- |||||||||| paclitaxel / Generic mfg., docetaxel / Generic mfg.
Journal: Selective and marked blockade of endothelial sprouting behavior using paclitaxel and related pharmacologic agents. (Pubmed Central) - Dec 16, 2021
Bioassays of human EC tubulogenesis, where both sprouting behavior and lumen formation can be rigorously evaluated, were used to demonstrate that addition of the microtubule-stabilizing drugs, paclitaxel, docetaxel, ixabepilone, and epothilone B, completely interferes with EC tip cells and sprouting behavior, while allowing for EC lumen formation...Remarkably, treatment of these cultures with a low dose of the microtubule-destabilizing drug, vinblastine, led to an identical result, with complete blockade of EC sprouting, but allowing for EC lumen formation...These findings reveal novel biological activities for pharmacologic agents that are widely utilized in multidrug chemotherapeutic regimens for the treatment of human malignant cancers. Overall, this work demonstrates that manipulation of microtubule stability selectively interferes with the ability of ECs to sprout, a necessary step to initiate and form branched capillary tube networks.
- |||||||||| Ixempra (ixabepilone) - Otsuka, R / Pharm, Halaven (eribulin mesylate) / Eisai
Biomarker, Trial completion date, Trial primary completion date, Biopsy: Pharmacodynamic Biomarkers of Standard Anti-microtubule Drugs as Assessed by Early Tumor Biopsy (clinicaltrials.gov) - Dec 14, 2021
P=N/A, N=35, Recruiting,
Overall, this work demonstrates that manipulation of microtubule stability selectively interferes with the ability of ECs to sprout, a necessary step to initiate and form branched capillary tube networks. Trial completion date: Aug 2022 --> Aug 2023 | Trial primary completion date: Jun 2022 --> Jun 2023
- |||||||||| lovastatin / Generic mfg.
Journal: Re-engineering natural products to engage new biological targets. (Pubmed Central) - Oct 28, 2021
This process is illustrated by numerous examples, including the conversion of epothilone to ixabepilone, erythromycin to azithromycin, and lovastatin to simvastatin...This Highlight details a handful of these studies, describing new compounds derived from natural products that have biological activity and cellular targets different from those evoked/engaged by the parent. Such re-engineering of natural products offers the potential for discovering compounds with interesting and unexpected biological activity.
- |||||||||| Ixempra (ixabepilone) - Otsuka, R / Pharm, Allarity Therap
Biomarker, Journal, IO biomarker: PTPRT Could Be a Treatment Predictive and Prognostic Biomarker for Breast Cancer. (Pubmed Central) - Oct 1, 2021
PTPRT might be primary resistance biomarkers for taxane, anthracycline, and ixabepilone but not be acquired resistance biomarkers...PTPRT could predict chemotherapy effectiveness and prognosis for breast cancer patients. PTPRT might inhibit tumor growth via disrupting the microtubule dynamics and cell cycle in breast cancer.
- |||||||||| Ixempra (ixabepilone) - Otsuka, R / Pharm, Allarity Therap
Clinical, Review, Journal: Ixabepilone: Overview of Effectiveness, Safety, and Tolerability in Metastatic Breast Cancer. (Pubmed Central) - Jul 28, 2021
Dose reductions did not appear to have an impact on the efficacy of ixabepilone plus capecitabine. Incorporation of ixabepilone into individualized treatment plans can extend progression-free survival in a patient population that continues to represent an unmet need.
- |||||||||| Cabometyx (cabozantinib tablet) / Takeda, Exelixis, Ipsen
Journal, PARP Biomarker: Development and validation of an LC-MS/MS generic assay platform for small molecule drug bioanalysis. (Pubmed Central) - Jul 23, 2021
Incorporation of ixabepilone into individualized treatment plans can extend progression-free survival in a patient population that continues to represent an unmet need. The generic approach has become a useful tool to further define the pharmacology of drugs studied in our laboratory and may be utilized as described, or as starting point to develop drug-specific assays with more extensive performance characterization.
