Delving into the Latest Updates on Voxtalisib Hydrochloride with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Voxtalisib

Target

PI3Kα x mTORC1 x mTORC2

Mechanism

PI3Kα inhibitors(Phosphatidylinositol 3 kinase alpha inhibitors), mTORC1 inhibitors(Mammalian target of Rapamycin (mTORC1) inhibitors), mTORC2 inhibitors(mTOR Complex 2 inhibitors)

Therapeutic Areas

NeoplasmsImmune System DiseasesEndocrinology and Metabolic Disease+ [7]

Active Indication-

Inactive Indication

Breast CancerChronic Lymphocytic LeukemiaColorectal Cancer+ [13]

Originator Organization

Sanofi

Active Organization-

Inactive Organization

EMD Serono, Inc.

Sanofi

Exelixis, Inc.

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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Structure

Molecular FormulaC13H14N6O

InChIKeyRGHYDLZMTYDBDT-UHFFFAOYSA-N

CAS Registry934493-76-2

This is a double blind, randomized, placebo-controlled, 2-arm, Phase 2 trial investigating the efficacy and safety of combination therapy of pimasertib plus SAR245409 and pimasertib placebo administered once per day compared to pimasertib administered twice per day plus SAR245409 placebo administered once per day in participants with previously treated unresectable low-grade serous ovarian or peritoneal carcinoma or serous borderline ovarian or peritoneal tumors.

Start Date30 Sep 2013

Sponsor / Collaborator

EMD Serono, Inc.

[+1]

NCT01587040 / CompletedPhase 1/2

International, Multicenter, Open-label, Treatment-extension Study for Subjects Who Completed a Phase 1 or Phase 2 Parental Study to Continue Receiving Treatment With SAR245408 or SAR245409 as a Monotherapy or as a Combination Regimen

Primary Objective:
The purpose of this study was to determine the long term safety and tolerability of SAR245408 and SAR245409 as a monotherapy or as part of a combination regimen in participants who were benefiting from treatment.

Start Date20 Jul 2012

Sponsor / Collaborator

Sanofi

NCT01596270 / CompletedPhase 1

A Phase 1 Dose-escalation Study of the Safety and Pharmacokinetics of a Tablet Formulation of SAR245409 Administered Daily to Patients With Solid Tumors or Lymphoma

Primary Objective:
- To evaluate the safety and tolerability of SAR245409 tablets administered once or twice a day in patients with solid tumors or lymphoma.
Secondary Objectives:
To evaluate blood levels of SAR245409 after administration of SAR245409 tablets once or twice a day in patients with solid tumors or lymphoma.
To evaluate the effect of food on blood levels of SAR245409 after administration of SAR245409 tablets in patients with solid tumors or lymphoma.
To evaluate the effect of SAR245409 on the body after administration of SAR245409 tablets once or twice a day in patients with solid tumors or lymphoma.
To obtain information on how SAR245409 administered once or twice a day to patients with solid tumors or lymphoma affect disease symptoms and study treatment side effects as reported by the patients on a questionnaire.
To explore the antitumor activity of SAR245409 tablets administered once or twice a day to patients with solid tumors or lymphoma.

Start Date01 Jun 2012

Sponsor / Collaborator

Sanofi

100 Clinical Results associated with Voxtalisib Hydrochloride

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100 Translational Medicine associated with Voxtalisib Hydrochloride

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100 Patents (Medical) associated with Voxtalisib Hydrochloride

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44

Literatures (Medical) associated with Voxtalisib Hydrochloride

01 Nov 2022·iScience

Integrative genomic analysis facilitates precision strategies for glioblastoma treatment

Article

Author: Zhang, Ping ; Yang, Chen ; Liu, Zhicheng ; Li, Yan ; Wang, Jingxuan ; Chen, Danyang ; Wu, Zhuojin ; Nie, Hao ; Liu, Na ; Tang, Zhouping ; Zhang, Cuntai ; Pan, Chao ; Xia, Feng ; Tang, Yingxin ; Li, Gaigai

Glioblastoma (GBM) is the most common form of malignant primary brain tumor with a dismal prognosis. Currently, the standard treatments for GBM rarely achieve satisfactory results, which means that current treatments are not individualized and precise enough. In this study, a multiomics-based GBM classification was established and three subclasses (GPA, GPB, and GPC) were identified, which have different molecular features both in bulk samples and at single-cell resolution. A robust GBM poor prognostic signature (GPS) score model was then developed using machine learning method, manifesting an excellent ability to predict the survival of GBM. NVP-BEZ235, GDC-0980, dasatinib and XL765 were ultimately identified to have subclass-specific efficacy targeting patients with a high risk of poor prognosis. Furthermore, the GBM classification and GPS score model could be considered as potential biomarkers for immunotherapy response. In summary, an integrative genomic analysis was conducted to advance individual-based therapies in GBM.

