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

Action

agonists

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 (United States)

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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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64

Literatures (Medical) associated with Glucopyranosyl lipid A

01 Dec 2024·The Veterinary Journal

Dose titration of intravenously administered gamma-hydroxybutyric acid for sedation in Holstein-Friesian calves

Article

Author: Cuypers, C. ; Alonso, B ; Devreese, M. ; Schauvliege, S. ; Devreese, M ; Schauvliege, S ; Cuypers, C ; Alonso, B.

Gamma-hydroxybutyric acid (GHB) is a short-chain fatty acid that can potentially provide safe, prolonged sedation with minimal cardiorespiratory effects. This preliminary trial, performed in 10 three-week-old male Holstein-Friesian calves, investigated the effects of GHB administered intravenously over 5 min at a dose of 100 (G100, n=2), 150 (G150, n=4) or 200 mg/kg (G200, n=4). Once lateral recumbency was achieved, scores for sedation depth (range: 0 = no sedation to 3 = marked) and response to noxious stimulation (range: 0 = strong to 3 = absent), heart rate (HR), respiratory rate (RR), mean arterial pressure (MAP) and arterial blood gases were monitored every 15 min until sternal recumbency. Times from end of administration to lateral recumbency and return to sternal/standing positions were recorded. Dose G100 resulted in mild sedation and ataxia without decubitus. Doses G150 and G200 respectively resulted in time to lateral recumbency 8 ± 2 and 9 ± 3 min, lasting 189 ± 41 and 283 ± 29 min, while overall median (range) scores for sedation were 3 (1-3) and 3 (2-3) respectively and response to noxious stimulation 0 (0-3) and 0 (0-3) respectively. The mean ± SD for HR was 110 ± 10 and 106 ± 11 bpm respectively; for MAP 87±9 and 94±5 mmHg respectively; and for RR 28 ± 5 and 26 ± 5 bpm respectively. The mean ± SD for arterial partial pressure of oxygen (PaO2) at these two dose rates was 74 ± 6 and 74 ± 2 mmHg respectively, while the arterial partial pressure of carbon dioxide oxygen (PaCO₂) was 53 ± 3 and 47 ± 0.8 mmHg respectively. Based on these preliminary results we conclude that GHB has the potential to be used as a long-acting sedative in calves. Further studies are needed to confirm this.

01 Jul 2024·The Lancet Infectious Diseases

Safety and immunogenicity of the co-administered Na-APR-1 and Na-GST-1 hookworm vaccines in school-aged children in Gabon: a randomised, controlled, observer-blind, phase 1, dose-escalation trial

Article

Author: Vodonou, Kafui G ; Dejon-Agobé, Jean Claude ; Bethony, Jeffrey M ; Massinga Loembe, Marguerite ; Adegnika, Ayola A ; Edoa, Jean Ronald ; Diemert, David J ; Bottazzi, Maria Elena ; Li, Guangzhao ; Adégbité, Bayodé R ; Hotez, Peter J ; Honkpehedji, Yabo Josiane ; Bikangui, Rodrigue ; Yazdanbakhsh, Maria ; van Leeuwen, Remko ; Zinsou, Jeannot F ; Grobusch, Martin P ; Kremsner, Peter G

