Basic Description

Synonyms	BCP23976 \| CI-1004 mesylate \| SCHEMBL2683037 \| 5I2Y40C5PX \| D03652 \| Darbufelone mesylate (USAN) \| (Z)-2-AMINO-5-((3,5-BIS(1,1-DIMETHYLETHYL)-4-HYDROXYPHENYL)METHYLENE)-4(5H)-THIAZOLONE MONOMETHANESULPHONATE (SALT) \| 5-[(Z)-3,5-Di-tert-butyl-4-hydroxybenz
Specifications & Purity	≥98%
Biochemical and Physiological Mechanisms	Darbufelone mesylate (CI-1004 mesylate) is a dual inhibitor of cellular PGF 2α and LTB 4 production. Darbufelone potently inhibits PGHS-2 ( IC 50 = 0.19 μM) but is much less potent with PGHS-1 ( IC 50 = 20 μM).
Storage Temp	Store at 2-8°C,Protected from light,Desiccated
Shipped In	Wet ice This product requires cold chain shipping. Ground and other economy services are not available.
Product Description	Darbufelone mesylate (CI-1004 mesylate) is a dual inhibitor of cellular PGF 2α and LTB 4 production. Darbufelone potently inhibits PGHS-2 ( IC 50 = 0.19 μM) but is much less potent with PGHS-1 ( IC 50 = 20 μM). In Vitro Darbufelone is a noncompetitive inhibitor of PGHS-2 (K i =10±5 μM). Darbufelone quenches the fluorescence of PGHS-2 at 325 nm (lambda(ex)=280 nm) with K d =0.98±0.03 μM.To test the putative anti-proliferative effect of Darbufelone, A549, H520 and H460 cell lines are used, which are established from three distinct pathological subtypes of NSCLC (adenocarcinoma, squamous and large cell lung cancer respectively). Increasing concentrations of Darbufelone, ranging from 5 to 60 μM, are tested for 72 h. The cell growth inhibition of these three cell lines gradually increases with higher drug concentration. The IC 50 of A549 and H520 are 20±3.6 and 21±1.8 μM, respectively, while the H460 has much lower IC 50 (15±2.7 μM). MCE has not independently confirmed the accuracy of these methods. They are for reference only. In Vivo Darbufelone is a dual inhibitor of cellular PGF2R and LTB4 production. Darbufelone is orally active and nonulcerogenic in animal models of inflammation and arthritis . When mice are treated with Darbufelone at dosage of 80 mg/kg/day, the tumor volumes decrease in a time-dependent manner. In contrast, lower dose of Darbufelone (20 or 40 mg/kg/day) dos not show any significant inhibition of tumor weight. At necropsy, the tumor weight in mice treated with Darbufelone (80 mg/kg/day) is reduced by 30.2% in comparison with control group. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Cell Assay A549 (CCL-185, lung adenocarcinoma cancer cell line), NCI-H520 (HTB-182, lung squamous cancer cell line) and NCI-H460 (HTB-177, lung large cell cancer cell line) cells are cultured in RPMI-1640, supplemented with 10% (v/v) heat-inactivated fetal bovine serum, 2 mM L-glutamine, 100 U/mL Penicillin G, and 100μg/mL Streptomycin. Cells are grown at 37°C in a humidified atmosphere of 95% air and 5% CO 2 and routinely passaged using 0.25% trypsin–EDTA. The effect of Darbufelone on human lung carcinoma cell viability is determined by MTT reduction assay. In brief, tumor cells growing in log-phase are trypsinized and seeded at 5×10 3 cells per well into 96-well plates and allowed to attach overnight. Medium in each well is replaced with fresh medium or medium containing various concentrations of Darbufelone (5-60 μM) in at least triplicate wells. Cells are cultured to another 72 h. After treatment, 1/10 volume of MTT solution (5 mg/mL) is added to each well, and the plate is incubated at 37°C for another 4 h. Two hundred microliters of DMSO is added to each well to solubilize the MTT-formazan product after removal of the medium. Absorbance at 595 nm is measured with a multi-well spectrophotometer. Growth inhibition is calculated as a percentage of the untreated controls. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal administration Mice C57Bl/6 male mice at 4-5 weeks are used. These mice are housed in air-conditioned quarters and are provided food and water ad libitum. On the day 0, Lewis Lung Carcinoma cells (1×10 6 ) are implanted into the left armpit of C57Bl/6 mice. The mice are randomly divided into four treatment groups of ten animals each. The day after inoculation (day 1), control group is treated with CMC-Na, and other groups are administered Darbufelone by gavage at doses of 20, 40, and 80 mg/kg/day . The treatment is continued till the end of the study. On day 14, animals are killed, and tumors are excised, weighed, and fixed in formalin for the further histochemical analysis. aladdin has not independently confirmed the accuracy of these methods. They are for reference only. Form:Solid IC50& Target:PGF 2α LTB 4 PGHS-2 0.19 μM (IC 50 ) PGHS-1 20 μM (IC 50 )

