Delving into the Latest Updates on Perflenapent/Perflisopent with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

FC-4112, QW-3600

Target

Potassium channel

Mechanism

Potassium channel modulators

Therapeutic Areas

Cardiovascular Diseases

Active Indication-

Inactive Indication

Cardiovascular Diseases

Originator Organization

Sonus Pharmaceuticals, Inc.

Active Organization-

Inactive Organization

Sonus Pharmaceuticals, Inc.

Drug Highest PhaseWithdrawn

First Approval Date

EU (17 Jul 1998),

Cardiovascular Diseases

Regulation-

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Structure

Molecular FormulaC5F12

InChIKeyNJCBUSHGCBERSK-UHFFFAOYSA-N

CAS Registry678-26-2

Dodecafluoropentane emulsion (DDFPe) is a fluorocarbon (FC) under clinical development as an oxygen therapeutic and is regulated as a blood substitute. Compared to all the prior FCs studied, DDFP is the most advantageous for oxygen delivery and it is active at a lower concentration (1/200th to 1/1000th the weight of other FCs). DDFP has a boiling point of 29 °C, is more water soluble than prior FCs, and following IV administration clears via exhalation. Prior FCs had boiling points ≥ 140 °C and were retained long-term in the body causing adverse events. DDFP is a gas at biological temperature while prior FCs were liquids. Gases deliver roughly 1000 times more oxygen than liquids. DDFPe has two mechanisms of action: (1) The size of the molecule is the smallest that is a liquid at room temperature; on a molar volume basis this equates to more dissolution of oxygen. (2) Because of its boiling point close to physiologic temperature, DDFP delivers oxygen more effectively than liquid FCs.Highlight PointsFluorocarbons (FCs) dissolve oxygen and other respirable gases.FC emulsions generally do not have biological effects of and by themselves, but rather they increase the oxygen carrying capacity of the blood.There are a variety of FCs that were developed in the past as blood substitutes but they all caused accumulation in humans leading to toxic responses.Dodecafluoropentane emulsion (DDFPe) is being developed as an oxygen therapeutic to increase the oxygen carrying capacity of the blood and oxygen delivery to tissues.

01 Sep 2023·Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine

An Experimental Study: Treatment of Subcutaneous C6 Glioma in Rats Using Acoustic Droplet Vaporization.

Article

Author: Yao, Lei ; Liu, Zheng ; Li, Hui ; Yin, Jiabei ; Luo, Tingting ; Yang, Guoliang

OBJECTIVE:

The objective of this study was to investigate the treatment effects of acoustic droplet vaporization (ADV) on tumors.

METHODS:

Experiments were conducted on subcutaneous C6 glioma implanted in 37 rats. Twenty-five rats were divided into five groups treated by ultrasound (US) + dodecafluoropentane (DDFP), US + microbubble (MB), US, DDFP, or saline, respectively. ADV was performed using DDFP droplets (2-5 μm) triggered by non-focused pulsed ultrasound. Macroscopic and histological changes of the tumor were compared with investigation of the tumor ablation effect of ADV. Tumor temperature was measured before and immediately after treatment to explore temperature changes. Furthermore, another 12 rats with bilateral tumors were divided into two groups. Six animals received ADV treatment on unilateral tumor, while another six received saline injection on unilateral tumor. The tumor blood perfusion, tumor volume and related immune response were measured.

RESULTS:

The tumors treated by ADV were partially damaged without significant temperature rise. For the animals with bilateral tumors, the tumor blood perfusion around the damaged area on the side receiving ADV still existed. Additionally, the bilateral tumors of animals treated with ADV were smaller than those of animals treated with saline, along with stronger immune response and more tumor cell apoptosis in tumors on both sides.

CONCLUSION:

The study demonstrated that ADV treatment could damage subcutaneous glioma in rats by mechanical effect and enhance systemic immune response to furtherly inhibit the tumor growth.

01 Aug 2023·Cancer research communications

Dodecafluoropentane Emulsion as a Radiosensitizer in Glioblastoma Multiforme.

Article

Author: Lickliter, Jason D ; Ruben, Jeremy ; Jennens, Ross ; Gzell, Cecelia ; Kichenadasse, Ganessan ; Zhou, Heling ; Stea, Baldassarre ; Mason, Ralph P ; Unger, Evan ; Becker, Jennifer

Purpose:

Glioblastoma multiforme (GBM) is a hypoxic tumor resistant to radiotherapy. The purpose of this study was to assess the safety and efficacy of a novel oxygen therapeutic, dodecafluoropentane emulsion (DDFPe), in chemoradiation treatment of GBM.

Experimental Design:

In this multicenter phase Ib/II dose-escalation study, patients were administered DDFPe via intravenous infusion (0.05, 0.10, or 0.17 mL/kg) while breathing supplemental oxygen prior to each 2 Gy fraction of radiotherapy (30 fractions over 6 weeks). Patients also received standard-of-care chemotherapy [temozolomide (TMZ)]. Serial MRI scans were taken to monitor disease response. Adverse events were recorded and graded. TOLD (tissue oxygenation level-dependent) contrast MRI was obtained to validate modulation of tumor hypoxia.

Results:

Eleven patients were enrolled. DDFPe combined with radiotherapy and TMZ was well tolerated in most patients. Two patients developed delayed grade 3 radiation necrosis during dose escalation, one each at 0.1 and 0.17 mL/kg of DDFPe. Subsequent patients were treated at the 0.1 mL/kg dose level. Kaplan-Meier analysis showed a median overall survival of 19.4 months and a median progression-free survival of 9.6 months, which compares favorably to historical controls. Among 6 patients evaluable for TOLD MRI, a statistically significant reduction in tumor T₁ was observed after DDFPe treatment.

Conclusions:

This trial, although small, showed that the use of DDFPe as a radiosensitizer in patients with GBM was generally safe and may provide a survival benefit. This is also the first time than TOLD MRI has shown reversal of tumor hypoxia in a clinical trial in patients. The recommended dose for phase II evaluation is 0.1 mL/kg DDFPe.Trial Registration: NCT02189109.

Significance:

This study shows that DDFPe can be safely administered to patients, and it is the first-in-human study to show reversal of hypoxia in GBM as measured by TOLD MRI. This strategy is being used in a larger phase II/III trial which will hopefully show a survival benefit by adding DDFPe during the course of fractionated radiation and concurrent chemotherapy.

100 Deals associated with Perflenapent/Perflisopent

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External Link

KEGG	Wiki	ATC	Drug Bank
-	Perflenapent/Perflisopent	V08DA03	DB11625

R&D Status

10 top approved records.

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Indication	Country/Location	Organization	Date
Cardiovascular Diseases	EU	Sonus Pharmaceuticals, Inc.	17 Jul 1998
Cardiovascular Diseases	IS	Sonus Pharmaceuticals, Inc.	17 Jul 1998
Cardiovascular Diseases	LI	Sonus Pharmaceuticals, Inc.	17 Jul 1998
Cardiovascular Diseases	NO	Sonus Pharmaceuticals, Inc.	17 Jul 1998

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ISC2015	Not Applicable	-	6	Dodecafluoropentane emulsion	gwxzsgtnsw(zqruyymsrw) = vwjtbutfdr wxtjoqaeva (ctmxytkixf ) View more	-	01 Feb 2015
ISC2013	Not Applicable	-	8	Dodecafluoropentane Emulsion (Single bolus (0.6 mL/kg))	ahfrkgfslr(zekqkanpga) = xcyabxlawb jzqskcavow (zdgdqwnpjr ) View more	-	01 Feb 2013