CROMOGLICATE LISETIL

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C33H36N2O12
Molecular Weight	652.6451
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCOC(=O)C1=CC(=O)C2=C(O1)C=CC=C2OCC(COC3=CC=CC4=C3C(=O)C=C(O4)C(=O)OCC)OC(=O)[C@@H](N)CCCCN

InChI

InChIKey=NGJJDHCBOKNREV-FQEVSTJZSA-N

InChI=1S/C33H36N2O12/c1-3-41-32(39)27-15-21(36)29-23(10-7-12-25(29)46-27)43-17-19(45-31(38)20(35)9-5-6-14-34)18-44-24-11-8-13-26-30(24)22(37)16-28(47-26)33(40)42-4-2/h7-8,10-13,15-16,19-20H,3-6,9,14,17-18,34-35H2,1-2H3/t20-/m0/s1

HIDE SMILES / InChI

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/anda/2000/75-271_Cromolyn%20Sodium_prntlbl.pdfhttps://www.accessdata.fda.gov/drugsatfda_docs/label/2004/18887slr020_intal_lbl.pdf
Curator's Comment: description was created based on several sources, including: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/090954s000lbl.pdf |http://www.rxlist.com/crolom-drug.htm | https://www.ncbi.nlm.nih.gov/pubmed/8809432

Cromolyn is a mast cell stabilizer. In vitro and in vivo animal studies have shown that cromolyn sodium inhibits the degranulation of sensitized mast cells, which occurs after exposure to specific antigens. Cromolyn sodium acts by inhibiting the release of histamine and SRS-A (slow-reacting substance of anaphylaxis) from the mast cell. Cromolyn is indicated in the management of patients with mastocytosis, prophylaxis (long-term control) of bronchial asthma, prevention of exercise-induced bronchospasm, prevention and treatment of seasonal and perennial allergic rhinitis The most frequently reported adverse reactions attributed to cromolyn sodium treatment were: throat irritation or dryness, bad taste, cough, wheeze, nausea.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
G-protein coupled receptor 35 11 Target ID: CHEMBL1293267 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22218743 \| https://www.ncbi.nlm.nih.gov/pubmed/3110245	Agonist 2752
Chloride channels 4 Target ID: Chloride channels Sources: https://www.ncbi.nlm.nih.gov/pubmed/1280136	Blocker 555	19.0 µM [IC50]
calcium ion import 8 Target ID: GO:0070509 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/18887slr020_intal_lbl.pdf	Blocker 555
mast cell activation 5 Target ID: GO:0045576 Sources: http://www.ncbi.nlm.nih.gov/pubmed/12396022	Inhibitor 8504

Conditions

Condition	Modality	Highest Phase	Product
Mastocytosis 6 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/090954s000lbl.pdf	Primary	Approved 8583	CROMOLYN SODIUM Approved Use GASTROCROM is indicated in the management of patients with mastocytosis. Use of this product has been associated with improvement in diarrhea, flushing, headaches, vomiting, urticaria, abdominal pain, nausea, and itching in some patients. Launch Date 1994
Bronchial asthma 50 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/18887slr020_intal_lbl.pdf	Preventing	Approved 8583	CROMOLYN SODIUM Approved Use Cromolyn sodium is a prophylactic agent indicated in the management of patients with bronchial asthma. Launch Date 1994
Allergic rhinitis 104 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/anda/2001/75-702_Cromolyn%20Sodium_prntlbl.pdf	Palliative	Approved 8583	CROMOLYN SODIUM Approved Use Cromolyn sodium is used to prevent and relieve nasal symptoms of hay fever and other nasal allergies. Launch Date 1994
Vernal keratoconjunctivitis 6 Sources: http://www.rxlist.com/crolom-drug.htm	Primary	Approved 8583	CROMOLYN SODIUM Approved Use Cromolyn sodium ophthalmic solution is indicated in the treatment of vernal keratoconjunctivitis, vernal conjunctivitis, and vernal keratitis. Launch Date 1994
Asthma 244 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/anda/2000/75-271_Cromolyn%20Sodium_prntlbl.pdf	Preventing	Approved 8583	CROMOLYN SODIUM Approved Use To help prevent asthma attacks. Launch Date 1994
Allergic rhinitis 104 Sources: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b34d36ca-4df4-458c-af0f-c0d0c9a025d9	Preventing	Approved 8583	NASALCROM Approved Use To prevent and relieve nasal symptoms of hay fever and other nasal allergies Launch Date 1997
Allergic conjunctivitis 101 Sources: https://www.medicines.org.uk/emc/PIL.31398.latest.pdf	Palliative	Approved 8583	OPTREX Approved Use Optrex is used for the prevention and treatment of eye allergies.

