Delving into the Latest Updates on Cromoglycate lisetil hydrochloride with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

5-[3-(2-carboxy-4-oxo-4H-5-chromenyloxy)-2-hydroxypropoxy]-4-oxo-4H-2-chromenecarboxylic acid, Cromoglicate, Cromoglicate lisetil

+ [8]

Target-

Mechanism

Histamine release inhibitors, Mast cells stabilizers

Therapeutic Areas

NeoplasmsImmune System DiseasesInfectious Diseases+ [5]

Active Indication-

Inactive Indication

AsthmaDermatitis, AtopicMastocytosis+ [3]

Originator Organization

Kyoto Pharmaceutical Industries Ltd.

Active Organization-

Inactive Organization

Leo Pharma, Inc.

Kyoto Pharmaceutical Industries Ltd.

Asahi Kasei Corp.

+ [1]

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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Structure

Molecular FormulaC33H38Cl2N2O12

InChIKeyVZZTWOVKCVPTSM-FJSYBICCSA-N

CAS Registry110816-78-9

View All Structures (3)

Hypereosinophilic syndrome (HES) is characterized by blood and tissue hypereosinophilia leading to organ damage. Gastrointestinal involvement is the third most common manifestation. We present a patient with idiopathic HES with secondary eosinophilic esophagitis (EoE), gastritis, and enteritis, corticosteroids-dependent, azathioprine- and mepolizumab-refractory. The patient achieved clinical and histopathologic remission following dupilumab treatment. A 28 year-old female presented with chronic episodic nausea and emesis since childhood and initial diagnosis of primary eosinophilic gastrointestinal disease (EGID), improved with corticosteroids, refractory to azathioprine. She was found to have peripheral eosinophilia and multifactorial anemia, with iron, B12, and folate deficiencies. Esophageal, gastric, duodenal, and terminal ileum biopsies showed significant eosinophilic infiltrate. Bone marrow biopsy at age 31 confirmed HES diagnosis. By age 32, she became total parental nutrition (TPN)-dependent. She failed trials of benralizumab and mepolizumab [anti-interleukin (IL)-5 inhibitors], and cromolyn (mast-cell stabilizer). After developing new esophageal stricture, we initiated dupilumab (IL-4/13 inhibitor), recently FDA-approved for EoE. After 9 weeks, esophageal stricture, gut tissue eosinophilia, and prior intestinal ulcerations resolved. She ceased TPN and is tolerating a non-restricted diet, with complete symptom resolution. Our patient's complete remission with dupilumab shows promise for broadening its use in treating GI involvement in HES, along with primary EGIDs.

01 Nov 2024·The American Journal of Sports Medicine

Mast Cells Mediate Acute Inflammatory Responses After Glenoid Labral Tears and Can Be Inhibited With Cromolyn in a Rat Model

Article

Author: Nguyen, Tam ; Tang, Liping ; Hoang, Le Q. ; Co, Cynthia M. ; Vaish, Bhavya ; Millett, Peter J. ; Borrelli, Joseph

Background: Injuries to the glenoid labrum have been recognized as a source of joint pain and discomfort, which may be associated with the inflammatory responses that lead to the deterioration of labral tissue. However, it is unclear whether the torn labrum prompts mast cell (MC) activation, resulting in synovial inflammatory responses that lead to labral tissue degeneration. Purpose: To determine the potential influence of activated MC on synovial inflammatory responses and subsequent labral tissue degeneration and shoulder function deterioration in a rat model by monitoring MC behavior and sequential inflammatory responses within the synovial tissue and labral tissue after injury, suture repair, and MC stabilizer administration. Study Design: Controlled laboratory study. Methods: Anteroinferior glenoid labral tears were generated in the right shoulder of rats (n = 20) and repaired using a tunneled suture technique. Synovial tissue inflammatory responses were modulated in some rats with intraperitoneal administration of an MC stabilizer—cromolyn (n = 10). At weeks 1 and 3, MC activation, synovial inflammatory responses, and labral degeneration were histologically evaluated. Simultaneously, gait analysis was performed before and after surgical repair to assess the worsening of the shoulder function after the injury and treatment. Results: Resident MC degranulation after labral injury (50.48% ± 8.23% activated at week 1) contributed to the initiation of synovial tissue inflammatory cell recruitment, inflammatory product release, matrix metalloproteinase-13, and subsequent labral tissue extracellular matrix degeneration. The administration of cromolyn, an MC stabilizer, was found to significantly diminish injury-mediated inflammatory responses (inflammatory cell infiltration and subsequent proinflammatory product secretion) and improve shoulder functional recovery. Conclusion: MC activation is responsible for labral tear–associated synovial inflammation and labral degeneration. The administration of cromolyn can significantly diminish the cascade of inflammatory reactions after labral injury. Clinical Relevance: Our findings support the concept that MC stabilizers may be used as a complementary therapeutic option in the treatment and repair of labral tears.

01 Aug 2024·Heliyon

Repurposing of known drugs from multiple libraries to identify novel and potential selective inhibitors of HDAC6 via in silico approach and molecular modeling

Article

Author: Erdogan, Buse ; Mert, Naz Mina ; Yelekçi, Kemal

Histone deacetylase 6 (HDAC6, Class IIb) is a promising target for anticancer drugs. So far, few nonselective HDAC inhibitors have received regulatory approval as anticancer agents. However, they are associated with cell toxicity. Thus, isoform-selective inhibitors may be desirable. Here, we conducted structure-based virtual screening of multiple libraries containing a total of 2,250,135 compounds against HDAC6. The top hits with good docking scores and potential selectivity over HDAC10 (Class IIb) were submitted to 100 ns molecular dynamics simulation to monitor their dynamic behaviors and stability in the binding pockets of these enzymes. Furthermore, the drug-likeness and ADMET properties of these hits were estimated computationally. Four diverse compounds from different sources, including NCI and ZINC databases (BDH33926500, CID667061, Cromolyn, and ZINC000103531486), show potential selectivity for HDAC6.

100 Deals associated with Cromoglycate lisetil hydrochloride

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External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB01003

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Pruritus	Phase 2	DE	Leo Pharma, Inc.	01 Nov 2012
Asthma	Phase 2	JP	-	-
Dermatitis, Atopic	Phase 2	JP	-	-
Mastocytosis	Phase 2	DE	LEO Pharma A/S	-
Mastocytosis	Phase 2	DE	LEO Pharma A/S	-
Psoriasis	Phase 2	-	Asahi Kasei Corp.	-
Psoriasis	Phase 2	DE	LEO Pharma A/S	-
Psoriasis	Phase 2	-	Kyoto Pharmaceutical Industries Ltd.	-
Rhinitis, Allergic	Phase 2	JP	-	-