MF-438
目录号 : GC36604
A stearoyl-CoA desaturase inhibitor
Cas No.:921605-87-0
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
MF438 is an inhibitor of stearoyl-CoA desaturase 1 (SCD1; IC50 = 2.3 nM for the rat enzyme), an enzyme that catalyzes the formation of a cis double bond at the ?9 position of stearoyl-CoA to produce oleoyl-CoA.1,2 It reduces spheroid formation in NCI H460 and patient-derived non-small cell lung cancer (NSCLC) cells in a concentration-dependent manner, an effect that can be blocked by oleic acid .3 MF438 (1 ?M) decreases the activity of aldehyde dehydrogenase 1A1 (ALDH1A1), a marker of cancer stem cells (CSCs), in NCI H460-derived spheroids when used at a concentration of 1 ?M. It acts synergistically with cisplatin to induce apoptosis and autophagy in patient-derived NSCLC cells.4
1.Léger, S., Black, C., Deschenes, D., et al.Synthesis and biological activity of a potent and orally bioavailable SCD inhibitor (MF-438)Bioorg. Med. Chem. Lett.20(2)499-502(2010) 2.Isabel, E., Powell, D.A., Black, W.C., et al.Biological activity and preclinical efficacy of azetidinyl pyridazines as potent systemically-distributed stearoyl-CoA desaturase inhibitorsBioorg. Med. Chem. Lett.21(1)479-483(2011) 3.Noto, A., Raffa, S., De Vitis, C., et al.Stearoyl-CoA desaturase-1 is a key factor for lung cancer-initiating cellsCell Death Dis.4(12)e947(2013) 4.Pisanu, M.E., Noto, A., De Vitis, C., et al.Blockade of stearoyl-CoA-desaturase 1 activity reverts resistance to cisplatin in lung cancer stem cellsCancer Lett.40693-104(2017)
| Cas No. | 921605-87-0 | SDF | |
| Canonical SMILES | FC(C1=CC=CC=C1OC2CCN(C3=NN=C(C4=NN=C(C)S4)C=C3)CC2)(F)F | ||
| 分子式 | C19H18F3N5OS | 分子量 | 421.44 |
| 溶解度 | DMSO: 62.5 mg/mL (148.30 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.3728 mL | 11.8641 mL | 23.7282 mL |
| 5 mM | 0.4746 mL | 2.3728 mL | 4.7456 mL |
| 10 mM | 0.2373 mL | 1.1864 mL | 2.3728 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
SCD1-Fatty Acid Desaturase Inhibitor MF-438 Alleviates Latent Inflammation Induced by Preservative-Free Prostaglandin Analog Eye Drops
J Inflamm Res 2022 Feb 8;15:793-806.PMID:35173454DOI:10.2147/JIR.S347784.
Introduction: Prostaglandin analogs are the first line of treatment in patients with glaucoma. Recently, many preservative-free prostaglandin analogs have been marketed to increase their tolerance in chronic use. However, potentially safer formulations have been reported to induce inflammation within ocular surface and adnexa, associated with pronounced activation of tissue macrophages. Aim: We aimed to evaluate the effect of a Stearoyl-CoA desaturase-1 (SCD1) inhibitor, MF-438, on the differentiation of monocytes exposed to eye drop detergents, representing saturated fatty acid derivatives. Methods: A culture of human peripheral blood monocytes was exposed to eye drops containing fatty acid derivatives (eye drop detergents), pf-latanoprost (Monoprost®, hydroxystearate macrogolglycerol - MGHS40) or pf-tafluprost (Taflotan®, polysorbate 80 - PS80), as well as pf-latanoprost+MF-438, MGHS40, and PS80. For the negative control C(-), monocytes were cultured in basal medium, and for the positive controls, monocytes were stimulated with Lipopolysaccharide (LPS) and Interferon γ (IFNγ) (M1 macrophages) or Interleukin-4 (IL-4) (M2 macrophages). The concentration of desaturase in the cell homogenates was determined by ELISA. The number of cells was counted under a microscope at 20x magnification. Results: The following concentrations of SCD1 (ng/mL) were measured: 7.8±0.3 - pf-latanoprost group; 1.5±0.4 - pf-tafluprost group; 6.8±0.7 - MGHS40 group; 0.4±0.002 - PS80 group; 0.9±0.02 - pf-latanoprost+MF-438 group; 5.4±1.6 - C(-) control; 0.5±0.04 - M1 control; 2.2±0.13 - M2 control. The percentages of macrophages in culture were 33.6%, 17.6%, 33%, 0%, 13.5%, 18.6%, 36.3%, and 39.3% for the pf-latanoprost, pf-tafluprost, MGHS40, PS80, pf-latanoprost+MF-438, C(-), M1, and M2 cultures, respectively. There was a strong correlation between SCD1 concentration and macrophage count in the culture (r=0.8, p<0.05). Conclusion: Inhibition of SCD1 in monocytes prevents their transformation into macrophages after exposure to saturated fatty acid derivatives contained in eye drops, which may contribute to the limitation of latent inflammation within ocular adnexa and could possibly translate into better tolerability of the topical treatment.
Synthesis and biological activity of a potent and orally bioavailable SCD inhibitor (MF-438)
Bioorg Med Chem Lett 2010 Jan 15;20(2):499-502.PMID:20004097DOI:10.1016/j.bmcl.2009.11.111.
