Delving into the Latest Updates on Amonafide Maleate with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Amonafide L-Malate(USAN)

+ [5]

Target

DNA x Top II

Action

inhibitors

Mechanism

DNA inhibitors(DNA inhibitors), Top II inhibitors(Topoisomerase II inhibitors)

Therapeutic Areas

NeoplasmsHemic and Lymphatic DiseasesUrogenital Diseases

Active Indication-

Inactive Indication

Acute Myeloid LeukemiaCastration-Resistant Prostatic Cancer

Originator Organization

Antisoma, Inc.

Active Organization-

Inactive Organization

Antisoma Research Ltd.

Antisoma, Inc.

License Organization-

Drug Highest PhasePendingPhase 3

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC20H23N3O7

InChIKeyJNZBHHQBPHSOMU-WNQIDUERSA-N

CAS Registry618863-54-0

Amonafide is a DNA intercalating agent and inhibitor of topoisomerase II that has been extensively studied in patients with malignant solid tumors. Amonafide has also been studied in patients with AML.
The purpose of this study is to assess the relative efficacy and safety of amonafide in combination with cytarabine compared to daunorubicin with cytarabine in subjects with documented secondary AML.

Start Date01 Jun 2007

Sponsor / Collaborator

Antisoma Research Ltd.

NCT00087854

/ CompletedPhase 1/2

Dose-Defining Study of a NAT2 Phenotype-Based Dosing Regimen of Intravenous Amonafide L-Malate Administered Weekly in Men With Androgen-Independent Prostate Cancer (AIPC)

The purpose of this study is to assess the safety and efficacy of Amonafide in men with androgen-independent prostate cancer, assigned to individualized doses of Amonafide based on acetylator phenotype information (doses adjusted on individual metabolism).

Start Date01 Mar 2004

Sponsor / Collaborator

Antisoma, Inc.

100 Clinical Results associated with Amonafide Maleate

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100 Translational Medicine associated with Amonafide Maleate

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100 Patents (Medical) associated with Amonafide Maleate

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316

Literatures (Medical) associated with Amonafide Maleate

17 Feb 2025·ACS Applied Bio Materials

Deciphering Binding Potential of Naphthalimide–Coumarin Conjugate with c-MYC G-Quadruplex for Developing Anticancer Agents: A Spectroscopic and Molecular Modeling Approach

Article

Author: Paul, Kamaldeep ; Gupta, Saurabh ; Luxami, Vijay

It has been well accumulated that G-quadruplex (G4-DNA) has great anticancer relevance, and various heterocyclic moieties have been synthesized and examined as potent G4-DNA binders with promising anticancer activity. Here, we have synthesized a series of naphthalimide-triazole-coumarin conjugates by substituting various amines and further examine their anticancer activity against 60 human cancer cell lines at 10 μM. One and five dose concentration results reveal low values of MG-MID GI₅₀ for compounds including 8a (3.18 μM), 8b (13.11 μM), 8e (7.68 μM) and 8f (1.75 μM). Further cell apoptosis manifests that all compounds can induce cell apoptosis in cancer cells by stabilizing the c-MYC promoter G-quadruplex. Therefore, the G-quadruplex-mediated pathway may be responsible for the apoptosis that these naphthalimide-coumarin compounds caused in cancer cells. Therefore, multispectroscopic techniques are employed to evaluate the binding of molecules with c-MYC G4-DNA where all four molecules readily bind to G4-DNA and stabilize it with a high binding constant, leading to inhibition of cancer cells and apoptosis of cancer cells. Binding studies toward ct-DNA disclose that these compounds do not interact with ds-DNA and thus selectively target G4-DNA to exert their anticancer activity. All the active compounds have greater affinity toward Human Serum Albumin (HSA) and can readily bind with HSA with a binding constant of 12 × 10⁴ M^-1 (8a), 13.0 × 10⁴ M^-1 (8b), 14.2 × 10⁴ M^-1 (8e), 16.3 × 10⁴ M^-1 (8f). Thus, the results disclose that inhibition and killing of cancer cells by these derivatives feasibly occur due to their ability to interact with c-MYC G-quadruplex forming promoters and their high affinity toward HSA unfold potent anticancer agents and can be taken further for clinical trials.

