 |
15 Diseases |  |
1 Trial |
|
1 Trial |  |
40 News |  |
- | E7820 / Eisai, indisulam (E7070) / Eisai
Journal: Native mass spectrometry of complexes formed by molecular glues reveals stoichiometric rearrangement of E3 ligases. (Pubmed Central) - Apr 19, 2024
Moreover, we uncovered that the DCAF15?:?DDA1?:?DDB1 E3 ligase self-associates into dimers and trimers when analysed alone at low salt concentrations (100 mM ammonium acetate) which dissociate into single copies of the complex at higher salt concentrations (500 mM ammonium acetate), or upon the addition of MG and POI, forming a 1?:?1?:?1 ternary complex. This work demonstrates the strength of nMS in TPD research, reveals novel binding mechanisms of the DCAF15 E3 ligase, and its self-association into dimers and trimers at reduced salt concentration during structural analysis.
- || E7820 / Eisai
P2 data, Journal: E7820, an anti-cancer sulfonamide, degrades RBM39 in patients with splicing factor mutant myeloid malignancies: a phase II clinical trial. (Pubmed Central) - Nov 29, 2023
This work demonstrates the strength of nMS in TPD research, reveals novel binding mechanisms of the DCAF15 E3 ligase, and its self-association into dimers and trimers at reduced salt concentration during structural analysis. No abstract available
- E7820 / Eisai
Trial termination, Metastases: FOLFIRI Alone Versus FOLFIRI Plus Bevacizumab Versus FOLFIRI Plus E7820 as Second-Line Therapy in Patients With Locally Advanced or Metastatic Colorectal Cancer (clinicaltrials.gov) - Nov 7, 2023
P1/2, N=5, Terminated, Sponsor: Eisai Inc.
No abstract available Completed --> Terminated; The study was terminated early as the combination of E7820 and FOLFIRI was deemed to be not tolerable, hence no efficacy analysis was conducted.
- Venclexta (venetoclax) / Roche, AbbVie, Walter and Eliza Hall Institute, E7820 / Eisai
E7820, an Anti-Cancer Sulfonamide, in Combination with Venetoclax in Patients with Splicing Factor Mutant Myeloid Malignancies: A Phase II Clinical Trial (SDCC - Halls G-H) - Nov 3, 2023 - Abstract #ASH2023ASH_1960;
P2
Secondary endpoints include overall and event-free survival. Correlative biomarker and pharmacodynamic parameters will be assessed as exploratory endpoints including effects on RBM39 protein levels, changes in global and key target splicing events, and evaluation of DCAF15 mRNA levels and response to therapy.
- ||||| E7820 / Eisai
Trial termination, Metastases: Irinotecan Plus E7820 Versus FOLFIRI in Second-Line Therapy in Patients With Locally Advanced or Metastatic Colon or Rectal Cancer (clinicaltrials.gov) - Nov 25, 2022
P1/2, N=82, Terminated, Sponsor: Eisai Inc.
Correlative biomarker and pharmacodynamic parameters will be assessed as exploratory endpoints including effects on RBM39 protein levels, changes in global and key target splicing events, and evaluation of DCAF15 mRNA levels and response to therapy. Completed --> Terminated; The study was terminated by the Sponsor due to E7820 plus irinotecan being potentially inferior to FOLFIRI
- E7820 / Eisai
A Phase II Clinical Trial of E7820 for Patients with Relapsed/Refractory Myeloid Malignancies with Mutations in Splicing Factor Genes (ENMCC - Hall D) - Nov 4, 2022 - Abstract #ASH2022ASH_5893;
P2
Although the efficacy of E7820 was limited, evidence of target engagement combined with the tolerability of RBM39 degradation serves as a proof of concept that splicing factor mutant disease can be targeted in humans. Combination therapies of E7820 with standard of care agents and the use of newer generation RBM39 degraders are in development.
- E7820 / Eisai
Attenuation of Graft-Versus-Host-Disease Via Genetic or Pharmacologic Inhibition of the RNA Splicing Factor RBM39 (ENMCC - 391-392) - Nov 4, 2022 - Abstract #ASH2022ASH_3452;
P2
Our results identify cell-type specific roles for RBM39 in hematopoiesis and immune cells and suggest a therapeutic approach for GVHD via direct modulation of RNA splicing. Of note, as the RBM39 degrader E7820 is currently in phase II clinical trials for relapsed myeloid neoplasms, our previous studies and this data identify a treatment for myeloid neoplasms in the post-transplant setting, where RBM39 degraders mediate both direct and immune-mediated anti-tumor effects while also attenuating GVHD via modulation of RNA splicing in T cells.
