Delving into the Latest Updates on AMXT-1501 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

+ [2]

Target-

Action

inhibitors

Mechanism

polyamine transport inhibitors

Therapeutic Areas

NeoplasmsNervous System DiseasesSkin and Musculoskeletal Diseases+ [1]

Active Indication

Brain Stem GliomaDiffuse Intrinsic Pontine GliomaEpendymoblastoma+ [8]

Inactive Indication

Breast CancerColorectal CancerDiffuse midline glioma, point mutation K27M in histone H3+ [11]

Originator Organization

Aminex Therapeutics, Inc.

Active Organization

Aminex Therapeutics, Inc.

Inactive Organization-

License Organization-

Drug Highest PhasePhase 1/2

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC32H68N6O2

InChIKeyUSNCWPSRPOWEBG-SSEXGKCCSA-N

CAS Registry441022-64-6

The purpose of this study is to evaluate the investigational drug AMXT 1501 (a pill taken by mouth) in combination with the drug difluoromethylornithine (DFMO) for infusion administered intravenously (IV; a liquid that continuously goes into your body through a tube that has been placed during a surgery into one of your veins). An investigational drug is one that has not been approved by the U.S. Food & Drug Administration (FDA), or any other regulatory authorities around the world for use alone or in combination with any drug, for the condition or illness it is being used to treat.
The goals of this part of the study are:
* Establish a recommended dose of AMXT 1501 in combination with DFMO for infusion
* Test the safety and tolerability of AMXT 1501 in combination with DFMO for infusion in patients with cancer
* To determine the activity of study treatments chosen based on:
* How each subject responds to the study treatment
* How long a subject lives without their disease returning/progressing

Start Date01 Oct 2025

Sponsor / Collaborator

Hershey Medical Center

[+1]

NCT05717153

/ RecruitingEarly Phase 1IIT

Intratumoral Extracellular Metabolic Impact of DFMO and AMXT 1501

This early phase I trial studies brain tumor (glioma) metabolism in response to eflornithine (DFMO) and polyamine transport inhibitor AMXT-1501 dicaprate (AMXT 1501) in patients with diffused or high grade glioma. Brain tumors use and produce certain molecules to survive and grow. DFMO is an irreversible inhibitor of ornithine decarboxylase, the enzyme catalyzing polyamine synthesis. AMXT 1501 is a polyamine transport inhibitor which prevents uptake of polyamines from the extracellular environment. This trial is being done to analyze how DFMO and AMXT 1501 affect brain tumor metabolism based on the molecules in the tumor's fluid.

Start Date01 Oct 2023

Sponsor / Collaborator

Mayo Clinic

[+1]

NCT05500508

/ TerminatedPhase 1/2

A Phase 1B/2A Study of the Safety, Tolerability and Initial Efficacy of Oral AMXT 1501 Dicaprate and Intravenous Difluoromethylornithine (DFMO) in Patients With Cancer

A Phase 1B/2A study will be conducted to establish safety and dose level of AMXT 1501 dicaprate in combination with IV DFMO, in cancer patients.

Start Date29 Nov 2022

Sponsor / Collaborator

Aminex Therapeutics, Inc.

100 Clinical Results associated with AMXT-1501

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100 Translational Medicine associated with AMXT-1501

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100 Patents (Medical) associated with AMXT-1501

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20

Literatures (Medical) associated with AMXT-1501

15 Jun 2025·International Journal of Cancer

Polyamine depletion limits progression of acute leukaemia

Article

Author: Norris, Murray D. ; Verhelst, Steven H. L. ; Gao, Weiman ; Burns, Mark R. ; Tanaka, Katsunori ; Haber, Michelle ; Karsa, Ayu ; Mayoh, Chelsea ; Somers, Klaartje ; Lock, Richard B. ; Spurling, Dayna ; Xiao, Lin ; Kotecha, Rishi S. ; Azfar, Mujahid ; Cheung, Laurence C. ; Vangheluwe, Peter ; Bongers, Angelika ; Guo, Xinyi ; Karsa, Mawar ; Ronca, Emma

AbstractCancer cells are addicted to polyamines, polycations essential for cellular function. While dual targeting of cellular polyamine biosynthesis and polyamine uptake is under clinical investigation in solid cancers, preclinical and clinical studies into its potential in haematological malignancies are lacking. Here we investigated the preclinical efficacy of polyamine depletion in acute leukaemia. The polyamine biosynthesis inhibitor difluoromethylornithine (DFMO) inhibited growth of a molecularly diverse panel of acute leukaemia cell lines, while non‐malignant cells were unaffected. Responsiveness to DFMO was linked to decreased levels of its molecular target, the rate‐limiting polyamine biosynthesis enzyme ODC1, and of the polyamine transporters ATP13A2 and ATP13A3. DFMO increased polyamine uptake and upregulated expression of polyamine transporters in acute leukaemia cells, a compensatory effect abolished by treatment with the polyamine transport inhibitor AMXT 1501. This drug, currently in a phase 1 clinical trial in solid tumours in combination with DFMO, potentiated the inhibitory effects of DFMO, and their combination synergistically inhibited the growth of acute leukaemia cell lines by inducing apoptosis. DFMO and AMXT 1501 limited disease progression in highly aggressive xenograft models of infant KMT2A‐rearranged leukaemia, even when treatment was initiated at high disease burden. Increased expression of c‐MYC was associated with enhanced sensitivity to the combination of DFMO and AMXT 1501, suggesting this oncoprotein as a potential predictive marker of response to the drug combination. In conclusion, targeting polyamine biosynthesis and polyamine uptake limits disease progression in models of acute leukaemia, supporting further preclinical and clinical investigation into this approach for acute leukaemia.