- |||||||||| patupilone (EPO 906) / Novartis
Journal: Design, Synthesis, and Biological Investigation of Epothilone B Analogues Featuring Lactone, Lactam, and Carbocyclic Macrocycles, Epoxide, Aziridine, and 1,1-Difluorocyclopropane and Other Fluorine Residues. (Pubmed Central) - Jun 24, 2021
Herein, we report the design, synthesis, and biological evaluation of a series of new epothilone B analogues equipped with novel structural motifs, including fluorine-containing residues, 12,13-difluorocyclopropyl moieties, mono- and dimethylated macrolactones, and 1-keto macrocyclic systems, as well as two N-substituted ixabepilone analogues in which the 12,13-epoxide and macrolactam NH moieties were replaced, the former with a substituted aziridine moiety and the latter with an NCO-alkyl residue (imide or carbamate). Biological evaluation of these analogues revealed a number of exceptionally potent epothilone B analogues, demonstrating the potency enhancing effects of the fluorine residues and the aziridinyl moiety within the structure of the epothilone molecule and providing new and useful structure-activity relationships within this class of compounds.
- |||||||||| Ixempra (ixabepilone) - Otsuka, R / Pharm, Allarity Therap, Avastin (bevacizumab) / Roche
Trial completion date, Trial primary completion date: Evaluation of Weekly Ixabepilone With or Without Biweekly Bevacizumab (clinicaltrials.gov) - Feb 9, 2021
P2, N=78, Active, not recruiting,
Active, not recruiting --> Completed | Trial completion date: Sep 2019 --> Sep 2020 Trial completion date: Feb 2026 --> Feb 2027 | Trial primary completion date: Feb 2021 --> Feb 2022
- |||||||||| Ixempra (ixabepilone) - Otsuka, R / Pharm, Allarity Therap
Journal, IO biomarker: A multi-scale systems pharmacology approach uncovers the anti-cancer molecular mechanism of Ixabepilone. (Pubmed Central) - Feb 2, 2021
In addition, Ixabepilone also decreases Bcl-2 protein expression and induces cytoprotective autophagy in human hepatic carcinoma and glioma cells. In conclusion, this study not only provides a feasible and alternative way exploring new molecular mechanisms of drugs by combing computation DTI prediction, but also reveals an effective strategy to reinforce the antitumor efficacy of Ixabepilone.
- |||||||||| Ixempra (ixabepilone) - Otsuka, R / Pharm, Halaven (eribulin mesylate) / Eisai
Biomarker, Trial completion date, Trial primary completion date, Biopsy: Pharmacodynamic Biomarkers of Standard Anti-microtubule Drugs as Assessed by Early Tumor Biopsy (clinicaltrials.gov) - Jan 6, 2021
P=N/A, N=35, Recruiting,
Trial completion date: Apr 2020 --> Dec 2022 | Trial primary completion date: Apr 2020 --> Dec 2021 Trial completion date: Aug 2021 --> Aug 2022 | Trial primary completion date: Jun 2021 --> Jun 2022
- |||||||||| vinorelbine tartrate / Generic mfg., irinotecan / Generic mfg.
Clinical, Review, Journal: Chemotherapy Options beyond the First Line in HER-Negative Metastatic Breast Cancer. (Pubmed Central) - Dec 17, 2020
However, no clear indication exists on what the best option is in some populations, such as heavily pretreated, elderly patients, triple-negative BC (TNBC), and those who do not respond to the first-line therapy. In this article, we summarize available literature evidence on different chemotherapy agents used beyond the first-line, in locally advanced or MBC patients, including rechallenge with anthracyclines and taxanes, antimetabolite and antimicrotubule agents, such as vinorelbine, capecitabine, eribulin, ixabepilone, and the newest developed agents, such as vinflunine, irinotecan, and etirinotecan.
- |||||||||| paclitaxel / Generic mfg.
Journal: High-resolution X-ray structure of three microtubule-stabilizing agents in complex with tubulin provide a rationale for drug design. (Pubmed Central) - Dec 5, 2020
In particular, the tubulin taxane-site inhibitors such as taxol analogs and epothilones have achieved great success in clinical trials...We here reported crystal complex structures for three taxane-site inhibitors, Ixabepilone, Epothilone B, and Epothilone D, which were determined to 2.4 Å, 2.4 Å, and 2.85 Å, respectively...On this basis, new derivatives with higher binding affinity to tubulin were designed and developed, which can form additional hydrogen bond interactions with tubulin. Overall, this work determined the mechanism of action of epothilones and provided a structural basis to design reasonably novel taxane-site inhibitors with simpler structure and improved pharmacokinetic properties.
