Delving into the Latest Updates on AZD-8055 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

AZD 8055, AZD8055

Target

mTORC1 x mTORC2

Action

inhibitors

Mechanism

mTORC1 inhibitors(Mammalian target of Rapamycin (mTORC1) inhibitors), mTORC2 inhibitors(mTOR Complex 2 inhibitors)

Therapeutic Areas

NeoplasmsNervous System DiseasesImmune System Diseases+ [2]

Active Indication-

Inactive Indication

Advanced cancerAdvanced Hepatocellular CarcinomaAdvanced Malignant Solid Neoplasm+ [2]

Originator Organization

AstraZeneca PLC

Active Organization-

Inactive Organization

AstraZeneca PLC

AstraZeneca Pharmaceuticals Co. Ltd.

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC25H31N5O4

InChIKeyKVLFRAWTRWDEDF-IRXDYDNUSA-N

CAS Registry1009298-09-2

Background:
- AZD8055 is an experimental cancer treatment drug that works by inhibiting a protein called mTOR, which is known to promote tumor cell and blood vessel growth and to control tumor s energy and nutrient levels. AZD8055 is the first drug that inhibits both types of mTOR protein and is expected to be more effective than prior mTOR inhibitors. However, more research is needed to determine its safety and effectiveness in treating brain tumors known as gliomas that have not responded to standard treatments.
Objectives:
- To evaluate the safety and effectiveness of AZD8055 in individuals with gliomas that have not responded to standard treatments.
Eligibility:
- Individuals at least 18 years of age who have been diagnosed with gliomas that have not responded to standard chemotherapy, surgery, or radiation.
Design:
Participants will be screened with a physical examination, medical history, blood tests, and tumor imaging studies.
Participants will be separated into two treatment groups: one group that will receive surgery to remove the glioma and one that will not have surgical treatment.
Participants in the nonsurgical treatment group will take AZD8055 by mouth daily for a 42-day cycle of treatment. Participants will keep a diary to record doses and keep track of any side effects.
Participants in the surgical treatment group will take AZD8055 by mouth daily for 7 days, and then will have tumor removal surgery. At least 3 weeks after surgery, participants will resume doses of AZD8055 and will continue to take the drug for as long as the tumor does not recur.
During treatment, participants will have regular visits to the clinical center, involving frequent blood and urine tests and other examinations to monitor the effects of treatment. Participants will have imaging studies to study the cancer's response to the treatment.
Participants will continue to have cycles of treatment for as long as the treatment continues to be effective and the side effects are not severe enough to stop participation in the study....

Start Date04 Mar 2011

Sponsor / Collaborator

National Cancer Institute

JPRN-jRCT2080220891

/ Unknown statusPhase 1

A Phase I, Open Label, Single-centre Study to Assess the Safety and Tolerability of the Tor Kinase Inhibitor AZD8055 Administered Orally to Japanese Patients With Advanced Solid Tumours

Start Date08 Oct 2009

Sponsor / Collaborator

AstraZeneca PLC

NCT00999882

/ CompletedPhase 1

A Phase I/II, Open-label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of Tor Kinase Inhibitor (AZD8055) in Asian Patients With Advanced Stage Hepatocellular Carcinoma (HCC) and With Mild or Moderate Hepatic Impairment

The main purpose of the study is to establish a safe dose of AZD8055 in patients with mild or moderate liver disease by providing information on any potential side effects this drug may cause and collecting data about how hepatocellular carcinoma responds to the drug.

Start Date01 Oct 2009

Sponsor / Collaborator

AstraZeneca PLC

100 Clinical Results associated with AZD-8055

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100 Translational Medicine associated with AZD-8055

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100 Patents (Medical) associated with AZD-8055

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551

Literatures (Medical) associated with AZD-8055

01 Mar 2025·NEURON

Glioma-induced alterations in excitatory neurons are reversed by mTOR inhibition

Article

Author: McKhann, Guy M ; Merricks, Edward M ; Sudhakar, Tejaswi D ; Chen, Cady ; Goldberg, Alexander R ; Humala, Nelson ; Peterka, Darcy S ; Das Sharma, Sohani ; Sims, Peter A ; Dovas, Athanassios ; Boassa, Daniela ; Olabarria, Markel ; Razavilar, Aida ; Gill, Brian J A ; Chokran, Cole ; Hargus, Gunnar ; Kotidis, Corina ; Mela, Angeliki ; Metz, Jordan B ; Calvaresi, Peter ; Bravo-Cordero, Jose Javier ; Bruce, Jeffrey N ; Hillman, Elizabeth M C ; Shokooh, Leila Abrishami ; Zhao, Hanzhi T ; Banu, Matei A ; Pereira, Brianna ; Rosenfeld, Steven S ; Megino-Luque, Cristina ; Saxena, Ankita ; Canoll, Peter ; Ellisman, Mark H ; Torres, Daniela ; Mahajan, Aayushi ; Viswanathan, Ashwin ; Xu, Weihao ; Schevon, Catherine A ; Bushong, Eric A ; McInvale, Julie J

Gliomas are aggressive neoplasms that diffusely infiltrate the brain and cause neurological symptoms, including cognitive deficits and seizures. Increased mTOR signaling has been implicated in glioma-induced neuronal hyperexcitability, but the molecular and functional consequences have not been identified. Here, we show three types of changes in tumor-associated neurons: (1) downregulation of transcripts encoding excitatory and inhibitory postsynaptic proteins and dendritic spine development and upregulation of cytoskeletal transcripts via neuron-specific profiling of ribosome-bound mRNA, (2) marked decreases in dendritic spine density via light and electron microscopy, and (3) progressive functional alterations leading to neuronal hyperexcitability via in vivo calcium imaging. A single acute dose of AZD8055, a combined mTORC1/2 inhibitor, reversed these tumor-induced changes. These findings reveal mTOR-driven pathological plasticity in neurons at the infiltrative margin of glioma and suggest new strategies for treating glioma-associated neurological symptoms.

