Delving into the Latest Updates on Vistusertib with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Vistusertib (JAN/INN)

+ [2]

Target

mTOR

Action

inhibitors

Mechanism

mTOR inhibitors(Serine/threonine-protein kinase mTOR inhibitors)

Therapeutic Areas

NeoplasmsRespiratory DiseasesSkin and Musculoskeletal Diseases+ [3]

Active Indication

metastatic non-small cell lung cancerBreast cancer recurrenthigh grade serous adenocarcinoma of ovary+ [11]

Inactive Indication

Advanced breast cancerAdvanced cancerCastration-Resistant Prostatic Cancer+ [19]

Originator Organization

AstraZeneca Pharmaceuticals Co. Ltd.

Active Organization

AstraZeneca PLC

National Cancer Institute

Inactive Organization

Acerta Pharma BV

Samsung Medical Center

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC25H30N6O3

InChIKeyJUSFANSTBFGBAF-IRXDYDNUSA-N

CAS Registry1009298-59-2

This phase I/II trial studies the best dose and side effects of navitoclax and how well it works when given together with vistusertib in treating patients with small cell lung cancer and solid tumors that have come back (relapsed). Drugs used in chemotherapy, such as navitoclax, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Vistusertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving navitoclax and vistusertib may work better than navitoclax alone in treating patients with small cell lung cancer and solid tumors.

Start Date20 Mar 2018

Sponsor / Collaborator

National Cancer Institute

NCT03166904

/ WithdrawnPhase 2IIT

AZD2014 in RICTOR Amplified Solid Cancer

Patients with RICTOR amplified refractory solid cancer will receive vistusertib(AZD2014). Study-arm is composed of 27 patients.
Vistusertib(AZD2014) 50mg BD continuous schedule of a 28 day cycle Tumour evaluation using RECIST 1.1 will be conducted at screening (within 28 days prior to first dose) and every 8 weeks relative to the date of first dose, up to week 40, then every 16 weeks until objective disease progression (within a window of +/- 7 days of the scheduled date).

Start Date01 Mar 2018

Sponsor / Collaborator

Samsung Medical Center

NCT03166176

/ WithdrawnPhase 2IIT

SAMSUNG MEDICAL CENTER

Patients with TSC1/2 mutated refractory solid cancer will receive vistusertib(AZD2014) monotherapy. Study-arm is composed of 27 patients. Vistusertib(AZD2014) 50mg BD continuous schedule of a 28 day cycle as a monotherapy

Start Date01 Mar 2018

Sponsor / Collaborator

Samsung Medical Center

100 Clinical Results associated with Vistusertib

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100 Translational Medicine associated with Vistusertib

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100 Patents (Medical) associated with Vistusertib

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228

Literatures (Medical) associated with Vistusertib

01 Feb 2025·Disease Models & Mechanisms

Use of metabolic imaging to monitor heterogeneity of tumour response following therapeutic mTORC1/2 pathway inhibition

Article

Author: Poulogiannis, George ; Hamm, Gregory ; Polanska, Urszula M. ; Brindle, Kevin ; Marshall, John F. ; Takats, Zoltan ; Yuneva, Mariia O. ; Sharma, Shreya ; Race, Alan M. ; Sansom, Owen J. ; Campbell, Andrew D. ; Goodwin, Richard J. A. ; Barry, Simon T. ; Dexter, Alex ; Ling, Stephanie ; Bunch, Josephine

ABSTRACTThe PI3K–mTOR–AKT pathway regulates tumour proliferation, gene expression and metabolism, but pathway inhibition induces heterogeneous feedback reactivation, limiting anti-tumour responses. Measuring heterogeneity of pathway inhibition in tissues using protein biomarker phosphorylation or location is challenging. An integrated multi-modal imaging workflow was developed to assess the heterogeneity of AZD2014 (mTORC1/2 inhibitor) response in a PTEN-null renal cancer model. Spatial responses of metabolite biomarkers were analysed by mass spectrometry imaging (MSI). Control and treated tumours were classified according to metabolite-defined regions enriched in control versus AZD2014-treated tumours, respectively. Noticeably, AZD2014-treated tumours retained regions similar to regions dominant in untreated tumours. Imaging mass cytometry analysis of protein biomarkers in ‘control-like’ regions following AZD2014 treatment showed reduced phospho-S6, indicating suppression, but retained high expression of the glucose transporter GLUT1. Increasing PI3K–AKT inhibition by combining with AZD8186 (PI3Kβ inhibitor) further decreased the control-like metabolic signature, showing PI3K-dependent resistance. This demonstrates that MSI-based workflows yield novel insights into the pharmacodynamic effects of mTORC1/2 inhibition in tumours, which classical biomarkers do not resolve. Coupling these workflows with spatial-omics approaches can deliver greater insights into heterogeneity of treatment response.

