Delving into the Latest Updates on Briciclib Sodium with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Briciclib, Briciclib sodium (USAN)

+ [2]

Target

CCND1 x EIF4E

Mechanism

CCND1 inhibitors(Cyclin D1 inhibitors), EIF4E inhibitors(Eukaryotic translation initiation factor 4E inhibitors), Apoptosis inducers

Therapeutic Areas

NeoplasmsImmune System DiseasesHemic and Lymphatic Diseases

Active Indication-

Inactive Indication

Acute Lymphoblastic LeukemiaAdvanced Malignant Solid NeoplasmRecurrent Lymphoma+ [1]

Originator Organization

Temple University Graduate School

Active Organization-

Inactive Organization

Traws Pharma, Inc.

Drug Highest PhaseDiscontinuedPhase 1

First Approval Date-

Regulation-

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Structure

Molecular FormulaC19H23Na2O10PS

InChIKeyUXOPXQJTLZERNS-MIIBGCIDSA-N

CAS Registry865784-01-6

View All Structures (2)

The main objectives of this study are to determine the safety profile of briciclib, an experimental anti-cancer drug, as it is administered intravenously once weekly as escalating doses in adult patients with advanced cancer and solid tumors, and to determine the highest dose of briciclib that can be safely given. Secondary objectives are to determine how the amount of briciclib in circulation changes over time and how much briciclib gets into the urine for excretion, and to document potential anti-tumor effects of briciclib.

Start Date01 Jun 2014

Sponsor / Collaborator

Traws Pharma, Inc.

NCT01049113 / TerminatedPhase 1

Phase 1, Dose Escalation Study To Assess the Safety, Pharmacokinetics and Activity of 2-Hour Continuous Intravenous Dosing of ON 013105 Administered Weekly in Patients With Relapsed/Refractory Lymphoma and Acute Lymphoid Leukemia

This is an open-label, dose-escalation Phase 1 study of the investigational agent, ON 013105. In laboratory animal studies, ON 013105 has demonstrated anti-cancer activity. The purpose of this study is to determine the highest dose of ON 013105 that can be given safely in patients with relapsed/refractory Lymphoma or B-cell Acute Lymphocytic Leukemia (Philadelphia chromosome negative). Patients will receive weekly 2-hour IV infusions of ON 013105 at higher and higher doses until intolerable side effects are observed. It is important to know the highest safe dose so additional studies can be done.

Start Date01 Nov 2009

Sponsor / Collaborator

Traws Pharma, Inc.

100 Clinical Results associated with Briciclib Sodium

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100 Translational Medicine associated with Briciclib Sodium

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100 Patents (Medical) associated with Briciclib Sodium

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3

Literatures (Medical) associated with Briciclib Sodium

01 Mar 2024·Journal of Investigative Dermatology

Eukaryotic Initiation Factor 4E (eIF4E) as a Target of Anti-Psoriatic Treatment

Article

Author: Painsi, Clemens ; Benezeder, Theresa ; Bordag, Natalie ; Wolf, Peter ; Pilic, Johannes ; Golob-Schwarzl, Nicole

Eukaryotic initiation factor 4E (eIF4E) has been known to play a critical role in the regulation of gene expression and essential cellular processes, such as proliferation, apoptosis and differentiation. In this study, we explored its role in the pathophysiology of psoriasis. The inhibition of eIF4E by small interfering RNA or briciclib, an eIF4E small molecule inhibitor, downregulated the expression of eIF4E itself and its two complex partners eIF4A and G, as well as other eIFs (eg, eIF1A, eIF2α, eIF3A, eIF3B, eIF5, and eIF6). This inhibition also abolished psoriatic inflammation in both the imiquimod and TGFß mouse model, as well as in a human 3 dimensional-psoriasis tissue model. Downregulation of eIF4E and the other eIFs by application of briciclib (particularly when given topically) was linked to the normalization of cellular proliferation, epidermal hyperplasia, levels of proinflammatory cytokines (eg, TNFα, IL-1b, IL-17, and IL-22), and keratinocyte differentiation markers (eg, KRT16 and FLG). These results demonstrate translational imbalance and underline the crucial role played by eIF4E and other eIFs in the pathophysiology of psoriasis. This work opens up avenues for the development of novel topical antipsoriatic treatment strategies by targeting eIF4E.