- | methotrexate / Generic mfg.
Journal: Role of integrin α2 in methotrexate-induced epithelial-mesenchymal transition in alveolar epithelial A549 cells. (Pubmed Central) - Oct 25, 2022
Finally, E7820, an ITGA2 inhibitor, suppressed MTX-induced EMT-related phenotypic changes, such as morphology and mRNA and protein expression of α-smooth muscle actin, a representative EMT marker. These findings suggest that ITGA2 may play a key role in MTX-induced EMT in alveolar epithelial cells.
- | E7820 / Eisai
Journal: Integrin alpha 2 is associated with tumor progression and postoperative recurrence in non-small cell lung cancer. (Pubmed Central) - Sep 25, 2022
These findings suggest that ITGA2 may play a key role in MTX-induced EMT in alveolar epithelial cells. Integrin alpha 2 may play a significant role in lung cancer adhesion and migration, and may lead to a higher risk of recurrence.
- ||| E7820 / Eisai
We also have E7820, an RBM39 degrader for splicing mutants open @MSKCancerCenter and @SylvesterCancer https://t.co/N6W2j4cBXB (Twitter) - May 20, 2022
- | E7820 / Eisai
Journal: Targeted protein degradation and regulation with molecular glue: past and recent discoveries. (Pubmed Central) - May 19, 2022
An immunomodulatory imide drug, thalidomide, and its derivatives have been used in the clinic and are a class of molecular glue that induces degradation of several neo-substrates. In this review, we summarize the development of molecular glues and share our opinions on the identification of novel molecular glues in an attempt to promote the concept and inspire further investigations.
- | E7820 / Eisai
Preclinical, Journal: The small-molecule protein ligand interface stabiliser E7820 induces differential cell line specific responses of integrin α2 expression. (Pubmed Central) - Oct 22, 2021
The results presented here indicate that E7820 may not be suitable to treat certain malignancies of musculoskeletal origin, due to the increase in integrin α2 expression it may induce. Further investigation of the differential functioning of CAPERα and the integrin α2 promoter in cells of various origin would however be necessary to more clearly differentiate between cell lines that will positively respond to E7820 from those that will not.
- || E7820 / Eisai
New P2 trial: A Study of E7820 in People With Bone Marrow (Myeloid) Cancers (clinicaltrials.gov) - Aug 27, 2021
P2, N=38, Recruiting, Sponsor: Memorial Sloan Kettering Cancer Center
- | E 7820 / Eisai, indisulam (E7070) / Eisai
Journal: Aryl Sulfonamides Induce Degradation of Aryl Hydrocarbon Receptor Nuclear Translocator through CRL4 E3 Ligase. (Pubmed Central) - Aug 4, 2021
In line with this finding, aryl sulfonamides inhibited the transcriptional activities of HIFs and AhR associated with ARNT. Our results collectively support novel regulatory roles of aryl sulfonamides in both hypoxic and xenobiotic responses.
- | ifosfamide / Generic mfg., tamoxifen / Generic mfg.
Biomarker, Journal, Tumor microenvironment, Pan tumor: A pan-cancer analysis of the HER family gene and their association with prognosis, tumor microenvironment, and therapeutic targets. (Pubmed Central) - Apr 10, 2021
Our results collectively support novel regulatory roles of aryl sulfonamides in both hypoxic and xenobiotic responses. These findings may elucidate the roles played by HER family gene in cancer progression and providing insights for further investigation of the HER family gene as potential targets in pan-cancer.
- | paclitaxel / Generic mfg.
Journal: Reversing microtubule-directed chemotherapeutic drug resistance by co-delivering α2β1 inhibitor and paclitaxel with nanoparticles in ovarian cancer. (Pubmed Central) - Oct 1, 2020
Applying MPEG-PLA to co-encapsulate integrin α2β1 inhibitor E7820 and MDCDs could effective reverse the MDCDs resistance, resulting in enhance anticancer effects while avoiding potential systemic toxicity in vitro and in vivo. In conclusion, the expression of integrin α2β1 contributes to the MDCDs resistance, while applying E7820 combination treatment by MPEG-PLA nanoparticles could reverse the resistance.
