Delving into the Latest Updates on Glucopyranosyl lipid A with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

GLA, GLA-SE, Glucopyranosyl lipid

+ [4]

Target

TLR4

Mechanism

TLR4 agonists(Toll like receptor 4 agonists)

Therapeutic Areas

NeoplasmsImmune System DiseasesHemic and Lymphatic Diseases+ [2]

Active Indication

Non-Hodgkin LymphomaMerkel Cell CarcinomaSarcoma

Inactive Indication

Follicular LymphomaInfluenza, HumanMelanoma+ [5]

Originator Organization

Merck & Co., Inc.

Active Organization

Merck & Co., Inc.

Inactive Organization

Immune Design Corp.

Protein Sciences Corp.

Drug Highest PhasePhase 2

First Approval Date-

RegulationOrphan Drug (US)

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Structure/Sequence

Molecular FormulaC94H180N3O22P

InChIKeyCYRPJUBABDDIFR-ADEWMWGLSA-N

CAS Registry1332714-01-8

The overall goal of this study is to evaluate the safety and immunogenicity of repeat-dose intratumoral G100 administration in patients with Cutaneous T Cell Lymphoma (CTCL) alone (Part 1) and following standard local radiation therapy or topical nitrogen mustard application (Part 2). Plaque, patch, or tumor lesions of CTCL may be injected. Disease will be assessed in all sites, including skin, nodes, and blood.

Start Date01 Jun 2019

Sponsor / Collaborator

Yale University

100 Clinical Results associated with Glucopyranosyl lipid A

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100 Translational Medicine associated with Glucopyranosyl lipid A

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100 Patents (Medical) associated with Glucopyranosyl lipid A

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1,410

Literatures (Medical) associated with Glucopyranosyl lipid A

01 Apr 2025·Tissue and Cell

Mandibular bone defect healing using polylactic acid–nano-hydroxyapatite–gelatin scaffold loaded with hesperidin and dental pulp stem cells in rat

Article

Author: Daneshi, Seyyed Sajad ; Mussin, Nadiar M ; Zare, Shahrokh ; Iraji, Aida ; Kurmanalina, Madina A ; Asadi-Yousefabad, Seyedeh-Leili ; Nowzari, Fariborz ; Mokhtarzadegan, Mohamad ; Ebrahimi, Reyhaneh ; Aliabadi, Ehsan ; Khosronejad, Arya ; Akbarizadeh, Fatemeh ; Arabion, Hamidreza ; Amiri, Mohammad Amin ; Tanideh, Nader ; Abbaspour, Shekofeh ; Zarei, Moein ; Tamadon, Amin

Addressing mandibular defects poses a significant challenge in maxillofacial surgery. Recent advancements have led to the development of various biomimetic composite scaffolds aimed at facilitating mandibular defect reconstruction. This study aimed to assess the regenerative potential of a novel composite scaffold consisting of polylactic acid (PLA), hydroxyapatite nanoparticles (n-HA), gelatin, hesperidin, and human dental pulp stem cells (DPSCs) in a rat model of mandibular bone defect. The PLA-HA-GLA composite was synthesized using solvent casting-leaching and freeze-drying methods and subsequently treated with 11 mg of hesperidin. The physicochemical properties of the PLA-HA-GLA and PLA-HA-GLA-HIS composites were analyzed by scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and thermal gravimetric analysis (TGA). Additionally, the mechanical properties and cytotoxicity of DPSCs were assessed. Subsequently, PLA-HA-GLA and PLA-HA-GLA-HIS scaffolds with or without DPSCs were implanted into mandibular bone defects in rats, followed by histopathological, histomorphometric, and cone-beam computed tomography (CBCT) evaluations after eight weeks. SEM analysis revealed the porous structure of the fabricated PLA-HA-GLA and PLA-HA-GLA-HIS composites without aggregation. FTIR and XRD analyses confirmed the presence of functional groups and elements associated with PLA, HA, GLA, and hesperidin in the composites. Although the PLA-HA-GLA-HIS composite exhibited good thermal stability, its mechanical properties decreased after the addition of hesperidin. The cell viability of DPSCs on the surface of the PLA-HA-GLA-HIS scaffolds was statistically significant compared to that of the control group. Furthermore, histopathological, histomorphometric, and radiological evaluations demonstrated that the implantation of the DPSC-loaded PLA-HA-GLA-HIS scaffold had a beneficial effect on bone tissue reconstruction in rats with mandibular defects. These findings highlight the potential of DPSC-loaded PLA-HA-GLA-HIS composite scaffolds for spongy bone tissue engineering and mandibular defect repair.