01 Jan 2025·Journal of Cancer

Mitochondrial Gene Scoring System: Predicting Prognosis and Precision Therapy for TACE Non-Response in Hepatocellular Carcinoma Patients

Article

Author: Wang, Yi-Xian ; Guo, Jia-Wei ; Wu, Wen-Ze ; Ma, Jian-Ying ; Xiong, Zhen-Yu ; Zhao, Zhen-Yu ; Wei, Wei ; Mei, Jie

Objective: Given the crucial role of mitochondria in the prognosis and treatment of hepatocellular carcinoma (HCC), we aim to develop two independent mitochondrial scoring systems to separately predict patient prognosis and the likelihood of transarterial chemoembolization non-response (TACE NR). Methods: Mitochondria-related candidate genes were selected and analyzed using univariate Cox and LASSO Cox regression analyses to create a risk prognosis score (RPS). Univariate and LASSO logistic regression analyses were used to establish the risk diagnosis score (RDS). Alternative therapies for patients with TACE NR were explored using TIDE and oncoPredict algorithms. The Seurat package was used to study the involvement of the RDS genes in HCC differentiation. Results: The RPS accurately predicts the 1-5 year survival rates of patients with HCC, where higher RPS values were associated with poorer survival outcomes. The RDS model demonstrated a commendable performance in diagnosing TACE NR, as patients with a higher RDS exhibited a greater likelihood of TACE NR. RDS was associated with the infiltration of various immune cells, and patients with lower RDS tended to have higher response rates to immunotherapy and increased sensitivity to JAK1, rapamycin, and AZD2014. By contrast, patients with higher RDS values and a higher probability of TACE NR had more responsive to paclitaxel, dasatinib, and vincristine, suggesting that these drugs are potential alternative therapies. Single-cell sequencing studies have identified ACSM2A as a key player in HCC differentiation and a potential target for therapeutic intervention. Conclusion: The RPS and RDS are important reference points for predicting outcomes and guiding treatment decisions in patients with HCC. Additionally, ACSM2A shows promise as a potential therapeutic target for HCC.

01 Dec 2024·European Journal of Cell Biology

Increased mTOR activity and RICTOR copy number in small cell lung carcinoma progression

Article

Author: Szalai, Fatime ; Nagy, Noémi ; Pápay, Judit ; Sebestyén, Anna ; Khoór, András ; Dankó, Titanilla ; Moldvai, Dorottya ; Sztankovics, Dániel ; Krencz, Ildikó

Small cell lung carcinoma (SCLC) is a highly malignant cancer with early metastatic dissemination and poor clinical outcomes. Mutations in the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway, including the frequently occurring rapamycin-insensitive protein (RICTOR) amplification, have been described in these tumours. Moreover, the associated mTOR hyperactivity could be exploited for personalised treatment. Our aim was to study mTOR activity, RICTOR amplification, and their role during SCLC progression. In situ mTOR activity and Rictor expression were characterised by immunohistochemistry in 50 primary and 50 brain metastatic tumours, and 14 paired SCLC patient samples. RICTOR copy number changes were analysed by fluorescence in situ hybridisation of the paired SCLC patient samples and in vivo experiments. Additionally, in vitro sensitivity to cisplatin and mTOR inhibitors was evaluated in SCLC cell lines harbouring RICTOR amplification and other mTOR pathway mutations. High Rictor expression and mTOR complex 2 (mTORC2) hyperactivity were significantly associated with brain metastases and worse overall survival. An increase in RICTOR copy number was observed in paired samples during progression. The importance of these alterations was confirmed both by the sensitising effect of vistusertib in vitro and the RICTOR copy number/expression changes in xenografts. Our study highlights the role of mTORC2 in SCLC progression. Early detection of RICTOR amplification in primary tumours and targeting mTORC2 in these cases may represent a promising novel strategy to develop personalised therapy for metastasis prevention.

100 Deals associated with Vistusertib

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External Link

KEGG	Wiki	ATC	Drug Bank
D10887	-	-	DB11925

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Advanced breast cancer	Phase 1	Portugal	AstraZeneca PLC	16 Jan 2014
Advanced breast cancer	Phase 1	Georgia	AstraZeneca PLC	16 Jan 2014
Advanced breast cancer	Phase 1	Hungary	AstraZeneca PLC	16 Jan 2014
Advanced breast cancer	Phase 1	Germany	AstraZeneca PLC	16 Jan 2014
Advanced breast cancer	Phase 1	France	AstraZeneca PLC	16 Jan 2014
Advanced breast cancer	Phase 1	Spain	AstraZeneca PLC	16 Jan 2014
Advanced breast cancer	Phase 1	Romania	AstraZeneca PLC	16 Jan 2014
Advanced breast cancer	Phase 1	United Kingdom	AstraZeneca PLC	16 Jan 2014
Advanced breast cancer	Phase 1	South Korea	AstraZeneca PLC	16 Jan 2014
Metastatic Clear Cell Renal Cell Carcinoma	Preclinical	United Kingdom	AstraZeneca PLC	01 Feb 2013

