Ezutromid | CAS#945531-77-1 | utrophin's translation modulator

Ezutromid
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WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 206444

CAS#: 945531-77-1

Description: Ezutromid, also known as BMN-195 and SMTC-1100, is a first orally bioavailable utrophin's translation modulator. Duchenne muscular dystrophy (DMD) is a lethal, progressive muscle wasting disease caused by a loss of sarcolemmal bound dystrophin, which results in the death of the muscle fibers leading to the gradual depletion of skeletal muscle.

Chemical Structure

Ezutromid

CAS# 945531-77-1

Product data Instruction

Theoretical Analysis

MedKoo Cat#: 206444
Name: Ezutromid
CAS#: 945531-77-1
Chemical Formula: C19H15NO3S
Exact Mass: 337.08
Molecular Weight: 337.390
Elemental Analysis: C, 67.64; H, 4.48; N, 4.15; O, 14.23; S, 9.50

Price and Availability

Size	Price	Availability
25mg	USD 150	2 weeks
100mg	USD 450	2 weeks
200mg	USD 750	2 weeks
500mg	USD 1450	2 weeks
1g	USD 2450	2 weeks
5g	USD 4950	2 weeks
Bulk inquiry Welcome, Customer: Please do not inquire quote if your intended use is for a patient since our products are for research use and for chemical synthesis use, not for human use . For in-stock products, we listed price in the web page. You may inquire prices for which sizes were not listed. If no price is listed, this means the product is not in stock at the moment, which may be available via custom synthesis. For cost-effective reason, minimum order of 1g is requested (typically very expensive). The lead time is usually 2-4 months. Quote of less than 1g will not be provided. MedKoo may not offer quote for below reasons: (1) current available synthetic method appears to be extremely expensive which is obviously not affordable to most customers; (2) Key raw material to make the product is temporally not available; (3) DEA controlled substances; (4) the product is under patent protection in customer’s country.

Synonym: BMN-195; BMN 195; BMN195; SMTC-1100; SMTC1100; SMTC 1100; VOX-C1100; Ezutromid

IUPAC/Chemical Name: 5-(ethylsulfonyl)-2-(naphthalen-2-yl)benzo[d]oxazole

InChi Key: KSGCNXAZROJSNW-UHFFFAOYSA-N

InChi Code: InChI=1S/C19H15NO3S/c1-2-24(21,22)16-9-10-18-17(12-16)20-19(23-18)15-8-7-13-5-3-4-6-14(13)11-15/h3-12H,2H2,1H3

SMILES Code: O=S(C1=CC=C(OC(C2=CC=C3C=CC=CC3=C2)=N4)C4=C1)(CC)=O

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

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Product Data:

Product Data

Instruction:

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Biological target:	Ezutromid (SMT C1100) is a first-in-class, orally active benzoxazole utrophin modulator with an EC50 of 0.91 μM.
In vitro activity:	SMT C1100 shows a maximal increase of four to five-fold compared to vehicle with an EC50 of 0.4 µM (Fig. 1A). In vitro dosing of human myoblasts with SMT C1100 leads to a 25% increase in utrophin mRNA (Fig. 1B) when compared to vehicle-only dosing after three days of treatment. Treatment of human DMD cells with SMT C1100 lead to a 2-fold increase in utrophin protein levels at an optimal concentration of 0.3 µM after 3 days of treatment (Fig. 1C). Reference: PLoS One. 2011 May 6;6(5):e19189. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3089598/
In vivo activity:	To confirm the in vivo activity of SMT C1100, the dystrophin-deficient mdx mouse was used to monitor any changes in the dystrophic phenotype after chronic dosing for several weeks. Fig. 3A demonstrates a two-fold increase in utrophin mRNA as determined by quantitative PCR from mdx mice dosed daily with SMT C1100 for 28 days compared to vehicle only. This data confirms SMT C1100 drives increased utrophin transcriptional expression in vivo and, more importantly, demonstrates increased utrophin staining at the required site of action - the sarcolemma - and independently from muscle work load. Reference: PLoS One. 2011 May 6;6(5):e19189. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3089598/

Solubility Data

	Solvent	Max Conc. mg/mL	Max Conc. mM
Solubility
	DMSO	6.5	19.27
	DMSO:PBS (pH 7.2) (1:2)	0.3	0.89
	DMF	2.0	5.93