Taxonomic Classification

Taxonomy Tree

Kingdom Organic compounds
- Superclass Benzenoids
  - Class Benzene and substituted derivatives
    - Subclass Phenylpropanes

Kingdom	Organic compounds
Superclass	Benzenoids
Class	Benzene and substituted derivatives
Subclass	Phenylpropanes
Intermediate Tree Nodes	Not available
Direct Parent	Phenylpropanes
Alternative Parents	Phenols Thiazolines N-acylimines Isothioureas Propargyl-type 1,3-dipolar organic compounds Carboxylic acids and derivatives Carboximidamides Azacyclic compounds Organopnictogen compounds Organic oxides Hydrocarbon derivatives Carbonyl compounds
Molecular Framework	Not available
Substituents	Phenylpropane - Phenol - Meta-thiazoline - Isothiourea - N-acylimine - Carboxylic acid derivative - Azacycle - Organoheterocyclic compound - Organic 1,3-dipolar compound - Propargyl-type 1,3-dipolar organic compound - Carboximidamide - Carbonyl group - Hydrocarbon derivative - Organic oxide - Organopnictogen compound - Organooxygen compound - Organonitrogen compound - Organic oxygen compound - Organic nitrogen compound - Aromatic heteromonocyclic compound
Description	This compound belongs to the class of organic compounds known as phenylpropanes. These are organic compounds containing a phenylpropane moiety.
External Descriptors	Not available
1. Djoumbou Feunang Y, Eisner R, Knox C, Chepelev L, Hastings J, Owen G, Fahy E, Steinbeck C, Subramanian S, Bolton E, Greiner R, and Wishart DS. ClassyFire: Automated Chemical Classification With A Comprehensive, Computable Taxonomy. Journal of Cheminformatics, 2016, 8:61. DOI: 10.1186/s13321-016-0174-y

Associated Targets(Human)

ALOX5 Tclin Arachidonate 5-lipoxygenase (6568 Activities)

Discover Target: ALOX5

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

PTGS1 Tclin Cyclooxygenase-1 (9233 Activities)

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Associated Targets(non-human)

Mus musculus (284745 Activities)

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Rattus norvegicus (775804 Activities)

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PTGS2 Prostaglandin G/H synthase 2 (17 Activities)

Discover Target: PTGS2

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

Mechanisms of Action

Mechanism of Action	Action Type	target ID	Target Name	Target Type	Target Organism	Binding Site Name	References

Names and Identifiers

IUPAC Name	(5Z)-2-amino-5-[(3,5-ditert-butyl-4-hydroxyphenyl)methylidene]-1,3-thiazol-4-one;methanesulfonic acid
INCHI	InChI=1S/C18H24N2O2S.CH4O3S/c1-17(2,3)11-7-10(8-12(14(11)21)18(4,5)6)9-13-15(22)20-16(19)23-13;1-5(2,3)4/h7-9,21H,1-6H3,(H2,19,20,22);1H3,(H,2,3,4)/b13-9-;
InChIKey	BAZGFSKJAVQJJI-CHHCPSLASA-N
Smiles	CC(C)(C)C1=CC(=CC(=C1O)C(C)(C)C)C=C2C(=O)N=C(S2)N.CS(=O)(=O)O
Isomeric SMILES	CC(C)(C)C1=CC(=CC(=C1O)C(C)(C)C)/C=C\2/C(=O)N=C(S2)N.CS(=O)(=O)O
Alternate CAS	139340-56-0
PubChem CID	6439420
MeSH Entry Terms	5-((3,5--bis(1,1-dimethylethyl)-4-hydroxyphenyl)methylene)-2-imino-4-thiazolidinone methanesulfonate;CI 1004;CI-1004;darbufelone;darbufelone mesylate;PD0136095-73
Molecular Weight	428.57

Certificates（CoA,COO,BSE/TSE and Analysis Chart)

C of A & Other Certificates(BSE/TSE, COO):

Analytical Chart:

Chemical and Physical Properties

Solubility	DMSO : 110 mg/mL (256.67 mM; Need ultrasonic) H2O : <0.1 mg/mL (ultrasonic;warming;heat to 60°C) (insoluble)
Molecular Weight	428.600 g/mol
XLogP3
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	3
Exact Mass	428.144 Da
Monoisotopic Mass	428.144 Da
Topological Polar Surface Area	164.000 Å²
Heavy Atom Count	28
Formal Charge	0
Complexity	609.000
Isotope Atom Count	0
Defined Atom Stereocenter Count	0
Undefined Atom Stereocenter Count	0
Defined Bond Stereocenter Count	1
Undefined Bond Stereocenter Count	0
The total count of all stereochemical bonds	1
Covalently-Bonded Unit Count	2

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SKU	Size	Availability	Price
D649896-5mg	5mg	Available within 8-12 weeks(?) Production requires sourcing of materials. We appreciate your patience and understanding.	$150.90
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Darbufelone mesylate - 98%, high purity , CAS No.139340-56-0