A series of stearoyl-CoA desaturase 1 (SCD1) inhibitors were developed. Investigations of enzyme potency and metabolism led to the identification of the thiadiazole-pyridazine derivative MF-438 as a potent SCD1 inhibitor. MF-438 exhibits good pharmacokinetics and metabolic stability, thereby serving as a valuable tool for further understanding the role of SCD inhibition in biological and pharmacological models of diseases related to metabolic disorders.
Targeting stearoyl-coa desaturase enhances radiation induced ferroptosis and immunogenic cell death in esophageal squamous cell carcinoma
Oncoimmunology 2022 Jul 15;11(1):2101769.PMID:35859734DOI:10.1080/2162402X.2022.2101769.
Overcoming resistance to radiation is a major challenge in cancer treatment. Stearoyl-coa desaturase (SCD1) is the enzyme responsible for oleic acid (OA) and palmitoleic acid (POA) formation. Here, we provided evidence that targeting SCD1 was capable of inducing ferroptosis and immunogenic cell death (ICD), thereby improving the radiation sensitivity of esophageal squamous cell carcinoma (ESCC). ESCC cell lines with high SCD1 expression were treated with MF-438 (SCD1 inhibitor) to determine cell viability. Colony formation assay was performed to evaluate the radiation sensitization of SCD1 inhibitor. Tumor cell ferroptosis and ICD was analyzed in MF-438, radiation therapy (RT) and the combination treatment group. The potential molecular mechanisms underlying MF-438 as a novel radiation sensitizer in ESCC were explored. We concluded by assessing SCD1 as a prognostic factor in ESCC. MF-438 exhibited antitumor activity in ESCC cells. Our outcomes revealed significant improvement of radiation sensitivity by MF-438. Moreover, the combination treatment enhanced tumor cell ferroptosis and ICD. Further analyses revealed SCD1 conferred radiation resistance via alleviating ferroptosis in tumor cells; targeting SCD1 inhibited the biosynthesis of OA and POA, and improved radiation induced ferroptosis in ESCC cells. Clinical analysis indicated high expression of SCD1 was associated with unfavorable survival in patients of ESCC. In summary, our results demonstrated that MF-438 acted as a ferroptosis inducer. Targeting SCD1 conferred the immunogenicity of ferroptotic cancer cells and increased the effectiveness of RT in ESCC. SCD1 could be considered as a useful prognostic indicator of survival in ESCC.
Early oleate deficiency leads to severe defects in fetal rat liver development
Iran J Basic Med Sci 2019 Sep;22(9):1010-1015.PMID:31807244DOI:10.22038/ijbms.2019.35084.8345.
Objectives: Oleate can be produced through de novo synthesis, which contributes to biological processes and signaling pathways. However, the role of this non-essential fatty acid in hepatic development remains unclear. The current study aimed to evaluate the influence of early oleate deficiency induced by the inhibitor of de novo oleate synthesis MF-438 on fetal rat liver development. Materials and methods: Female Wistar rats with an average weight of 200±20 g were subjected to this study. After mating, pregnant rats were divided into three groups and gavaged with the vehicle, MF 438 or MF-438 plus oleate from day 3 of pregnancy for five days. Obtained fetuses were sacrificed and the liver tissues were retrieved. Hepatic morphological index, biochemical markers, and gene expression of hepatic development markers were analyzed using Hematoxylin-Eosine, spectrometry, and real-time PCR techniques, respectively. Results: Relatively, deficient morphological indices and hepatic maturation markers were observed in fetus livers of the inhibitor-treated group. In comparison to the other two groups, total hepatic protein and glycogen content were increased with treatment of MF-438 plus oleate. Hepatocyte nuclear factor 1α, alpha fetoprotein, albumin, and cytochrome P450 gene expression were also significantly increased in the group treated with both MF-438 and oleate. Conclusion: Our data indicate that oleate availability during early embryo development is linked with fetal rat liver development.
Rapid Alpha-Synuclein Toxicity in a Neural Cell Model and Its Rescue by a Stearoyl-CoA Desaturase Inhibitor
Int J Mol Sci 2020 Jul 22;21(15):5193.PMID:32707907DOI:10.3390/ijms21155193.
Genetic and biochemical evidence attributes neuronal loss in Parkinson's disease (PD) and related brain diseases to dyshomeostasis of the 14 kDa protein α-synuclein (αS). There is no consensus on how αS exerts toxicity. Explanations range from disturbed vesicle biology to proteotoxicity caused by fibrillar aggregates. To probe these mechanisms further, robust cellular toxicity models are needed, but their availability is limited. We previously reported that a shift from dynamic multimers to monomers is an early event in αS dyshomeostasis, as caused by familial PD (fPD)-linked mutants such as E46K. Excess monomers accumulate in round, lipid-rich inclusions. Engineered αS '3K' (E35K+E46K+E61K) amplifies E46K, causing a PD-like, L-DOPA-responsive motor phenotype in transgenic mice. Here, we present a cellular model of αS neurotoxicity after transducing human neuroblastoma cells to express yellow fluorescent protein (YFP)-tagged αS 3K in a doxycycline-dependent manner. αS-3K::YFP induction causes pronounced growth defects that accord with cell death. We tested candidate compounds for their ability to restore growth, and stearoyl-CoA desaturase (SCD) inhibitors emerged as a molecule class with growth-restoring capacity, but the therapeutic window varied among compounds. The SCD inhibitor MF-438 fully restored growth while exerting no apparent cytotoxicity. Our αS bioassay will be useful for elucidating compound mechanisms, for pharmacokinetic studies, and for compound/genetic screens.