Delving into the Latest Updates on Foslinanib with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Foslinanib, Foslinanib (USAN/INN), Trx-818 free acid

+ [2]

Target-

Action

inhibitors, stimulants

Mechanism

Angiogenesis inhibitors, Apoptosis stimulants

Therapeutic Areas

NeoplasmsDigestive System DisordersEndocrinology and Metabolic Disease+ [1]

Active Indication

Locally Advanced Unresectable CarcinomaUnresectable Hepatocellular CarcinomaAdvanced Neuroendocrine Neoplasm+ [4]

Inactive Indication

Advanced Hepatocellular CarcinomaAdvanced Malignant Solid NeoplasmLung Cancer+ [1]

Originator Organization

TaiRx, Inc.

Active Organization

TaiRx, Inc.

Inactive Organization-

Drug Highest PhasePhase 2

First Approval Date-

RegulationOrphan Drug (United States)

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Structure/Sequence

Molecular FormulaC16H13FNNa2O6P

InChIKeyHANFVYCDGRSZSD-UHFFFAOYSA-N

CAS Registry1256037-62-3

View All Structures (2)

CVM-1118 is a new small molecule chemical entity being developed as a potential anti-cancer therapeutic by TaiRx, Inc. CVM-1118 is a potent anti-cancer agent in numerous human cancer cell lines. The safety of administrating CVM-1118 on human has been evaluated from the phase 1 study. The objective of the phase 2 study is to further investigate the efficacy of CVM-1118 with nivolumab for subjects with unresectable advanced hepatoma.

Start Date23 May 2022

Sponsor / Collaborator

TaiRx, Inc.

NCT04336124

/ CompletedPhase 1

A Phase I Safety and Pharmacokinetic Study of CVM-1118 Extended-Release Capsules Administered Orally to Patients With Advanced Cancers

CVM-1118 Immediate-release (IR) Capsule and CVM-1118 Extended-release (ER) Capsule are proprietary oncology products developed by TaiRx, Inc. for the treatment of patients suffering from advanced cancer. Due to the short elimination half-life of CVM-1118 IR capsules, the extended release (ER) formulation, containing mini-tablets in hard capsule, has been developed to prolong the drug absorption and longer exposure after oral administration. The designed dose of CVM-1118 ER was 200 mg per capsule to provide a more patient-compliant and safe dosage of CVM-1118. The clinical study CVMEX-001 is therefore designed to evaluate the safety and pharmacokinetics of CVM-1118 extend release (ER) Capsule (200 mg/capsule) in patients with advanced cancer.

Start Date25 May 2020

Sponsor / Collaborator

TaiRx, Inc.

NCT03600233

/ Active, not recruitingPhase 2

A Phase II, Open-label Study of CVM-1118 Administered Orally to Patients With Advanced Neuroendocrine Tumors

CVM-1118 (TRX-818) is a new small molecule chemical entity being developed as a potential anti-cancer therapeutic by TaiRx, Inc. CVM-1118 is a potent anti-cancer agent in numerous human cancer cell lines. The safety of administrating CVM-1118 on human is evaluated from the phase 1 study. The objectives of the phase 2 study is to further investigate the efficacy of CVM-1118 for patients with advanced neuroendocrine tumors.

Start Date15 Dec 2018

Sponsor / Collaborator

TaiRx, Inc.

100 Clinical Results associated with Foslinanib

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100 Translational Medicine associated with Foslinanib

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100 Patents (Medical) associated with Foslinanib

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4

Literatures (Medical) associated with Foslinanib

01 Aug 2024·Angiogenesis

Vascular mimicry in zebrafish fin regeneration: how macrophages build new blood vessels

