Delving into the Latest Updates on Nedometinib with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

2-((2-fluoro-4-iodophenyl)amino)-N-(2-hydroxyethoxy)-1-methyl-1H-pyrrolo[2,3-b]pyridine-3-carboxamide, NFlection Therapeutics/Stanford University/H Lee Moffitt Cancer Center

+ [1]

Target

MEK

Action

inhibitors

Mechanism

MEK inhibitors(Dual specificity mitogen-activated protein kinase kinase inhibitors)

Therapeutic Areas

NeoplasmsNervous System DiseasesCongenital Disorders+ [3]

Active Indication

Nephrosis, CongenitalNeurofibromatosis 1

Inactive Indication

Epidermal NevusNevus sebaceusSquamous Cell Carcinoma

Originator Organization

Stanford University

Active Organization

NFlection Therapeutics, Inc.Startup

Inactive Organization

H. Lee Moffitt Cancer Center & Research Institute, Inc.

Stanford University

Drug Highest PhasePhase 2

First Approval Date-

RegulationOrphan Drug (European Union)

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Structure/Sequence

Molecular FormulaC17H16FIN4O3

InChIKeySENAOZROGSYRTD-UHFFFAOYSA-N

CAS Registry2252314-46-6

This study of NFX-179 is an open-label study, evaluating safety, tolerability, pharmacodynamic activity, and the clinical effect in subjects with Epidermal Nevus(ENS). NFX-179 is formulated as a gel for topical administration. NFX-179 has been shown in animal studies and in human extracts to suppress p-ERK with systemic absorption of NFX-179 following topical application to be extremely low, based on serum values observed in animal studies.
Primary objectives:
To determine the pharmacodynamic activity of NFX-179 Gel as defined by suppression of phospho-ERK (p-ERK) levels in Target EN in treatment group after 12 weeks of once-daily (QD) application
To determine the safety and tolerability of treatment with NFX-179 Gel 1.50% applied QD for 12 weeks.
Secondary objectives:
-Clinical effect of NFX-179 Gel 1.5% defined as the percent change in EN volume after 12 weeks of QD application

Start Date01 Jun 2023

Sponsor / Collaborator

Stanford University

[+1]

NCT05005845

/ CompletedPhase 2

A Randomized, Double-Blind, Vehicle-Controlled, Parallel Group Phase 2 Dose-Response Study to Determine Safety and Effectiveness of Two Concentrations of NFX-179 Gel in Subjects With Cutaneous Neurofibromas

This is a randomized, double-blind, vehicle-controlled, parallel group dose response study evaluating the safety and effectiveness of 2 concentrations of NFX-179 Gel in subjects with cutaneous neurofibromas. At Visit 1, the investigator will identify 10 Target cNFs that fulfil the enrollment criteria. The Target cNFs must be located on the subject's face, anterior trunk, or upper extremities. Two Target cNFs must be on the face and 8 must be on the anterior trunk or upper extremities. The study medication will be applied topically QD to the Target cNFs for 182days (26 weeks). During the duration of the study subjects will be evaluated for safety and efficacy.

Start Date20 Sep 2021

Sponsor / Collaborator

NFlection Therapeutics, Inc.Startup

NCT04435665

/ CompletedPhase 2

A Randomized, Double-Blind, Vehicle-Controlled, Parallel Group Phase 2a Study to Determine Safety, Tolerability, Pharmacokinetics, and Pharmacodynamic Activity of NFX-179 Gel in Subjects With Cutaneous Neurofibromas

This study will enroll and treat subjects with cutaneous neurofibromas with NFX-179, a topical study drug. Eligible subjects will receive treatment for 28 days and be observed by a study doctor for approximately 56 days. Subjects will be randomly assigned to 1 of 4 treatment groups. 3 of the treatment groups will receive a specific dose NFX-179, and 1 group will receive placebo. The subject, study doctor, and NFlection Therapeutics will not know what treatment group each subject is assigned. Study participation requires at least 7 clinic visits, blood, urine, and tissue collection, images of the treated cutaneous neurofibromas, electrocardiograms, and information regarding the subject's medical and disease history.