C_max

Value	Dose	Co-administered	Analyte	Population
46.69 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28856569/	17.1 mg single, respiratory dose: 17.1 mg route of administration: Respiratory experiment type: SINGLE co-administered: IBUPROFEN	IBUPROFEN	CROMOLYN plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
96.75 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28856569/	34.2 mg single, respiratory dose: 34.2 mg route of administration: Respiratory experiment type: SINGLE co-administered: IBUPROFEN	IBUPROFEN	CROMOLYN plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
0.24 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28856569/	17.1 mg single, respiratory dose: 17.1 mg route of administration: Respiratory experiment type: SINGLE co-administered: IBUPROFEN	IBUPROFEN	CROMOLYN cerebrospinal fluid	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
0.34 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28856569/	34.2 mg single, respiratory dose: 34.2 mg route of administration: Respiratory experiment type: SINGLE co-administered: IBUPROFEN	IBUPROFEN	CROMOLYN cerebrospinal fluid	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
156 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32944204/	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:		CROMOLYN plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
236 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32944204/	80 mg single, oral dose: 80 mg route of administration: Oral experiment type: SINGLE co-administered:		CROMOLYN plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
338 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32944204/	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:		CROMOLYN plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
526 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32944204/	80 mg single, oral dose: 80 mg route of administration: Oral experiment type: SINGLE co-administered:		CROMOLYN plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
1.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28856569/	17.1 mg single, respiratory dose: 17.1 mg route of administration: Respiratory experiment type: SINGLE co-administered: IBUPROFEN	IBUPROFEN	CROMOLYN plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
1.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28856569/	34.2 mg single, respiratory dose: 34.2 mg route of administration: Respiratory experiment type: SINGLE co-administered: IBUPROFEN	IBUPROFEN	CROMOLYN plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
62.4 mg 1 times / day multiple, intranasal Dose: 62.4 mg, 1 times / day Route: intranasal Route: multiple Dose: 62.4 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/402406	unhealthy, 25 years (range: 5-51 years) Health Status: unhealthy Age Group: 25 years (range: 5-51 years) Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/402406	Sources: https://pubmed.ncbi.nlm.nih.gov/402406
200 mg 4 times / day multiple, oral Recommended Dose: 200 mg, 4 times / day Route: oral Route: multiple Dose: 200 mg, 4 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/090954s000lbl.pdf	unhealthy, adult Health Status: unhealthy Age Group: adult Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/090954s000lbl.pdf	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/090954s000lbl.pdf
2 % multiple, ophthalmic Dose: 2 % Route: ophthalmic Route: multiple Dose: 2 % Sources: https://pubmed.ncbi.nlm.nih.gov/22118312	unhealthy, adult Health Status: unhealthy Age Group: adult Sources: https://pubmed.ncbi.nlm.nih.gov/22118312	Sources: https://pubmed.ncbi.nlm.nih.gov/22118312

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP 303

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP 303	substrate 4014 Sources: https://pdf.hres.ca/dpd_pm/00015714.PDF#page=2 Page: 2.0	no

