Delving into the Latest Updates on Aminoflavone with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

+ [2]

Target

p53

Action

stimulants

Mechanism

p53 stimulants(Tumor protein p53 stimulants), Apoptosis stimulants

Therapeutic Areas

NeoplasmsSkin and Musculoskeletal DiseasesDigestive System Disorders+ [3]

Active Indication-

Inactive Indication

Advanced Malignant Solid NeoplasmBreast cancer recurrentEstrogen receptor positive breast cancer+ [10]

Originator Organization

National Cancer Institute

Active Organization-

Inactive Organization

Tigris Pharmaceuticals

National Cancer Institute

Kirax Corp.

License Organization-

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC16H11F3N2O2

InChIKeyRTUZVPPGTJRELI-UHFFFAOYSA-N

CAS Registry165179-35-1

This phase I trial studies the side effects and best dose of AFP464 in treating patients with metastatic or refractory solid tumors that cannot be removed by surgery. Drugs used in chemotherapy, such as AFP464, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

Start Date01 Jul 2006

Sponsor / Collaborator

National Cancer Institute

100 Clinical Results associated with Aminoflavone

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100 Translational Medicine associated with Aminoflavone

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100 Patents (Medical) associated with Aminoflavone

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42

Literatures (Medical) associated with Aminoflavone

01 Jan 2023·Annals of Translational Medicine

Systematic pan-cancer analysis identifies cGAS as an immunological and prognostic biomarker

Article

Author: Chen, Peng ; Yang, Xian ; Yu, Lingfeng ; Fang, Huipeng ; Chen, Yujie ; Huang, Zhijian ; He, Hao ; Wang, Feng ; Wang, Peiyuan

BackgroundThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus causes novel coronavirus disease 2019 (COVID-19), which is characterized by pneumonia, cytokine storms, and lymphopenia. Due to immunosuppression, cancer patients may be more susceptible to SARS-CoV-2 and have more serious complications. According to recent research, cyclic GMP-AMP synthase (cGAS) could be a potential SARS-CoV-2 sensor. However, at present, no studies have been conducted on cGAS gene alterations in pan-cancer. This study aimed to discover therapeutic implications for COVID-19-infected tumor patients by performing a comprehensive analysis of cGAS in malignant tumors.MethodscGAS expression matrices were obtained from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Cancer Cell Line Encyclopedia (CCLE) databases, which were used to evaluate cGAS expression in various tumors, its prognostic value, and its relationship to the immune microenvironment, microsatellite instability (MSI), immune neoantigens, gene mutations, immune checkpoints, MSI, tumor mutational burden (TMB), mismatch repair (MMR) genes, and DNA methyltransferases (DNMT). We also used the cBioPortal, Human Protein Atlas (HPA), and GeneMANIA databases to explore the types of changes, gene networks and immunofluorescence localization, and protein expression of these genes.ResultsCompared to normal tissues, cGAS was highly expressed in 13 types of cancer (e.g., lung cancer) and lowly expressed in other cancers (e.g., pancreatic cancer). cGAS expression was associated with prognosis in nine cancers, such as renal clear cell carcinoma (P<0.05). Furthermore, deep deletion was the most common type of cGAS genomic mutation. DNMT, immune infiltration levels, TMB, MSI, MMR genes, neoantigens, and immune checkpoints were all correlated with cGAS expression. Moreover, we used the GSE30589 dataset to investigate the post-SARS-CoV infection changes in cGAS expression in vitro. Finally, mithramycin, MI219, AFP464, aminoflavone, kahalide F, AT13387, doxorubicin, and other drugs increased the sensitivity of cGAS expression. According to the evidence presented above, cGAS may become an important target for cancer therapy.ConclusionsThis study discovered that SARS-CoV-2-infected cancer patients might experience changes in their tumor environment as a result of cGAS, making patients with tumors expressing high cGAS more susceptible to COVID-19 and possibly a worsening prognosis. Furthermore, cGAS may be a novel biomarker for diagnosing and treating COVID-19-infected tumor patients.

01 Apr 2020·Cancer ResearchQ1 · MEDICINE

Thermal Proteome Profiling Identifies Oxidative-Dependent Inhibition of the Transcription of Major Oncogenes as a New Therapeutic Mechanism for Select Anticancer Compounds

Q1 · MEDICINE

Article

Author: Singh, Madhurendra ; Carlson, Joseph W. ; Zubarev, Roman ; Rihani, Ali ; Hjerpe, Elisabet ; Selivanova, Galina ; Visnes, Torkild ; Shi, Yao ; Joneborg, Ulrika ; Peuget, Sylvain ; Moyano-Galceran, Lidia ; Gaetani, Massimiliano ; Saei, Amir Ata ; Helleday, Thomas ; Hartman, Johan ; Sanz, Gema ; Zhu, Jiawei ; Lehti, Kaisa ; Lindström, Mikael S. ; Chen, Xinsong