- | E 7820 / Eisai
Journal: Structural Basis and Kinetic Pathway of RBM39 Recruitment to DCAF15 by a Sulfonamide Molecular Glue E7820. (Pubmed Central) - Jun 28, 2020
Our kinetic studies revealed that aryl sulfonamide and RBM39 bind to DCAF15 in a synergistic manner. The structural and kinetic studies confirm aryl sulfonamides as molecular glues in the recruitment of RBM39 and provide a framework for future efforts to utilize DCAF15 to degrade other proteins of interest.
- | E 7820 / Eisai
Journal: Structural complementarity facilitates E7820-mediated degradation of RBM39 by DCAF15. (Pubmed Central) - Apr 22, 2020
We show that DCAF15 adopts a new fold stabilized by DDA1, and that extensive protein-protein contacts between the ligase and substrate mitigate low affinity interactions between aryl-sulfonamides and DCAF15. Our data demonstrate how aryl-sulfonamides neo-functionalize a shallow, non-conserved pocket on DCAF15 to selectively bind and degrade RBM39 and the closely related splicing factor RBM23 without the requirement for a high-affinity ligand, which has broad implications for the de novo discovery of molecular glue degraders.
- | Erbitux (cetuximab) / Eli Lilly, EMD Serono, Opdivo (nivolumab) / Ono Pharma, BMS
Biomarker, Journal, PD(L)-1 Biomarker: Integrins as A New Target for Cancer Treatment. (Pubmed Central) - Mar 2, 2020
Despite the great progress in the development of targeted therapies for different types of cancer utilizing monoclonal antibodies (e.g., cetuximab for colorectal cancer and head and neck cancer therapy), kinase inhibitors (e.g., sorafenib for kidney cancer and gastrointestinal stromal tumours therapy), and immunomodulatory treatments (e.g., nivolumab and pembrolizumab for melanoma therapy and lung cancer therapy), there is still a need to search for new, more effective treatments...There are different groups of anti-integrin drugs: monoclonal antibodies (e.g., abituzumab) and other such as cilengitide, E7820 and MK-0429...Studies have shown that patient selection using biomarkers might improve the efficacy of anti-integrin cancer treatment. Many preclinical models have demonstrated promising results using integrin visualization for cancer detection and treatment efficacy monitoring; however, these strategies require further evaluation in humans.
- | E 7820 / Eisai
Journal: Collagen facilitates the colorectal cancer stemness and metastasis through an integrin/PI3K/AKT/Snail signaling pathway. (Pubmed Central) - Aug 30, 2019
Many preclinical models have demonstrated promising results using integrin visualization for cancer detection and treatment efficacy monitoring; however, these strategies require further evaluation in humans. Combining E7820 and chemotherapeutic agents to block the integrin α2β1/PI3K/AKT/Snail signaling pathway revealed dramatic enhanced tumor suppression and provided an innovative approach for clinical colorectal cancer treatment.
- | E7820 / Eisai
Trial completion, Trial completion date: An Open-label, Dose Escalation, Pharmacodynamic, Pharmacokinetic, and Effect of Food Phase 1 Study of E7820 to Determine the Maximum Tolerated Dose Following Twice Daily Oral Administration in Subjects With Unresectable Solid Tumors (clinicaltrials.gov) - Feb 6, 2018
P1, N=41, Completed, Sponsor: Eisai Inc.
Combining E7820 and chemotherapeutic agents to block the integrin α2β1/PI3K/AKT/Snail signaling pathway revealed dramatic enhanced tumor suppression and provided an innovative approach for clinical colorectal cancer treatment. Active, not recruiting --> Completed | Trial completion date: Dec 2018 --> Nov 2017
- | E7820 / Eisai
Biomarker, Trial completion, Metastases: A Phase II Study of the Safety and Efficacy of E7820 Plus Cetuximab in Colorectal Cancer, Preceded by a Run-in Study in Advanced Solid Tumors (clinicaltrials.gov) - Sep 14, 2017
P2, N=41, Completed, Sponsor: Eisai Inc.
Active, not recruiting --> Completed | Trial completion date: Dec 2018 --> Nov 2017 Active, not recruiting --> Completed
- |||| E7820 / Eisai
Trial completion, Trial primary completion date, Metastases: Irinotecan Plus E7820 Versus FOLFIRI in Second-Line Therapy in Patients With Locally Advanced or Metastatic Colon or Rectal Cancer (clinicaltrials.gov) - Aug 28, 2017
P1/2, N=82, Completed, Sponsor: Eisai Inc.
