Delving into the Latest Updates on Irinotecan-eluting beads with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

DEBIRI, Irinotecan bead, PARAGON Bead

+ [2]

Target

Top I

Action

inhibitors

Mechanism

TOP1 inhibitors(DNA topoisomerase I inhibitors)

Therapeutic Areas

NeoplasmsNervous System DiseasesDigestive System Disorders+ [1]

Active Indication

Bile Duct NeoplasmsColorectal CancerGlioma+ [1]

Inactive Indication-

Originator Organization

Singapore General Hospital Pte Ltd.

Active Organization

Singapore General Hospital Pte Ltd.

Inactive Organization-

License Organization-

Drug Highest PhaseApproved

First Approval Date-

Regulation-

Login to view timeline

Structure/Sequence

Molecular FormulaC33H38N4O6

InChIKeyUWKQSNNFCGGAFS-XIFFEERXSA-N

CAS Registry97682-44-5

In order to extract the profiles of patients receiving DEBIRI treatment at best, the investigators proposed the establishment of a national prospective cohort to collect information on the greatest number of patients treated with DEBIRI. This cohort will allow a better understanding of the effectiveness, tolerance, feasibility and differences of practices at national level for this approach. These data will assist in the development of clinical trials in situations that appear to be most promising in clinical practice.

Start Date03 Feb 2016

Sponsor / Collaborator

Fédération Francophone de la Cancérologie Digestive

NCT02110953

/ TerminatedPhase 1IIT

Phase I Study of Drug-Eluting Irinotecan Beads (DEBIRI) in Refractory Metastatic Colorectal Cancer With Liver-Only or Liver-Predominant Disease

This phase I trial studies the side effects and best dose of irinotecan-eluting beads in treating patients with colon or rectal cancer that has spread to the liver and does not respond to treatment with standard therapy. Irinotecan-eluting beads are tiny beads that have been loaded with irinotecan hydrochloride, a chemotherapy drug. Drugs used in chemotherapy, such as irinotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or stopping them from dividing. This treatment delivers the chemotherapy directly to the tumor area inside the liver instead of to the whole body as with systemic delivery of the drug. Irinotecan-eluting beads may work better that standard chemotherapy in treating patients with colon or rectal cancer that has spread to the liver.

Start Date29 Jan 2016

Sponsor / Collaborator

The Fox Chase Cancer Center

[+1]

100 Clinical Results associated with Irinotecan-eluting beads

Login to view more data

100 Translational Medicine associated with Irinotecan-eluting beads

Login to view more data

100 Patents (Medical) associated with Irinotecan-eluting beads

Login to view more data

9,055

Literatures (Medical) associated with Irinotecan-eluting beads

03 May 2025·Journal of Biomolecular Structure and Dynamics

Synergy between human DNA ligase I and topoisomerase 1 unveils new therapeutic strategy for the management of colorectal cancer

Article

Author: Sashidhara, Koneni V. ; Maurya, Pooja ; Banerjee, Dibyendu ; Siddiqi, Mohammad Imran ; Gupta, Sampa ; Krishna, Shagun ; Rawat, Rohit Singh

DNA topoisomerase 1 (Topo 1) is a pivotal player in various DNA processes, including replication, repair, and transcription. It serves as a target for anticancer drugs like camptothecin and its derivatives (Topotecan and SN-38/Irinotecan). However, the emergence of drug resistance and the associated adverse effects, such as alopecia, anemia, dyspnea, fever, chills, and painful or difficult urination, pose significant challenges in Topo 1-targeted therapy, necessitating urgent attention. Human DNA Ligase 1 (hLig I), recognized primarily for its role in DNA replication and repair of DNA breaks, intriguingly exhibits a DNA relaxation activity akin to Topo 1. This raised the hypothesis that hLig I might compensate for Topo 1 inhibition, contributing to resistance against Topo 1 inhibitors. To explore this hypothesis, we assessed the efficacy of hLig I inhibition alone and in combination with Topo 1 in cancer cells. As anticipated, the overexpression of hLig I was observed after Topo 1 inhibition in colorectal cancer cells, affirming our hypothesis. Previously identified as an inhibitor of hLig I's DNA relaxation activity, compound 27 (C 27), when combined with Topotecan, demonstrated a synergistic antiproliferative effect on colorectal cancer cells. Notably, cells with downregulated hLig I (via siRNA, inhibitors, or genetic manipulation) exhibited significantly heightened sensitivity to Topotecan. This observation strongly supports the concept that hLig I contribute to resistance against clinically relevant Topo 1 inhibitors in colorectal cancers. In conclusion, our findings offer evidence for the synergistic impact of combining hLig I inhibitors with Topotecan in the treatment of colorectal cancers, providing a promising strategy to overcome resistance to Topo 1 inhibitors.

