A939572 | A-939572 | CAS#1032229-33-6 | SCD1 inhibitor

MedKoo Cat#: 526965 | Name: A939572

Description:

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

A939572 is is a potent and orally bioavailable inhibitor of stearoyl-CoA desaturase1 (SCD1) with IC50 value of 37nM. Stearoyl-CoA desaturase 1 is a novel molecular therapeutic target for clear cell renal cell carcinoma. A939572 treatment restricted SCD1-induced tumor progression and inhibited EMT phenotype of cancer cells in vivo, and counteracted the effects of overexpression of SCD1 inhibited Gefitinib-induced apoptosis, decreased cell vitality and impaired ability of migration and invasion.

Chemical Structure

A939572

CAS#1032229-33-6

Theoretical Analysis

MedKoo Cat#: 526965

Name: A939572

CAS#: 1032229-33-6

Chemical Formula: C20H22ClN3O3

Exact Mass: 387.1350

Molecular Weight: 387.86

Elemental Analysis: C, 61.93; H, 5.72; Cl, 9.14; N, 10.83; O, 12.37

Price and Availability

Size	Price	Availability
50mg	USD 450.00	2 Weeks
100mg	USD 750.00	2 Weeks
200mg	USD 1,250.00	2 Weeks
500mg	USD 2,675.00	2 Weeks
1g	USD 4,550.00	2 Weeks
2g	USD 7,750.00	2 Weeks

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Synonym

A939572; A-939572; A 939572; SCD1 Inhibitor; Stearoyl-CoA Desaturase 1 Inhibitor;

IUPAC/Chemical Name

4-(2-chlorophenoxy)-N-[3-[(methylamino)carbonyl]phenyl]-1-piperidinecarboxamide

InChi Key

DPYTYQFYDLYWHZ-UHFFFAOYSA-N

InChi Code

InChI=1S/C20H22ClN3O3/c1-22-19(25)14-5-4-6-15(13-14)23-20(26)24-11-9-16(10-12-24)27-18-8-3-2-7-17(18)21/h2-8,13,16H,9-12H2,1H3,(H,22,25)(H,23,26)

SMILES Code

O=C(N1CCC(OC2=CC=CC=C2Cl)CC1)NC3=CC=CC(C(NC)=O)=C3

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:

A939572 is a stearoyl-CoA desaturase1 (SCD1) inhibitor with IC50 values of <4 nM and 37 nM for mSCD1 and hSCD1, respectively.

In vitro activity:

To test whether SCD activity is necessary for PDAC, this study analyzed the role of SCD1 in human PDAC cell line, PANC-1. PANC-1 reduced its proliferation by treatment with A939572 (10–100 μM) for 2 days (Fig. 5A). However, this study did not observe induction of cytotoxicity by A939572 (Fig. 5B). Western blot analysis showed induction of phosphorylation and expression of eIF2α by 5 and 20 μM of A939572 in PANC-1 (Fig. 5C). However, A939572 treatment did not induce the cleavage of Caspase-3 (Fig. 5C) or PARP (data not shown), indicating that the suppression of SCD1 induces the UPR but does not induce cell death in PANC-1. Reference: Pancreas. 2021 Feb 1;50(2):219-226. https://pubmed.ncbi.nlm.nih.gov/33565799/

In vivo activity:

To further investigate the correlation between MUFAs and FAAH activity in the liver, HFD-fed WT, CB1R−/−, and htgCB1R−/− mice were treated with vehicle or 5 mg/kg/d of the SCD1 inhibitor A939572 for 12 wk. A939572 treatment effectively inhibited SCD1 activity in the liver and reversed the HFD-induced decrease in hepatic FAAH activity and the associated increase in hepatic AEA levels in WT and htgCB1R−/− mice, but not in the CB1R−/− mice (Fig. 5). In WT and htgCB1R−/− mice, but not in CB1R−/− mice, the SCD1 inhibitor also normalized plasma insulin levels as well as liver triglyceride content and improved glucose tolerance and insulin sensitivity (Fig. 5). These results clearly support the link between the hepatic endocannabinoid/CB1R system and SCD1 activity. Reference: Proc Natl Acad Sci U S A. 2013 Nov 19; 110(47): 18832–18837. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3839776/