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03366103 (CTgov)	Phase 1/2	Refractory Malignant Solid Neoplasm \| Recurrent Lung Small Cell Carcinoma \| Non-small cell lung cancer stage IIIA \| Relapsed Solid Neoplasm \| Metastatic Solid Tumor \| Non-small cell lung cancer stage IIIB \| metastatic non-small cell lung cancer \| Unresectable Solid Neoplasm	15	Vistusertib+Navitoclax (Phase 1 - Dose Level 1)	sqtabtseuv(bfcnhowhma) = ygttjshmoj mhesxtjqnm (nuvbwgxkxh, jnkidmneqv - aqdkoptjny) View more	-	03 May 2023
				Vistusertib+Navitoclax (Phase 1 - Dose Level 2)	sqtabtseuv(bfcnhowhma) = mmxgwiapvz mhesxtjqnm (nuvbwgxkxh, upxrcqvrzr - qcjzjvvkks) View more
NCT02730923 (VICTORIA, Pubmed \| JAMA Oncol)	Phase 1/2	Metastatic endometrial cancer	75	Vistusertib + Anastrozole	vnqroxhzfs(tluewexbos) = wabjpsczms mdcyfsynkx (lzkhbhnsmi, 54.7%) View more	Positive	12 May 2022
				Anastrozole	vnqroxhzfs(tluewexbos) = vbyywseuum mdcyfsynkx (lzkhbhnsmi, 22.2%) View more
NCT03071874 (CTNI-54, SNO2021)	Phase 2	Meningioma	-	Vistusertib 125mg twice daily	lirfyfikns(djlzxjneuk) = qitjlfacyc rxtiwqvtyz (smxwjyrajy, 26% - 65) View more	Positive	12 Nov 2021
NCT03071874 (ASCO 12021 \| ASCO 22021) Manual	Phase 2	Meningioma	-	vistusertib 125 mg	(wsljfmmqem) = ftlehomaso yhqsjftfmm (jojsobiqbw, 29.3 - 70.0)	Positive	20 May 2021
NCT03205046 (CTgov)	Phase 1/2	Diffuse Large B-Cell Lymphoma \| Richter's syndrome	25	Vistusertib+Acalabrutinib (Acalabrutinib 100 mg BID* Plus Vistusertib BID* Continuous)	xksmgxoefi(tuvrdemorw) = rvnysxlaql jkxjvfkmxq (qjxowfhpeo, dlclgexqyh - iaxavlmgjl) View more	-	06 Jan 2021
				Vistusertib+Acalabrutinib (Acalabrutinib 100 mg BID* Plus Vistusertib BID* Intermittent)	xksmgxoefi(tuvrdemorw) = qlktwyksyu jkxjvfkmxq (qjxowfhpeo, biansbxsyr - jksnsrydal) View more
NCT02831257 (CTgov)	Phase 2	Meningioma \| Neurofibromatosis 2	18	AZD2014	vkwfrnagyo(eayzstcazi) = mxcqrvahkk pcutexcowe (akrpavxqfc, iboroqjlhi - htjpiahack) View more	-	22 Dec 2020
NCT02619864 (CCTG, Pubmed) Manual	Phase 1	Glioblastoma Multiforme	15	vistusertib+temozolomide	(hqnejilpea) = Vistusertib 125 mg BID in combination with TMZ 150 mg/m2 daily for 5 days yhnbrqqhkj (xkbjumaebq ) View more	Positive	01 Aug 2020
NCT02752204 (TORCH, Pubmed) Manual	Phase 2	Diffuse Large B-Cell Lymphoma	36	vistusertib	(dgbonaujbt) = nrmbtrhzev ficasplhii (yvledgmtfu, 1.61 - 2.14) View more	Positive	01 Oct 2019
				vistusertib	(vnkgsibqrd) = bphgiwwnei ndvaaurtwl (tpwbgwidvy ) View more
NCT03106155 \| NCT03366675 \| NCT02593019 (ASCO 12019 \| ASCO 22019) Manual	Phase 2	Small Cell Lung Cancer	50	AZD1775 (Patients with MYC family amplification or co-alteration in CDKN2A and TP53)	(xebqyxkwur) = SUKSES-C & -N1 (n = 1, 3.2%) bygnhserom (ustmzswviu )	Negative	26 May 2019
				AZD1775 (non-biomarker)
NCT02640755 (14C, CTgov)	Phase 1	Advanced Malignant Solid Neoplasm	4	[14C]-AZD2014 ([14C]-AZD2014 (Period 1 [Day 1 - 8]))	rikgqynpdm(wskvlwbmdi) = nnsnvjjbeu nhhhqrbknv (xwspbiwpta, eqmgtptcun - deiasytdgx) View more	-	22 Apr 2019
				[14C]-AZD2014+AZD2014 ([14C]-AZD2014 Then AZD2014 Monotherapy)	hgjtuyhwxx(cxwhzgmknd) = dhgltnlkdl twcusbhkdh (fegzuqanfs, ilbrrpemvp - geutjnavqb) View more