Delving into the Latest Updates on Verubulin with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Azixa, Veribulin, Verubulin (USAN/INN)

+ [6]

Target

Tubulin

Mechanism

Tubulin inhibitors

Therapeutic Areas

NeoplasmsNervous System Diseases

Active Indication

Brain Cancer

Inactive Indication

Brain metastasesColorectal CancerGlioblastoma+ [5]

Originator Organization

Immune Pharmaceuticals, Inc.

Active Organization

Immune Pharmaceuticals, Inc.

Inactive Organization

Myrexis, Inc.

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

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Structure

Molecular FormulaC17H17N3O

InChIKeySNHCRNMVYDHVDT-UHFFFAOYSA-N

CAS Registry827031-83-4

This is a phase 0 study that will enable an assessment of biodistribution and estimation of absorbed dose in humans based on data collected from five healthy volunteers, which is typically the minimum number required by the FDA for first-in-human studies to assess dosimetry of a new tracer. The evaluation of the brain imaging of thirty additional subjects in the 2nd part of the study will lead to a descriptive assessment of the targeting and pharmacokinetics of MPC6827 in the brain and between normal and diseased brain.

Start Date08 Jan 2021

Sponsor / Collaborator

Columbia University

NCT01285414 / CompletedPhase 2

A Phase 2 Study of Verubulin With Radiation Therapy and Temozolomide in Subjects Newly Diagnosed With Glioblastoma Multiforme

This, international, multi-center, Phase 2 study of verubulin will be conducted in patients with newly diagnosed Glioblastoma Multiforme (GBM). The study will be conducted in two parts. Part A is an open-label dose finding study that will determine the safety and tolerability of verubulin in combination with standard treatment. Part B is a randomized open-label study that will investigate progression-free survival and overall survival of patients receiving verubulin, at the dose determined in Part A, in combination with standard treatment versus standard treatment alone.

Start Date01 Dec 2010

Sponsor / Collaborator

Myrexis, Inc.

NCT00892931 / CompletedPhase 2

Phase 2 Study of Azixa (MPC-6827) for the Treatment of Patients With Recurrent Glioblastoma Multiforme

The purpose of this study is to determine the safety and effectiveness of Azixa in patients with recurrent glioblastoma multiforme

Start Date01 Apr 2009

Sponsor / Collaborator

Myrexis, Inc.

100 Clinical Results associated with Verubulin

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100 Translational Medicine associated with Verubulin

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100 Patents (Medical) associated with Verubulin

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16

Literatures (Medical) associated with Verubulin

27 Mar 2023·Pharmaceuticals (Basel, Switzerland)

Binding Parameters of [¹¹C]MPC-6827, a Microtubule-Imaging PET Radiopharmaceutical in Rodents.

Article

Author: Bhoopal, Bhuvanachandra ; Gollapelli, Krishna Kumar ; Krizan, Ivan ; Craft, Suzanne ; Mintz, Akiva ; Bansode, Avinash H. ; Solingapuram Sai, Kiran Kumar ; Damuka, Naresh ; Miller, Mack

Impairment and/or destabilization of neuronal microtubules (MTs) resulting from hyper-phosphorylation of the tau proteins is implicated in many pathologies, including Alzheimer's disease (AD), Parkinson's disease and other neurol. disorders.Increasing scientific evidence indicates that MT-stabilizing agents protect against the deleterious effects of neurodegeneration in treating AD.To quantify these protective benefits, we developed the first brain-penetrant PET radiopharmaceutical, [11C]MPC-6827, for in vivo quantification of MTs in rodent and nonhuman primate models of AD.Mechanistic insights revealed from recently reported studies confirm the radiopharmaceutical's high selectivity for destabilized MTs.To further translate it to clin. settings, its metabolic stability and pharmacokinetic parameters must be determinedHere, we report in vivo plasma and brain metabolism studies establishing the radiopharmaceutical-binding constants of [11C]MPC-6827.Binding constants were extrapolated from autoradiog. experiments; pretreatment with a nonradioactive MPC-6827 decreased the brain uptake >70%.It exhibited ideal binding characteristics (typical of a CNS radiopharmaceutical) including LogP (2.9), Kd (15.59 nM), and Bmax (11.86 fmol/mg).Most important, [11C]MPC-6827 showed high serum and metabolic stability (>95%) in rat plasma and brain samples.