- |||||||||| Ixempra (ixabepilone) - Otsuka, R / Pharm, Oncology Venture, Tafinlar (dabrafenib) / Novartis
Review, Journal: Thiazole-containing compounds as therapeutic targets for cancer therapy. (Pubmed Central) - Oct 27, 2020
This review presents current research on thiazoles and elucidates their biological importance in anticancer drug discovery. The findings may aid researchers in the rational design of more potent and bio-target specific anticancer drug molecules.
- |||||||||| Ixempra (ixabepilone) - Otsuka, R / Pharm, Allarity Therap, Synribo (omacetaxine mepesuccinate) / Stragen, Teva, Istodax (romidepsin) / Astellas, BMS
[VIRTUAL] High-Throughput Drug Screening of FDA-Approved Antineoplastic Drugs for the Treatment of Aggressive Meningiomas () - Oct 24, 2020 - Abstract #SNO2020SNO_669;
Among them, Bortezomib exhibited the most pronounced effect by up to 80% of apoptotic cells (P < 0.001). In summary, by utilizing a high-throughput drug screening we were able to identify Bortezomib, Carfilzomib, Omacetaxine, Ixabepilone, and Romidepsin as potent antineoplastic agents for the treatment of aggressive meningiomas.
- |||||||||| paclitaxel / Generic mfg.
Retrospective data, Journal: Prevalence of peripheral neuropathy associated with chemotherapy in four oncology centers of Colombia. (Pubmed Central) - Sep 23, 2020
Chemotherapy-induced peripheral neuropathy is a frequent adverse reaction to daily cancer therapy in Colombian patients managed with taxanes, alkylators, proteasome inhibitors, and epothilone B analogs. Hence, it is necessary to establish more successful diagnostic methods and incorporate validated scales in the routine evaluation of all patients receiving these medications in our environment.
- |||||||||| Onzeald (etirinotecan pegol) / Nektar Therap
Trial completion, Trial completion date, Metastases: ATTAIN: A Study of Etirinotecan Pegol (NKTR-102) Versus Treatment of Physician's Choice (TPC) in Patients With Metastatic Breast Cancer Who Have Stable Brain Metastases and Have Been Previously Treated With an Anthracycline, a Taxane, and Capecitabine (clinicaltrials.gov) - Aug 24, 2020
P3, N=178, Completed,
Hence, it is necessary to establish more successful diagnostic methods and incorporate validated scales in the routine evaluation of all patients receiving these medications in our environment. Active, not recruiting --> Completed | Trial completion date: Mar 2021 --> Jul 2020
- |||||||||| Ixempra (ixabepilone) - Otsuka, R / Pharm, Allarity Therap, Avastin (bevacizumab) / Roche
Enrollment closed: Evaluation of Weekly Ixabepilone With or Without Biweekly Bevacizumab (clinicaltrials.gov) - Jul 1, 2020
P2, N=78, Active, not recruiting,
Active, not recruiting --> Completed | Trial completion date: Mar 2021 --> Jul 2020 Recruiting --> Active, not recruiting
- |||||||||| Ixempra (ixabepilone) - Otsuka, R / Pharm, Allarity Therap, Avastin (bevacizumab) / Roche
Enrollment open: Evaluation of Weekly Ixabepilone With or Without Biweekly Bevacizumab (clinicaltrials.gov) - Jun 4, 2020
P2, N=88, Recruiting,
These findings will help to minimise the risk of CIPN by encouraging increased surveillance and earlier dose adjustment of high-risk agents in phase I trials. Suspended --> Recruiting
- |||||||||| Halaven (eribulin mesylate) / Eisai, vinorelbine tartrate / Generic mfg.
Eribulin promotes a distinct immunogenic gene expression signature as compared with paclitaxel (Virtual Meeting II: E-Posters) - May 16, 2020 - Abstract #AACRII2020AACR-II_633;
Recently, the combination of the PD-L1 inhibitor atezolizumab with the taxane nab-paclitaxel was found to prolong progression-free survival in patients with metastatic TNBC...The effects of 5 MTAs used for the treatment of TNBC, paclitaxel, docetaxel, ixabepilone, vinorelbine, and eribulin, on the expression of antitumor cytokines and other immunomodulatory genes in myeloid and TNBC cells was evaluated...Together, these results provide evidence that MTAs have different immune modulatory properties and suggest that the specific immune signatures initiated by different MTAs need to be considered for their optimal use with targeted agents, including checkpoint inhibitors. These studies were funded by Eisai.
