Delving into the Latest Updates on Itarnafloxin with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Quarfloxin

+ [1]

Target

G4

Mechanism

G4 inhibitors(G-Quadruplex inhibitors)

Therapeutic Areas

NeoplasmsImmune System DiseasesHemic and Lymphatic Diseases

Active Indication-

Inactive Indication

Advanced Malignant Solid NeoplasmCarcinoid TumorChronic lymphocytic leukaemia refractory+ [3]

Originator Organization

Cylene Pharmaceuticals, Inc.

Active Organization-

Inactive Organization

TetraGene LLC

Cylene Pharmaceuticals, Inc.

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC35H33FN6O3

InChIKeyWOQIDNWTQOYDLF-CGAIIQECSA-N

CAS Registry865311-47-3

This is a Phase 2, open-label, multicenter, efficacy and safety study of quarfloxin in patients with low or intermediate grade neuroendocrine cancer. The purpose of this study is to evaluate the rate of clinical benefit response to quarfloxin treatment including the reduction in secretory symptoms of flushing and/or diarrhea or the reduction quantifiable hormones or other biochemical tumor markers.

Start Date01 Oct 2008

Sponsor / Collaborator

Cylene Pharmaceuticals, Inc.

NCT00955292

/ TerminatedPhase 1

A Phase I, Multicenter, Open-label, Dose-Escalation, Safety, Pharmacokinetic and Pharmacodynamic Study of Quarfloxin Administered Intravenously Weekly for Three Weeks of a Four Week Cycle in Patients With Advanced Solid Tumors or Lymphomas

This phase 1 study of quarfloxin (CX-3543) is designed to test the safety, tolerability, and highest safe dose of this drug when administered intravenously weekly for three weeks of a four week cycle in patients with advanced solid tumors.

Start Date01 Jul 2007

Sponsor / Collaborator

Cylene Pharmaceuticals, Inc.

NCT00485966

/ WithdrawnPhase 2

A Phase 2, Multi-Center, Open Label Study Evaluating Clinical Efficacy, Safety, and Pharmacodynamic Effects of Quarfloxacin (CX-3543) in Patients With Relapsed or Refractory B-Cell Chronic Lymphocytic Leukemia (B-CLL)

This is a Phase 2, open-label, multicenter, efficacy, safety, and pharmacodynamic study of CX-3543 in patients with relapsed or refractory B-cell chronic lymphocytic leukemia (CLL).

Start Date01 Jun 2007

Sponsor / Collaborator

Cylene Pharmaceuticals, Inc.

100 Clinical Results associated with Itarnafloxin

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100 Translational Medicine associated with Itarnafloxin

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100 Patents (Medical) associated with Itarnafloxin

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17

Literatures (Medical) associated with Itarnafloxin

22 Nov 2024·Briefings in Bioinformatics

Machine learning–enabled virtual screening indicates the anti-tuberculosis activity of aldoxorubicin and quarfloxin with verification by molecular docking, molecular dynamics simulations, and biological evaluations

Article

Author: Li, Liang ; Zheng, Si ; Wang, Min ; Gu, Yaowen ; Zhao, Yelin ; Gu, Yuzhen ; Chen, Ting ; Yu, Xia ; Li, Jiao ; Jiang, Rui

AbstractDrug resistance in Mycobacterium tuberculosis (Mtb) is a significant challenge in the control and treatment of tuberculosis, making efforts to combat the spread of this global health burden more difficult. To accelerate anti-tuberculosis drug discovery, repurposing clinically approved or investigational drugs for the treatment of tuberculosis by computational methods has become an attractive strategy. In this study, we developed a virtual screening workflow that combines multiple machine learning and deep learning models, and 11 576 compounds extracted from the DrugBank database were screened against Mtb. Our screening method produced satisfactory predictions on three data-splitting settings, with the top predicted bioactive compounds all known antibacterial or anti-TB drugs. To further identify and evaluate drugs with repurposing potential in TB therapy, 15 screened potential compounds were selected for subsequent computational and experimental evaluations, out of which aldoxorubicin and quarfloxin showed potent inhibition of Mtb strain H37Rv, with minimal inhibitory concentrations of 4.16 and 20.67 μM/mL, respectively. More inspiringly, these two compounds also showed antibacterial activity against multidrug-resistant TB isolates and exhibited strong antimicrobial activity against Mtb. Furthermore, molecular docking, molecular dynamics simulation, and the surface plasmon resonance experiments validated the direct binding of the two compounds to Mtb DNA gyrase. In summary, our effective comprehensive virtual screening workflow successfully repurposed two novel drugs (aldoxorubicin and quarfloxin) as promising anti-Mtb candidates. The verification results provide useful information for the further development and clinical verification of anti-TB drugs.