01 Dec 2024·International Immunopharmacology

Single-cell transcriptomics reveals tumor microenvironment changes and prognostic gene signatures in hepatocellular carcinoma

Article

Author: Li, Xiangqian ; Wu, Yilin ; Liang, Yong ; Xie, Tong ; Lu, Ying ; Ding, Zhilong ; Zhu, WeiJie ; Zhang, Cui ; Hu, Yihuai ; Zhong, Fei ; Ren, Shiying ; Zhai, Yangyang ; Wang, Shiyan ; Chen, Yunli

BACKGROUNDHepatocellular Carcinoma (HCC) is the most common type of primary liver cancer, accounting for the majority of liver cancer cases. Hepatocellular Carcinoma not only exhibits high heterogeneity but also possesses an immune-suppressive tumor microenvironment that promotes tumor evasion, posing substantial difficulties for efficient therapy. Our aim is to utilize single-cell RNA transcriptome data to investigate the dynamic changes in the tumor microenvironment during the malignant progression of HCC, the communication among immune cells, and the marker genes associated with patient prognosis.METHODSWe constructed expression matrices from open single-cell RNA transcriptome data (GSE149614) of HCC patients (representing stages I-IV), establishing single-cell RNA transcriptional atlases for different stages of HCC progression. For each stage, we conducted cell subgroup analysis to identify cell types at each stage. Horizontally, we explored the dynamic changes of the same cell type across different stages, performing trajectory analysis and prognosis analysis. Vertically, we investigated pairwise comparisons of different stages of HCC progression, probing the dynamic alterations in tumor microenvironment immune cell signaling pathways. Finally, potential drugs for the treatment of HCC were predicted based on relevant genes.FINDINGSAs the HCC advances towards increased malignancy, there is a shift in the predominant composition of the tumor microenvironment, with a decline in the dominance of hepatic cells. Tumor-infiltrating immune cells migrate and accumulate within the tumor microenvironment, where T cells and myeloid cells display distinct patterns of change. Genes associated with cancer-associated fibroblasts (CAFs) and T cells are correlated with adverse patient outcomes. In the late stages of HCC, the tumor microenvironment is infiltrated by more myeloid-derived suppressor cells (MDSCs), and a prognostic model constructed based on genes related to myeloid cells can predict patient outcomes. Additionally, in the analysis of transcription factors, YY1 and MYC are found to be highly expressed. Cell communication analysis among tumor-infiltrating immune cells reveals significant differences in the main signaling pathways at different stages of HCC progression. Finally, drug sensitivity analysis based on key genes identifies Acetalax, Allopurinol, and Amonafide as potential candidates for HCC treatment.

01 Dec 2024·Biochemical Genetics

Comprehensive Analysis of the SUMO-related Signature: Implication for Diagnosis, Prognosis, and Immune Therapeutic Approaches in Cervical Cancer

Article

Author: Li, Xiuting ; Zhang, Xing ; Zhang, Yan ; Cao, Jian ; Liu, Haohan ; Lin, Ning ; Ding, Bo ; Liu, Fengying ; Nie, Yamei ; Wang, Shizhi ; Hu, Jing ; Yan, Wenjing ; Chen, Xue

SUMOylation, an important post-translational protein modification, plays a critical role in cancer development and immune processes. This study aimed to construct diagnostic and prognostic models for cervical cancer (CC) using SUMOylation-related genes (SRGs) and explore their implications for novel clinical therapies. We analyzed the expression profiles of SRGs in CC patients and identified 15 SRGs associated with CC occurrence. After the subsequent qPCR verification of 20 cases of cancer and adjacent tissues, 13 of the 15 SRGs were differentially expressed in cancer tissues. Additionally, we identified molecular markers associated with the prognosis and recurrence of CC patients, based on SRGs. Next, a SUMOScore, based on SRG expression patterns, was generated to stratify patients into different subgroups. The SUMOScore showed significant associations with the tumor microenvironment, immune function features, immune checkpoint expression, and immune evasion score in CC patients, highlighting the strong connection between SUMOylation factors and immune processes. In terms of immune therapy, our analysis identified specific chemotherapy drugs with higher sensitivity in the subgroups characterized by high and low SUMOScore, indicating potential treatment options. Furthermore, we conducted drug sensitivity analysis to evaluate the response of different patient subgroups to conventional chemotherapy drugs. Our findings revealed enrichment of immune-related pathways in the low-risk subgroup identified by the prognostic model. In conclusion, this study presents diagnostic and prognostic models based on SRGs, accompanied by a comprehensive index derived from SRGs expression patterns. These findings offer valuable insights for CC diagnosis, prognosis, treatment, and immune-related analysis.

