiraterone acetate using endogenous biomarker coproporphyrin I.

Organic anion transporting polypeptide (OATP) 1B1 and OATP1B3 are important hepatic transporters. We previously identified OATP1B3 being critically implicated in the disposition of abiraterone. We aimed to further investigate the effects of abiraterone on the activities of OATP1B1 and OATP1B3 utilizing a validated endogenous biomarker coproporphyrin I (CP-I). We utilized OATP1B-transfected cells to characterize the inhibitory potential of abiraterone against OATP1B-mediated uptake of CP-I. Inhibition constant (Ki) was incorporated into our physiologically based pharmacokinetic (PBPK) modeling to simulate the systemic exposures of CP-I among cancer populations receiving either our model-informed 500 mg or clinically approved 1000 mg abiraterone acetate (AA) dosage. Simulated data were compared with clinical CP-I concentrations determined among our 9 metastatic prostate cancer patients receiving 500 mg AA treatment. Abiraterone inhibited OATP1B3- but not OATP1B1-mediated uptake of CP-I in vitro, with an estimated Ki of 3.93 µM. Baseline CP-I concentrations were simulated to be 0.81 {plus minus} 0.26 ng/mL, and determined to be 0.72 {plus minus} 0.16 ng/mL among metastatic prostate cancer patients, both of which were higher than those observed for healthy subjects. PBPK simulations revealed an absence of OATP1B3-mediated interaction between abiraterone and CP-I. Our clinical observations confirmed that CP-I concentrations remained comparable to baseline levels up to 12 weeks post 500 mg AA treatment. Using CP-I as an endogenous biomarker, we identified the inhibition of abiraterone on OATP1B3 but not OATP1B1 in vitro, which was predicted and observed to be clinically insignificant. We concluded that the interaction risk between AA and substrates of OATP1Bs is low. Significance Statement We utilized the endogenous biomarker coproporphyrin I (CP-I) and identified abiraterone as a moderate inhibitor of organic anion transporting polypeptide (OATP) 1B3 in vitro. Subsequent physiologically based pharmacokinetic (PBPK) simulations and clinical observations suggested an absence of OATP1B-mediated interaction between abiraterone and CP-I among prostate cancer patients. This multi-pronged study concluded that the interaction risk between abiraterone acetate and substrates of OATP1Bs is low, demonstrating the application of PBPK-CP-I modelling in predicting OATP1B-mediated interaction implicating abiraterone.