AbstractIdentification of the molecular mechanism of action (MoA) of bioactive compounds is a crucial step for drug development but remains a challenging task despite recent advances in technology. In this study, we applied multidimensional proteomics, sensitivity correlation analysis, and transcriptomics to identify a common MoA for the anticancer compounds RITA, aminoflavone (AF), and oncrasin-1 (Onc-1). Global thermal proteome profiling revealed that the three compounds target mRNA processing and transcription, thereby attacking a cancer vulnerability, transcriptional addiction. This led to the preferential loss of expression of oncogenes involved in PDGF, EGFR, VEGF, insulin/IGF/MAPKK, FGF, Hedgehog, TGFβ, and PI3K signaling pathways. Increased reactive oxygen species level in cancer cells was a prerequisite for targeting the mRNA transcription machinery, thus conferring cancer selectivity to these compounds. Furthermore, DNA repair factors involved in homologous recombination were among the most prominently repressed proteins. In cancer patient samples, RITA, AF, and Onc-1 sensitized to poly(ADP-ribose) polymerase inhibitors both in vitro and ex vivo. These findings might pave a way for new synthetic lethal combination therapies.Significance: These findings highlight agents that target transcriptional addiction in cancer cells and suggest combination treatments that target RNA processing and DNA repair pathways simultaneously as effective cancer therapies.

01 Jan 2019·Journal of Cellular PhysiologyQ2 · BIOLOGY

AhR ligand aminoflavone suppresses α6‐integrin–Src–Akt signaling to attenuate tamoxifen resistance in breast cancer cells

Q2 · BIOLOGY

Article

Author: Denham, Laura J. ; Nagaraj, Gayathri ; Opoku‐Agyeman, Anna ; Soto, Ubaldo ; Brantley, Eileen J. ; Schiff, Rachel ; Davis, Melissa B. ; Mavingire, Nicole ; Wooten, Jonathan V. ; Khan, Salma ; Guevara, Ashley ; Cavalli, Fiorella ; Rowland, Leah K. ; Loaiza‐Pérez, Andrea Irene ; Adeoye, Olayemi ; Jenkins, Brittany D. ; Campbell, Petreena S.

More than 40% of patients with luminal breast cancer treated with endocrine therapy agent tamoxifen demonstrate resistance. Emerging evidence suggests tumor initiating cells (TICs) and aberrant activation of Src and Akt signaling drive tamoxifen resistance and relapse. We previously demonstrated that aryl hydrocarbon receptor ligand aminoflavone (AF) inhibits the expression of TIC gene α6‐integrin and disrupts mammospheres derived from tamoxifen‐sensitive breast cancer cells. In the current study, we hypothesize that tamoxifen‐resistant (TamR) cells exhibit higher levels of α6‐integrin than tamoxifen‐sensitive cells and that AF inhibits the growth of TamR cells by suppressing α6‐integrin–Src–Akt signaling. In support of our hypothesis, TamR cells and associated mammospheres were found to exhibit elevated α6‐integrin expression compared with their tamoxifen‐sensitive counterparts. Furthermore, tumor sections from patients who relapsed on tamoxifen showed enhanced α6‐integrin expression. Gene expression profiling from the TCGA database further revealed that basal‐like breast cancer samples, known to be largely unresponsive to tamoxifen, demonstrated higher α6‐integrin levels than luminal breast cancer samples. Importantly, AF reduced TamR cell viability and disrupted TamR mammospheres while concomitantly reducing α6‐integrin messenger RNA and protein levels. In addition, AF and small interfering RNA against α6‐integrin blocked tamoxifen‐stimulated proliferation of TamR MCF‐7 cells and further sensitized these cells to tamoxifen. Moreover, AF reduced Src and Akt signaling activation in TamR MCF‐7 cells. Our findings suggest elevated α6‐integrin expression is associated with tamoxifen resistance and AF suppresses α6‐integrin–Src–Akt signaling activation to confer activity against TamR breast cancer.

100 Deals associated with Aminoflavone

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Estrogen receptor positive breast cancer	Phase 2	United States	Tigris Pharmaceuticals	01 May 2011
Triple Negative Breast Cancer	Phase 2	-	Tigris Pharmaceuticals	01 Apr 2010
Breast cancer recurrent	Phase 2	United States	National Cancer Institute	01 Jul 2006
Metastatic breast cancer	Phase 2	United States	National Cancer Institute	01 Jul 2006
Metastatic Solid Tumor	Phase 2	United States	National Cancer Institute	01 Jul 2006
Ovarian Epithelial Carcinoma	Phase 2	United States	National Cancer Institute	01 Jul 2006
Primary peritoneal carcinoma	Phase 2	United States	National Cancer Institute	01 Jul 2006
recurrent primary peritoneal cavity cancer	Phase 2	United States	National Cancer Institute	01 Jul 2006
Renal Cell Carcinoma	Phase 2	United States	National Cancer Institute	01 Jul 2006
Advanced Malignant Solid Neoplasm	Phase 2	United States	National Cancer Institute	01 Jun 2006

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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 1	Solid tumor	24	AFP464	hlupoqbgpr(ktwmdtrnzv) = Pulmonary toxicity is dose limiting ecywudjgzb (ivbyjbnsex )	-	20 May 2011
AACR2009	Phase 1	Triple Negative Breast Cancer	-	Vorinostat	ffojgwjbko(tljhsuwvra) = xlbqjaxufd srbmtkwhrd (reawnlgogu )	-	01 May 2009
AACR2009	Phase 1	Triple Negative Breast Cancer	-	Aminoflavone Prodrug	ffojgwjbko(tljhsuwvra) = rcyaorpuqw srbmtkwhrd (reawnlgogu )	-	01 May 2009