Delving into the Latest Updates on Etalocib sodium with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Etalocib

+ [4]

Target

5-LOX x LTB4R x PPARγ

Mechanism

5-LOX inhibitors(Arachidonate 5-lipoxygenase inhibitors), LTB4R antagonists(Leukotriene B4 receptor antagonists), PPARγ agonists(Peroxisome proliferator-activated receptor γ agonists)

Therapeutic Areas

NeoplasmsDigestive System DisordersEndocrinology and Metabolic Disease+ [1]

Active Indication-

Inactive Indication

Non-Small Cell Lung CancerPancreatic Cancer

Originator Organization

Eli Lilly & Co.

Active Organization-

Inactive Organization

Eli Lilly & Co.

Drug Highest PhasePendingPhase 2

First Approval Date-

Regulation-

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Structure

Molecular FormulaC33H33FNaO6

InChIKeyIIAIFGQWVPLOLQ-UHFFFAOYSA-N

CAS Registry152608-41-8

View All Structures (2)

AbstractPneumocystis pneumonia (PCP) is a fungal pulmonary disease with high mortality in immunocompromised patients. Neutrophils are essential in defending against fungal infections; however, their role in PCP is controversial. Here we aim to investigate the effects of neutrophil extracellular traps (NETs) on Pneumocystis clearance and lung injury using a mouse model of PCP. Intriguingly, although neutrophils play a fundamental role in defending against fungal infections, NETs failed to eliminate Pneumocystis, but instead impaired the killing of Pneumocystis. Mechanically, Pneumocystis triggered Leukotriene B4 (LTB4)‐dependent neutrophil swarming, leading to agglutinative NET formation. Blocking Leukotriene B4 with its receptor antagonist Etalocib significantly reduced the accumulation and NET release of neutrophils in vitro and in vivo, enhanced the killing ability of neutrophils against Pneumocystis, and alleviated lung injury in PCP mice. This study identifies the deleterious role of agglutinative NETs in Pneumocystis infection and reveals a new way to prevent NET formation, which provides new insights into the pathogenesis of PCP.

01 Jul 2020·The Ocular SurfaceQ2 · MEDICINE

RvE1 uses the LTB4 receptor BLT1 to increase [Ca2+]i and stimulate mucin secretion in cultured rat and human conjunctival goblet cells

Q2 · MEDICINE

Article

Author: Serhan, Charles N ; Fjærvoll, Haakon K ; Utheim, Tor P ; Fjærvoll, Ketil A ; Bair, Jeffery A ; Yang, Menglu ; Hodges, Robin R ; Lippestad, Marit ; Dartt, Darlene A

PURPOSESpecialized pro-resolving lipid mediator resolvin (Rv) E1 stimulates secretion including mucins from conjunctival goblet cells. RvE1 can use both its ChemR23 receptor and the LTB₄ receptor BLT1 to increase [Ca²⁺]_i. The purpose of this study was to determine the expression of ChemR23 and BLT1 and receptors on conjunctival goblet cells and the respective roles these two receptors play in goblet cell responses to RvE1.METHODSGoblet cells were cultured from male rat or human conjunctiva from both sexes. Western blotting analysis, reverse transcription PCR and immunofluorescence microscopy were used to demonstrate the expression of ChemR23 and BLT1 in conjunctival goblet cells. High molecular weight glycoprotein secretion was determined using an enzyme-linked lectin assay. Signaling pathways were studied by measuring the increase in [Ca²⁺]_i using fura 2/AM.RESULTSChemR23 and BLT1 and receptors were present on both rat and human conjunctival goblet cells. The BLT1 inhibitors LY293111 and U75302 significantly blocked RvE1-and LTB₄-stimulated [Ca²⁺]_i increase. RvE1-and LTB₄-stimulated [Ca²⁺]_i and secretion increases were blocked by BLT1-targeted siRNA. RvE1-stimulated [Ca²⁺]_i and secretion increases were also blocked by ChemR23-targeted siRNA. Addition of RvE1 2 min before or simultaneously with LTB₄ desensitized the LTB₄ [Ca²⁺]_i response. Addition of RvE1 and LTB₄ simultaneously caused secretion that was decreased compared to either response alone.CONCLUSIONRvE1, in addition to the ChemR23 receptor, uses the BLT1 receptor to increase [Ca²⁺]_i and stimulate secretion in both rat and human cultured conjunctival goblet cells.

01 Apr 2018·International ImmunopharmacologyQ2 · MEDICINE

Substance P-regulated leukotriene B4 production promotes acute pancreatitis-associated lung injury through neutrophil reverse migration

Q2 · MEDICINE

Article

Author: Wu, Zengkai ; Hu, Guoyong ; Wan, Rong ; Han, Xiao ; Li, Bin ; Dai, Juanjuan ; Ye, Xin ; Chen, Congying ; Ni, Jianbo ; Wang, Xingpeng ; Wu, Jianghong

Leukotriene B4 (LTB4) is a potent chemoattractant and inflammatory mediator involved in multiple inflammatory diseases. Substance P (SP) has been reported to promote production of LTB4 in itch-associated response in vivo and in some immune cells in vitro. Here, we investigated the role of LTB4 in acute pancreatitis (AP), AP-associated acute lung injury (ALI) and the related mechanisms of LTB4 production in AP. In vivo, murine AP model was induced by caerulein and lipopolysaccharide or L-arginine. The levels of LTB4 and its specific receptor BLT1 were markedly upregulated in both AP models. Blockade of BLT1 by LY293111 attenuated the severity of AP, decreased neutrophil reverse transendothelial cell migration (rTEM) into the circulation and alleviated the severity of ALI. In vitro, treatment of pancreatic acinar cells with SP increased LTB4 production. Furthermore, SP treatment increased phosphorylation of protein kinase C (PKC) α and mitogen activated protein kinases (MAPKs), including extracellular signal-regulated kinase (ERK), p-38 MAPK and c-Jun NH2-terminal kinase (JNK). Finally, blockade of neurokinin-1 receptor by CP96345 significantly attenuated the severity of AP and decreased the level of LTB4 when compared to AP group. In summary, these results show that SP regulates the production of LTB4 via PKCα/MAPK pathway, which further promotes AP-associated ALI through neutrophil rTEM.

100 Deals associated with Etalocib sodium

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External Link

KEGG	Wiki	ATC	Drug Bank
-	Etalocib sodium	-	DB12850

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Non-Small Cell Lung Cancer	Phase 2	IL	Eli Lilly & Co.	01 Sep 2003
Non-Small Cell Lung Cancer	Phase 2	US	Eli Lilly & Co.	01 Sep 2003
Non-Small Cell Lung Cancer	Phase 2	DE	Eli Lilly & Co.	01 Sep 2003
Non-Small Cell Lung Cancer	Phase 2	CA	Eli Lilly & Co.	01 Sep 2003
Non-Small Cell Lung Cancer	Phase 2	NL	Eli Lilly & Co.	01 Sep 2003
Non-Small Cell Lung Cancer	Phase 2	ES	Eli Lilly & Co.	01 Sep 2003
Pancreatic Cancer	Phase 2	US	Eli Lilly & Co.	01 Jan 2003

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ASCO2006	Phase 2	Advanced Lung Non-Small Cell Carcinoma	201	LY293111 200 mg BID	(xuqndcsxvy) = krdkfazjli kumgefizxg (fbfakcuinr ) View more	Negative	20 Jun 2006
				LY293111 600 mg BID	(xuqndcsxvy) = tduhlasxbm kumgefizxg (fbfakcuinr ) View more