11 Apr 2025·ACS Pharmacology & Translational Science

PSP205, a Novel Phenyl Sulfonyl Piperidine, Induces Apoptotic Cell Death in Colon Cancer by Modulating Coat Protein Complex-Mediated Vesicle Trafficking

Article

Author: Neamati, Nouri ; Samanta, Soma ; Roy, Joyeeta ; Ljungman, Mats ; Debnath, Bikash

The endoplasmic reticulum (ER) stress and autophagic pathways offer attractive targets for the development of new cancer drugs. Here, we identified a novel phenyl sulfonyl piperidine, PSP205, that induces prolonged ER-stress-mediated autophagy and apoptosis in colon cancer cells. Transcriptome analysis of cells exposed to PSP205 unveiled transcriptional upregulation of genes associated with the ER stress response or unfolded protein response (UPR), in addition to vesicle transport. Among the top upregulated genes, DNAJB9, XBP1, PDIA4, HSPA5, SEC24D, and SEC11C are implicated in ER stress. Gene set enrichment analysis revealed the enrichment of gene sets involved in the UPR, mTORC1 signaling, hypoxia, the P53 pathway, apoptosis, and the ER-Golgi-vesicle-mediated transport pathway. Mechanistic studies showed that PSP205 acts on the IRE1-TRAF2-JNK pathway to modulate autophagic flux, leading to macroautophagy, ER-phagy, and deformation of Golgi. Our study also demonstrated that PSP205 decreases the expression of the COPI coat complex subunit beta 2 (COPB2) in the presence of COPB2 siRNA. Furthermore, PSP205 synergistically killed colon cancer cells in combination with proteasome and topoisomerase inhibitors. Cumulatively, our findings suggest that PSP205 targets cancer cells via a novel mechanism, specifically by decreasing the level of COPB2, which has not been extensively studied in the context of cancer therapy development and warrants further investigation.

01 Apr 2025·Bioorganic Chemistry

Design, synthesis, and molecular dynamics-driven evaluation of quinoline-sulfonamide derivatives as potent and selective EGFR inhibitors with promising anti-cancer efficacy and safety profiles

Article

Author: Elkelesh, Islam A ; Elgohary, Mohamed K ; Khaleel, Eman F ; Eldehna, Wagdy M ; Elkotamy, Mahmoud S ; Abdel-Aziz, Hatem A ; Alkabbani, Mahmoud Abdelrahman

The creation of new molecules that target EGFR is essential for the progression of cancer treatment. This study synthesized and evaluated 16 quinoline-sulfonamide derivatives for their potential as anti-cancer agents. Compound 8c, which contains a methoxy group on the benzenesulfonamide tail, exhibited notable EGFR inhibitory activity (IC₅₀ = 0.161 µM), similar to that of Erlotinib (IC₅₀ = 0.142 µM). Compound 8c demonstrated enhanced in-vitro cytotoxicity against HCT-116, MCF-7, HeLa, and HepG2 cancer cell lines. Studies on the cell cycle and apoptosis demonstrated that compound 8c caused G1/S arrest and markedly enhanced apoptosis in HepG2 cells. In-vivo, compound 8c demonstrated comparable and/or superior efficacy compared to doxorubicin in decreasing tumor volume, weight, TNF-alpha, and COX-2 levels in the SEC model, alongside improved histopathological and immunohistochemical results. Molecular docking and dynamic simulations confirmed its stable binding to EGFR, exhibiting superior stability metrics in comparison to Erlotinib. Pharmacokinetic and toxicity evaluations indicated that compound 8c exhibits favorable drug-like properties and a safer toxicity profile. These findings identify compound 8c as a potential candidate for the development of safe and effective anti-cancer therapies, necessitating additional preclinical investigations.