01 Mar 2025·Biochemistry and Biophysics Reports

An integrated machine learning framework for developing and validating a prognostic risk model of gastric cancer based on endoplasmic reticulum stress-associated genes

Article

Author: Liu, Lei ; Wei, Gang ; Wang, Yan ; Liu, Ru

Background:

Gastric cancer (GC), a prevalent and deadly malignancy, demonstrates poor survival outcomes. Evidence has emerged indicating that disruptions in endoplasmic reticulum homeostasis are significantly implicated in the onset and progression of various oncological conditions. This study was designed to construct a prognostic model based on genes related to endoplasmic reticulum stress(ERS) to predict survival outcomes in patients with GC.

Methods:

Expression profiling data for GC samples were extracted and analyzed from TCGA-STAD, revealing 214 genes related to endoplasmic reticulum stress that show differential expression when compared with normal gastric tissue. Building on these insights, a prognostic model was formulated using data from TCGA-STAD and validated through subsequent analyses of GEO datasets. The tumor immune dysfunction and exclusion(TIDE) algorithm was applied to determine the susceptibility of individuals in high- and low-risk categories to immunotherapy. The presence of immune and stromal cells within the tumor microenvironment was assessed with the aid of the ESTIMATE algorithm. Sensitivity variations to prevalent anticancer drugs between the risk groups were evaluated using the Genomics of Drug Sensitivity in Cancer(GDSC) database, and prospective therapeutic agents were confirmed through molecular docking techniques.

Results:

Thirty-one endoplasmic reticulum stress (ERS)-related differentially expressed genes (DEGs) crucial for prognosis in GC were pinpointed. These DEGs were then used to construct a prognostic model and were considered as independent prognostic factors for GC patients. This risk model proved to have a good predictive performance for estimating the overall survival of these patients. The patients placed into the high-risk group showed worse results and lower sensitivity to immunotherapy. Moreover, five specific targeted therapy drugs, namely BMS-754807, Dasatinib, JQ1, AZD8055 and SB505124, produced better results in the treatment of the high-risk group of patients.

Conclusions:

A new molecular prognostic model associated with ERS was established and validated for GC and showed relatively good discriminative and predictive ability. This model greatly expands the collection of weapons in the armoury of prognostic analysis in GC.

01 Feb 2025·PLANT GROWTH REGULATION

The role of TOR in response to chilling stress in the Solanum lycopersicum L

Author: Xing, Hongyun ; Yu, Yang ; Fan, Haiyan ; Yang, Zhi ; Meng, Xiangnan ; Cui, Na ; Ding, Qi ; Zhang, Yujiao ; Wang, Haoran

Tomato production in northern China is often susceptible to chilling stress, which seriously affects the growth and development, yield and quality of tomato.Recently, we found that the target of rapamycin (TOR) might be involved in the response to chilling of tomato.So we exogenously applied TOR inhibitor AZD8055 and activator MHY1485 to clarify the role of TOR signaling in tomato response to chilling stress.The research results showed that the damage caused by chilling stress was relieved due to the TOR signaling was inhibited by AZD8055.The development degree of seedlings and root activity increased compared with the control group, while the chilling injury index decreased.At the same time, after the AZD8055 treatment, the REC and MDA contents were significantly decreased, and membrane lipid damage was reduced.NBT and DAB staining results showed that the color was lighter, and the area was smaller under AZD8055 treatment while the contents of O₂- and H₂O₂ increased.Under chilling stress, the application of AZD8055 increased the activity of the antioxidases SOD, CAT, POD, GR, and APX and improved the expression of the SOD, CAT, POD, GR, and APX antioxidase genes.Photosynthetic efficiency, chlorophyll content, energy dissipation and Fv/Fm also improved.The GSH content was reduced, and the GSSG content was increased.In addition, the contents of ASA and soluble protein also increased.Therefore, TOR signaling played a neg. regulatory role in tomato response to chilling stress.

100 Deals associated with AZD-8055

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External Link

KEGG	Wiki	ATC	Drug Bank
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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Glioma	Phase 2	-	AstraZeneca Pharmaceuticals Co. Ltd.	-
Advanced cancer	Phase 1	-	AstraZeneca PLC	02 Sep 2010
Lymphoma	Phase 1	-	AstraZeneca PLC	02 Sep 2010
Advanced Hepatocellular Carcinoma	Phase 1	Hong Kong	AstraZeneca PLC	01 Oct 2009
Advanced Hepatocellular Carcinoma	Phase 1	South Korea	AstraZeneca PLC	01 Oct 2009
Advanced Malignant Solid Neoplasm	Phase 1	United States	AstraZeneca PLC	01 Jul 2008
Advanced Malignant Solid Neoplasm	Phase 1	France	AstraZeneca PLC	01 Jul 2008
Advanced Malignant Solid Neoplasm	Phase 1	United Kingdom	AstraZeneca PLC	01 Jul 2008

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00973076 (Pubmed \| Invest New Drugs)	Phase 1	Advanced Malignant Solid Neoplasm	19	AZD8055	edumowidmh(abgqriwhvt) = one dose limiting toxicity (n=1) of increased alanine aminotransferase was observed in the 90 mg BID cohort (n=1) hbazrzytau (ipcahkjhqi ) View more	-	01 Jun 2013
NCT00731263 (ASCO2011)	Phase 1	Advanced Malignant Solid Neoplasm	49	AZD8055	qqrkxdqgmf(rwgrkwlqhc) = kkymevmgkh gilgeljkpw (tpydcjoaye ) View more	-	20 May 2011