	Solvent	mg/mL	mM
Solubility
	DMSO	47.0	121.05
	DMF	1.0	2.58
	DMF:PBS (pH 7.2) (1:1)	0.5	1.29
	Ethanol	2.8	7.09

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 387.86 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. Skrypek K, Balog S, Eriguchi Y, Asahina K. Inhibition of Stearoyl-CoA Desaturase Induces the Unfolded Protein Response in Pancreatic Tumors and Suppresses Their Growth. Pancreas. 2021 Feb 1;50(2):219-226. doi: 10.1097/MPA.0000000000001737. PMID: 33565799; PMCID: PMC7880535. 2. Lucarelli G, Ferro M, Loizzo D, Bianchi C, Terracciano D, Cantiello F, Bell LN, Battaglia S, Porta C, Gernone A, Perego RA, Maiorano E, Cobelli O, Castellano G, Vincenti L, Ditonno P, Battaglia M. Integration of Lipidomics and Transcriptomics Reveals Reprogramming of the Lipid Metabolism and Composition in Clear Cell Renal Cell Carcinoma. Metabolites. 2020 Dec 13;10(12):509. doi: 10.3390/metabo10120509. PMID: 33322148; PMCID: PMC7763669. 3. Liu J, Cinar R, Xiong K, Godlewski G, Jourdan T, Lin Y, Ntambi JM, Kunos G. Monounsaturated fatty acids generated via stearoyl CoA desaturase-1 are endogenous inhibitors of fatty acid amide hydrolase. Proc Natl Acad Sci U S A. 2013 Nov 19;110(47):18832-7. doi: 10.1073/pnas.1309469110. Epub 2013 Nov 4. PMID: 24191036; PMCID: PMC3839776. 4. Paton CM, Ntambi JM. Loss of stearoyl-CoA desaturase activity leads to free cholesterol synthesis through increased Xbp-1 splicing. Am J Physiol Endocrinol Metab. 2010 Dec;299(6):E1066-75. doi: 10.1152/ajpendo.00388.2010. Epub 2010 Oct 5. PMID: 20923962; PMCID: PMC3006250.

In vitro protocol:

In vivo protocol:

1. Liu J, Cinar R, Xiong K, Godlewski G, Jourdan T, Lin Y, Ntambi JM, Kunos G. Monounsaturated fatty acids generated via stearoyl CoA desaturase-1 are endogenous inhibitors of fatty acid amide hydrolase. Proc Natl Acad Sci U S A. 2013 Nov 19;110(47):18832-7. doi: 10.1073/pnas.1309469110. Epub 2013 Nov 4. PMID: 24191036; PMCID: PMC3839776. 2. Paton CM, Ntambi JM. Loss of stearoyl-CoA desaturase activity leads to free cholesterol synthesis through increased Xbp-1 splicing. Am J Physiol Endocrinol Metab. 2010 Dec;299(6):E1066-75. doi: 10.1152/ajpendo.00388.2010. Epub 2010 Oct 5. PMID: 20923962; PMCID: PMC3006250.