100 Deals associated with Irinotecan-eluting beads

Login to view more data

External Link

KEGG	Wiki	ATC	Drug Bank
-	-	L01XX19	-

R&D Status

10 top approved records.

Login

to view more data

Indication	Country/Location	Organization	Date
Bile Duct Neoplasms	-	Singapore General Hospital Pte Ltd.	-
Colorectal Cancer	-	Singapore General Hospital Pte Ltd.	-
Glioma	-	Singapore General Hospital Pte Ltd.	-
Liver Cancer	-	Singapore General Hospital Pte Ltd.	-

Login to view more data

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01839877 (FFCD-1201 \| FFCD 1201, CTgov)	Phase 2	colon cancer liver metastasis	58	systemic FOLFOX+DEBIRI	(cnjsymwiii) = xdmwsoetnr jkkrcsrxyh (jnlgpmjcmh, pdnldmbkpi - lxovkvpeqg) View more	-	08 Oct 2024
ASCO2023	Not Applicable	Colorectal Liver Metastases	101	Irinotecan-eluting HepaSphere chemoembolization plus HAIC	(xzuhbdckpn) = 27.7% rmpuvkdifx (rndoofvnui ) View more	Positive	31 May 2023
NCT01839877 (FFCD-1201, Pubmed \| Br J Cancer)	Phase 2	Colorectal Liver Metastases First line	-	DEBIRI plus mFOLFOX6	(hrzeafeqqh) = wzkojekpeq ovisgskiay (phruadnpaf ) View more	-	18 Aug 2020
NCT02015754 (CTgov)	Phase 2	Colorectal Liver Metastases	14	TACE+DEBIRI	jichtaeajd(wxsecnuqpv) = wercqjlnsv svecbtdoyl (ixvpdxbnxa, zijxltzftn - ssmgqggfwo) View more	-	22 Mar 2018
ASCO_GI2015	Phase 2	Colorectal Liver Metastases	-	DEBIRI	(baaeqajwij) = vadlcpueqx edfgffvtqo (dfrcpzttlr ) View more	Positive	20 Jan 2015
ASCO_GI2013	Not Applicable	Colorectal Liver Metastases Neoadjuvant	10	DEBIRI	wbcdaocyfa(mzkgjtzzmf) = xipdixvwij riugwdmczk (vqadmmrkxj ) View more	-	01 Feb 2013
ASCO_GI2012	Phase 3	Colorectal Liver Metastases	74	Polyvinyl alcohol microspheres loaded with irinotecan	ogxrfmhwjz(luvhnlqqus) = aofwddlcjb sjzfmjuuxh (egkgjprmem ) View more	Positive	01 Feb 2012
ASCO_GI2012	Phase 3	Colorectal Liver Metastases	74	Systemic chemotherapy	ogxrfmhwjz(luvhnlqqus) = svqnkqgnfq sjzfmjuuxh (egkgjprmem ) View more	Positive	01 Feb 2012
ASCO2011	Not Applicable	Lung Cancer	16	drug-eluting beads (Segmental pulmonary arterial chemoembolization (SPACE) + RFA)	czjhhqshyy(ccxvztbnbu) = 1 bronco-pleural fistula (5%) pjmazfobrq (retnzoglxp ) View more	-	20 May 2011
ASCO2010	Not Applicable	Hepatocellular Carcinoma	56	DEB-TACE with epirubicin drug-eluting beads	(gznnatggag) = qrfthkwuqk ucahdsnztw (vdhfceqalo ) View more	-	20 May 2010
PRECISION V (ASCO2010)	Not Applicable	Hepatocellular Carcinoma	212	PRECISION TACE with drug-eluting beads (DC Beads)	(gtjdsjaycu) = dxjbnvjwyq ihkxyedadi (kihhcnmqtk )	-	20 May 2010
PRECISION V (ASCO2010)	Not Applicable	Hepatocellular Carcinoma	212	PRECISION TACE with drug-eluting beads (conventional transarterial chemoembolization (cTACE))	(gtjdsjaycu) = lgdlcqkkjz ihkxyedadi (kihhcnmqtk )	-	20 May 2010