01 Mar 2025·Molecular Oncology

The polyamine transporter ATP13A3 mediates difluoromethylornithine‐induced polyamine uptake in neuroblastoma

Article

Author: Xiao, Lin ; Guo, Xinyi ; Norris, Murray D. ; Mayoh, Chelsea ; Ronca, Emma ; Pandher, Ruby ; Verhelst, Steven H. L. ; Bongers, Angelika ; Gao, Weiman ; Van den Haute, Chris ; Karsa, Ayu ; Burns, Mark R. ; Karsa, Mawar ; Azfar, Mujahid ; Vangheluwe, Peter ; Haber, Michelle ; Schoofs, Arthur ; Fayt, Youri ; Somers, Klaartje ; Spurling, Dayna

High‐risk neuroblastomas, often associated with MYCN protooncogene amplification, are addicted to polyamines, small polycations vital for cellular functioning. We have previously shown that neuroblastoma cells increase polyamine uptake when exposed to the polyamine biosynthesis inhibitor difluoromethylornithine (DFMO), and this mechanism is thought to limit the efficacy of the drug in clinical trials. This finding resulted in the clinical development of polyamine transport inhibitors, including AMXT 1501, which is presently under clinical investigation in combination with DFMO. However, the mechanisms and transporters involved in DFMO‐induced polyamine uptake are unknown. Here, we report that knockdown of ATPase 13A3 (ATP13A3), a member of the P5B‐ATPase polyamine transporter family, limited basal and DFMO‐induced polyamine uptake, attenuated MYCN‐amplified and non‐MYCN‐amplified neuroblastoma cell growth, and potentiated the inhibitory effects of DFMO. Conversely, overexpression of ATP13A3 in neuroblastoma cells increased polyamine uptake, which was inhibited by AMXT 1501, highlighting ATP13A3 as a key target of the drug. An association between high ATP13A3 expression and poor survival in neuroblastoma further supports a role of this transporter in neuroblastoma progression. Thus, this study identified ATP13A3 as a critical regulator of basal and DFMO‐induced polyamine uptake and a novel therapeutic target for neuroblastoma.

31 Dec 2024·Emerging Microbes & Infections

AMXT-1501 targets membrane phospholipids against Gram-positive and -negative multidrug-resistant bacteria

Article

Author: Wen, Zewen ; Zheng, Jinxin ; Xiong, Yanpeng ; Zhang, Fan ; Liu, Xiaoju ; Liu, Xiaoming ; Lin, Zhiwei ; Meng, Qingyin ; Yu, Zhijian ; Deng, Qiwen ; Li, Peiyu

The rapid proliferation of multidrug-resistant (MDR) bacterial pathogens poses a serious threat to healthcare worldwide. Carbapenem-resistant (CR) Enterobacteriaceae, which have near-universal resistance to available antimicrobials, represent a particularly concerning issue. Herein, we report the identification of AMXT-1501, a polyamine transport system inhibitor with antibacterial activity against Gram-positive and -negative MDR bacteria. We observed minimum inhibitory concentration (MIC)₅₀/MIC₉₀ values for AMXT-1501 in the range of 3.13-12.5 μM (2.24-8.93 μg /mL), including for methicillin-resistant Staphylococcus aureus (MRSA), CR Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. AMXT-1501 was more effective against MRSA and CR E. coli than vancomycin and tigecycline, respectively. Subinhibitory concentrations of AMXT-1501 reduced the biofilm formation of S. aureus and Enterococcus faecalis. Mechanistically, AMXT-1501 exposure damaged microbial membranes and increased membrane permeability and membrane potential by binding to cardiolipin (CL) and phosphatidylglycerol (PG). Importantly, AMXT-1501 pressure did not induce resistance readily in the tested pathogens.

100 Deals associated with AMXT-1501

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Endometrial Carcinoma	Phase 3	United States	Aminex Therapeutics, Inc.	29 Nov 2022
Endometrial Carcinoma	Phase 3	Australia	Aminex Therapeutics, Inc.	29 Nov 2022
Malignant Mesothelioma of Peritoneum	Phase 3	United States	Aminex Therapeutics, Inc.	29 Nov 2022
Malignant Mesothelioma of Peritoneum	Phase 3	Australia	Aminex Therapeutics, Inc.	29 Nov 2022
Non-Small Cell Lung Cancer	Phase 3	Australia	Aminex Therapeutics, Inc.	29 Nov 2022
Non-Small Cell Lung Cancer	Phase 3	United States	Aminex Therapeutics, Inc.	29 Nov 2022
Papillary thyroid cancer	Phase 3	Australia	Aminex Therapeutics, Inc.	29 Nov 2022
Papillary thyroid cancer	Phase 3	United States	Aminex Therapeutics, Inc.	29 Nov 2022
Stomach Cancer	Phase 3	Australia	Aminex Therapeutics, Inc.	29 Nov 2022
Stomach Cancer	Phase 3	United States	Aminex Therapeutics, Inc.	29 Nov 2022

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03536728 (986, SITC2024)	Phase 1	Advanced Malignant Solid Neoplasm \| Advanced cancer	-	AMXT 1501	ffdmlymtzg(xmfqtzcydm) = 36 reports jraxbziuki (abqecvsehi ) View more	Positive	05 Nov 2024