1: She K, Fang S, Du W, Fan X, He J, Pan H, Huang L, He P, Huang J. SCD1 is required for EGFR-targeting cancer therapy of lung cancer via re-activation of EGFR/PI3K/AKT signals. Cancer Cell Int. 2019 Apr 18;19:103. doi: 10.1186/s12935-019-0809-y. PMID: 31019378; PMCID: PMC6472070. 2: Piao C, Cui X, Zhan B, Li J, Li Z, Li Z, Liu X, Bi J, Zhang Z, Kong C. Inhibition of stearoyl CoA desaturase-1 activity suppresses tumour progression and improves prognosis in human bladder cancer. J Cell Mol Med. 2019 Mar;23(3):2064-2076. doi: 10.1111/jcmm.14114. Epub 2018 Dec 27. PMID: 30592142; PMCID: PMC6378218. 3: Skrypek K, Balog S, Eriguchi Y, Asahina K. Inhibition of Stearoyl-CoA Desaturase Induces the Unfolded Protein Response in Pancreatic Tumors and Suppresses Their Growth. Pancreas. 2021 Feb 1;50(2):219-226. doi: 10.1097/MPA.0000000000001737. PMID: 33565799; PMCID: PMC7880535. 4: Chen J, Wang Y, Meng W, Zhao R, Lin W, Xiao H, Liao Y. Stearoyl-CoA Desaturases1 Accelerates Non-Small Cell Lung Cancer Metastasis by Promoting Aromatase Expression to Improve Estrogen Synthesis. Int J Mol Sci. 2023 Apr 6;24(7):6826. doi: 10.3390/ijms24076826. PMID: 37047797; PMCID: PMC10095487. 5: Chen P, Tian J, Zhou Y, Chen Y, Zhang H, Jiao T, Huang M, Zhang H, Huang P, Yu AM, Gonzalez FJ, Bi H. Metabolic Flux Analysis Reveals the Roles of Stearate and Oleate on CPT1C-mediated Tumor Cell Senescence. Int J Biol Sci. 2023 Apr 9;19(7):2067-2080. doi: 10.7150/ijbs.80822. PMID: 37151873; PMCID: PMC10158022. 6: von Roemeling CA, Marlow LA, Wei JJ, Cooper SJ, Caulfield TR, Wu K, Tan WW, Tun HW, Copland JA. Stearoyl-CoA desaturase 1 is a novel molecular therapeutic target for clear cell renal cell carcinoma. Clin Cancer Res. 2013 May 1;19(9):2368-80. doi: 10.1158/1078-0432.CCR-12-3249. Epub 2013 Apr 30. PMID: 23633458; PMCID: PMC3644999. 7: Paton CM, Ntambi JM. Loss of stearoyl-CoA desaturase activity leads to free cholesterol synthesis through increased Xbp-1 splicing. Am J Physiol Endocrinol Metab. 2010 Dec;299(6):E1066-75. doi: 10.1152/ajpendo.00388.2010. Epub 2010 Oct 5. PMID: 20923962; PMCID: PMC3006250. 8: Lucarelli G, Ferro M, Loizzo D, Bianchi C, Terracciano D, Cantiello F, Bell LN, Battaglia S, Porta C, Gernone A, Perego RA, Maiorano E, Cobelli O, Castellano G, Vincenti L, Ditonno P, Battaglia M. Integration of Lipidomics and Transcriptomics Reveals Reprogramming of the Lipid Metabolism and Composition in Clear Cell Renal Cell Carcinoma. Metabolites. 2020 Dec 13;10(12):509. doi: 10.3390/metabo10120509. PMID: 33322148; PMCID: PMC7763669. 9: Bednarski T, Olichwier A, Opasinska A, Pyrkowska A, Gan AM, Ntambi JM, Dobrzyn P. Stearoyl-CoA desaturase 1 deficiency reduces lipid accumulation in the heart by activating lipolysis independently of peroxisome proliferator- activated receptor α. Biochim Biophys Acta. 2016 Dec;1861(12 Pt A):2029-2037. doi: 10.1016/j.bbalip.2016.10.005. Epub 2016 Oct 15. PMID: 27751891. 10: Yang XN, Wang YK, Zhu X, Xiao XR, Dai MY, Zhang T, Qu Y, Yang XW, Qin HB, Gonzalez FJ, Li F. Metabolic Activation of Elemicin Leads to the Inhibition of Stearoyl-CoA Desaturase 1. Chem Res Toxicol. 2019 Oct 21;32(10):1965-1976. doi: 10.1021/acs.chemrestox.9b00112. Epub 2019 Sep 10. PMID: 31468958; PMCID: PMC7397737. 11: Hu X, Xiang J, Li Y, Xia Y, Xu S, Gao X, Qiao S. Inhibition of Stearoyl-CoA Desaturase 1 Potentiates Anti-tumor Activity of Amodiaquine in Non-small Cell Lung Cancer. Biol Pharm Bull. 2022 Apr 1;45(4):438-445. doi: 10.1248/bpb.b21-00843. Epub 2022 Feb 3. PMID: 35110426. 12: Liu J, Cinar R, Xiong K, Godlewski G, Jourdan T, Lin Y, Ntambi JM, Kunos G. Monounsaturated fatty acids generated via stearoyl CoA desaturase-1 are endogenous inhibitors of fatty acid amide hydrolase. Proc Natl Acad Sci U S A. 2013 Nov 19;110(47):18832-7. doi: 10.1073/pnas.1309469110. Epub 2013 Nov 4. PMID: 24191036; PMCID: PMC3839776.