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

Action

inhibitors

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

Borderline serous tumour of ovaryBreast CancerChronic Lymphocytic Leukemia+ [16]

Originator Organization

Sanofi

Active Organization-

Inactive Organization

License Organization

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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Structure/Sequence

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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90

Literatures (Medical) associated with Voxtalisib Hydrochloride

01 Feb 2023·Neuropharmacology

The common genes involved in the pathogenesis of Alzheimer's disease and type 2 diabetes and their implication for drug repositioning

Article

Author: Yuan, Xin ; Wang, Ju ; Wang, Hao ; Zhang, Fengyu ; Zhang, Meidi ; Wang, Qiuchen

BACKGROUNDThe prevalences of Alzheimer's disease (AD) and type 2 diabetes (T2D) continuously increase with the aging of world population. Clinical and epidemiological studies indicate that T2D is an important risk factor for AD. However, the mechanisms underlying the linkage of the two disorders are still not fully elucidated. The aim of this study is to explore the molecular mechanisms of their comorbidity and potential drug targets for AD treatment.METHODSWe first compiled comprehensive lists of genes associated with AD and T2D, respectively. Then, we investigated the signatures of the shared genes and screened for interactions between the hub genes. Subsequently, we used Autodock Vina to perform molecular docking to predict new drug candidates. Lastly, structure and dynamics of docking results were examined by molecular dynamics simulation to verify drug reliability.RESULTSWe obtained 917 AD-associated genes, 631 T2D-associated genes and 175 shared genes between the two disorders for subsequent analyses. Functional analysis revealed that metabolic process, lipid and atherosclerosis, AMPK signaling pathway, insulin resistance, chemokines and cytokines were enriched in the shared genes. In addition, 50 central hub genes were identified, including IL6, TNF, INS, IL1B, AKT1, VEGFA, IL10, TP53, PTGS2, TLR4, and others. Finally, we predicted new drug candidates (verdoheme and stannsoporfin) that could be potentially used for AD treatment.CONCLUSIONSOur study confirmed that there are important shared genes and pathways between AD and T2D, which may provide clues to reveal the molecular mechanism underlying the pathophysiology of the two diseases and help us to discover novel drug candidates for the treatment of AD. The results may also provide clues into identification of new targets and strategies for prevention and therapy of T2D that predisposes to AD.

01 Dec 2022·European Journal of Pharmacology

Phenotypic screening identifies hydroxypyridone anti-fungals as novel medicines for the prevention of hypertrophic scars

Article

Author: Cellek, Selim ; Lapthorn, Alice Ruth ; Sullivan, Justine Victoria ; Ilg, Marcus Maximillian ; Dziewulski, Peter

Although hypertrophic scarring affects ∼91% of burn patients annually, there is no drug to prevent this common complication. Hypertrophic scars are a result of dysregulated wound healing, characterised by persistent myofibroblast transformation and the excessive accumulation of extracellular matrix (ECM). Due to the multi-mechanistic nature of the scarring process, target-based approaches for identifying novel drugs have failed. Primary human dermal fibroblasts, derived from burn scar tissue, were exposed to transforming growth factor-beta 1 (TGF-β1) to induce myofibroblast transformation. A phenotypic screening assay, measuring alpha-smooth muscle actin (α-SMA) expression, was developed to screen 1,954 approved drugs. Drugs that elicited >80% inhibition of α-SMA expression, and >80% cell viability were progressed as candidate drugs. Anti-myofibroblast activity of the candidates was confirmed before investigating their effects on extracellular matrix (ECM) production and keratinocyte epithelial-mesenchymal transition (EMT). TGF-β1 induced myofibroblast transformation in primary human dermal fibroblasts (E_max = >3 ng/mL). The assay was optimised and validated (Z' = 0.59), before screening 1,954 approved drugs. 90 drugs were identified as hits and hydroxypyridone anti-fungals selected for further testing. Concentration-response curves for these drugs confirmed their concentration-dependent anti-myofibroblast activity (IC₅₀ = 1.4 - 16.7 μM). Hydroxypyridone anti-fungals were also found to successfully reduce ECM production and keratinocyte EMT. This is the first study to screen approved drugs in primary human dermal fibroblasts. Hydroxypyridone anti-fungals were found to prevent myofibroblast transformation, ECM production and keratinocyte EMT suggesting they could be repurposed to prevent hypertrophic scarring.

