Synonym
CAY10566; CAY-10566; CAY 10566; SCD1 inhibitor 28c
IUPAC/Chemical Name
3-[4-(2-chloro-5-fluorophenoxy)-1-piperidinyl]-6-(5-methyl-1,3,4-oxadiazol-2-yl)-pyridazine
InChi Key
WFOFPVXMPTVOTJ-UHFFFAOYSA-N
InChi Code
InChI=1S/C18H17ClFN5O2/c1-11-21-24-18(26-11)15-4-5-17(23-22-15)25-8-6-13(7-9-25)27-16-10-12(20)2-3-14(16)19/h2-5,10,13H,6-9H2,1H3
SMILES Code
CC1=NN=C(C2=NN=C(N3CCC(OC4=CC(F)=CC=C4Cl)CC3)C=C2)O1
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
>3 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
2934.99.03.00
Biological target:
CAY10566 is a potent, orally bioavailable and selective stearoyl-CoA desaturase1 (SCD1) inhibitor with IC50s of 4.5 and 26 nM in mouse and human enzymatic assays, respectively.
In vitro activity:
In this study, it was hypothesized that the inhibition of SCD1 (by CAY10566) would block the synthesis of cis-9, trans-11 CLA in bovine mammary alveolar cells (MAC-T) cells. Results showed that MAC-T cells incubated with 10 nM CAY10566 for 12 h (CAY) produced less cis-9, trans-11 CLA (p < 0.01), lower 14:1/(14:1 + 14:0)% (p < 0.01), more trans-11 18:1 (TVA) accumulation (p < 0.01), and reduced SCD1 mRNA levels (p < 0.01) compared with the control group (CON). Moreover, the mRNA abundances of sterol regulatory element-binding protein 1 [SREBPF1], acyl-CoA synthetase short-chain family member 2 [ACSS2], and lipin 1 [LPIN1] were significantly elevated when SCD1 was inhibited in the CAY group (p < 0.05). Taken together, CAY10566 inhibition of SCD1 resulted in lower cis-9, trans-11 CLA synthesis ability, and SREBF1, ACSSS2, and LPIN1 were negatively associated with SCD1. These findings not only provide the direct evidence that cis-9, trans-11 CLA synthesis is catalyzed by SCD1, but also help us understand the responses of MAC-T cells to SCD1 inhibition.
Reference: Lipids. 2018 Jun;53(6):647-652. https://doi.org/10.1002/lipd.12077
In vivo activity:
After establishment of palpable tumors, the mice are treated with vehicle or SCD1 inhibitor (2.5 mg/kg CAY10566 orally twice daily). The effect of SCD1 inhibition on the Akt-driven tumors is greater than on the Ras-driven tumors, with the mean tumor volume at day 13 or 14 post therapy, relative to untreated tumors, 0.5±0.04 and 0.67±0.05 respectively (P=0.01 for Ras-Akt comparison, by two-tailed t test).
Reference: Proc Natl Acad Sci U S A. 2013 May 28;110(22):8882-7. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23671091/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
25.0 |
64.13 |
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
389.82
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 |
In vitro protocol:
1. Wang T, Lee H, Zhen Y. Responses of MAC-T Cells to Inhibited Stearoyl-CoA Desaturase 1 during cis-9, trans-11 Conjugated Linoleic Acid Synthesis. Lipids. 2018 Jun;53(6):647-652. doi: 10.1002/lipd.12077. PMID: 30277580.
2. Mohammadzadeh F, Mosayebi G, Montazeri V, Darabi M, Fayezi S, Shaaker M, Rahmati M, Baradaran B, Mehdizadeh A, Darabi M. Fatty Acid Composition of Tissue Cultured Breast Carcinoma and the Effect of Stearoyl-CoA Desaturase 1 Inhibition. J Breast Cancer. 2014 Jun;17(2):136-42. doi: 10.4048/jbc.2014.17.2.136. Epub 2014 Jun 27. PMID: 25013434; PMCID: PMC4090315.