- |||||||||| Ixempra (ixabepilone) - Otsuka, R / Pharm, Allarity Therap, Erbitux (cetuximab) / Eli Lilly, EMD Serono
Trial completion: Neo-Adjuvant Study in Triple Negative Breast Cancer Patients (clinicaltrials.gov) - May 15, 2020
P2, N=40, Completed,
These studies were funded by Eisai. Active, not recruiting --> Completed
- |||||||||| paclitaxel / Generic mfg.
Review, Journal: Taxane and epothilone-induced peripheral neurotoxicity: From pathogenesis to treatment. (Pubmed Central) - Apr 23, 2020
The typical TIPN clinical presentation is mainly comprised of numbness and paresthesia, in a stocking-and-glove distribution and may progress more proximally over time, with paclitaxel being more neurotoxic than docetaxel...There are currently no neuroprotective strategies to reduce the risk of TIPN, and symptomatic treatments are very limited. This review critically examines the pathogenesis, incidence, risk factors (both clinical and pharmacogenetic), clinical phenotype and management of TIPN.
- |||||||||| Ixempra (ixabepilone) - Otsuka, R / Pharm, Allarity Therap, Avastin (bevacizumab) / Roche
Trial suspension: Evaluation of Weekly Ixabepilone With or Without Biweekly Bevacizumab (clinicaltrials.gov) - Apr 10, 2020
P2, N=88, Suspended,
This review critically examines the pathogenesis, incidence, risk factors (both clinical and pharmacogenetic), clinical phenotype and management of TIPN. Recruiting --> Suspended
- |||||||||| paclitaxel / Generic mfg.
Journal: An Easy and Efficient Strategy for the Enhancement of Epothilone Production Mediated by TALE-TF and CRISPR/dcas9 Systems in Sorangium cellulosum. (Pubmed Central) - Feb 13, 2020
The transcriptional regulation mechanism of TALE-TF-VP64 and the competition mechanism with endogenous transcriptional factor were investigated by electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP), demonstrating the combination of the P3 promoter and TALE-TF element and the competition between TALE-TF and endogenous transcriptional protein. This is the first report on the transcriptional regulation of the epothilone biosynthetic gene cluster in S. cellulosum using the TALE-TF and dCas9-VP64 systems, and the regulatory mechanism of the TALE-TF system for epothilone biosynthesis in S. cellulosum was also firstly revealed, thus shedding light on the metabolic engineering of S. cellulosum to improve epothilone yields substantially and promoting the application of epothilones in the biomedical industry.
- |||||||||| Ixempra (ixabepilone) - Otsuka, R / Pharm, Oncology Venture, patupilone (EPO 906) / Novartis
Progress toward development of a more acid stable epothilone for use as an ADC payload (Exhibit Hall A, Pennsylvania Convention Center) - Feb 13, 2020 - Abstract #ACSSp2020ACS_Sp_9300;
We chose the epothilone analog iso-fludelone as the basis for our synthesis, and we were ultimately successful in our efforts to synthesize a linker-equipped version. Biological evaluation confirmed potency comparable to that of epothilone B, an encouraging result in our efforts to develop an epothilone as a potential ADC payload.
- |||||||||| Ixempra (ixabepilone) - Otsuka, R / Pharm, Oncology Venture, patupilone (EPO 906) / Novartis
Progress toward development of a more acid stable epothilone for use as an ADC payload (Exhibit Hall B/C, Pennsylvania Convention Center) - Feb 13, 2020 - Abstract #ACSSp2020ACS_Sp_8033;
We chose the epothilone analog iso-fludelone as the basis for our synthesis, and we were ultimately successful in our efforts to synthesize a linker-equipped version. Biological evaluation confirmed potency comparable to that of epothilone B, an encouraging result in our efforts to develop an epothilone as a potential ADC payload.
- |||||||||| Ixempra (ixabepilone) - Otsuka, R / Pharm, Oncology Venture
Functional studies of the non-ribosomal peptide synthetase cyclization domain in epothilone biosynthesis using site-directed mutagenesis (Exhibit Hall A, Pennsylvania Convention Center) - Feb 13, 2020 - Abstract #ACSSp2020ACS_Sp_3850;
A previously developed LC/MS assay for determining the 2-methylthiazole product was adapted in order to monitor product formation among the mutants in comparison to the wild type. These results contribute to an understanding of the function of each tunnel and provide insight to how the protein modules of the PKS-NRPS biosynthetic starter units work together to catalyze the formation of 2-methylthiazole.