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 ; Tang, Yingxin ; Xia, Feng ; 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.

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
Diffuse Large B-Cell Lymphoma	Phase 2	Germany	Sanofi	01 Oct 2011
Diffuse Large B-Cell Lymphoma	Phase 2	United States	Sanofi	01 Oct 2011
Diffuse Large B-Cell Lymphoma	Phase 2	Netherlands	Sanofi	01 Oct 2011
Diffuse Large B-Cell Lymphoma	Phase 2	France	Sanofi	01 Oct 2011
Diffuse Large B-Cell Lymphoma	Phase 2	Belgium	Sanofi	01 Oct 2011
Diffuse Large B-Cell Lymphoma	Phase 2	Australia	Sanofi	01 Oct 2011
Mantle cell lymphoma refractory	Phase 2	Australia	Sanofi	01 Oct 2011
Hormone receptor positive HER2 negative breast cancer	Phase 2	France	Sanofi	01 Jun 2010
Hormone receptor positive HER2 negative breast cancer	Phase 2	Spain	Sanofi	01 Jun 2010
Hormone receptor positive HER2 negative breast cancer	Phase 2	United States	Sanofi	01 Jun 2010

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01936363 (EMR 20006-012, Pubmed) Manual	Phase 2	Ovarian Serous Adenocarcinoma	65	SAR245409+pimasertib	(emyznezdyv) = ftpgoiaqjr zkfgrkiroc (rkbggduwif, 3.5 - 19.7) View more	Negative	01 Feb 2020
				Placebo+pimasertib	(emyznezdyv) = yffavdsxlz zkfgrkiroc (rkbggduwif, 5.4 - 22.8) View more
NCT01587040 (CTgov)	Phase 1/2	Neoplasms	61	SAR245408 (SAR245408: Monotherapy)	etqxvsiitu(xaoorjhavl) = gzkzrrsaeg lnatvqhhpn (bqvhjsnsvs, viiqhilmal - qykpahwfze) View more	-	11 Jun 2019
				SAR245408 (SAR245408: Combination Regimen)	etqxvsiitu(xaoorjhavl) = iwpydoajqn lnatvqhhpn (bqvhjsnsvs, qitkddklzq - whmosuzswe) View more
NCT01390818 (Pubmed \| Med J Aust) Manual	Phase 1	Advanced Malignant Solid Neoplasm	146	pimasertib+voxtalisib	(stdnbsknsz) = pimasertib 60 mg and voxtalisib 70 mg hxeosujaze (xmhzkcbnnc ) View more	Negative	01 Dec 2018
NCT01936363 (EMR 20006-012, CTgov)	Phase 2	Ovarian Cancer \| Borderline serous tumour of ovary	65	Pimasertib once daily+Pimasertib placebo+SAR245409 (Pimasertib (Once Daily) Plus SAR245409)	(gnhbasmyyw) = rnmvtdrqyw ppiqolrkjz (algxxroqeu, gkkhbdofjh - yezvvwoamz) View more	-	07 Apr 2017
				Pimasertib twice daily+SAR245409 placebo (Pimasertib (Twice Daily) Plus SAR245409 Placebo)	(gnhbasmyyw) = lobxjycfka ppiqolrkjz (algxxroqeu, hqrkizaxuf - dnjcbaksvm) View more
NCT00704080 (Pubmed \| Neuro Oncol) Manual	Phase 1	High grade glioma	54	radiotherapy+voxtalisib +temozolomide	(ygdcmucbxj) = The maximum tolerated doses were 90 mg q.d. and 40 mg b.i.d. for voxtalisib in combination with TMZ nhgkaafmbi (iaxlpqjxys ) View more	Positive	01 Sep 2015
				voxtalisib +temozolomide
NCT01390818 (ASCO2012)	Phase 1	Solid tumor	20	pimasertib	(ybzdsepfmv) = bdyjcpgzyu bvtderkixc (nnmlbqxlfv )	-	20 May 2012
				SAR245409	(ybzdsepfmv) = tcuclbeqyk bvtderkixc (nnmlbqxlfv )
ASCO2010	Phase 1	Advanced cancer	79	XL765	voscihcgej(adqmhqlakq) = nbbyptwlad nrdxooygra (kxsturhqsc ) View more	-	20 May 2010