Start Date21 Aug 2020

Sponsor / Collaborator

NFlection Therapeutics, Inc.Startup

100 Clinical Results associated with Nedometinib

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100 Translational Medicine associated with Nedometinib

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100 Patents (Medical) associated with Nedometinib

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5

Literatures (Medical) associated with Nedometinib

03 May 2024·Science Advances

Effect of NFX-179 MEK inhibitor on cutaneous neurofibromas in persons with neurofibromatosis type 1

Article

Author: Kincaid, John ; Horwath, Patrice ; Le, Lu Q. ; Kempers, Steven ; Plotkin, Scott R. ; Powala, Christopher ; Kochendoerfer, Gerd G. ; DuBois, Janet ; Dhawan, Sunil ; Sarin, Kavita Y. ; Webster, Guy F. ; de Souza, Mark P. ; Bradshaw, Mark ; Tu, John H. ; Shahryari, Jahanbanoo ; Wilson, David ; O'Mara, Chris

This phase 2a trial investigated the efficacy of NFX-179 Topical Gel, a metabolically labile MEK inhibitor, in the treatment of cutaneous neurofibromas (cNFs) in neurofibromatosis type 1. Forty-eight participants were randomized to four treatment arms: NFX-179 Topical Gel 0.05%, 0.15%, and 0.5% or vehicle applied once daily to five target cNFs for 28 days. Treatment with NFX-179 Topical Gel resulted in a dose-dependent reduction in p-ERK levels in cNFs at day 28, with a 47% decrease in the 0.5% NFX-179 group compared to the vehicle ( P = 0.0001). No local or systemic toxicities were observed during the treatment period, and systemic concentrations of NFX-179 remained below 1 ng/ml. In addition, 20% of cNFs treated with 0.5% NFX-179 Topical Gel showed a ≥50% reduction in volume compared to 6% in the vehicle group by ruler measurement with calculated volume ( P = 0.021). Thus, NFX-179 Topical Gel demonstrated significant inhibition of MEK in cNF with excellent safety and potential therapeutic benefit.

01 Nov 2023·Chemical biology & drug design

Synthesis of novel pyrimido[4,5-b]quinolines as potential anticancer agents and HER2 inhibitors.

Article

Author: Kadry, Hanan H ; Zaher, Ashraf F ; Ibrahim, Nahla Said M ; Mohamed, Khaled O

A series of N-arylpyrimido[4,5-b]quinolines 3a-e and 2-aryl-2,3-dihydropyrimido[4,5-b]quinoline-4(1H)-ones 5a-e was designed and synthesized as potential anticancer agents against breast cancer. Compounds 3e, 5a, 5b, 5d, and 5e showed promising activity against the MCF-7 cell line. Among them, compound 5b was the most active with IC₅₀ of 1.67 μM. Compound 5b promoted apoptosis and induced cell cycle arrest at S phase. 5b increased the level of pro-apoptotic proteins p53, Bax, and caspase-7 and inhibited the anti-apoptotic protein Bcl-2. Furthermore, all the synthesized compounds were docked into the crystal structure of HER2 (PBD: 3 pp0). Compounds 3e, 5a, 5b, 5d, and 5e showed good energy scores and binding modes. Finally, Compound 5b was evaluated on the HER2 assay and revealed good inhibition with IC₅₀ of 0.073 μM.