- |||||||||| Ixempra (ixabepilone) - Otsuka, R / Pharm, Halaven (eribulin mesylate) / Eisai
Biomarker, Trial primary completion date, Biopsy: Pharmacodynamic Biomarkers of Standard Anti-microtubule Drugs as Assessed by Early Tumor Biopsy (clinicaltrials.gov) - Feb 6, 2020
P=N/A, N=35, Recruiting,
These results contribute to an understanding of the function of each tunnel and provide insight to how the protein modules of the PKS-NRPS biosynthetic starter units work together to catalyze the formation of 2-methylthiazole. Trial primary completion date: Jun 2020 --> Jun 2021
- |||||||||| paclitaxel / Generic mfg.
Journal: Mitochondrial dysfunction in the pathogenesis of chemotherapy-induced peripheral neuropathy. (Pubmed Central) - Jan 21, 2020
We will review the studies reporting the nature of mitochondrial dysfunction evoked by chemotherapy in terms of changes in mitochondrial morphology, bioenergetics and reactive oxygen species (ROS) generation. Furthermore, we will discuss the in vivo effects of pharmacological interventions that counteract chemotherapy-evoked mitochondrial dysfunction and ameliorate pain-like behavior.
- |||||||||| Ixempra (ixabepilone) - Otsuka, R / Pharm, Oncology Venture, patupilone (EPO 906) / Novartis, paclitaxel / Generic mfg.
Journal: Synthesis, anticancer activity and cytotoxicity of 7-O-β-D-galactosyl-PEG-epothilone B. (Pubmed Central) - Jan 17, 2020
Herein, 7-O-β-D-galactosyl-PEG-epothilone B 6 was synthesized. It showed that the toxicity of the synthesized compound was 1/182 of the epothilone B. In addition, compound 6 also had significant anticancer activity under the action of enzyme.
- |||||||||| Onzeald (etirinotecan pegol) / Nektar Therap
Enrollment closed, Metastases: ATTAIN: A Study of Etirinotecan Pegol (NKTR-102) Versus Treatment of Physician's Choice (TPC) in Patients With Metastatic Breast Cancer Who Have Stable Brain Metastases and Have Been Previously Treated With an Anthracycline, a Taxane, and Capecitabine (clinicaltrials.gov) - Jan 15, 2020
P3, N=178, Active, not recruiting,
It showed that the toxicity of the synthesized compound was 1/182 of the epothilone B. In addition, compound 6 also had significant anticancer activity under the action of enzyme. Recruiting --> Active, not recruiting
- |||||||||| paclitaxel / Generic mfg.
Journal: Paclitaxel Enhances the Innate Immunity by Promoting NLRP3 Inflammasome Activation in Macrophages. (Pubmed Central) - Jan 2, 2020
Consistent with the in vitro results, intraperitoneal administration of paclitaxel significantly increased serum IL-1β levels, reduced bacterial burden, dampened infiltration of inflammatory cells in the liver, and improved animal survival in a mouse model of bacterial infection. Collectively, our data indicate that paclitaxel potentiated NLRP3 inflammasome activation by inducing α-tubulin acetylation and thereby conferred enhanced antibacterial innate responses, suggesting its potential application against pathogenic infections beyond its use as a chemotherapeutic agent.
- |||||||||| Ixempra (ixabepilone) - Otsuka, R / Pharm, Allarity Therap, Abraxane (albumin-bound paclitaxel) / BMS, Otsuka
Biomarker, Journal: A Pharmacogenetic Prediction Model of Progression-Free Survival in Breast Cancer using Genome-Wide Genotyping Data from CALGB 40502 (Alliance). (Pubmed Central) - Dec 23, 2019
A final model included 13 SNPs in addition to clinical covariates (prior taxane status, hormone receptor status, disease-free interval, and presence of visceral metastases) with an AUC integrated over time of 0.81, an increase compared to an AUC of 0.64 for a model with clinical covariates alone. This model may be of value in predicting progression-free survival with microtubule targeting agents and may inform reverse translational studies to understand differential response to these drugs.
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