17 Jun 2024·ChemBioChem

Systematic Evaluation of Benchmark G4 Probes and G4 Clinical Drugs using three Biophysical Methods: A Guideline to Evaluate Rapidly G4‐Binding Affinity

Article

Author: Teulade‐Fichou, M.‐P. ; Beauvineau, C. ; Lavergne, T. ; Dejeu, J. ; Laigre, E. ; Defrancq, E. ; Bonnet, H. ; Verga, D.

AbstractG‐quadruplex DNA structures (G4) are proven to interfere with most genetic and epigenetic processes. Small molecules binding these structures (G4 ligands) are invaluable tools to probe G4‐biology and address G4‐druggability in various diseases (cancer, viral infections). However, the large number of reported G4 ligands (>1000) could lead to confusion while selecting one for a given application. Herein we conducted a systematic affinity ranking of 11 popular G4 ligands vs 5 classical G4 sequences using FRET‐melting, G4‐FID assays and SPR. Interestingly SPR data globally align with the rankings obtained from the two semi‐quantitative assays despite discrepancies due to limits and characteristics of each assay. In the whole, PhenDC3 emerges as the most potent binder irrespective of the G4 sequence. Immediately below PDS, PDC‐360A, BRACO19, TMPyP4 and RHPS4 feature strong to medium binding again with poor G4 topology discrimination. More strikingly, the G4 drugs Quarfloxin, CX5461 and c‐PDS exhibit weak affinity with all G4s studied. Finally, NMM and Cu‐ttpy showed heterogeneous behaviors due, in part, to their physicochemical particularities poorly compatible with screening conditions. The remarkable properties of PhenDC3 led us to propose its use for benchmarking FRET‐melting and G4‐FID assays for rapid G4‐affinity evaluation of newly developed ligands.

01 Dec 2023·International Journal for Parasitology: Drugs and Drug Resistance

Effects of the G-quadruplex-binding drugs quarfloxin and CX-5461 on the malaria parasite Plasmodium falciparum

Article

Author: Cicuta, Pietro ; Craven, Holly M ; Blagborough, Andrew M ; Merrick, Catherine J ; Nettesheim, Guilherme

Plasmodium falciparum is the deadliest causative agent of human malaria. This parasite has historically developed resistance to most drugs, including the current frontline treatments, so new therapeutic targets are needed. Our previous work on guanine quadruplexes (G4s) in the parasite's DNA and RNA has highlighted their influence on parasite biology, and revealed G4 stabilising compounds as promising candidates for repositioning. In particular, quarfloxin, a former anticancer agent, kills blood-stage parasites at all developmental stages, with fast rates of kill and nanomolar potency. Here we explored the molecular mechanism of quarfloxin and its related derivative CX-5461. In vitro, both compounds bound to P. falciparum-encoded G4 sequences. In cellulo, quarfloxin was more potent than CX-5461, and could prevent establishment of blood-stage malaria in vivo in a murine model. CX-5461 showed clear DNA damaging activity, as reported in human cells, while quarfloxin caused weaker signatures of DNA damage. Both compounds caused transcriptional dysregulation in the parasite, but the affected genes were largely different, again suggesting different modes of action. Therefore, CX-5461 may act primarily as a DNA damaging agent in both Plasmodium parasites and mammalian cells, whereas the complete antimalarial mode of action of quarfloxin may be parasite-specific and remains somewhat elusive.

100 Deals associated with Itarnafloxin

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External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB06638

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Carcinoid Tumor	Phase 2	US	Cylene Pharmaceuticals, Inc.	01 Oct 2008
Neuroendocrine Carcinoma	Phase 2	US	Cylene Pharmaceuticals, Inc.	01 Oct 2008
Chronic lymphocytic leukaemia refractory	Phase 2	US	Cylene Pharmaceuticals, Inc.	01 Jun 2007
Advanced Malignant Solid Neoplasm	Phase 2	US	Cylene Pharmaceuticals, Inc.	01 Jul 2005
Lymphoma	Phase 2	US	Cylene Pharmaceuticals, Inc.	01 Jul 2005
Chronic Lymphocytic Leukemia	Phase 2	-	TetraGene LLC	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ASCO2007	Phase 1	HR-positive/HER2-low Solid Tumors	-	CX-3543	nhkcthpvgq(iowjglympv) = No drug related serious adverse events (SAEs) were encountered sghdjzyhwq (imapyplfqh ) View more	-	20 Jun 2007