01 Jan 2013·Clinical Cancer ResearchQ1 · MEDICINE

Combined Administration of Rituximab and ON 013105 Induces Apoptosis in Mantle Cell Lymphoma Cells and Reduces Tumor Burden in a Mouse Model of Mantle Cell Lymphoma

Q1 · MEDICINE

Article

Author: Kumar, Ramesh ; Papadopoulos, Evangelos ; Reddy, E. Premkumar ; Kuzontkoski, Paula M. ; Shrivastava, Ashutosh ; Groopman, Jerome E. ; Gillum, Amanda M. ; Reddy, M.V. Ramana ; Prasad, Anil

AbstractPurpose: Mantle cell lymphoma (MCL) is an incurable B-cell lymphoma, and new therapeutic strategies are urgently needed.Experimental Design: The effects of ON 013105, a novel benzylstyryl sulfone kinase inhibitor, alone or with doxorubicin or rituximab, were examined in Granta 519 and Z138C cells. For in vivo studies, CB17/SCID mice were implanted subcutaneously with Z138C cells and treated with various combinations of ON 013105, doxorubicin, and rituximab. Tumor burden and body weight were monitored for 28 days.Results: ON 013105 induced mitochondria-mediated apoptosis in MCL cells. Death was preceded by translocation of tBid to the mitochondria and cytochrome c release. In addition, ON 013105–treated cells exhibited reduced levels of cyclin D1, c-Myc, Mcl-1, and Bcl-xL. Using nuclear magnetic resonance (NMR) spectroscopy, we showed specific binding of ON 013105 to eIF4E, a critical factor for the initiation of protein translation. We proffer that this drug–protein interaction preferentially prevents the translation of the aforementioned proteins and may be the mechanism by which ON 013105 induces apoptosis in MCL cells. Efficacy studies in a mouse xenograft model showed that ON 013105 inhibited MCL tumor growth and that combining ON 013105 with rituximab reduced tumor burden further with negligible unwanted effects.Conclusions: Our findings suggest that ON 013105, alone or in combination with rituximab, may be a potent therapeutic agent to treat MCLs. Clin Cancer Res; 19(1); 85–95. ©2012 AACR.

01 Sep 2012·Pharmaceutical ResearchQ3 · MEDICINE

Preclinical Pharmacokinetic and Pharmacodynamic Evaluation of Novel Anticancer Agents, ON01910.Na (Rigosertib, Estybon™) and ON013105, for Brain Tumor Chemotherapy

Q3 · MEDICINE

Article

Author: Silpa Nuthalapati ; M. V. Ramana Reddy ; Ping Guo ; James M. Gallo ; Qingyu Zhou ; Stephen Cosenza ; E. Premkumar Reddy ; Hua Lv

PURPOSETo evaluate a mitotic inhibitor, ON01910.Na, as a potential chemotherapeutic agent for brain tumors using a series of PK/PD studies, which led to the evaluation of its structural analog, ON013105, a prodrug of the more lipophilic product, ON013100.METHODSSystemic PK characterization of ON01910 and ON013105 was completed in healthy mice. Using an orthotopic U87 glioma mouse model, brain and brain tumor distribution under steady-state conditions were evaluated for ON01910.Na and ON013105/ON013100; anticancer potential following a multiple-dose schedule of 250 mg/kg/day IP for 7 days was evaluated for ON01910.Na.RESULTSON01910 exhibited low brain and brain tumor distribution with quasi-steady-state brain/plasma (Css(brain)/Css(plasma)) and brain tumor/plasma (Css(brain tumor)/Css(plasma)) concentration ratios of 0.03 ± 0.02 and 0.14 ± 0.08, respectively. Significant antiangiogenic potential and antiproliferative capacity of ON01910 in the intracerebral model was absent. ON013100 showed high brain and brain tumor penetration with Css(brain)/Css(plasma) and Css(brain tumor)/Css(plasma) ratios of 0.92 ± 0.26 and 1.35 ± 0.40, respectively; its prodrug ON013105 showed negligible brain and brain tumor penetration.CONCLUSIONSON013105, not ON01910.Na, was identified as a potential anticancer drug candidate for further investigation in brain tumor chemotherapy based on the properties of ON013100.

100 Deals associated with Briciclib Sodium

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External Link

KEGG	Wiki	ATC	Drug Bank
D10694	-	-	DB12004

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Advanced Malignant Solid Neoplasm	Phase 1	US	Traws Pharma, Inc.	01 Jun 2014
Acute Lymphoblastic Leukemia	Phase 1	US	Traws Pharma, Inc.	01 Nov 2009
Recurrent Lymphoma	Phase 1	US	Traws Pharma, Inc.	01 Nov 2009
Refractory Lymphoma	Phase 1	US	Traws Pharma, Inc.	01 Nov 2009