Delving into the Latest Updates on E-7820 with Synapse

Overview

Basic Info

Drug Type

Degradable Molecular Glue

Synonyms

+ [1]

Target

CD49b x RBM39

Action

inhibitors

Mechanism

CD49b inhibitors(integrin subunit alpha 2 inhibitors), RBM39 inhibitors(RNA binding motif protein 39 inhibitors)

Therapeutic Areas

NeoplasmsHemic and Lymphatic DiseasesOther Diseases+ [3]

Active Indication

Acute Myeloid LeukemiaChronic Myelomonocytic LeukemiaMyelodysplastic Syndromes+ [3]

Inactive Indication

Advanced Colorectal AdenocarcinomaAdvanced Malignant Solid NeoplasmColonic Cancer+ [4]

Originator Organization

Eisai Co., Ltd.

Active Organization

Cancer Therapy & Research Center Endowment

Eisai, Inc.

Inactive Organization-

License Organization-

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC17H12N4O2S

InChIKeyLWGUASZLXHYWIV-UHFFFAOYSA-N

CAS Registry289483-69-8

The researchers are doing this study to find out whether E7820 is an effective treatment for people with relapsed/refractory myeloid cancers with mutations in splicing factor genes. Participants will have acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), or chronic myelomonocytic leukemia (CMML).

Start Date13 Aug 2021

Sponsor / Collaborator

Memorial Sloan Kettering Cancer Center

[+1]

NCT01347645

/ TerminatedPhase 1/2

An Open-Label, Multicenter, Randomized Phase Ib/II Study of Irinotecan Plus E7820 Versus FOLFIRI in Second-Line Therapy in Patients With Locally Advanced or Metastatic Colon or Rectal Cancer

The purpose of the Phase Ib portion is to find out the highest dose of study drug that can safely be given when tested in a small group of subjects.
The purpose of the Phase II portion is to find out how safe the study drug is when taken at the highest dose in a larger group of subjects.

Start Date30 Sep 2011

Sponsor / Collaborator

Eisai, Inc.

[+1]

100 Clinical Results associated with E-7820

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100 Translational Medicine associated with E-7820

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100 Patents (Medical) associated with E-7820

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45

Literatures (Medical) associated with E-7820

17 Mar 2025·Oncogene

Targeting RBM39 suppresses tumor growth and sensitizes osteosarcoma cells to cisplatin

Article

Author: Kang, Tiebang ; Zhang, Xia ; Zheng, Lisi ; Zeng, Cuiling ; Zhong, Li ; Wang, Jingxuan ; Zhang, Changlin ; Chen, Wanqi ; Zhang, Ruhua ; Lv, Dongming

Osteosarcoma is one of the most common malignant primary bone tumors and lacks effective therapeutic targets. Recent studies have reported that RNA binding proteins (RBPs) could serve as promising therapeutic targets for cancers, as their critical roles in transcriptional regulation and RNA splicing. Nevertheless, the potential of pharmacologically inhibiting RBPs as a therapeutic strategy for patients with osteosarcoma remains unclear. In this study, we identified the RNA-binding protein RBM39 as a promising therapeutic target for osteosarcoma. RBM39 is essential for cell viability, and a higher expression of RBM39 was associated with poor prognosis in osteosarcoma. Mechanistically, RBM39 served as a coactivator of c-Jun to transcriptionally upregulate DKK1, leading to the activation of the GSK3β-NF-κB pathway. Importantly, our results reveal that the pharmacological depletion of RBM39 by using the anti-cancer aryl sulfonamide (E7820), a drug known for its oral bioavailability and safe administration, effectively represses osteosarcoma growth and sensitizes osteosarcoma cells to cisplatin treatment both in vitro and in vivo. Our findings unveil the crucial role of RBM39 in modulating tumor growth and cisplatin sensitivity in osteosarcoma cells, suggesting that the combination of aryl sulfonamides with cisplatin may benefit patients with osteosarcoma.

01 Dec 2024·Genes & Genomics

Recent advances in anticancer mechanisms of molecular glue degraders: focus on RBM39-dgrading synthetic sulfonamide such as indisulam, E7820, tasisulam, and chloroquinoxaline sulfonamide

Review

Author: Kim, Joo-Young ; Jang, Ji Hoon ; Lee, Tae-Jin

Synthetic sulfonamide anticancer drugs, including E7820, indisulam, tasisulam, and chloroquinoxaline sulfonamide, exhibit diverse mechanisms of action and therapeutic potential, functioning as molecular glue degraders. E7820 targets RBM39, affecting RNA splicing and angiogenesis by suppressing integrin α2. Phase I studies have demonstrated some stability in advanced solid malignancies; however, further efficacy studies are required. Indisulam causes G1 cell cycle arrest and delays the G1/S transition by modulating splicing through RBM39 degradation via DCAF15. Despite its limited initial efficacy, it shows promise in combination therapies, particularly for hematopoietic malignancies and gliomas. Tasisulam inhibits VEGF signaling, suppresses angiogenesis, and induces apoptosis. Although early trials indicated broad activity, safety concerns have halted its development. Chloroquinoxaline sulfonamide, initially investigated for cell cycle arrest and topoisomerase II inhibition, was discontinued owing to its limited efficacy and toxicity, despite promising initial results. Recent studies revealed the structural interaction of E7820 with DCAF15 and RBM39, although phase II trials on myeloid malignancies have shown limited efficacy. Indisulam is effective against glioblastoma and neuroblastoma, with potential synergy in combination therapies and metabolic disruption. Recent research on tasisulam reveals its potential in cancer therapy by targeting RBM39 degradation through DCAF15-mediated pathways. Understanding these mechanisms could lead to new treatments that affect alternative splicing and improve cancer therapies Overall, although these drugs exhibit promising mechanisms of action, further research is required to optimize their clinical efficacy and safety.