BACKGROUNDA human hookworm vaccine is being developed to protect children against iron deficiency and anaemia associated with chronic infection with hookworms. Necator americanus aspartic protease-1 (Na-APR-1) and N americanus glutathione S-transferase-1 (Na-GST-1) are components of the blood digestion pathway critical to hookworm survival in the host. Recombinant Na-GST-1 and catalytically inactive Na-APR-1 (Na-APR-1[M74]) adsorbed to Alhydrogel were safe and immunogenic when delivered separately or co-administered to adults in phase 1 trials in non-endemic and endemic areas. We aimed to investigate the safety and immunogenicity of these antigens in healthy children in a hookworm-endemic area.METHODSThis was a randomised, controlled, observer-blind, phase 1, dose-escalation trial, conducted in a clinical research centre, in 60 children aged six to ten years in Lambaréné, a hookworm-endemic region of Gabon. Healthy children (determined by clinical examination and safety laboratory testing) were randomised 4:1 to receive co-administered Na-GST-1 on Alhydrogel plus Na-APR-1(M74) on Alhydrogel and glucopyranosyl lipid A in aqueous formulation (GLA-AF), or co-administered ENGERIX-B hepatitis B vaccine (HBV) and saline placebo, injected into the deltoid of each arm. Allocation to vaccine groups was observer-masked. In each vaccine group, children were randomised 1:1 to receive intramuscular injections into each deltoid on two vaccine schedules, one at months 0, 2, and 4 or at months 0, 2, and 6. 10 μg, 30 μg, and 100 μg of each antigen were administered in the first, second, and third cohorts, respectively. The intention-to-treat population was used for safety analyses; while for immunogenicity analyses, the per-protocol population was used (children who received all scheduled vaccinations). The primary outcome was to evaluate the vaccines' safety and reactogenicity in healthy children aged between six and ten years. The secondary outcome was to measure antigen-specific serum IgG antibody levels at pre-vaccination and post-vaccination timepoints by qualified ELISAs. The trial is registered with ClinicalTrials.gov, NCT02839161, and is completed.FINDINGSBetween Jan 23 and Oct 3, 2017, 137 children were screened, of whom 76 were eligible for this trial. 60 children were recruited, and allocated to either 10 μg of the co-administered antigens (n=8 for each injection schedule), 30 μg (n=8 for each schedule), 100 μg (n=8 for each schedule), or HBV and placebo (n=6 for each schedule) in three sequential cohorts. Co-administration of the vaccines was well tolerated; the most frequent solicited adverse events were mild-to-moderate injection-site pain, observed in up to 12 (75%) of 16 participants per vaccine group, and mild headache (12 [25%] of 48) and fever (11 [23%] of 48). No vaccine-related serious adverse events were observed. Significant anti-Na-APR-1(M74) and anti-Na-GST-1 IgG levels were induced in a dose-dependent manner, with peaks seen 14 days after the third vaccinations, regardless of dose (for Na-APR-1[M74], geometric mean levels [GML]=2295·97 arbitrary units [AU] and 726·89 AU, while for Na-GST-1, GMLs=331·2 AU and 21·4 AU for the month 0, 2, and 6 and month 0, 2, and 4 schedules, respectively). The month 0, 2, and 6 schedule induced significantly higher IgG responses to both antigens (p=0·01 and p=0·04 for Na-APR-1[M74] and Na-GST-1, respectively).INTERPRETATIONCo-administration of recombinant Na-APR-1(M74) and Na-GST-1 to school-aged Gabonese children was well tolerated and induced significant IgG responses. These results justify further evaluation of this antigen combination in proof-of-concept controlled-infection and efficacy studies in hookworm-endemic areas.FUNDINGEuropean Union Seventh Framework Programme.

01 Mar 2024·EFSA Journal

Safety and efficacy of a feed additive consisting of narasin (Monteban® G100) for chickens for fattening (Elanco GmbH)

Article

Author: López Puente, Secundino ; Ramos, Fernando ; Vettori, Maria Vittoria ; López-Alonso, Marta ; Mayo, Baltasar ; Bampidis, Vasileios ; Rossi, Barbara ; Marcon, Francesca ; Christensen, Henrik ; Azimonti, Giovanna ; Teodorovic, Ivana ; Navarro-Villa, Alberto ; Holczknecht, Orsolya ; Finizio, Antonio ; Pechová, Alena ; Kouba, Maryline ; Rychen, Guido ; Gropp, Jürgen ; Pettenati, Elisa ; Petkova, Mariana ; Galobart, Jaume ; Woutersen, Ruud ; Villa, Roberto Edoardo ; Dusemund, Birgit ; Durjava, Mojca ; Bastos, Maria de Lourdes