01 Nov 2022·Pathology - Research and Practice

Voxtalisib and low intensity pulsed ultrasound combinatorial effect on glioblastoma multiforme cancer stem cells via PI3K/AKT/mTOR

Article

Author: Uysal, Ayşegül ; Tutak, Irmak ; Ozdil, Berrin

BACKGROUNDGlioblastoma (GBM) is the most aggressive brain tumor contributed to tumor growth by cancer stem cells (CSCs). Targeting CSCs is vital to preventing differentiation into cancer cells, their proliferation, and treatment resistance. According to research, PI3K/AKT/mTOR signaling is active in GBM and GBMCSCs. Anticancer medications combined with ultrasound application have been proposed as a strategy to increase the drug intake of cancer cells. This study aims to investigate the effects of inhibition of PI3K/ AKT/ mTOR pathway with dual inhibitor Voxtalisib (Vox; also known as XL765) and low intensity pulsed ultrasound (LIPUS) combinations in GBM and GBMCSCs in the point of cell survival. F-actin was also used to evaluate cell motility.MATERIALS AND METHODSGBMCSCs were isolated from the human glioblastoma U87 MG cell line using the fluorescence-activated cell sorting (FACS) method. Cells were exposed to various concentrations of Vox, LIPUS, and their combinations. Cell count and viability assay was used to determine drug delivery doses. F-actin and mTOR immunofluorescence staining were used to identify cytoskeletal alterations and PI3K/AKT/mTOR signal pathway suppression, respectively. Additionally, the migration capacity of cells was shown with standard wound-healing experiments.RESULTSHigh doses of Vox+LIPUS inhibited mTOR and decreased the viability in both cell groups. Inhibiting mTOR activated autophagy, and LIPUS increased autophagy in GBM cells. However, GBMCSCs were resistant to autophagy even at high drug dosages. Both in GBM and GBMCSCs, combinations of Vox and LIPUS were observed to decrease F-actin density and cell motility.CONCLUSIONSThe combination of Vox+LIPUS has increased drug effectiveness in targeted GBM and GBMCSCs. Combinatory treatment with PI3K/AKT/mTOR signaling pathway and LIPUS has been thought to help develop more effective therapeutic approaches for GBM.

17 Jun 2022·Evidence-Based Complementary and Alternative Medicine

β-Carotene Attenuates Apoptosis and Autophagy via PI3K/AKT/mTOR Signaling Pathway in Necrotizing Enterocolitis Model Cells IEC-6

Article

Author: Peng, Kun ; Zhou, Chonggao ; Xu, Guang ; Li, Bixiang ; Ma, Tidong ; Zhao, Fan

Background. Necrotizing enterocolitis (NEC) is a devastating disease affecting the gastrointestinal tract in the newborn period. In recent years, the role of apoptosis and autophagy in intestinal mucosal barrier dysfunction has come into prominence in research regarding the pathogenesis of NEC. β-Carotene is a well-known vitamin A precursor, and its content in breast milk is relatively high, especially in the colostrum. In the present study, we investigated the protective effect of β-carotene on necrotizing enterocolitis model cells IEC-6 induced by lipopolysaccharide (LPS). Methods. CCK-8 assay was performed to evaluate cell viability. The Annexin V-FITC/PI method was used to detect apoptosis. Western blotting was utilized to measure the expression levels of proteins. Immunofluorescence analysis was used to assess the autophagy of IEC-6 cells. Results. Our findings indicated that β-carotene inhibited the apoptosis of IEC-6 cells by downregulating cleaved caspase-3 levels and Bax levels and upregulating Bcl-2 levels, reducing cell autophagy via downregulating LC3II/I ratio and upregulating p62 levels. In addition, the expression of p-PI3K, p-AKT, and p-mTOR was upregulated after β-carotene treatment. Interestingly, these changes induced by β-carotene were partially reversed by rapamycin and voxtalisib. Conclusion. In conclusion, our findings indicated that β-carotene can attenuate apoptosis and autophagy of IEC-6 cells induced by LPS via activating the PI3K/AKT/mTOR signaling pathway. Therefore, β-carotene may be a promising drug used in the clinical treatment of NEC.

