Delving into the Latest Updates on Ancrod with Synapse

Overview

Basic Info

Drug Type

Fusion protein

Synonyms

Ancrod (USAN/INN), NM-V, Viprinex

Target

Fibrinogen

Mechanism

Fibrinogen inhibitors

Therapeutic Areas

Hemic and Lymphatic DiseasesOther DiseasesNervous System Diseases+ [2]

Active Indication-

Inactive Indication

Acute Ischemic StrokeBrain InfarctionDeafness+ [3]

Originator Organization

AbbVie, Inc.

Active Organization-

Inactive Organization

Neurobiological Technologies, Inc.

Nordmark Arzneimittel GmbH & Co. KG

AbbVie, Inc.

+ [1]

Drug Highest PhaseDiscontinuedNDA/BLA

First Approval Date-

RegulationOrphan Drug (US)

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Gene Sequence

Sequence Code 57437379

Source: *****

Two series of new VV-hemorphin-5 analogs with structures Val-Val-Tyr-Xxx-Trp-Thr-Gln-NH₂ and Adam-Val-Val-Tyr-Xxx-Trp-Thr-Gln-NH₂ , where Xxx is Ac5c (1-aminocyclopentane-1-carboxylic acid), Ac6c (1-aminocyclohexane-1-carboxylic acid), Ac7c (1-aminocycloheptane-1-carboxylic acid), and Adam is the low-molecular-weight lipophilic adamantyl building block, were synthesized, characterized electrochemically and evaluated for antioxidant, anti-hyperalgesia, and anticonvulsant activity. The design of the compounds followed the strategy to improve the propensity for aqueous solubility and/or to increase their affinity for the target receptor or enzyme. The partition coefficient value shows that the peptide scaffold goes from hydrophilic to lipophilic with the increasing size of the cycloalkane ring and even more with the introduction of the adamantane. The peptides C5-V and C7-V were the only analogs that provoked an immediate antinociceptive effect changing the mechanical pain threshold. The six new peptide analogs produced a significant and long-lasting carrageenan model of inflammatory pain in rats. While the adamantane hemorphin analog Ad7-V was the only compound with the potency to suppress psychomotor seizures in the 6-Hz test, the C6-V and Ad6-V exhibited protective activity against the seizure spread in the maximal electroshock seizure test in mice. The active analogs did not show neurotoxicity or sedative effects. Our results revealed a structure-related specific activity of a newly designed hemorphin analog that could be used as a template for future modification and preparation of compounds with potential analgesic and anticonvulsant activity.

01 Sep 2023·European Archives of Oto-Rhino-Laryngology

Randomized, placebo-controlled study on efficacy, safety and tolerability of drug-induced defibrinogenation for sudden sensorineural hearing loss: the lessons learned

Article

Author: Strieth, Sebastian ; Canis, Martin ; Ihler, Friedrich ; Spiegel, Jennifer L ; Mejzlik, Jan ; Fořt, Tomáš ; Bertlich, Mattis ; Becker, Sven ; Weiss, Bernhard G ; Lenarz, Thomas ; Olzowy, Bernhard