100 Deals associated with Amonafide Maleate

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External Link

KEGG	Wiki	ATC	Drug Bank
-	Amonafide Maleate	-	DB05022

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Acute Myeloid Leukemia	Phase 3	Argentina	Antisoma Research Ltd.	01 Jun 2007
Acute Myeloid Leukemia	Phase 3	Germany	Antisoma Research Ltd.	01 Jun 2007
Acute Myeloid Leukemia	Phase 3	Poland	Antisoma Research Ltd.	01 Jun 2007
Acute Myeloid Leukemia	Phase 3	Italy	Antisoma Research Ltd.	01 Jun 2007
Acute Myeloid Leukemia	Phase 3	France	Antisoma Research Ltd.	01 Jun 2007
Acute Myeloid Leukemia	Phase 3	Israel	Antisoma Research Ltd.	01 Jun 2007
Acute Myeloid Leukemia	Phase 3	Belgium	Antisoma Research Ltd.	01 Jun 2007
Acute Myeloid Leukemia	Phase 3	Canada	Antisoma Research Ltd.	01 Jun 2007
Acute Myeloid Leukemia	Phase 3	Australia	Antisoma Research Ltd.	01 Jun 2007
Acute Myeloid Leukemia	Phase 3	Ecuador	Antisoma Research Ltd.	01 Jun 2007

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00715637 (Pubmed \| J Urol \| J Clin Oncol) Manual	Phase 3	Acute Myeloid Leukemia First line	433	cytarabine+amonafide	(tzidhtztbn) = dmbosaitkv bhxqugbfgi (cncgkexjyd ) View more	Negative	10 Apr 2015
NCT00715637 (Pubmed \| J Urol \| J Clin Oncol) Manual	Phase 3	Acute Myeloid Leukemia First line	433	daunorubicin+cytarabine	(tzidhtztbn) = vyhfhtbpsj bhxqugbfgi (cncgkexjyd ) View more	Negative	10 Apr 2015
ACCEDE (ASCO2011)	Phase 3	Relapsing acute myeloid leukemia	433	AS1413 plus cytarabine	zxpmfqfxub(ajfjceizxy) = igtfvnulbt czcculgivv (nkhttsqaed )	Negative	20 May 2011
ACCEDE (ASCO2011)	Phase 3	Relapsing acute myeloid leukemia	433	Daunorubicin plus cytarabine	zxpmfqfxub(ajfjceizxy) = vjrhwdhbgc czcculgivv (nkhttsqaed )	Negative	20 May 2011
ASCO2010	Not Applicable	Acute Myeloid Leukemia \| Treatment related acute myeloid leukaemia	88	amonafide (tAML)	(dqartjegil) = kbrqqtpyvu eejvzhycag (gcvyxsrcty ) View more	-	20 May 2010
ASCO2010	Not Applicable		88	amonafide (MDS→AML)	(dqartjegil) = zeghadchng eejvzhycag (gcvyxsrcty ) View more	-	20 May 2010
ASCO2008	Phase 2	Acute Myeloid Leukemia	88	Amonafide 600 mg/m2 + ara-C 200 mg/m2	(gortsbcvkc) = tjzswkyzqj usdgfrdumd (asddvzeaxt ) View more	-	20 May 2008
ASCO2007	Phase 2	Acute Myeloid Leukemia	80	Amonafide 600 mg/m2/day + CIV ara-C 200 mg/m2/day	(xmmqlzrywt) = kxroqiuihk iuessjpwmd (orvogtcgic ) View more	-	20 Jun 2007
ASCO2006	Phase 1	Acute Myeloid Leukemia	20	Amonafide	fukcofimis(zjddijhlfw) = cshjhxzrto crtosfgzeg (nsjaokxdcw ) View more	-	20 Jun 2006
ASCO2005	Phase 1	Acute Myeloid Leukemia	26	Amonafide + Cytosine Arabinoside (AraC)	(rdvylywawm) = kaplwufsgz aclenydryq (fadypslsqd ) View more	-	01 Jun 2005