100 Deals associated with Voxtalisib Hydrochloride

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External Link

KEGG	Wiki	ATC	Drug Bank
-	Voxtalisib Hydrochloride	-	DB12400

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Follicular Lymphoma	Phase 2	US	Sanofi	01 Oct 2011
Hormone receptor positive HER2 negative breast cancer	Phase 2	FR	Sanofi	01 Jun 2010
Hormone receptor positive HER2 negative breast cancer	Phase 2	US	Sanofi	01 Jun 2010
Hormone receptor positive HER2 negative breast cancer	Phase 2	ES	Sanofi	01 Jun 2010
Breast Cancer	Phase 2	FR	Sanofi	-
Breast Cancer	Phase 2	US	Sanofi	-
Breast Cancer	Phase 2	US	Sanofi	-
Breast Cancer	Phase 2	ES	Sanofi	-
Breast Cancer	Phase 2	FR	Sanofi	-
Breast Cancer	Phase 2	ES	Sanofi	-

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Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01936363 (EMR 20006-012, Pubmed) Manual	Phase 2	Ovarian Serous Adenocarcinoma	65	SAR245409+pimasertib	(lmuympcvsh) = kxfyvwbhni sgvsvshxjy (niiqtsmvvr, 3.5 - 19.7) View more	Negative	01 Feb 2020
				Placebo+pimasertib	(lmuympcvsh) = elpaquryih sgvsvshxjy (niiqtsmvvr, 5.4 - 22.8) View more
NCT01587040 (CTgov)	Phase 1/2	Neoplasms	61	SAR245408 (SAR245408: Monotherapy)	wggywtxqyu(lvbwoocylw) = kzvhjxahoc rtzvynivnn (dwdwyfsubq, ytuietxfbe - xuobxjdxlm) View more	-	11 Jun 2019
				SAR245408 (SAR245408: Combination Regimen)	wggywtxqyu(lvbwoocylw) = nduigfahxd rtzvynivnn (dwdwyfsubq, vgptzilkqg - abfrhukmrs) View more
NCT01390818 (Pubmed \| Med J Aust) Manual	Phase 1	Advanced Malignant Solid Neoplasm	146	pimasertib+voxtalisib	(devbykcbor) = pimasertib 60 mg and voxtalisib 70 mg feplsencda (keuvpeftkl ) View more	Negative	01 Dec 2018
NCT01936363 (EMR 20006-012, CTgov)	Phase 2	Ovarian Cancer	65	Pimasertib once daily+Pimasertib placebo+SAR245409 (Pimasertib (Once Daily) Plus SAR245409)	(jfxskjcfog) = krupvopxkk iaszvwprvt (jqyiirppym, ujkqpxeyev - hslubatwtx) View more	-	07 Apr 2017
				Pimasertib twice daily+SAR245409 placebo (Pimasertib (Twice Daily) Plus SAR245409 Placebo)	(jfxskjcfog) = xwmprinwqf iaszvwprvt (jqyiirppym, jwdnyivyer - splzpiqfjl) View more
NCT00704080 (Pubmed \| Neuro Oncol) Manual	Phase 1	High grade glioma	54	radiotherapy+voxtalisib +temozolomide	(cdzfpkuqpi) = The maximum tolerated doses were 90 mg q.d. and 40 mg b.i.d. for voxtalisib in combination with TMZ oijuidecyx (vftpecxfcx ) View more	Positive	01 Sep 2015
				voxtalisib +temozolomide
NCT01390818 (ASCO2012)	Phase 1	Solid tumor	20	pimasertib	(zosekcygkb) = mkftvwleiz lxwbvlreps (snesakedrc )	-	20 May 2012
				SAR245409	(zosekcygkb) = uwlstoxuem lxwbvlreps (snesakedrc )
ASCO2010	Phase 1	Advanced cancer	79	XL765	etaqnvacau(pirotziryo) = edziibtvjj pkyxwxhago (inpodqegui ) View more	-	20 May 2010