Sourcing

Vendor/Aggregator	ID	URL
3B Scientific (Wuhan) Corp	3B2-1127	http://www.3bsc.com/index/pro_info.php?id=54843
abcr GmbH	AB540456	http://www.abcr.com/shop/en/AB540456
Acadechem	ACDC-030058	http://acadechemical.com/product/1820
Achemo Scientific Limited	AC-85374	http://www.achemo.com/search/?Keyword= 16110-51-3
AHH Chemical co.,ltd	MT-00052	http://www.ahhchemical.com/product/MT-00052.html
AK Scientific, Inc. (AKSCI)	O542	http://www.aksci.com/item_detail.php?cat=O542
Ambeed	A839184	https://www.ambeed.com/products/16110-51-3.html
Ambinter	Amb20243267	http://www.ambinter.com/reference/20243267
Angene	AGN-PC-07Y4GQ	http://www.angenechemical.com/productshow/AGN-PC-07Y4GQ.html
Anward	ANW-71958	http://www.anward.com/pro_result/58409
Aurora Fine Chemicals LLC	A13.110.125	http://online.aurorafinechemicals.com/info?ID=A13.110.125
BioSynth	J-009783	https://www.biosynth.com/en/products/all-products/products/J-009783.html
BLD Pharm	BD53784	http://www.bldpharm.com/products/16110-51-3.html
ChemMol	30102492	http://www.chemmol.com/chemmol/30102492.html
ChemMol	44002046	http://www.chemmol.com/chemmol/44002046.html
Chemspace	CSSS00020617570	https://chem-space.com/CSSS00020617570
Clearsynth	CS-L-00099	https://www.clearsynth.com/en/CSL00099.html
CSNpharm	CSN17084	https://www.csnpharm.com/products/cromolyn.html
DC Chemicals	DC20926	http://www.dcchemicals.com/product_show-DC20926.html
eNovation Chemicals	D926914	https://www.enovationchem.com/ProductDetails.asp?ProductID=D926914
Finetech	FT-0601561	http://www.finetechnology-ind.com/prod/detail/pub/16110-51-3.html
Matrix Scientific	97021	https://www.matrixscientific.com/097021.html
MolPort	MolPort-005-934-024	https://www.molport.com/shop/molecule-link/MolPort-005-934-024
Smolecule	S591882	https://www.smolecule.com/products/s591882
THE BioTek	bt-315145	https://www.thebiotek.com/product/others/bt-315145