Article

Author: Fazzari, Jennifer ; Djonov, Valentin ; Senk, Anita

AbstractVascular mimicry has been thoroughly investigated in tumor angiogenesis. In this study, we demonstrate for the first time that a process closely resembling tumor vascular mimicry is present during physiological blood vessel formation in tissue regeneration using the zebrafish fin regeneration assay. At the fin-regenerating front, vasculature is formed by mosaic blood vessels with endothelial-like cells possessing the morphological phenotype of a macrophage and co-expressing both endothelial and macrophage markers within single cells. Our data demonstrate that the vascular segments of the regenerating tissue expand, in part, through the transformation of adjacent macrophages into endothelial-like cells, forming functional, perfused channels and contributing to the de novo formation of microvasculature. Inhibiting the formation of tubular vascular-like structures by CVM-1118 prevents vascular mimicry and network formation resulting in a 70% shorter regeneration area with 60% reduced vessel growth and a complete absence of any signs of regeneration in half of the fin area. Additionally, this is associated with a significant reduction in macrophages. Furthermore, depleting macrophages using macrophage inhibitor PLX-3397, results in impaired tissue regeneration and blood vessel formation, namely a reduction in the regeneration area and vessel network by 75% in comparison to controls.

01 Mar 2016·Pharmacology & TherapeuticsQ1 · MEDICINE

Tumor cell vascular mimicry: Novel targeting opportunity in melanoma

Q1 · MEDICINE

Review

Author: Seftor, Richard E B ; Chao, Jun-Tzu ; Chien, Du-Shieng ; Hendrix, Mary J C ; Chu, Yi-Wen ; Seftor, Elisabeth A

In 1999, the American Journal of Pathology published an article, entitled "Vascular channel formation by human melanoma cells in vivo and in vitro: vasculogenic mimicry" by Maniotis and colleagues, which ignited a spirited debate for several years and earned the journal's distinction of a "citation classic" (Maniotis et al., 1999). Tumor cell vasculogenic mimicry (VM), also known as vascular mimicry, describes the plasticity of aggressive cancer cells forming de novo vascular networks and is associated with the malignant phenotype and poor clinical outcome. The tumor cells capable of VM share the commonality of a stem cell-like, transendothelial phenotype, which may be induced by hypoxia. Since its introduction as a novel paradigm for melanoma tumor perfusion, many studies have contributed new findings illuminating the underlying molecular pathways supporting VM in a variety of tumors, including carcinomas, sarcomas, glioblastomas, astrocytomas, and melanomas. Of special significance is the lack of effectiveness of angiogenesis inhibitors on tumor cell VM, suggesting a selective resistance by this phenotype to conventional therapy. Facilitating the functional plasticity of tumor cell VM are key proteins associated with vascular, stem cell, extracellular matrix, and hypoxia-related signaling pathways--each deserving serious consideration as potential therapeutic targets and diagnostic indicators of the aggressive, metastatic phenotype. This review highlights seminal findings pertinent to VM, including the effects of a novel, small molecular compound, CVM-1118, currently under clinical development to target VM, and illuminates important molecular pathways involved in the suppression of this plastic, aggressive phenotype, using melanoma as a model.

25 Nov 2010·Journal of Medicinal ChemistryQ1 · MEDICINE

Design, Synthesis, and Preclinical Evaluation of New 5,6- (or 6,7-) Disubstituted-2-(fluorophenyl)quinolin-4-one Derivatives as Potent Antitumor Agents

Q1 · MEDICINE

Article

Author: Lee, Kuo-Hsiung ; Way, Tzong-Der ; Wang, Sheng-Hung ; Qian, Keduo ; Huang, Li-Jiau ; Chou, Li-Chen ; Huang, Chi-Hung ; Lin, Hui-Yi ; Hsu, Mei-Hua ; Dong, Yizhou ; Tsai, Meng-Tung ; Kuo, Sheng-Chu