01 Oct 2022·Bioorganic & Medicinal Chemistry Letters

Radiosynthesis and evaluation of [11C]AG-488, a dual anti-angiogenetic and anti-tubulin PET ligand

Article

Author: Carberry, Patrick ; Chaly, Thomas ; Neelamegam, Ramesh ; Mintz, Akiva ; Molotkov, Andrei ; Dileep Kumar, J S

Combinations of antiangiogenic and cytotoxic agents show promising results in the treatment of cancer. However, there is a lack of single agent with both antiangiogenic and cytotoxic activities for clinical application. AG-488 aka FLAG-003 is a novel ligand with established antiangiogenetic properties via activation of receptor thymidine kinase (RTK) and anti-tubulin properties in tumor cells. AG-488 is also reported to reduce tumor volume and prolong survival in preclinical animal models of glioblastoma multiforme, breast cancer and is in clinical stage. Higher expression of RTKs and tubulins is reported in various cancers. This study reveals the development of [¹¹C]AG-488, a high affinity dual target inhibitor binding to RTK and anti-tubulin activities. We rationale that antiangiogenic RTK and anti-tubulin activity of [¹¹C]AG-488 may enhance the tumor to tissue ratio, assisting in cancer drug development. [¹¹C]AG-488 was synthesized in 35 ± 5 % radiochemical yield by radiomethylating the corresponding phenolate using [¹¹C]CH₃I. MicroPET studies in mice indicated blood-brain barrier penetration of [¹¹C]AG-488 and retention in the brain. However, blocking studies with antitubulin and RTK agent HD-800 and microtubule depolymerizing agent MPC-6827 show increased binding of [¹¹C]AG-488 in brain. The pattern of tracer binding in blocking conditions is similar to the baseline conditions. The higher binding may be due to the increased plasma uptake of radiotracer or the formation of more free tubulins due to microtubule dynamic instability during the blocking conditions.

01 Mar 2019·Bioorganic ChemistryQ2 · CHEMISTRY

Discovery of novel quinazolines as potential anti-tubulin agents occupying three zones of colchicine domain

Q2 · CHEMISTRY

Article

Author: Xu, Jinyi ; Shuai, Wen ; Xu, Shengtao ; Zhu, Zheying ; Liu, Jie ; Yao, Hong ; Xu, Feijie ; Cheng, Keguang ; Li, Wenlong ; Yin, Ying

A series of novel quinazolines as tubulin inhibitors occupying three zones of colchicine domain have been designed and synthesized inspired by the recently disclosed crystal structure of verubulin analogue 6 with tubulin. Among the newly synthesized compounds, 19c showed noteworthy potency against K562, HepG2, KB, HCT-8 and MDB-MB-231 cancer cells. In vitro microtubule polymerization assays identified 19c as a potent tubulin assembly inhibitor, the binding mode of which with tubulin was confirmed by molecular modeling studies to occupy three zones of tubulin domain. Furthermore, 19c disrupted the intracellular microtubule network, caused G2/M phase arrest, induced cell apoptosis and depolarized mitochondria of K562 cells. 19c also reduced the cell migration and disrupted the capillary-like tube formation of human umbilical vein endothelial cells (HUVECs). Importantly, 19c significantly and dose dependently inhibited tumor growth in H22 liver cancer xenograft mouse model. All these results suggested that 19c deserves further research as a novel and potential anti-tubulin agent for the treatment of cancers.

100 Deals associated with Verubulin

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External Link

KEGG	Wiki	ATC	Drug Bank
D10029	-	-	DB05585

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Neurodegenerative Diseases	Phase 2	US	Myrexis, Inc.	25 Sep 2020
Refractory Malignant Solid Neoplasm	Phase 2	US	Myrexis, Inc.	01 Mar 2005
Brain Cancer	Phase 2	-	Immune Pharmaceuticals, Inc.	-
Colorectal Cancer	Phase 2	US	Immune Pharmaceuticals, Inc.	-
Glioblastoma Multiforme	Preclinical	US	Myrexis, Inc.	01 Apr 2009
Recurrent Glioblastoma	Preclinical	US	Myrexis, Inc.	01 Apr 2009
Brain metastases	Discovery	US	Immune Pharmaceuticals, Inc.	03 Jan 2016
Melanoma	Discovery	US	Immune Pharmaceuticals, Inc.	29 Dec 2015
Glioblastoma	Discovery	US	Immune Pharmaceuticals, Inc.	19 Dec 2015

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ASCO2011	Phase 2	Recurrent Glioblastoma	31	Verubulin	pkdfglwrkj(rrhwavilae) = hrmgasubel jvkyqpdnll (zpwjvhkayg, 3% - 25%) View more	Positive	20 May 2011
ASCO2010	Not Applicable	Recurrent Glioblastoma	19	MPC-6827	(ahhmuqvdje) = xlurczbdhs uevjnqjvgf (kexextynrh, [1.3 - 7.1]) View more	-	20 May 2010
ASCO2010	Not Applicable	Metastatic melanoma	22	MPC-6827	(mkgbtpwyrk) = jhoggcxwny bolqulmbtf (xfsccrneyv, [1.7 - 5.5])	-	20 May 2010
AACR2009	Phase 1	Solid tumor	48	Azixa	(egpufaqzel) = vdvnblqqet vddetsridq (mzlejkzkma )	-	01 May 2009
ASCO2007	Phase 1	HR-positive/HER2-low Solid Tumors \| Brain metastases	-	MPC-6827	(sfkzqhrsjt) = zwxttbkpit lpebinhxai (yhcxbofett )	-	20 Jun 2007