Preparing Stock Solutions

The following data is based on the product molecular weight 337.39 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:	1. Tinsley JM, Fairclough RJ, Storer R, Wilkes FJ, Potter AC, Squire SE, Powell DS, Cozzoli A, Capogrosso RF, Lambert A, Wilson FX, Wren SP, De Luca A, Davies KE. Daily treatment with SMTC1100, a novel small molecule utrophin upregulator, dramatically reduces the dystrophic symptoms in the mdx mouse. PLoS One. 2011 May 6;6(5):e19189. doi: 10.1371/journal.pone.0019189. PMID: 21573153; PMCID: PMC3089598.
In vitro protocol:	1. Tinsley JM, Fairclough RJ, Storer R, Wilkes FJ, Potter AC, Squire SE, Powell DS, Cozzoli A, Capogrosso RF, Lambert A, Wilson FX, Wren SP, De Luca A, Davies KE. Daily treatment with SMTC1100, a novel small molecule utrophin upregulator, dramatically reduces the dystrophic symptoms in the mdx mouse. PLoS One. 2011 May 6;6(5):e19189. doi: 10.1371/journal.pone.0019189. PMID: 21573153; PMCID: PMC3089598.
In vivo protocol:	1. Tinsley JM, Fairclough RJ, Storer R, Wilkes FJ, Potter AC, Squire SE, Powell DS, Cozzoli A, Capogrosso RF, Lambert A, Wilson FX, Wren SP, De Luca A, Davies KE. Daily treatment with SMTC1100, a novel small molecule utrophin upregulator, dramatically reduces the dystrophic symptoms in the mdx mouse. PLoS One. 2011 May 6;6(5):e19189. doi: 10.1371/journal.pone.0019189. PMID: 21573153; PMCID: PMC3089598.

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1: Chatzopoulou M, Claridge TDW, Davies KE, Davies SG, Elsey DJ, Emer E, Fletcher AM, Harriman S, Robinson N, Rowley JA, Russell AJ, Tinsley JM, Weaver R, Wilkinson IVL, Willis NJ, Wilson FX, Wynne GM. Isolation, Structural Identification, Synthesis, and Pharmacological Profiling of 1,2-trans-Dihydro-1,2-diol Metabolites of the Utrophin Modulator Ezutromid. J Med Chem. 2020 Mar 12;63(5):2547-2556. doi: 10.1021/acs.jmedchem.9b01547. Epub 2019 Oct 25. PMID: 31599580.

2: Wilkinson IVL, Perkins KJ, Dugdale H, Moir L, Vuorinen A, Chatzopoulou M, Squire SE, Monecke S, Lomow A, Geese M, Charles PD, Burch P, Tinsley JM, Wynne GM, Davies SG, Wilson FX, Rastinejad F, Mohammed S, Davies KE, Russell AJ. Chemical Proteomics and Phenotypic Profiling Identifies the Aryl Hydrocarbon Receptor as a Molecular Target of the Utrophin Modulator Ezutromid. Angew Chem Int Ed Engl. 2020 Feb 3;59(6):2420-2428. doi: 10.1002/anie.201912392. Epub 2020 Jan 3. PMID: 31755636; PMCID: PMC7003794.

3: Muntoni F, Tejura B, Spinty S, Roper H, Hughes I, Layton G, Davies KE, Harriman S, Tinsley J. A Phase 1b Trial to Assess the Pharmacokinetics of Ezutromid in Pediatric Duchenne Muscular Dystrophy Patients on a Balanced Diet. Clin Pharmacol Drug Dev. 2019 Oct;8(7):922-933. doi: 10.1002/cpdd.642. Epub 2019 Jan 16. PMID: 30650257.

4: Shawi F, Perras C, Severn M. Emerging Drugs for Duchenne Muscular Dystrophy. 2017 Jun 1. In: CADTH Issues in Emerging Health Technologies. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2016–2021. 161. PMID: 29369577.

5: Chatzopoulou M, Conole D, Emer E, Rowley JA, Willis NJ, Squire SE, Gill B, Brough S, Wilson FX, Wynne GM, Davies SG, Davies KE, Russell AJ. Structure- activity relationships of 2-pyrimidinecarbohydrazides as utrophin modulators for the potential treatment of Duchenne muscular dystrophy. Bioorg Med Chem. 2022 Sep 1;69:116812. doi: 10.1016/j.bmc.2022.116812. Epub 2022 May 18. PMID: 35772287.

6: Babbs A, Berg A, Chatzopoulou M, Davies KE, Davies SG, Edwards B, Elsey DJ, Emer E, Guiraud S, Harriman S, Lecci C, Moir L, Peters D, Robinson N, Rowley JA, Russell AJ, Squire SE, Tinsley JM, Wilson FX, Wynne GM. 2-Arylbenzo[d]oxazole Phosphinate Esters as Second-Generation Modulators of Utrophin for the Treatment of Duchenne Muscular Dystrophy. J Med Chem. 2020 Jul 23;63(14):7880-7891. doi: 10.1021/acs.jmedchem.0c00807. Epub 2020 Jul 10. PMID: 32551645.

7: Chatzopoulou M, Emer E, Lecci C, Rowley JA, Casagrande AS, Moir L, Squire SE, Davies SG, Harriman S, Wynne GM, Wilson FX, Davies KE, Russell AJ. Decreasing HepG2 Cytotoxicity by Lowering the Lipophilicity of Benzo[d]oxazolephosphinate Ester Utrophin Modulators. ACS Med Chem Lett. 2020 Nov 4;11(12):2421-2427. doi: 10.1021/acsmedchemlett.0c00405. PMID: 33335663; PMCID: PMC7734801.

8: Vuorinen A, Wilkinson IVL, Chatzopoulou M, Edwards B, Squire SE, Fairclough RJ, Bazan NA, Milner JA, Conole D, Donald JR, Shah N, Willis NJ, Martínez RF, Wilson FX, Wynne GM, Davies SG, Davies KE, Russell AJ. Discovery and mechanism of action studies of 4,6-diphenylpyrimidine-2-carbohydrazides as utrophin modulators for the treatment of Duchenne muscular dystrophy. Eur J Med Chem. 2021 Aug 5;220:113431. doi: 10.1016/j.ejmech.2021.113431. Epub 2021 Apr 20. PMID: 33915371.

9: Wang ZH, Wang DH. Cu-Catalyzed Synthesis of Benzoxazole with Phenol and Cyclic Oxime. Org Lett. 2022 Jan 21;24(2):782-785. doi: 10.1021/acs.orglett.1c04322. Epub 2021 Dec 29. PMID: 34965140.

10: Reinig AM, Mirzaei S, Berlau DJ. Advances in the Treatment of Duchenne Muscular Dystrophy: New and Emerging Pharmacotherapies. Pharmacotherapy. 2017 Apr;37(4):492-499. doi: 10.1002/phar.1909. Epub 2017 Mar 10. PMID: 28152217.

11: Babbs A, Berg A, Chatzopoulou M, Davies KE, Davies SG, Edwards B, Elsey DJ, Emer E, Figuccia ALA, Fletcher AM, Guiraud S, Harriman S, Moir L, Robinson N, Rowley JA, Russell AJ, Squire SE, Thomson JE, Tinsley JM, Wilson FX, Wynne GM. Synthesis of SMT022357 enantiomers and in vivo evaluation in a Duchenne muscular dystrophy mouse model. Tetrahedron. 2020 Jan 10;76(2):130819. doi: 10.1016/j.tet.2019.130819. PMID: 32713969; PMCID: PMC7369641.

12: Soblechero-Martín P, López-Martínez A, de la Puente-Ovejero L, Vallejo- Illarramendi A, Arechavala-Gomeza V. Utrophin modulator drugs as potential therapies for Duchenne and Becker muscular dystrophies. Neuropathol Appl Neurobiol. 2021 Oct;47(6):711-723. doi: 10.1111/nan.12735. Epub 2021 Jun 4. PMID: 33999469; PMCID: PMC8518368.

13: Chancellor DR, Davies KE, De Moor O, Dorgan CR, Johnson PD, Lambert AG, Lawrence D, Lecci C, Maillol C, Middleton PJ, Nugent G, Poignant SD, Potter AC, Price PD, Pye RJ, Storer R, Tinsley JM, van Well R, Vickers R, Vile J, Wilkes FJ, Wilson FX, Wren SP, Wynne GM. Discovery of 2-arylbenzoxazoles as upregulators of utrophin production for the treatment of Duchenne muscular dystrophy. J Med Chem. 2011 May 12;54(9):3241-50. doi: 10.1021/jm200135z. Epub 2011 Apr 15. PMID: 21456623.

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