01 Feb 2025·Phytomedicine

Synergistic antimicrobial efficacy of glabrol and colistin through micelle-based co-delivery against multidrug-resistant bacterial pathogens

Article

Author: Cai, Yawei ; Zhang, Mengying ; Mei, Chen ; Liu, Ying ; Wu, Shuaicheng ; Wang, Hongjun ; Qu, Shaoqi

BACKGROUNDWidespread bacterial infection and the spread of multidrug resistance (MDR) exhibit increasing threats to the public and thus require new antibacterial strategies. Coupled with the current slow pace of antibiotic development, the use of antibiotic adjuvants to revitalize existing antibiotics offers great potential.PURPOSEWe aim to explore the synergistic antimicrobial mechanism of glabrol (GLA) and colistin (COL) while developing an innovative multifunctional micelle-based drug delivery system to enhance therapeutic efficacy.METHODSThe synergy between GLA and COL was assessed through a combination of high-throughput screening and checkerboard analysis techniques. Moreover, we performed fluorescence-based assays to investigate the underlying mechanisms of action of the GLA and COL combination. We also developed a multifunctional drug delivery platform that integrates GLA and COL into co-loaded composite micelles, aimed at improving antibacterial efficacy against peritoneal sepsis and chronic bacterial wound infections caused by diverse microbial pathogens.RESULTSWe have discovered that natural flavonoids found in plants act synergistically with colistin against MDR bacterial infections, effectively improving its efficacy through a co-delivery strategy. The combination therapy consisting of GLA and COL exhibits enhanced antibacterial efficacy and is capable of clearing 99% of MDR Gram-positive and Gram-negative bacteria in 4 h. Mechanistic studies showed that COL increases the outer membrane permeability, which promotes the adhesion of GLA to the inner membrane, disrupting bacterial metabolism, and ultimately leading to bacterial death. Furthermore, a novel pH-responsive hydrogel system was developed and dispersed with GLA and COL co-loaded composite micelles to mitigate the selective pressure of antibiotics with fewer side effects. Lastly, such a system showed high efficacy in two animal models.CONCLUSIONOur findings provide a potential therapeutic option using a co-delivery system functionalized with combination therapy, to address the prevalent infections caused by complex bacterial infections and even MDR bacterial infections.

01 Feb 2025·Journal of Ethnopharmacology

Glabridin inhibits proliferation and migration in hepatocellular carcinoma by regulating multi-targets

Article

Author: Wang, Fei ; Lu, Yi ; Liu, Yifei ; Yang, Yanfang ; Wu, Mojiao ; Yuan, Chong ; Wu, Hezhen

ETHNOPHARMACOLOGICAL RELEVANCEGlycyrrhiza uralensis Fisch. (GC) is widely utilized in traditional Chinese medicine (TCM) for its properties in Qi tonification, heat clearing, and detoxification. Within TCM theory, Qi is also implicated in tumor development. Numerous TCM formulas containing GC are used for their anti-tumor effects, and contemporary pharmacological research has demonstrated that ethyl acetate extracts (EAe) of GC, along with potential bioactive compounds like glabridin (Gla), possess anti-tumor properties. Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and a major challenge to global healthcare, with high incidence and poor prognosis. Nevertheless, the effects and mechanisms of action of Gla in inhibiting HCC have not been extensively studied.AIM OF STUDYThis study aims to elucidate the effects and mechanisms of action of Gla against HCC by in vitro and in vivo experiments.METHODSThe inhibitory effects of ethyl acetate extract (EAe) of GC and its bioactive compounds on HCC were studied using a drug-cell interaction system equipped with UPLC-MS/MS and high-throughput screening methods in vitro. RNA sequencing (RNA-seq) and bioinformatics technologies were employed to detect the differentially expressed genes (DEGs) and pathways in HepG2 cells. The findings were further validated using quantitative real-time PCR (qPCR) and Western blot (WB) assays. Additionally, an in vivo tumor-bearing mouse model established with H22 cells was utilized to examine alterations in tumor tissues via hematoxylin-eosin (HE) staining. Immunohistochemistry was used to assess the protein expression levels of hub targets within each group.RESULTSBoth in vitro and in vivo experiments demonstrated the effects of EAe against HCC, identifying Gla was one of its main bioactive compounds. Integration of RNA-seq data with clinical databases revealed that Gla inhibited HCC by up-regulating the expression levels of DUSP5, ZFP36, KLF10, and NR4A1, while down-regulating RMI2 expression. These findings were further validated by Gene Expression Omnibus (GEO), qPCR, WB and immunohistochemistry assays.CONCLUSIONSGla regulates the expression levels of DUSP5, ZFP36, KLF10, NR4A1, and RMI2 to against HCC, providing valuable insights for the application of Gla in HCC treatment.

