Delving into the Latest Updates on Halofuginone Hydrobromide with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

(+/-)-trans-7-bromo-6-chloro-3-(3-(3-hydroxy-2-piperidyl)-acetonyl)-4(3H)-quinazolinone, Halofuginone, Halofuginone hydrobromide (USAN)

+ [6]

Target

Collagen

Mechanism

Collagen inhibitors, Angiogenesis inhibitors

Therapeutic Areas

NeoplasmsImmune System DiseasesNervous System Diseases+ [6]

Active Indication-

Inactive Indication

Bladder CancerCoronary RestenosisLiver Cirrhosis+ [4]

Originator Organization

Akashi Therapeutics Inc

Active Organization-

Inactive Organization

Collgard Biopharmaceuticals Ltd.

Akashi Therapeutics Inc

Processa Pharmaceuticals, Inc.

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

RegulationOrphan Drug (US)

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Structure

Molecular FormulaC16H18Br2ClN3O3

InChIKeySJUWEPZBTXEUMU-AJYMSAGVSA-N

CAS Registry64924-67-0

This study, HALO-DMD-03, is a follow-on study to HALO-DMD-01 and HALO-DMD-02, and allows continued open-label access to HT-100 for subjects who have completed these studies. HALO-DMD-03 will provide safety and strength and function data on continuous long-term dosing. Data from this study will be used to inform the safety, tolerability, and dose selection for a future trial of HT-100 in boys with Duchenne Muscular Dystrophy (DMD).

Start Date01 May 2015

Sponsor / Collaborator

Akashi Therapeutics Inc

NCT01978366 / TerminatedPhase 2

An Open Label Extension Study of HT-100 in Patients With Duchenne Muscular Dystrophy Who Have Completed Protocol HALO-DMD-01

This study is designed to provide 6-months continuous dosing with the study medication, called HT-100, on participants who successfully completed the predecessor study (HALO-DMD-01). The main purpose of this study is to assess chronic safety, tolerability, pharmacodynamic activity (testing the drug's effect on DMD) and population pharmacokinetics (measuring how much drug is in the bloodstream) in participants with a broad spectrum of Duchenne muscular dystrophy (DMD).

Start Date01 Oct 2013

Sponsor / Collaborator

Processa Pharmaceuticals, Inc.

NCT01847573 / TerminatedPhase 1/2

A Phase 1b Open Label, Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of HT-100 in Patients With Duchenne Muscular Dystrophy

The main purpose of this study is to test the safety and tolerability of different, increasing doses of an experimental medication called HT-100 in boys and young men with Duchenne muscular dystrophy (DMD). The study medication, HT-100, is a medicine that may help promote healthy muscle regeneration, diminish inflammation and the resulting damage to muscle, and decrease the scar tissue that forms in the muscles of children with DMD. In this study, pharmacokinetic sampling, or measurements of the amount of HT-100 in the bloodstream will also be taken.

Start Date01 May 2013

Sponsor / Collaborator

Processa Pharmaceuticals, Inc.

100 Clinical Results associated with Halofuginone Hydrobromide

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100 Translational Medicine associated with Halofuginone Hydrobromide

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100 Patents (Medical) associated with Halofuginone Hydrobromide

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575

Literatures (Medical) associated with Halofuginone Hydrobromide

01 Dec 2024·Journal of Molecular Histology

Halofuginone ameliorates the susceptibility to atrial fibrillation by activating the PI3K/Akt signaling pathway

Article

Author: Zhao, Xiaolong ; Shen, Chunjian ; Zhang, Jing ; Xu, Feng

Atrial fibrillation (AF) is the most common cardiac arrhythmia in clinical practice. Halofuginone (HF) exerts beneficial effects on organ fibrosis, periodontitis, and cancer. However, the effect of HF against AF remains unknown. During the induction of AF, the rats were intragastrically administered HF (5 mg/kg and 10 mg/kg) daily for 7 consecutive days. Cardiac function was evaluated through echocardiographic analysis. The presence of pathological changes and interstitial fibrosis in the left atrial tissues were investigated. Intracellular Ca²⁺ homeostasis and mitochondrial function in atrial tissues were evaluated. The activation of the PI3K/Akt signaling pathway was examined, and an allosteric Akt inhibitor, MK-2206, was applied to confirm the involvement of the PI3K/Akt signaling pathway in the protection against AF by HF. The administration of HF resulted in a prolongation of the atrial effective refractory period (AERP), a reduction in both the duration and inducibility of AF, and a decrease in atrial weight, heart weight, atrial weight/body weight ratio, and heart weight/body weight ratio in rats with AF. In addition, the administration of HF resulted in a reduction in left atrial diameter (LAD) and an increase in left ventricular internal diameter diastolic (LVIDd), ejection fraction (EF), and fractional shortening (FS), while having no effect on left ventricular internal diameter systolic (LVIDs). The pathological changes and cardiac fibrosis observed in rats with AF were mitigated by HF. Moreover, HF enhanced mitochondrial function, suppressed cardiomyocyte apoptosis, and activated the PI3K/Akt pathway in AF rats. Furthermore, the protective effect against AF was also observed in an in vitro model. The effects of HF on fibrosis markers, intracellular Ca²⁺ homeostasis, mitochondrial function, and cardiac apoptosis were blocked by MK-2206. HF alleviated the susceptibility to AF in vivo and in vitro via the activation of the PI3K/Akt signaling pathway.

