Delving into the Latest Updates on Noscapine with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

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

+ [12]

Target-

Action-

Mechanism-

Therapeutic Areas

Respiratory Diseases

Active Indication

Cough

Inactive Indication

Chronic Lymphocytic LeukemiaLow Grade B-Cell Non-Hodgkin's LymphomaRefractory Multiple Myeloma+ [1]

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

Janssen Oncology, Inc.

Drug Highest PhaseApproved

First Approval Date-

RegulationOrphan Drug (United States)

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Structure/Sequence

Molecular FormulaC22H23NO7

InChIKeyAKNNEGZIBPJZJG-MSOLQXFVSA-N

CAS Registry128-62-1

Natural α-noscapine is an antitussive agent approved by the FDA, known for its low cytotoxicity even at high concentrationsRecently, it has shown that noscapine and its derivatives exhibit significant anticancer effects against a variety of cancer cell lines.To improve its therapeutic potential, this study focused on the synthesis of a series of novel isoxazole-conjugated noscapinoids, which were then assessed for their cytotoxic properties in vitro.The reaction of N-propargylic noscapine with in situ generated (Z)-N-hydroxybenzimidoyl chloride yielded the desired noscapinoids containing isoxazoles.The newly synthesized compounds showed considerable cytotoxic activity, with IC₅₀ ranging from 1.2 to 21.3μM, surpassing noscapine (IC₅₀: 31 and 65.5μM) across all evaluated cell lines, while exhibiting minimal toxicity to normal cells (IC₅₀ > 300μM).Mol. docking anal. of 2,3-dihydrobenzo[b][1,4]dioxin-6-yl containing isoxazole-conjugated noscapinoid derivative (IC₅₀ ranging 1.2 and 9.4μM across different cancer cell lines), indicated the highest binding affinity to tubulin (ΔG binding of -24.99 kcal/mol) and effectively induced apoptosis in cancer cells to a greater degree.

01 Feb 2025·Molecular and Cellular Biochemistry

Investigating the chemo-preventive role of noscapine in lung carcinoma via therapeutic targeting of human aurora kinase B

Article

Author: Hassan, Md Imtaiyaz ; Yousuf, Mohd ; Noor, Saba ; Ansari, Mohammad Ahmad ; Raza, Ali ; Ashraf, Anam ; Islam, Khursheed Ul ; Hussain, Afzal ; Choudhury, Arunabh

Lung carcinoma is the major contributor to global cancer incidence and one of the leading causes of cancer-related mortality worldwide. Irregularities in signal transduction events, genetic alterations, and mutated regulatory genes trigger cancer development and progression. Selective targeting of molecular modulators has substantially revolutionized cancer treatment strategies with improvised efficacy. The aurora kinase B (AURKB) is a critical component of the chromosomal passenger complex and is primarily involved in lung cancer pathogenesis. Since AURKB is an important therapeutic target, the design and development of its potential inhibitors are attractive strategies. In this study, noscapine was selected and validated as a possible inhibitor of AURKB using integrated computational, spectroscopic, and cell-based assays. Molecular docking analysis showed noscapine occupies the substrate-binding pocket of AURKB with strong binding affinity. Subsequently, MD simulation studies confirmed the formation of a stable AURKB-noscapine complex with non-significant alteration in various trajectories, including RMSD, RMSF, Rg, and SASA. These findings were further experimentally validated through fluorescence binding studies. In addition, dose-dependent noscapine treatment significantly attenuated recombinant AURKB activity with an IC₅₀ value of 26.6 µM. Cell viability studies conducted on A549 cells and HEK293 cells revealed significant cytotoxic features of noscapine on A549 cells. Furthermore, Annexin-PI staining validated that noscapine triggered apoptosis in lung cancer cells, possibly via an intrinsic pathway. Our findings indicate that noscapine-based AURKB inhibition can be implicated as a potential therapeutic strategy in lung cancer treatment and can also provide a novel scaffold for developing next-generation AURKB-specific inhibitors.

09 Jan 2025·Journal of Medicinal Chemistry

Discovery of N-Trifluoromethylated Noscapines as Novel and Potent Agents for the Treatment of Glioblastoma

Article

Author: Cui, Guangwei ; Zhang, Yongqiang ; Wang, Pan ; Fan, Yuhang ; Zhu, Yuxin ; Deng, Haiyang ; Yang, Yue ; Wei, Jinlian ; Li, Jian ; Ma, Yiwen

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.

100 Deals associated with Noscapine

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External Link

KEGG	Wiki	ATC	Drug Bank
D01036	Noscapine	R05DA07	DB06174

R&D Status

Approved

10 top approved records.

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

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Refractory Multiple Myeloma	Preclinical	United States	Janssen Oncology, Inc.	01 Dec 2007
Relapse multiple myeloma	Preclinical	United States	Janssen Oncology, Inc.	01 Dec 2007
Chronic Lymphocytic Leukemia	Preclinical	United States	University of Southern California	01 Mar 2000
Low Grade B-Cell Non-Hodgkin's Lymphoma	Preclinical	United States	University of Southern California	01 Mar 2000

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ERS2014	Not Applicable	Bronchial Spasm	-	Chloroquine	ghmhjocdpw(znfkjklskh) = zsawwlyach lpwmkrcegk (xskolsgiev )	-	01 Sep 2014
				Noscapine	ghmhjocdpw(znfkjklskh) = ylzryvvayc lpwmkrcegk (xskolsgiev )
AACR2010	Not Applicable	Breast Cancer	-	Noscapine and Doxorubicin	fypmzxenxx(trhpmgsgab) = gryjulfbun fqjorpwbpz (onwflrjyus )	-	15 Apr 2010
				MNCs	ssobnblftd(bqhgodfulk) = jmmvfmuuea nhfdjzoapk (hlcnzhbohc ) View more