Delving into the Latest Updates on AGM-1470 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

O-(chloroacetylcarbamoyl)fumagillol, O-chloroacetylcarbamoylfumagillol

+ [2]

Target

VEGFR2

Mechanism

VEGFR2 antagonists(Vascular endothelial growth factor receptor 2 antagonists), Aminopeptidase inhibitors

Therapeutic Areas

Neoplasms

Active Indication

Neoplasms

Inactive Indication

Bladder CancerBreast CancerKaposi Sarcoma+ [7]

Originator Organization

Takeda Pharmaceutical Co., Ltd.

Active Organization

Harvard Medical School

Inactive Organization

Takeda Pharmaceutical Co., Ltd.

The University of Texas MD Anderson Cancer Center

Anderson University

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

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Structure

Molecular FormulaC19H28ClNO6

InChIKeyMSHZHSPISPJWHW-PVDLLORBSA-N

CAS Registry129298-91-5

To assess toxicity and determine the MTD of intravenous TNP-470 administered weekly in patients with AIDS-related Kaposi's sarcoma. To assess pharmacokinetics and tumor response of the drug.
Since evidence shows that neovascularization is important in the development of Kaposi's sarcoma, drugs that inhibit angiogenesis, such as TNP-470, may be of benefit in patients with the disease.

Start Date-

Sponsor / Collaborator

National Institute of Allergy & Infectious Diseases

NCT00038701 / TerminatedPhase 2IIT

Phase II Study of Gemcitabine-Based Chemoradiation and TNP-470 for Patients With Locally Advanced, Nonmetastatic Adenocarcinoma of the Pancreas

The goal is to assess survival and patterns of failure in patients treated with Gemzar-based chemoradiation and TNP-470 for locally advanced adenocarcinoma of the pancreas.

Start Date01 Aug 1999

Sponsor / Collaborator

The University of Texas MD Anderson Cancer Center

100 Clinical Results associated with AGM-1470

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100 Translational Medicine associated with AGM-1470

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100 Patents (Medical) associated with AGM-1470

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470

Literatures (Medical) associated with AGM-1470

01 Nov 2023·Life Sciences

Inhibition of adipose tissue angiogenesis prevents rebound weight gain after caloric restriction in mice fed a high-fat diet

Article

Author: Jin, Bo-Yeong ; Jeong, Yong Taek ; Seo, Kwan Sik ; Lee, Hye-Jin ; Kim, Dong-Hoon ; Choi, Sang-Hyun ; Lee, Jun-Seok ; Park, Mi-Rae ; Kim, Nam Hoon ; Wada, Tsutomu

AIMSWe investigated whether modulation of white adipose tissue (WAT) vasculature regulates rebound weight gain (RWG) after caloric restriction (CR) in mice fed a high-fat diet (HFD).MAIN METHODSWe compared changes in energy balance, hypothalamic neuropeptide gene expression, and characteristics of WAT by RT-qPCR, ELISA, immunohistochemistry, and adipose-derived stromal vascular fraction spheroid sprouting assay in obese mice fed a HFD ad libitum (HFD-AL), mice under 40 % CR for 3 or 4 weeks, mice fed HFD-AL for 3 days after CR (CRAL), and CRAL mice treated with TNP-470, an angiogenic inhibitor.KEY FINDINGSWAT angiogenic genes were expressed at low levels, but WAT vascular density was maintained in the CR group compared to that in the HFD-AL group. The CRAL group showed RWG, fat regain, and hyperphagia with higher expression of angiogenic genes and reduced pericyte coverage of the endothelium in WAT on day 3 after CR compared to the CR group, indicating rapidly increased angiogenic activity after CR. Administration of TNP-470 suppressed RWG, fat regain, and hyperphagia only after CR compared to the CRAL group. Changes in circulating leptin levels and hypothalamic neuropeptide gene expression were correlated with changes in weight and fat mass, suggesting that TNP-470 suppressed hyperphagia independently of the hypothalamic melanocortin system. Additionally, TNP-470 increased gene expression related to thermogenesis, fuel utilization, and browning in brown adipose tissue (BAT) and WAT, indicating TNP-470-induced increase in thermogenesis.SIGNIFICANCEModulation of the WAT vasculature attenuates RWG after CR by suppressing hyperphagia and increasing BAT thermogenesis and WAT browning.