Active, not recruiting --> Completed Active, not recruiting --> Completed | Trial primary completion date: Sep 2014 --> Jun 2015
- E7820 / Eisai
Trial primary completion date: An Open-label, Dose Escalation, Pharmacodynamic, Pharmacokinetic, and Effect of Food Phase 1 Study of E7820 to Determine the Maximum Tolerated Dose Following Twice Daily Oral Administration in Subjects With Unresectable Solid Tumors (clinicaltrials.gov) - Mar 31, 2016
P1, N=41, Active, not recruiting, Sponsor: Eisai Inc.
Active, not recruiting --> Completed | Trial primary completion date: Sep 2014 --> Jun 2015 Trial primary completion date: Jul 2014 --> Apr 2014
- | E7820 / Eisai
Biomarker, Enrollment closed, Enrollment change, Trial initiation date, Trial primary completion date, Metastases: A Phase II Study of the Safety and Efficacy of E7820 Plus Cetuximab in Colorectal Cancer, Preceded by a Run-in Study in Advanced Solid Tumors (clinicaltrials.gov) - Jan 28, 2016
P2, N=41, Active, not recruiting, Sponsor: Eisai Inc.
Trial primary completion date: Jul 2014 --> Apr 2014 Completed --> Active, not recruiting | N=99 --> 41 | Initiation date: Aug 2006 --> Sep 2007 | Trial primary completion date: May 2010 --> Dec 2009
- E7820 / Eisai
Enrollment change: Dosing and Safety Study of E7820 in Patients With a Malignant Solid Tumor or Lymphoma (clinicaltrials.gov) - Dec 24, 2014
P1, N=37, Completed, Sponsor: Eisai Inc.
Completed --> Active, not recruiting | N=99 --> 41 | Initiation date: Aug 2006 --> Sep 2007 | Trial primary completion date: May 2010 --> Dec 2009 N=60 --> 37
- | E7820 / Eisai
Trial completion: Dosing and Safety Study of E7820 in Patients With a Malignant Solid Tumor or Lymphoma (clinicaltrials.gov) - Dec 21, 2014
P1, N=37, Completed, Sponsor: Eisai Inc.
N=60 --> 37 No longer recruiting --> Completed
- ||| E7820 / Eisai
Enrollment closed, Metastases: Irinotecan Plus E7820 Versus FOLFIRI in Second-Line Therapy in Patients With Locally Advanced or Metastatic Colon or Rectal Cancer (clinicaltrials.gov) - Apr 28, 2014
P1/2, N=95, Active, not recruiting, Sponsor: Eisai Inc.
No longer recruiting --> Completed Recruiting --> Active, not recruiting
- | E7820 / Eisai
New P1 trial: An Open-label, Dose Escalation, Pharmacodynamic, Pharmacokinetic, and Effect of Food Phase 1 Study of E7820 to Determine the Maximum Tolerated Dose Following Twice Daily Oral Administration in Subjects With Unresectable Solid Tumors (clinicaltrials.gov) - Jan 21, 2013
P1, N=41, Active, not recruiting, Sponsor: Eisai Inc.
- |||| E7820 / Eisai
Biomarker, Trial completion, Metastases: A Phase II Study of the Safety and Efficacy of E7820 Plus Cetuximab in Colorectal Cancer, Preceded by a Run-in Study in Advanced Solid Tumors (clinicaltrials.gov) - Dec 5, 2012
P2, N=99, Completed, Sponsor: Eisai Inc.
Recruiting --> Active, not recruiting Active, not recruiting --> Completed
- E7820 / Eisai
Trial completion, Metastases: FOLFIRI Alone Versus FOLFIRI Plus Bevacizumab Versus FOLFIRI Plus E7820 as Second-Line Therapy in Patients With Locally Advanced or Metastatic Colorectal Cancer (clinicaltrials.gov) - Apr 3, 2012
P1/2, N=5, Completed, Sponsor: Eisai Inc.
Active, not recruiting --> Completed Terminated --> Completed
- ||| E7820 / Eisai
Trial initiation date, Metastases: Irinotecan Plus E7820 Versus FOLFIRI in Second-Line Therapy in Patients With Locally Advanced or Metastatic Colon or Rectal Cancer (clinicaltrials.gov) - Jan 5, 2012
P1/2, N=95, Active, not recruiting, Sponsor: Eisai Inc.
Terminated --> Completed Initiation date: Apr 2011 --> Oct 2011