01 Dec 2023·Leukemia

E7820, an anti-cancer sulfonamide, degrades RBM39 in patients with splicing factor mutant myeloid malignancies: a phase II clinical trial

Article

Author: Hogg, Simon J ; Mi, Xiaoli ; Taylor, Justin ; Lu, Sydney X ; Bourcier, Jessie ; Wysocki, Mateusz ; Stahl, Maximilian ; Chaudhry, Sana ; Watts, Justin ; Rahman, Jahan ; Bewersdorf, Jan Philipp ; Stein, Eytan M ; Abdel-Wahab, Omar ; Chandhok, Namrata Sonia ; Totiger, Tulasigeri M ; Derkach, Andriy

100 Deals associated with E-7820

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External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB12505

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Rectal Cancer	Phase 2	Argentina	Eisai, Inc.	30 Sep 2011
Metastatic Colorectal Carcinoma	Phase 2	Russia	Eisai, Inc.	04 Mar 2010
Metastatic Colorectal Carcinoma	Phase 2	United States	Eisai, Inc.	04 Mar 2010
Metastatic Colorectal Carcinoma	Phase 2	Ukraine	Eisai, Inc.	04 Mar 2010
Metastatic Colorectal Carcinoma	Phase 2	Australia	Eisai, Inc.	04 Mar 2010
Metastatic Colorectal Carcinoma	Phase 2	India	Eisai, Inc.	04 Mar 2010
Advanced Colorectal Adenocarcinoma	Phase 1	Canada	Eisai, Inc.	24 Sep 2007
Advanced Colorectal Adenocarcinoma	Phase 1	United States	Eisai, Inc.	24 Sep 2007
Advanced Malignant Solid Neoplasm	Phase 1	Canada	Eisai, Inc.	24 Sep 2007
Advanced Malignant Solid Neoplasm	Phase 1	United States	Eisai, Inc.	24 Sep 2007

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01347645 (CTgov)	Phase 1/2	Rectal Cancer \| Colonic Cancer	82	E7820+irinotecan (Phase 1b, All Participants)	nwhstuqnax(zorasxovgw) = krpcjiclqi sgcmxluzsf (blyqxsbgmy, azkvxedrrm - jljcwdycjz)	-	25 Nov 2022
NCT01347645 (CTgov)	Phase 1/2	Rectal Cancer \| Colonic Cancer	82	E7820+Irinotecan (Phase 2: E7820 70 mg + Irinotecan)	(gqmmjccejp) = zvehyxqvmm dbibtpswsn (hoewbcuhmq, nwziwgtteq - zpteuhuvhs) View more	-	25 Nov 2022
NCT05024994 (ASH 12022 \| ASH 22022) Manual	Phase 2	Myeloid Tumor	12	E7820	(bzhuxvmahd) = gwajhuylpc svnaomztat (fqsmihsxje, 1.5 - NR) View more	Positive	15 Nov 2022
NCT01773421 (CTgov)	Phase 1	Advanced Malignant Solid Neoplasm \| Unresectable Solid Neoplasm	45	E7820 (Treatment Phase Part A: E7820 50 mg Fed)	nhjwctqafk(sjfzhubeqt) = exchiestvd dlyiqsllqg (svtjrkouuv, xvtculwscw - mdgglefkyo) View more	-	18 Jan 2020
NCT01773421 (CTgov)	Phase 1		45	E7820 (Treatment Phase Part A: E7820 50 mg Fasted)	nhjwctqafk(sjfzhubeqt) = udprmvifgj dlyiqsllqg (svtjrkouuv, xiiqpgrzwn - pcqmgjfssw) View more	-	18 Jan 2020
ASCO2010	Phase 2	Refractory Colorectal Carcinoma \| Metastatic Colorectal Carcinoma	28	E7820	hffhmxltxb(xrwgfsehbk) = E7820 related-grade 3 toxicities included increased AST (3/28, 11%), increased ALT (2/28, 7%), and diarrhea, hypomagnesemia, decreased glomerular filtration rate and elevated creatinine (1/28, 3% in each) mefosxdwvn (osfffgztku ) View more	Negative	20 May 2010
ASCO2008	Phase 1	HR-positive/HER2-low Solid Tumors	17	E7820	(bmgqnvqshc) = dhamgbtekk rmdskmfuhk (jrszhxtcbe ) View more	-	20 May 2008
ASCO2006	Phase 1	Solid tumor	30	E7820	(lnunwhalqe) = vcyerjeumx cskqdppgib (qipnykpjyk )	-	20 Jun 2006