11 Oct 2023·Science Translational MedicineQ1 · MEDICINE

Development of a MEK inhibitor, NFX-179, as a chemoprevention agent for squamous cell carcinoma

Q1 · MEDICINE

Article

Author: Tsai, Kenneth Y ; Fenn, Peter ; Kincaid, John ; Sarin, Kavita Y ; Sun, Wenchao ; Prieto, Karol ; Sell, Brittney ; Bronson, Roderick T ; Wootton, Michael A ; Chavez-Chiang, Omar ; Duncton, Matthew A J ; Plotkin, Scott R ; de Moran Segura, Carlos ; de Souza, Mark P ; Powala, Christopher ; Shahryari, Jahanbanoo ; Nguyen, Jonathan ; Kochendoerfer, Gerd G ; Morefield, Elaine

Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer. Although cSCC contributes to substantial morbidity and mortality in high-risk individuals, deployment of otherwise effective chemoprevention of cSCC is limited by toxicities. Our systematic computational drug repurposing screen predicted that selumetinib, a MAPK (mitogen-activated protein kinase) kinase inhibitor (MEKi), would reverse transcriptional signatures associated with cSCC development, consistent with our genomic analysis implicating MEK as a chemoprevention target. Although systemic MEKi suppresses the formation of cSCC in mice, systemic MEKi can cause severe adverse effects. Here, we report the development of a metabolically labile MEKi, NFX-179, designed to potently and selectively suppress the MAPK pathway in the skin before rapid metabolism in the systemic circulation. NFX-179 was identified on the basis of its biochemical and cellular potency, selectivity, and rapid metabolism upon systemic absorption. In our ultraviolet-induced cSCC mouse model, topical application of NFX-179 gel reduced the formation of new cSCCs by an average of 60% at doses of 0.1% and greater at 28 days. We further confirmed the localized nature of these effects in an additional split-mouse randomized controlled study where suppression of cSCC was observed only in drug-treated areas. No toxicities were observed. NFX-179 inhibits the growth of human SCC cell lines in a dose-dependent manner, and topical NFX-179 application penetrates human skin and inhibits MAPK signaling in human cSCC explants. Together, our data provide a compelling rationale for using topical MEK inhibition through the application of NFX-179 gel as an effective strategy for cSCC chemoprevention.

100 Deals associated with Nedometinib

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Epidermal Nevus	Phase 2	United States	NFlection Therapeutics, Inc.Startup	01 Jun 2023
Nevus sebaceus	Phase 2	United States	NFlection Therapeutics, Inc.Startup	01 Jun 2023
Nephrosis, Congenital	Phase 2	United States	NFlection Therapeutics, Inc.Startup	21 Aug 2020
Neurofibromatosis 1	Phase 2	United States	NFlection Therapeutics, Inc.Startup	21 Aug 2020
Squamous Cell Carcinoma	Preclinical	United Kingdom	NFlection Therapeutics, Inc.Startup	06 Jun 2020
Squamous Cell Carcinoma	Preclinical	United Kingdom	Stanford University	06 Jun 2020
Squamous Cell Carcinoma	Preclinical	United Kingdom	H. Lee Moffitt Cancer Center & Research Institute, Inc.	06 Jun 2020

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05005845 (PRNewswire) Manual	Phase 2	Neurofibromatosis 1	199	NFX‑179 0.5%	hibinxjigh(ezppchbtat) = fuwpwyjyvw ohgjujolzr (crpkitpyko )	Positive	13 Nov 2023
				NFX‑179 1.5%	hibinxjigh(ezppchbtat) = zrsurmuhnd ohgjujolzr (crpkitpyko )
NCT04435665 (CTgov)	Phase 2	Nephrosis, Congenital \| Neurofibromatosis 1	48	Placebo (Vehicle Arm (Placebo))	ddesxfuurh(ajgischdug) = farwoibznb irqedxrhus (mvlcpxmdpt, vwpvtvofgp - qvcewzprzl) View more	-	09 Aug 2022
				NFX-179 (NFX-179 Gel Low (0.05%))	ddesxfuurh(ajgischdug) = lqrbushrhm irqedxrhus (mvlcpxmdpt, ozcaepvbyw - qekbvlairy) View more