07 Oct 2024·Journal of Cell Biology

Integrated stress response activator halofuginone protects mice from diabetes-like phenotypes

Article

Author: Bertolotti, Anne ; Rai, Shashank ; Szaruga, Maria ; Pitera, Aleksandra P.

The integrated stress response (ISR) is a vital signaling pathway initiated by four kinases, PERK, GCN2, HRI and PKR, that ensure cellular resilience and protect cells from challenges. Here, we investigated whether increasing ISR signaling could rescue diabetes-like phenotypes in a mouse model of diet-induced obesity (DIO). We show that the orally available and clinically approved GCN2 activator halofuginone (HF) can activate the ISR in mouse tissues. We found that daily oral administration of HF increases glucose tolerance whilst reducing weight gain, insulin resistance, and serum insulin in DIO mice. Conversely, the ISR inhibitor GSK2656157, used at low doses to optimize its selectivity, aggravates glucose intolerance in DIO mice. Whilst loss of function mutations in mice and humans have revealed that PERK is the essential ISR kinase that protects from diabetes, our work demonstrates the therapeutic value of increasing ISR signaling by activating the related kinase GCN2 to reduce diabetes phenotypes in a DIO mouse model.

02 Sep 2024·ChemBioChem

Chemoproteomic Strategy Identifies PfUCHL3 as the Target of Halofuginone

Article

Author: Zhao, Mei‐Mei ; Zhao, Mei-Mei ; Wei, Chun-Yan ; Yu, Si-Miao ; Zheng, Yong‐Zhe ; Zeng, Ke‐Wu ; Wei, Chun‐Yan ; Yu, Si‐Miao ; Liu, Zheng‐Ping ; Zhang, Ji-Chao ; Tu, Peng-Fei ; Tu, Peng‐Fei ; Zheng, Yong-Zhe ; Zeng, Ke-Wu ; Liu, Zheng-Ping ; Zhang, Ji‐Chao ; Wang, Heng

AbstractThe human malaria parasite Plasmodium falciparum (P. falciparum) continues to pose a significant public health challenge, leading to millions of fatalities globally. Halofuginone (HF) has shown a significant anti‐P. falciparum effect, suggesting its potential as a therapeutic agent for malaria treatment. In this study, we synthesized a photoaffinity labeling probe of HF to identify its direct target in P. falciparum. Our results reveal that ubiquitin carboxyl‐terminal hydrolase 3 (PfUCHL3) acts as a crucial target protein of HF, which modulates parasite growth in the intraerythrocytic cycle. In particular, we discovered that HF potentially forms hydrogen bonds with the Leu10, Glu11, and Arg217 sites of PfUCHL3, thereby inducing an allosteric effect by promoting the embedding of the helix 6’ region on the protein surface. Furthermore, HF disrupts the expression of multiple functional proteins mediated by PfUCHL3, specifically those that play crucial roles in amino acid biosynthesis and metabolism in P. falciparum. Taken together, this study highlights PfUCHL3 as a previously undisclosed druggable target of HF, which contributes to the development of novel anti‐malarial agents in the future.

100 Deals associated with Halofuginone Hydrobromide

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External Link

KEGG	Wiki	ATC	Drug Bank
D04413	Halofuginone Hydrobromide	-	DB04866

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Muscular Dystrophy, Duchenne	Phase 2	US	Processa Pharmaceuticals, Inc.	01 Oct 2013
Bladder Cancer	Phase 2	GB	Collgard Biopharmaceuticals Ltd.	-
Bladder Cancer	Phase 2	IL	Collgard Biopharmaceuticals Ltd.	-
Coronary Restenosis	Phase 2	US	-	-
Liver Cirrhosis	Phase 2	IL	Collgard Biopharmaceuticals Ltd.	-
Neoplasms	Phase 2	-	Collgard Biopharmaceuticals Ltd.	-
Neoplasms	Phase 2	NL	-	-
Neoplasms	Phase 2	BE	-	-
Renal fibrosis	Phase 2	IL	Collgard Biopharmaceuticals Ltd.	-
Scleroderma, Systemic	Phase 2	GB	Collgard Biopharmaceuticals Ltd.	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ARVO2022	Not Applicable	-	-	Halofuginone	cpikongjxr(nkyvximukk) = jihktjumvw xupidxkxbq (nhkjjzmsco ) View more	-	01 May 2022
				PBS	cpikongjxr(nkyvximukk) = sgcgtwnbyc xupidxkxbq (nhkjjzmsco ) View more
ASTRO	Not Applicable	Lung Cancer	-	Halofuginone (Control group)	fexmcwzbtv(sprjfvgxki) = Immunohistochemistry study revealed decrease level of TGF-Î²1 expression in the halofuginone group and the combined group than in any other groups. The TGF-Î²1 level measured with ELISA also showed the similar results owwxdettve (myhniprdcp ) View more	-	01 Nov 2012
				Halofuginone group