Our previous exploration of 2-phenylquinolin-4-ones (2-PQs) has led to an anticancer drug candidate 2-(2-fluorophenyl)-6,7-methylenedioxyquinolin-4-one monosodium phosphate (CHM-1-P-Na). In order to develop additional new drug candidates, novel 2-PQs were designed, synthesized, and evaluated for cytotoxic activity. Most analogues, including 1b, 2a,b, 3a,b, 4a,b, and 5a,b, exhibited significant inhibitory activity (IC(50) of 0.03-8.2 μM) against all tested tumor cell lines. As one of the most potent analogue, 2-(3-fluorophenyl)-5-hydroxy-6-methoxyquinolin-4-one (3b) selectively inhibited 14 out of 60 cancer cell lines in a National Cancer Institute (NCI) evaluation. Preliminary mechanism of action study suggested that 3b had a significant effect on the tyrosine autophosphorylation of insulin-like growth factor-1 receptor (IGF-1R). Safety pharmacology profiling of 3b showed no significant effect on normal biological functions of most enzymes tested. Furthermore, sodium 2-(3-fluorophenyl)-6-methoxy-4-oxo-1,4-dihydroquinolin-5-yl phosphate (15), the monophosphate of 3b, exceeded the activity of doxorubicin and was comparable to CHM-1-P-Na in a Hep3B xenograft nude mice model. In summary, 15 is a promising clinical candidate and is currently under preclinical study.

100 Deals associated with Foslinanib

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External Link

KEGG	Wiki	ATC	Drug Bank
D11639	-	-	DB16172

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Unresectable Hepatocellular Carcinoma	Phase 2	Taiwan Province	TaiRx, Inc.	23 May 2022
Advanced Neuroendocrine Neoplasm	Phase 2	Taiwan Province	TaiRx, Inc.	15 Dec 2018
Gastro-Enteropancreatic Neuroendocrine Tumor	Phase 2	Taiwan Province	TaiRx, Inc.	15 Dec 2018
Neuroendocrine Carcinoma	Phase 2	Taiwan Province	TaiRx, Inc.	15 Dec 2018
Neuroendocrine neoplasm of lung	Phase 2	Taiwan Province	TaiRx, Inc.	15 Dec 2018
Neuroendocrine tumor of pancreas	Phase 2	Taiwan Province	TaiRx, Inc.	15 Dec 2018
Advanced cancer	Phase 1	United States	TaiRx, Inc.	12 Jul 2018
Advanced Hepatocellular Carcinoma	Phase 1	Taiwan Province	TaiRx, Inc.	12 Jul 2018
Advanced Hepatocellular Carcinoma	Phase 1	United States	TaiRx, Inc.	12 Jul 2018
Lung Cancer	Discovery	China	TaiRx, Inc.	15 Dec 2018

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03600233 (ESMO2024) Manual	Phase 2	Advanced Neuroendocrine Neoplasm	34	CVM-1118 200mg BID	(qbnsatbgop) = rttbxelxlu sqcctoajrt (ungytakqsb, 5.9 - 23.8) View more	Positive	13 Sep 2024
NCT05257590 (ASCO2024) Manual	Phase 2	Advanced Hepatocellular Carcinoma	31	CVM-1118 200 mg BID + nivolumab 240 mg Q2W	(nbbaaakugy) = vtjaerwnyp beiprivnie (ettmoaovit ) View more	Positive	24 May 2024
NCT03600233 (ASCO2023) Manual	Phase 2	Advanced Neuroendocrine Neoplasm	21	CVM-1118 200-300 mg BID	(zdlimbrrbp) = ibbkeimvay wuaivpizqw (ehwhdfejfj, 14–50) View more	Positive	31 May 2023
NCT02507544 \| NCT02703298 (ASCO 12017 \| ASCO 22017) Manual	Phase 1	Advanced cancer	28	CVM-1118 (US)	(wwdoyqsndn) = 2 DLTs (grade 5 dehydration and grade 3 fatigue) were reported at cohort 6 (800 mg/daily) ywkhagvsnu (tucfdjmuga ) View more	Positive	05 Jun 2017
NCT02507544 \| NCT02703298 (ASCO 12017 \| ASCO 22017) Manual	Phase 1	Advanced cancer	28	CVM-1118 (Taiwan)		Positive	05 Jun 2017