Delving into the Latest Updates on Noscapine with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

(−)-narcotine, (−)-α-narcotine, Narcosine

+ [12]

Target-

Mechanism-

Therapeutic Areas

Respiratory Diseases

Active Indication

Cough

Inactive Indication

Chronic Lymphocytic LeukemiaLow Grade B-Cell Non-Hodgkin's Lymphoma

Originator Organization

Dongbei Pharmaceutical Group Co. Shenyang No 1 Pharm Co. Ltd.

Active Organization

Dongbei Pharmaceutical Group Co. Shenyang No 1 Pharm Co. Ltd.Qinghai Pharmaceutical Factory Co. Ltd.

Inactive Organization

University of Southern California

Drug Highest PhaseApproved

First Approval Date-

RegulationOrphan Drug (US)

Login to view timeline

Structure/Sequence

Molecular FormulaC22H23NO7

InChIKeyAKNNEGZIBPJZJG-MSOLQXFVSA-N

CAS Registry128-62-1

The search for new and effective chemotherapeutic agents for the treatment of glioblastoma (GBM) represents an unmet need in drug discovery. Herein, a class of novel N-trifluoromethylated noscapines has been disclosed. Among them, 9'-bromo-N-trifluoromethyl noscapine 15c displayed superior in vitro anti-GBM potency. Unexpectedly, in contrast with the general N-trifluoromethyl amines, these compounds exhibited good hydrolytic stability and further investigation of this distinct stability revealed a novel strategy for the structure modification of tetrahydroisoquinoline alkaloids, where N-methyl could be bioisosterically replaced with trifluoromethyl. Furthermore, 15c showed excellent BBB permeability and good in vivo anti-GBM activity and could efficiently suppress the migration of GBM cells, while no apparent toxicity was observed, thus representing an attractive lead for further drug discovery. Further mechanistic studies revealed that 15c exhibited an ability to induce G2/M-phase arrest in GBM cells associated with the disruption of tubulin polymerization, which is consistent with the mechanism of action of noscapine.

07 Jan 2025·Current Cancer Drug Targets

WITHDRAWN: Network Pharmacology and In vitro Experiments Reveal that Noscapine Induces Ros-mediated Apoptosis and Cell Cycle Arrest via PI3K/Akt/FoxO3a Signaling Pathway in Human Bladder Cancer Cells

Article

Author: Su, Yao ; Yang, Jin ; Chen, Lin

Since the authors are not responding to the editor’s requests to fulfill the editorial requirement, therefore, the article has been withdrawn from the journal Current Cancer Drug Targets. Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused. The Bentham Editorial Policy on Article Withdrawal can be found at https://benthamscience.com/editorial-policies-main.php BENTHAM SCIENCE DISCLAIMER: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultane-ously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submit-ting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.

01 Jan 2025·European Journal of Medicinal Chemistry

In silico inspired design of urea noscapine congeners as anticancer agents: Chemical synthesis and experimental evaluation using breast cancer cells and a xenograft mouse model

Article

Author: Kantevari, Srinivas ; Naik, Pradeep K ; Nayek, Arnab ; Reddy, Praveen Kumar ; Pragyandipta, Pratyush ; Naik, Eeshara

A series of semisynthetic noscapine-urea congeners (7a-7h) as potential tubulin-binding agents are being developed by integrating a urea pharmacophore at the C-9 position of the noscapine scaffold. Their binding affinity to tubulin was predicted through molecular docking, molecular dynamics (MD) simulations, and the MM-PBSA approach. These molecules were subsequently chemically synthesized and assessed using breast cancer cell lines (MCF-7 and MDA-MB-231) and normal human embryonic kidney cells (HEK). Both the docking score and the predicted binding free energy (ΔG_bind,pred) revealed that urea congeners had a stronger affinity towards tubulin than noscapine and effectively inhibited the proliferation of all cancer cell types without affecting normal healthy cells. The results indicated that compound 7g exhibited the most promise and was chosen for further studies. Moreover, MDA-MB-231 cells treated with 7g at its IC₅₀ concentration showed morphological changes such as membrane blebbing, fragmented nuclei, and the presence of apoptotic bodies. Apoptosis induction was further confirmed by flow cytometry. Moreover, the tubulin binding assay revealed a greater binding affinity with an equilibrium dissociation constant (KD) of 42 ± 2.4 μM for compound 7g. The number of MCF-7 cells engrafted as breast tumors in nude mice was found to be reduced significantly without any adverse effects. Noscapine is already in clinical trials, but the urea noscapine congener offers an advantage because of its increased potency without impacting the nontoxic profile of noscapine.

100 Deals associated with Noscapine

Login to view more data

External Link

KEGG	Wiki	ATC	Drug Bank
D01036	Noscapine	R05DA07	DB06174

R&D Status

Approved

10 top approved records.

Login

to view more data

Indication	Country/Location	Organization	Date
Cough	CN	Dongbei Pharmaceutical Group Co. Shenyang No 1 Pharm Co. Ltd.	-
Cough	CN	Qinghai Pharmaceutical Factory Co. Ltd.	-

Developing

10 top R&D records.

Login

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Chronic Lymphocytic Leukemia	Phase 3	US	University of Southern California	01 Mar 2000
Low Grade B-Cell Non-Hodgkin's Lymphoma	Phase 3	US	University of Southern California	01 Mar 2000

Login to view more data

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ERS2014	Not Applicable	Bronchial Spasm	-	Chloroquine	lqedhkxzxl(hqxkoouoil) = kwzrvwdmhn oftlxoxdaz (pkvscdffcb )	-	01 Sep 2014
				Noscapine	lqedhkxzxl(hqxkoouoil) = byyhlxapdj oftlxoxdaz (pkvscdffcb )
AACR2010	Not Applicable	Breast Cancer	-	Noscapine and Doxorubicin	aerdaxcamk(uogvhozeet) = etlpflvyix goatktpfpm (kiradunwug )	-	15 Apr 2010
				MNCs	qflbkkeghe(wonnnlbmsj) = vxdkcagcph dkmwxzldqp (ibubtalhne ) View more