In vivo protocol:
1. Kamphorst JJ, Cross JR, Fan J, de Stanchina E, Mathew R, White EP, Thompson CB, Rabinowitz JD. Hypoxic and Ras-transformed cells support growth by scavenging unsaturated fatty acids from lysophospholipids. Proc Natl Acad Sci U S A. 2013 May 28;110(22):8882-7. doi: 10.1073/pnas.1307237110. Epub 2013 May 13. PMID: 23671091; PMCID: PMC3670379.
1: Fayezi S, Ghaffari Novin M, Darabi M, Norouzian M, Nouri M, Farzadi L, Darabi M. Primary Culture of Human Cumulus Cells Requires Stearoyl-Coenzyme A Desaturase 1 Activity for Steroidogenesis and Enhancing Oocyte In Vitro Maturation. Reprod Sci. 2018 Jun;25(6):844-853. doi: 10.1177/1933719117698578. Epub 2017 Mar 27. PubMed PMID: 28345489.
2: Yu XQ, Cai C, Du X, Shen W. [Effect of hypoxia-inducible factor-2α/stearoyl-CoA desaturase-1 pathway on biological behaviors of hepatoma cells induced by hypoxia]. Zhonghua Gan Zang Bing Za Zhi. 2016 Jul 20;24(7):506-512. doi: 10.3760/cma.j.issn.1007-3418.2016.07.005. Chinese. PubMed PMID: 27784428.
3: Wang Y, da Cruz TC, Pulfemuller A, Grégoire S, Ferveur JF, Moussian B. INHIBITION OF FATTY ACID DESATURASES IN Drosophila melanogaster LARVAE BLOCKS FEEDING AND DEVELOPMENTAL PROGRESSION. Arch Insect Biochem Physiol. 2016 May;92(1):6-23. doi: 10.1002/arch.21329. Epub 2016 Apr 1. PubMed PMID: 27037621.
4: Ralston JC, Mutch DM. SCD1 inhibition during 3T3-L1 adipocyte differentiation remodels triacylglycerol, diacylglycerol and phospholipid fatty acid composition. Prostaglandins Leukot Essent Fatty Acids. 2015 Jul;98:29-37. doi: 10.1016/j.plefa.2015.04.008. Epub 2015 Apr 28. PubMed PMID: 25959085.
5: Koeberle A, Pergola C, Shindou H, Koeberle SC, Shimizu T, Laufer SA, Werz O. Role of p38 mitogen-activated protein kinase in linking stearoyl-CoA desaturase-1 activity with endoplasmic reticulum homeostasis. FASEB J. 2015 Jun;29(6):2439-49. doi: 10.1096/fj.14-268474. Epub 2015 Feb 12. PubMed PMID: 25678624.
6: Mohammadzadeh F, Mosayebi G, Montazeri V, Darabi M, Fayezi S, Shaaker M, Rahmati M, Baradaran B, Mehdizadeh A, Darabi M. Fatty Acid Composition of Tissue Cultured Breast Carcinoma and the Effect of Stearoyl-CoA Desaturase 1 Inhibition. J Breast Cancer. 2014 Jun;17(2):136-42. doi: 10.4048/jbc.2014.17.2.136. Epub 2014 Jun 27. PubMed PMID: 25013434; PubMed Central PMCID: PMC4090315.
7: Koeberle A, Shindou H, Harayama T, Shimizu T. Palmitoleate is a mitogen, formed upon stimulation with growth factors, and converted to palmitoleoyl-phosphatidylinositol. J Biol Chem. 2012 Aug 3;287(32):27244-54. doi: 10.1074/jbc.M111.274829. Epub 2012 Jun 14. PubMed PMID: 22700983; PubMed Central PMCID: PMC3411066.
8: Masuda M, Ting TC, Levi M, Saunders SJ, Miyazaki-Anzai S, Miyazaki M. Activating transcription factor 4 regulates stearate-induced vascular calcification. J Lipid Res. 2012 Aug;53(8):1543-52. doi: 10.1194/jlr.M025981. Epub 2012 May 23. PubMed PMID: 22628618; PubMed Central PMCID: PMC3540843.
