A Double Blind, Randomized, Phase II-III Maintenance Study of SR48692 Versus Placebo in Patients With Extensive Stage Small Cell Lung Cancer Following a First Line Chemotherapy With Cisplatin + Etoposide

To demonstrate an increase in overall survival for patients with newly diagnosed extended stage small cell lung cancer when treated with SR48692 versus placebo, after an initial response (complete or partial response or stable) to first line cisplatin plus etoposide.
Primary objective: comparison of overall survival between patients in the control arm and the meclinertant arm.
Secondary objectives: comparison of the progression free survival, the time to progression, the clinical benefit, the quality of life, the toxicity and safety between patients in the control arm and the meclinertant arm.

Start Date01 Oct 2002

Sponsor / Collaborator

Sanofi

100 Clinical Results associated with Meclinertant

100 Translational Medicine associated with Meclinertant

100 Patents (Medical) associated with Meclinertant

311

Literatures (Medical) associated with Meclinertant

24 Mar 2025·Endocrinology

Neurotensin Regulates Primate Ovulation Via Multiple Neurotensin Receptors

Article

Author: Shrestha, Ketan ; Duffy, Diane M ; Curry, Thomas E ; Miller, Jessica S ; Pearson, Andrew C ; Jensen, Hannah J

AbstractNeurotensin (NTS), a small neuropeptide, was recently established as a key paracrine mediator of ovulation. NTS mRNA is highly expressed by granulosa cells in response to the luteinizing hormone surge, and multiple NTS receptors are expressed by cells of the ovulatory follicle. To identify the role of NTS receptors NTSR1 and SORT1 in ovulation in vivo, the dominant follicle of cynomolgus macaques (Macaca fascicularis) was injected with either vehicle control, the general NTS receptor antagonist SR142948, the NTSR1-selective antagonist SR48692, or the SORT1-selective antagonist AF38469. hCG was then administered to initiate ovulatory events. Ovulation was successful in all control-injected follicles. Rupture sites were smaller or absent after injection with NTS receptor antagonists. Histological analysis of follicles injected with SR142948, SR48692, or AF38469 revealed increased red blood cell extravasation and pooling in the follicle antrum when compared to controls. NTS receptor antagonist-injected follicles also showed dysregulated capillary formation and reduced luteinization of the granulosa cell layer. Prior in vitro studies showed that NTS significantly increased monkey ovarian microvascular endothelial cell (mOMEC) migration, while decreasing monolayer permeability. The NSTR1 antagonist SR48692 or siRNA knockdown of NTSR1 abrogated the ability of NTS to stimulate mOMEC migration and to decrease monolayer permeability. Similar experiments performed with the SORT1 antagonist AF38469 or siRNA knockdown of SORT1 also resulted in ablation of NTS-mediated changes in migration and permeability after SORT1 signaling was impaired. Together, these data implicate both NTSR1 and SORT1 to be critical mediators of NTS-stimulated ovulation, luteinization, and angiogenesis of the ovulatory follicle.

01 Feb 2025·Frontiers of Medicine

Decreased neurotensin induces ovulatory dysfunction via the NTSR1/ERK/EGR1 axis in polycystic ovary syndrome

Article

Author: Zhai, Junyu ; Chu, Weiwei ; Sun, Yun ; Wang, Dongshuang ; Zhang, Meiling ; Du, Yanzhi ; Chen, Zi-Jiang ; Wang, Wang-Sheng

Polycystic ovary syndrome (PCOS) is the predominant cause of subfertility in reproductive-aged women; however, its pathophysiology remains unknown. Neurotensin (NTS) is a member of the gut-brain peptide family and is involved in ovulation; its relationship with PCOS is unclear. Here, we found that NTS expression in ovarian granulosa cells and follicular fluids was markedly decreased in patients with PCOS. In the in vitro culture of cumulus-oocyte complexes, the neurotensin receptor 1 (NTSR1) antagonist SR48692 blocked cumulus expansion and oocyte meiotic maturation by inhibiting metabolic cooperation and damaging the mitochondrial structure in oocytes and surrounding cumulus cells. Furthermore, the ERK1/2-early growth response 1 pathway was found to be a key downstream mediator of NTS/NTSR1 in the ovulatory process. Animal studies showed that in vivo injection of SR48692 in mice reduced ovulation efficiency and contributed to irregular estrus cycles and polycystic ovary morphology. By contrast, NTS partially ameliorated the ovarian abnormalities in mice with dehydroepiandrosterone-induced PCOS. Our findings highlighted the critical role of NTS reduction and consequent abnormal NTSR1 signaling in the ovulatory dysfunction of PCOS, suggesting a potential strategy for PCOS treatment.

01 Oct 2024·International Journal of Biological Macromolecules

Revealing the graded activation mechanism of neurotensin receptor 1

Article

Author: Hu, Jianping ; Zhang, Xinyu ; Su, Jingjie ; Sun, Xiaohan ; Wu, Zhixiang ; Li, Chunhua

Graded activation contributes to the precise regulation of GPCR activity, presenting new opportunities for drug design. In this work, a total of 10 μs enhanced-sampling simulations are performed to provide molecular insights into the binding dynamics differences of the neurotensin receptor 1 (NTSR1) to the full agonist SRI-9829, partial agonist RTI-3a and inverse agonist SR48692. The possible graded activation mechanism of NTSR1 is revealed by an integrated analysis utilizing the reweighted potential of mean force (PMF), deep learning (DL) and transfer entropy (TE). Specifically, the orthosteric pocket is observed to undergo expansion and contraction, with the G-protein-binding site experiencing interconversions among the inactive, intermediate and active-like states. Detailed structural comparisons capture subtle conformational differences arising from ligand binding in allosteric signaling, which can well explain the graded activation. Critical microswitches that contribute to graded activation are efficiently identified with the DL model. TE calculations enable the visualization of allosteric communication networks within the receptor, elucidating the driver-responder relationships associated with signal transduction. Fortunately, the dissociation of the full agonist from the orthosteric pocket is observed. The current findings systematically reveal the mechanism of NTSR1 graded activation, and also provide implications for structure-based drug design.

100 Deals associated with Meclinertant

External Link

KEGG	Wiki	ATC	Drug Bank
-	Meclinertant	-	DB06455

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Extensive stage Small Cell Lung Cancer	Discovery	Netherlands	Sanofi	01 Oct 2002
Extensive stage Small Cell Lung Cancer	Discovery	Italy	Sanofi	01 Oct 2002
Extensive stage Small Cell Lung Cancer	Discovery	Hungary	Sanofi	01 Oct 2002
Extensive stage Small Cell Lung Cancer	Discovery	Russia	Sanofi	01 Oct 2002
Extensive stage Small Cell Lung Cancer	Discovery	Argentina	Sanofi	01 Oct 2002
Extensive stage Small Cell Lung Cancer	Discovery	Poland	Sanofi	01 Oct 2002
Extensive stage Small Cell Lung Cancer	Discovery	Brazil	Sanofi	01 Oct 2002
Extensive stage Small Cell Lung Cancer	Discovery	Mexico	Sanofi	01 Oct 2002
Extensive stage Small Cell Lung Cancer	Discovery	Australia	Sanofi	01 Oct 2002
Extensive stage Small Cell Lung Cancer	Discovery	United Kingdom	Sanofi	01 Oct 2002

Clinical Result

Indication

Phase

Evaluation

View All Results

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

AI Agents Built for Biopharma Breakthroughs

Accelerate discovery. Empower decisions. Transform outcomes.

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis