ML349 | CAS#890819-86-0 | APT2 inhibitor

MedKoo Cat#: 530452 | Name: ML349

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Description:

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

ML349 is a reversible APT2 inhibitor with Ki = 120 nM. ML349 is highly selective within the serine hydrolase enzyme family, it could still interact with other cellular targets. In human cell lysates, biotinylated-ML349 enriches a recurring set of proteins, including metabolite kinases and flavin-dependent oxidoreductases that are potentially enhanced by avidity-driven multimeric interactions. ML349 achieves target engagement and hydrolase selectivity in living mice.

Chemical Structure

ML349

CAS#890819-86-0

Theoretical Analysis

MedKoo Cat#: 530452

Name: ML349

CAS#: 890819-86-0

Chemical Formula: C23H24N2O4S2

Exact Mass: 454.1021

Molecular Weight: 454.56

Elemental Analysis: C, 60.51; H, 5.30; N, 6.14; O, 14.02; S, 14.04

Price and Availability

Size	Price	Availability	Quantity
5mg	USD 230.00
25mg	USD 570.00

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Related CAS #

No Data

Synonym

ML349; ML-349; ML 349.

IUPAC/Chemical Name

(5,5-dioxido-3a,9b-dihydro-4H-thieno[3,2-c]thiochromen-2-yl)(4-(4-methoxyphenyl)piperazin-1-yl)methanone

InChi Key

JIFSCAIWCCQTRF-UHFFFAOYSA-N

InChi Code

InChI=1S/C23H24N2O4S2/c1-29-18-8-6-17(7-9-18)24-10-12-25(13-11-24)23(26)20-14-16-15-31(27,28)21-5-3-2-4-19(21)22(16)30-20/h2-9,14,16,22H,10-13,15H2,1H3

SMILES Code

COC1=CC=C(N2CCN(C(C3=CC4C(C(C=CC=C5)=C5S(C4)(=O)=O)S3)=O)CC2)C=C1

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

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

More Info

Product Data

Product Data

Instruction

View handling instruction

Biological target:

ML349 is a potent and specific acyl protein thioesterase 2(APT2)/lysophospholipase 2 (LYPLA2) inhibitor with a Ki of 120 nM.

In vitro activity:

While the active-site competitive acyl protein thioesterase 2 inhibitor ML349 (Ki = 120 nM) is highly selective within the serine hydrolase enzyme family, it could still interact with other cellular targets. In human cell lysates, biotinylated-ML349 enriches a recurring set of proteins, including metabolite kinases and flavin-dependent oxidoreductases that are potentially enhanced by avidity-driven multimeric interactions. Reference: ACS Med Chem Lett. 2016 Dec 9;8(2):215-220. https://pubmed.ncbi.nlm.nih.gov/28197315/

In vivo activity:

In the UVB radiation period, 5 mg/kg ML349 was injected intraperitoneally into mice prior to the treatment with UV. While melanoma was first diagnosed 37 days after the final UV irradiation in mice without treatment, ML349 delayed the onset of melanoma to 56 days. Furthermore, 90 days after the final UVR, melanoma was diagnosed in 23% (3/13) or 64% (7/11) of mice with or without ML349 treatment, respectively (p = 0.0366; Fig. 4h). Reference: Nat Commun. 2019 Feb 20;10(1):877. https://pubmed.ncbi.nlm.nih.gov/30787281/

	Solvent	mg/mL	mM
Solubility
	DMF	5.0	11.00
	DMSO	11.4	25.00
	DMSO:PBS (pH 7.2) (1:2)	0.3	0.73

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 454.56 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. Won SJ, Eschweiler JD, Majmudar JD, Chong FS, Hwang SY, Ruotolo BT, Martin BR. Affinity-Based Selectivity Profiling of an In-Class Selective Competitive Inhibitor of Acyl Protein Thioesterase 2. ACS Med Chem Lett. 2016 Dec 9;8(2):215-220. doi: 10.1021/acsmedchemlett.6b00441. PMID: 28197315; PMCID: PMC5304287. 2. Chen S, Han C, Miao X, Li X, Yin C, Zou J, Liu M, Li S, Stawski L, Zhu B, Shi Q, Xu ZX, Li C, Goding CR, Zhou J, Cui R. Targeting MC1R depalmitoylation to prevent melanomagenesis in redheads. Nat Commun. 2019 Feb 20;10(1):877. doi: 10.1038/s41467-019-08691-3. PMID: 30787281; PMCID: PMC6382811.

In vitro protocol:

Won SJ, Eschweiler JD, Majmudar JD, Chong FS, Hwang SY, Ruotolo BT, Martin BR. Affinity-Based Selectivity Profiling of an In-Class Selective Competitive Inhibitor of Acyl Protein Thioesterase 2. ACS Med Chem Lett. 2016 Dec 9;8(2):215-220. doi: 10.1021/acsmedchemlett.6b00441. PMID: 28197315; PMCID: PMC5304287.

In vivo protocol:

Chen S, Han C, Miao X, Li X, Yin C, Zou J, Liu M, Li S, Stawski L, Zhu B, Shi Q, Xu ZX, Li C, Goding CR, Zhou J, Cui R. Targeting MC1R depalmitoylation to prevent melanomagenesis in redheads. Nat Commun. 2019 Feb 20;10(1):877. doi: 10.1038/s41467-019-08691-3. PMID: 30787281; PMCID: PMC6382811.

1: Vujic I, Sanlorenzo M, Esteve-Puig R, Vujic M, Kwong A, Tsumura A, Murphy R, Moy A, Posch C, Monshi B, Rappersberger K, Ortiz-Urda S. Acyl protein thioesterase 1 and 2 (APT-1, APT-2) inhibitors palmostatin B, ML348 and ML349 have different effects on NRAS mutant melanoma cells. Oncotarget. 2016 Feb 9;7(6):7297-306. doi: 10.18632/oncotarget.6907. PubMed PMID: 26771141; PubMed Central PMCID: PMC4872786. 2: Won SJ, Davda D, Labby KJ, Hwang SY, Pricer R, Majmudar JD, Armacost KA, Rodriguez LA, Rodriguez CL, Chong FS, Torossian KA, Palakurthi J, Hur ES, Meagher JL, Brooks CL 3rd, Stuckey JA, Martin BR. Molecular Mechanism for Isoform-Selective Inhibition of Acyl Protein Thioesterases 1 and 2 (APT1 and APT2). ACS Chem Biol. 2016 Dec 16;11(12):3374-3382. PubMed PMID: 27748579. 3: Adibekian A, Martin BR, Chang JW, Hsu KL, Tsuboi K, Bachovchin DA, Speers AE, Brown SJ, Spicer T, Fernandez-Vega V, Ferguson J, Cravatt BF, Hodder P, Rosen H. Characterization of a Selective, Reversible Inhibitor of Lysophospholipase 2 (LYPLA2). 2013 Apr 8 [updated 2014 Sep 18]. Probe Reports from the NIH Molecular Libraries Program [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2010-. Available from http://www.ncbi.nlm.nih.gov/books/NBK189927/ PubMed PMID: 24624468. 4: Adibekian A, Martin BR, Chang JW, Hsu KL, Tsuboi K, Bachovchin DA, Speers AE, Brown SJ, Spicer T, Fernandez-Vega V, Ferguson J, Cravatt BF, Hodder P, Rosen H. Characterization of a Selective, Reversible Inhibitor of Lysophospholipase 1 (LYPLA1). 2013 Apr 8 [updated 2014 Jan 13]. Probe Reports from the NIH Molecular Libraries Program [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2010-. Available from http://www.ncbi.nlm.nih.gov/books/NBK189924/ PubMed PMID: 24624465. 5: Hulce JJ, Joslyn C, Speers AE, Brown SJ, Spicer T, Fernandez-Vega V, Ferguson J, Cravatt BF, Hodder P, Rosen H. An in Vivo Active Carbamate-based Dual Inhibitor of Lysophospholipase 1 (LYPLA1) and Lysophospholipase 2 (LYPLA2). 2013 Dec 9 [updated 2014 Sep 18]. Probe Reports from the NIH Molecular Libraries Program [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2010-. Available from http://www.ncbi.nlm.nih.gov/books/NBK259193/ PubMed PMID: 25506974.