AbstractPurposeDisturbance of cochlear microcirculation is discussed as final common pathway of various inner ear diseases. Hyperfibrinogenemia causing increased plasma viscosity is a possible factor for a critical reduction of cochlear blood flow that might lead to sudden sensorineural hearing loss (SSHL). The aim was to determine the efficacy and safety of drug-induced defibrinogenation by ancrod for SSHL.MethodsDouble-blind, randomized, placebo-controlled, multicenter, parallel group, phase II (proof-of-concept) study (planned enrollment: 99 patients). Patients received an infusion of ancrod or placebo (day 1) followed by subcutaneous administrations (day 2, 4, 6). Primary outcome was the change in pure tone audiogram air conduction average until day 8.ResultsThe study was terminated early due to slow recruiting (31 enrolled patients: 22 ancrod, 9 placebo). A significant improvement of hearing loss was registered in both groups (ancrod: − 14.3 dB ± 20.4 dB, − 39.9% ± 50.4%; placebo: − 22.3 dB ± 13.7 dB, − 59.1% ± 38.0%). A statistically significant group-difference was not detected (p = 0.374). Placebo response of 33.3% complete and 85.7% at least partial recovery was observed. Plasma fibrinogen levels were reduced significantly by ancrod (baseline: 325.2 mg/dL, day 2: 107.2 mg/dL). Ancrod was tolerated well, no adverse drug reaction was of severe intensity, no serious adverse events occurred.ConclusionAncrod reduced fibrinogen levels that support its mechanism of action. The safety profile can be rated positively. Since the planned number of patients could not be enrolled, no efficacy conclusion can be drawn. The high rate of placebo response challenges clinical trials for SSHL and needs to be considered in future investigations.Trial registrationsThis study was registered in the EU Clinical Trials Register, EudraCT-No. 2012-000066-37 at 2012-07-02.

03 Aug 2022·Journal of the American Chemical Society

Precision Navigation of Hepatic Ischemia–Reperfusion Injury Guided by Lysosomal Viscosity-Activatable NIR-II Fluorescence

Article

Author: Tang, Bo ; Zhang, Wei ; Zhou, Chunmiao ; Liu, Zhenzhen ; Li, Ping ; Liu, Jihong ; Wang, Xin ; James, Tony D. ; Li, Mengmei ; Zhang, Wen ; Wu, Luling

Hepatic ischemia-reperfusion injury (HIRI) is responsible for postoperative liver dysfunction and liver failure. Precise and rapid navigation of HIRI lesions is critical for early warning and timely development of pretreatment plans. Available methods for assaying liver injury fail to provide the exact location of lesions in real time intraoperatively. HIRI is intimately associated with oxidative stress which impairs lysosomal degradative function, leading to significant changes in lysosomal viscosity. Therefore, lysosomal viscosity is a potential biomarker for the precise targeting of HIRI. Hence, we developed a viscosity-activatable second near-infrared window fluorescent probe (NP-V) for the detection of lysosomal viscosity in hepatocytes and mice during HIRI. A reactive oxygen species-malondialdehyde-cathepsin B signaling pathway during HIRI was established. We further conducted high signal-to-background ratio NIR-II fluorescence imaging of HIRI mice. The contour and boundary of liver lesions were delineated, and as such the precise intraoperative resection of the lesion area was implemented. This research demonstrates the potential of NP-V as a dual-functional probe for the elucidation of HIRI pathogenesis and the direct navigation of HIRI lesions in clinical applications.

100 Deals associated with Ancrod

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External Link

KEGG	Wiki	ATC	Drug Bank
D02938	Ancrod	B01AD09	DB05099

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Brain Infarction	NDA/BLA	TW	Neurobiological Technologies, Inc.	01 Sep 2005
Brain Infarction	NDA/BLA	NL	Neurobiological Technologies, Inc.	01 Sep 2005
Brain Infarction	NDA/BLA	US	Neurobiological Technologies, Inc.	01 Sep 2005
Brain Infarction	NDA/BLA	GB	Neurobiological Technologies, Inc.	01 Sep 2005
Brain Infarction	NDA/BLA	CZ	Neurobiological Technologies, Inc.	01 Sep 2005
Hearing Loss, Sensorineural	NDA/BLA	-	Nordmark Arzneimittel GmbH & Co. KG	-
Hearing Loss, Sensorineural	NDA/BLA	-	AbbVie, Inc.	-
Hearing Loss, Sensorineural	NDA/BLA	-	AbbVie, Inc.	-
Hearing Loss, Sensorineural	NDA/BLA	-	Nordmark Arzneimittel GmbH & Co. KG	-
Heparin-induced thrombocytopenia and thrombosis	NDA/BLA	US	Abbott Laboratories	-