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of the coccidiostat narasin (Monteban® G100) for chickens for fattening. In a previous opinion, uncertainties remained on the identification and characterisation of the non-genetically modified production strain of the active substance narasin. The Panel could not conclude either on the safety of Monteban® G100 for chickens for fattening or on the efficacy of the additive at the minimum applied concentration. The FEEDAP Panel excluded risks for environment but the risk for sediment compartment could not be assessed. The applicant provided supplementary information to cover the data gaps and substituted the narasin production strain from Streptomyces spp. NRRL 8092 to Streptomyces spp. NRRL B-67771. The information submitted to taxonomically identify the production strain did not allow to assign it to any described microbial species. Based on the information provided, the Panel concluded that the use of Monteban® G100 did not raise safety concerns as regards the production strain for the target animal, consumer, user and environment. The Panel concluded that 70 mg narasin/kg complete feed was safe for chickens for fattening with a margin of safety of 1.4; narasin from Monteban® G100 was unlikely to increase shedding of Salmonella Enteritidis, Salmonella Typhimurium and Campylobacter jejuni. Narasin, when used in chickens for fattening at 70 mg/kg feed, was not expected to pose a risk to the aquatic compartment and to sediment, while a risk for the terrestrial compartment could not be excluded. No risk for groundwater was expected, nor for secondary poisoning via the terrestrial food chain, but the risk of secondary poisoning via the aquatic food chain could not be excluded. The Panel concluded that 60 mg narasin/kg feed was efficacious in controlling coccidiosis in chickens for fattening.

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
Non-Hodgkin Lymphoma	Phase 2	-	Merck & Co., Inc.	-
Merkel Cell Carcinoma	Phase 1	-	Merck & Co., Inc.	-
Sarcoma	Phase 1	-	Merck & Co., Inc.	-
Follicular Lymphoma	Discovery	-	-	03 Feb 2016
Melanoma	Discovery	United States	Immune Design Corp.	28 Feb 2015
Myxoid Liposarcoma	Discovery	United States	Immune Design Corp.	28 Feb 2015
Non-Small Cell Lung Cancer	Discovery	United States	Immune Design Corp.	28 Feb 2015
Ovarian Cancer	Discovery	United States	Immune Design Corp.	28 Feb 2015
Soft Tissue Sarcoma	Discovery	United States	Immune Design Corp.	28 Feb 2015
Influenza, Human	Discovery	United States	Protein Sciences Corp.	01 Jun 2010

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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	kkdgzntzmp(wypaubexzr) = icdpptnjxx ldihljkytp (vzxrwqzoyn ) View more	-	21 Mar 2022
EULAR2021	Not Applicable	-	100	Subacromial injections of GLA	(vmziglwlgf) = lrecsvjnlx crnzhzhilm (jgqmqyhysa )	Positive	02 Jun 2021
				Subacromial injections of PRP	(vmziglwlgf) = nglrgxtxdk crnzhzhilm (jgqmqyhysa )
NCT02387125 (Pubmed \| Oncoimmunology) Manual	Phase 1	Locally Advanced Malignant Neoplasm	79	cyclophosphamide+glucopyranosyl lipid A+CMB305	(eiotboenbq) = fatigue (34.2%), nausea (26.6%), and injection-site pain (24.1%) lbmjojbhag (ylrswwrpxm )	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)	nhybqdbulv(kowgugycjw) = ewnoaqnoxy bwlgoxiqur (ipzudrhmgr, oyaqmzsbpx - iazoowovam) View more	-	09 Sep 2020
				G100 (Part 1: Local Radiation + G100 10μg/Tumor)	nhybqdbulv(kowgugycjw) = pmgjqdlluq bwlgoxiqur (ipzudrhmgr, nqgkghqdcv - lyuktxuigg) View more
NCT02501473 (P367, SITC2018)	Phase 1/2	Neoplasms	-	G100	lenvgdxejc(cixafwcooi) = tqqtqgffbw mgsrouybuw (lvmyenbsng )	Positive	06 Nov 2018
				Anti-OX40 antibody	lenvgdxejc(cixafwcooi) = noftknhhza mgsrouybuw (lvmyenbsng )
SITC2018	Not Applicable	-	-	G100 (Transfer-pull regimen)	aqylnnbdyr(firvkchjuy) = wiptgkjlru mwdqqzioit (fsfhswxnhb )	Positive	06 Nov 2018
AACR2017	Not Applicable	Sarcoma	15	IT G100	rmhadenevi(rstdzkkrwv) = ncozfmcnjx rpyhozceqn (apbbheiaze ) View more	-	01 Jul 2017
				G100 (Radiation)	yygjiuoisz(skrefnrkva) = ikycmyseev jetsprcpfq (uvahwavrht )
NCT02501473 (3475-174 \| IMDZ-G142 \| MK-3475-174, ASCO 12017 \| ASCO 22017) Manual	Phase 1/2	Follicular Lymphoma	-	Glucopyranosyl lipid A	(wffjancqbp) = none gqwkdjkcdg (lktmejwpqh ) View more	Positive	05 Jun 2017