01 Sep 2022·Annals of Translational Medicine

Rutaecarpine prevents the malignant biological properties of breast cancer cells by the miR-149-3p/S100A4 axis

Article

Author: Xiong, Chao ; Li, Peng ; Xiong, Yi ; Shan, Xuehua

BackgroundBreast cancer (BC) is a frequent malignancy that endangers women's health, and its fatality rate ranks 1st among female malignancies. Research has shown that rutaecarpine (RUT), which is a Chinese herbal medicine, blocks the proliferation of cancer cells by a variety of molecular mechanisms. However, the possible effects and mechanism of RUT in the autophagy and angiogenesis of BC cells has not been clearly articulated.MethodsMiR-149-3p and S100A4 expression levels were assessed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and the optimal concentration and time of RUT was confirmed by Cell Counting Kit-8 (CCK-8) assays of the BC cells. After treatment, changes in cell proliferation and the cell cycle were evaluated by CCK-8 assays, clone formation assays, and flow cytometry, and the levels of apoptosis, autophagy, and angiogenesis-related proteins were identified by Western blot. The targeted regulation of miR-149-3p on S100A4 was also examined by luciferase reporter assays.ResultsWe found that RUT inhibited cell growth and upregulated miR-149-3p in MDA-MB-231 cells. In relation to the biological function activity, RUT attenuated proliferation and angiogenesis, and induced cell-cycle arrest and autophagy by miR-149-3p in the MDA-MB-231 cells. Additionally, miR-149-3p downregulated S100A4 by targeting binding to S100A4, and S100A4 was required for miR-149-3p to play a role in BC progression. We also discovered that an autophagy agonist (rapamycin) or an angiogenesis inhibitor (TNP-470) changed BC progression mediated by the RUT/miR-149-3p/S100A4 axis.ConclusionsRUT blocks the malignant behaviors of BC cells through the miR-149-3p/S100A4 axis and thus alters autophagy and angiogenesis. Thus, the RUT-mediated miR-149-3p/S100A4 axis might be an underlying therapeutic agent and target for BC.

01 Jan 2022·American journal of translational research

Methionine aminopeptidase 2 as a potential target in pancreatic ductal adenocarcinoma.

Article

Author: Hubert, Ayala ; Benny, Ofra ; Panigrahy, Dipak ; Orehov, Natalie ; Esa, Rawnaq ; Zamir, Gideon ; Schwob, Ouri ; Steinberg, Eliana ; Stern, Tal

Pancreatic ductal adenocarcinoma (PDA) is an aggressive metastatic cancer with a very low survival rate. This tumor is hypovascularized and characterized by severe hypoxic regions, yet these regions are not impeded by the oxidative stress in their microenvironment. PDA's high resilience raises the need to find new effective therapeutic targets. This study investigated the suitability of methionine aminopeptidase 2 (MetAp2), a metallopeptidase known to play an important role in tumor progression, as a new target for treating PDA. In our examination of patient-derived PDA tissues, we found that MetAp2 is highly expressed in metastatic regions compared with primary sites. At the cellular level, we found that the basal expression levels of MetAp2 in pancreatic cancer cells were higher than its levels in endothelial cells. Pancreatic cancer cells showed a significant suppression of proliferation in a dose-dependent manner upon exposure to TNP-470, a selective MetAp2 inhibitor. In addition, a significant reduction in glutathione (GSH) levels - known for its importance in alleviating oxidative stress - was detected in all treated cells, suggesting a possible anti-cancer activity mechanism that would be feasible for treating highly hypoxic PDA tumors. Furthermore, in an orthotopic pancreatic cancer murine model, systemic oral treatment with a MetAp2 inhibitor significantly reduced tumors' growth. Taken together, our findings indicate that MetAp2 enhances tumor sensitivity to hypoxia and may provide an effective target for treating hypoxic tumors with high expression levels of MetAp2.

100 Deals associated with AGM-1470

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External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB08633

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Lymphoma	Preclinical	US	-	-
Locally Advanced Pancreatic Adenocarcinoma	Discovery	US	The University of Texas MD Anderson Cancer Center	01 Aug 1999
Breast Cancer	Discovery	US	-	-
Breast Cancer	Discovery	-	Takeda Pharmaceutical Co., Ltd.	-
Kaposi Sarcoma	Discovery	-	Takeda Pharmaceutical Co., Ltd.	-
Kaposi Sarcoma	Discovery	US	-	-
Kidney Neoplasms	Discovery	US	-	-
Pancreatic Cancer	Discovery	-	Takeda Pharmaceutical Co., Ltd.	-
Pancreatic Cancer	Discovery	US	Anderson University	-
Renal Cell Carcinoma	Discovery	-	Takeda Pharmaceutical Co., Ltd.	-