PubMed

Title	Date	PubMed
Mast cells mediate the microvascular inflammatory response to systemic hypoxia.	2003-01	12391033
Single dose of ketotifen fumarate .025% vs 2 weeks of cromolyn sodium 4% for allergic conjunctivitis.	2002-11-15	12431044
Long-term management of asthma in children: effectiveness of inhaled corticosteroids compared to other medications.	2002-11	12518556
Inhalation and deposition of nebulized sodium cromoglycate in two different particle size distributions in children with asthma.	2002-11	12357479
A comparison of the efficacy and tolerability of olopatadine hydrochloride 0.1% ophthalmic solution and cromolyn sodium 2% ophthalmic solution in seasonal allergic conjunctivitis.	2002-10	12462286
Sodium cromoglycate and doxantrazole are oxygen radical scavengers.	2002-10	12412677
Mast cells as a target of rheumatoid arthritis treatment.	2002-09	12396022
[Enhancing effects of ion-pair complexes on skin permeation of cromolyn in vitro].	2002-09	12235858
The role of sodium cromolyn in treatment of paraquat-induced pulmonary fibrosis in rat.	2002-09	12220965
24-hour efficacy of once-daily desloratadine therapy in patients with seasonal allergic rhinitis [ISRCTN32042139].	2002-08-05	12162793
In vitro deposition of the respirable fraction of dry powder inhalations determined by laser diffractometry and inertial impaction.	2002-08	12227195
Inhaled sodium cromoglycate in children with asthma.	2002-08	12149542
Cause and effect relationship between myocardial mast cell number and matrix metalloproteinase activity.	2002-08	12124196
Water dynamics in channel hydrates investigated using H/D exchange.	2002-07-25	12100853
Effects of topical anti-inflammatory and antiallergic eyedrops on prostaglandin E2-induced aqueous flare elevation in pigmented rabbits.	2002-07	12096966
Fluticasone for the treatment of symptomatic bronchial asthma in children treated with sodium cromogylate--a prospective, randomised trial.	2002-06-28	12117660
[Exercise-induced asthma. Not a reason to be benched].	2002-06-27	12154481
Management of suspected acute viral upper respiratory tract infection in children with intranasal sodium cromoglicate: a randomised controlled trial.	2002-06-22	12090980
The combination of nebulized sodium cromoglycate and salbutamol in the treatment of moderate-to-severe asthma in children.	2002-06	12144644
Efficacy and patient satisfaction with cromolyn sodium nasal solution in the treatment of seasonal allergic rhinitis: a placebo-controlled study.	2002-06	12117084
Improved strategies and new treatment options for allergic rhinitis.	2002-06	12090644
Allergic rhinitis remains an important disease.	2002-06	12090642
One-year trial on safety and normal linear growth with flunisolide HFA in children with asthma.	2002-06	12086199
(S)nifty treatment for pollen allergies.	2002-06	12085791
Balancing safety and efficacy in the treatment of pediatric asthma.	2002-06	12063513
Generalized bullae in an infant.	2002-06	12056971
The effect of disodium cromoglycate, budesonide, and cyclosporin A on interleukin-4, interleukin-5, and interleukin-13 secretions in Der p I-stimulated T cells from house dust mite-sensitive atopic and nonatopic individuals.	2002-05-11	12001789
Perinatal immunomodulation.	2002-05	12389669
Management of allergic and nonallergic rhinitis.	2002-05	12173440
Effect of interventions during acute respiratory syncytial virus bronchiolitis on subsequent long term respiratory morbidity.	2002-05	12150194
Ischaemic preconditioning and mast cell histamine release: microdialysis of isolated rat hearts.	2002-05	12123626
Floating a metered-dose inhaler is not an accurate measure of remaining medicine.	2002-05	12027080
Relative lung and systemic bioavailability of sodium cromoglycate inhaled products using urinary drug excretion post inhalation.	2002-05	12015790
Nebulized budesonide inhalation suspension compared with cromolyn sodium nebulizer solution for asthma in young children: results of a randomized outcomes trial.	2002-05	11986448
Airway hyperresponsiveness to adenosine induced by lipopolysaccharide in Brown Norway rats.	2002-05	11976275
Interaction of S100 proteins with the antiallergic drugs, olopatadine, amlexanox, and cromolyn: identification of putative drug binding sites on S100A1 protein.	2002-04-12	11944917
Use of intranasal cromolyn sodium for allergic rhinitis.	2002-04	11936930
Effects of budesonide inhalation suspension on hypothalamic-pituitary-adrenal-axis function in infants and young children with persistent asthma.	2002-03	11926625
Inhaled sodium cromoglycate in children with asthma.	2002-03	11867840
Efficacy and safety of inhaled steroid and cromone treatment in school-age children: a randomized pragmatic pilot study.	2002-02	12000495
Using case management to increase antiinflammatory medication use among a managed care population with asthma.	2002-02	11883740
Medical management of Cronkhite-Canada syndrome.	2002-02	11846261
Assessment of the relationship between hyperalgesia and peripheral inflammation in magnesium-deficient rats.	2002-01-18	11860153
Topical treatment of pyoderma gangraenosum.	2002	12399665
[Inhalation therapy].	2001-12	11937990
Reasons for and costs of hospitalization for pediatric asthma: a prospective 1-year follow-up in a population-based setting.	2001-12	11846871
Therapy choices beyond antihistamines. Vasomotor rhinitis.	2001-11	12420500
[A sniffing child].	2001	12092406
[Effects of orally available prodrug of cromoglycic acid on collagen-induced arthritis mice].	1999-10	10629873
Pro-drugs for the oral delivery of disodium cromoglycate.	1988-01	3132335

Patents

Sample Use Guides

In Vivo Use Guide

Two metered inhalations four times daily at regular intervals (asthma).

Route of Administration: Respiratory

In Vitro Use Guide

Cromoglycate (the active component of cromoglicate lisetil) significantly inhibits histamine release from lung and tonsillar mast cells at 1000 uM.

Name

Type

Language

Cromoglicate lisetil [WHO-DD]

Preferred Name

English

CROMOGLICATE LISETIL

Official Name

English

cromoglicate lisetil [INN]

Common Name

English

DIETHYL 5,5'-((2-HYDROXYTRIMETHYLENE)DIOXY)BIS(4-OXO-4H-1-BENZOPYRAN-2-CARBOXYLATE), ESTER WITH L-LYSINE

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C29714