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

Mechanism

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

Therapeutic Areas

NeoplasmsNervous System DiseasesCongenital Disorders+ [3]

Active Indication

Nephrosis, CongenitalNeurofibromatosis 1Neurofibromatoses

Inactive Indication

Epidermal NevusNevusNevus sebaceus+ [1]

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 (EU)

Structure

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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18

Literatures (Medical) associated with Nedometinib

01 Jul 2024·Forensic Toxicology

The biological effects and thermal degradation of NPB-22, a synthetic cannabinoid

Article

Author: Maeno, Tomokazu ; Doi, Takahiro ; Igarashi, Kai ; Nagasawa, Akemichi ; Uemura, Nozomi ; Yuzawa, Katsuhiro ; Suzuki, Toshinari ; Takeda, Akihiro ; Inomata, Akiko ; Suzuki, Atsuko ; Shimizu, Seiko ; Tagami, Takaomi ; Nakajima, Jun'ichi ; Asada, Akiko

AbstractPurposeNPB-22 (quinolin-8-yl 1-pentyl-1H-indazole-3-carboxylate), Adamantyl-THPINACA (N-(1-adamantantyl)-1-[(tetrahydro-2H-pyran-4-yl)methyl]-1H-indazole-3-carboxamide), and CUMYL-4CN-B7AICA (1-(4-cyanobutyl)-N-(2-phenylpropan-2-yl)-1H- pyrrolo[2,3-b]pyridine-3-carboxamide), synthetic cannabinoids were evaluated in terms of CB1 (cannabinoid receptor type 1) and CB2 (cannabinoid receptor type 2) activities, and their biological effects when inhaled similar to cigarettes were examined.MethodsThe half maximal effective concentration values of the aforementioned synthetic cannabinoids at the CB1 and CB2 were investigated using [35S]guanosine-5’-O-(3-thio)-triphosphate binding assays. In addition, their biological effects were evaluated using the inhalation exposure test with mice. The smoke generated was recovered by organic solvents in the midget impingers, and the thermal degradation compounds of the smoke components were identified and quantified using a liquid chromatography–photo diode array detector.ResultsNPB-22 and Adamantyl-THPINACA had equivalent CB1 activity in in vitro assays. Meanwhile, NPB-22 had a weaker biological effect on some items on the inhalation exposure test than Adamantyl-THPINACA. When analyzing organic solvents in the midget impingers, it was revealed that NPB-22 was degraded to 8-quinolinol and pentyl indazole 3-carboxylic acid by combustion. In addition, these degradation compounds did not have CB1 activity.ConclusionIt was estimated that the biological effects of NPB-22 on the inhalation exposure test weakened because it underwent thermal degradation by combustion, and the resultant degradation compounds did not have any CB1 activity in vitro.

03 May 2024·Science Advances

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

Article

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

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	US	NFlection Therapeutics, Inc.Startup	01 Jun 2023
Nevus sebaceus	Phase 2	US	NFlection Therapeutics, Inc.Startup	01 Jun 2023
Nephrosis, Congenital	Phase 2	US	NFlection Therapeutics, Inc.Startup	21 Aug 2020
Neurofibromatosis 1	Phase 2	US	NFlection Therapeutics, Inc.Startup	21 Aug 2020
Neurofibromatoses	Phase 2	-	NFlection Therapeutics, Inc.Startup	-
Nevus	Discovery	GB	NFlection Therapeutics, Inc.Startup	06 Jun 2020
Squamous Cell Carcinoma	Discovery	GB	Stanford University	06 Jun 2020
Squamous Cell Carcinoma	Discovery	GB	NFlection Therapeutics, Inc.Startup	06 Jun 2020
Squamous Cell Carcinoma	Discovery	GB	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%	bkoocidkzy(gkffmymkrq) = hpdafbryhg jxrzkyysre (nxfitysvna )	Positive	13 Nov 2023
				NFX‑179 1.5%	bkoocidkzy(gkffmymkrq) = ujhonicttt jxrzkyysre (nxfitysvna )
NCT04435665 (CTgov)	Phase 2	Nephrosis, Congenital \| Neurofibromatosis 1	48	Placebo (Vehicle Arm (Placebo))	asjqgupcra(yupcexpsiv) = fktbvtpndg hewfxgrwwb (ubvundgzzb, hkrhkgiomo - ymucszyrqt) View more	-	09 Aug 2022
				NFX-179 (NFX-179 Gel Low (0.05%))	asjqgupcra(yupcexpsiv) = mdnnnymluk hewfxgrwwb (ubvundgzzb, xyyedrhdcb - bfwfnguspg) View more