100 Deals associated with Glucopyranosyl lipid A

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Follicular Lymphoma	Phase 2	-	-	03 Feb 2016
Melanoma	Phase 2	US	Immune Design Corp.	28 Feb 2015
Myxoid Liposarcoma	Phase 2	US	Immune Design Corp.	28 Feb 2015
Non-Small Cell Lung Cancer	Phase 2	US	Immune Design Corp.	28 Feb 2015
Ovarian Cancer	Phase 2	US	Immune Design Corp.	28 Feb 2015
Soft Tissue Sarcoma	Phase 2	US	Immune Design Corp.	28 Feb 2015
Influenza, Human	Phase 2	US	Protein Sciences Corp.	01 Jun 2010
Non-Hodgkin Lymphoma	Phase 2	-	Merck & Co., Inc.	-
Merkel Cell Carcinoma	Phase 1	-	Merck & Co., Inc.	-
Sarcoma	Phase 1	-	Merck & Co., Inc.	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02501473 (Pubmed \| Leuk Lymphoma)	Phase 1/2	Follicular Lymphoma	-	Intratumoral G100	bhdwmthggs(frudpywrdb) = lrvktjnafl klmibmpwsk (azlbqpquds ) View more	-	21 Mar 2022
EULAR2021	Not Applicable	-	100	Subacromial injections of GLA	(oquojjbcjm) = nvhydzmftk gdywdlbxol (mxrbyrjrzb )	Positive	02 Jun 2021
				Subacromial injections of PRP	(oquojjbcjm) = emlktawupm gdywdlbxol (mxrbyrjrzb )
NCT02387125 (Pubmed \| Oncoimmunology) Manual	Phase 1	Locally Advanced Malignant Neoplasm	79	cyclophosphamide+glucopyranosyl lipid A+CMB305	(heyxjffazr) = fatigue (34.2%), nausea (26.6%), and injection-site pain (24.1%) cxybuwgolw (ypxfmezmkv )	Positive	19 Nov 2020
NCT02501473 (P367 \| 3475-174 \| P327 \| IMDZ-G142 \| MK-3475-174, CTgov)	Phase 1/2	Follicular Lymphoma	52	G100 (Part 1: Local Radiation + G100 5μg/Tumor)	hwhpmdbekp(ggrldcxxcm) = jpcxavufam iudnmwbifk (jhdilataku, niznlsfrmx - jkngiqtgtb) View more	-	09 Sep 2020
				G100 (Part 1: Local Radiation + G100 10μg/Tumor)	hwhpmdbekp(ggrldcxxcm) = yaivszasza iudnmwbifk (jhdilataku, bdnappvkvh - gehhekpgdd) View more
NCT02501473 (P367, SITC2018)	Phase 1/2	Neoplasms	-	G100	lkrlxbolcn(jyhfcjhozc) = jqamkdsrac znfpxhnnhg (hrtqfwuvdp )	Positive	06 Nov 2018
				Anti-OX40 antibody	lkrlxbolcn(jyhfcjhozc) = gjvhddstss znfpxhnnhg (hrtqfwuvdp )
SITC2018	Not Applicable	-	-	G100 (Transfer-pull regimen)	mkiiilqnxz(dpvytyantr) = draekjbbry aasomgwsyl (rllgeyrcih )	Positive	06 Nov 2018
AACR2017	Not Applicable	Sarcoma	15	IT G100	lmzmyiaflw(orvbjysdwr) = mntwnlrhyi dgtdnlwego (qdyytcfppx ) View more	-	01 Jul 2017
				G100 (Radiation)	nuidkrzohn(vvhutumtzd) = spponnmjqs gxrmisbpxi (wqjhwygpsr )
NCT02501473 (3475-174 \| IMDZ-G142 \| MK-3475-174, ASCO 12017 \| ASCO 22017) Manual	Phase 1/2	Follicular Lymphoma	-	Glucopyranosyl lipid A	(jvqggovfvy) = none amzrmshaow (ptmpfbyzaf ) View more	Positive	05 Jun 2017