Lipofermata

Specifications / Handling

More Information
Product Details
Synonyms	5′-Bromo-5-phenyl-spiro[3H-1,3,4-thiadiazole-2,3′-indoline]-2′-one; CB16.2
Product Type	Chemical
Properties
Formula	C₁₅H₁₀BrN₃OS
MW	360.2
CAS	297180-15-5
Purity Chemicals	≥98% (HPLC)
Appearance	Off-white solid.
Solubility	Soluble in DMSO (20mg/ml) and DMF (25mg/ml). Slightly soluble in Ethanol (1mg/ml).
InChi Key	RRBYYBWDUNSVAW-UHFFFAOYSA-N
Smiles	BrC1=CC=C(NC(C23NN=C(C4=CC=CC=C4)S3)=O)C2=C1
Shipping and Handling
Shipping	AMBIENT
Short Term Storage	+4°C
Long Term Storage	-20°C
Handling Advice	Keep cool and dry.
Use/Stability	Stable for at least 2 years after receipt when stored at -20°C.
Documents
MSDS	Download PDF
Product Specification Sheet
Datasheet	Download PDF

Product-specific References

Description

Lipofermata is an inhibitor of fatty acid transport, blocking fatty acid transport protein 2 (FATP2), and was identified afterwards as a FATP1 inhibitor as well. Inhibition was specific for long and very long chain fatty acids but not medium (C6-C10) fatty acids in myocytes (mmC2C12), pancreatic β cells (rnINS-1E), intestinal epithelial cells (hsCaco-2) and hepatocytes (hsHepG2), as well as primary human adipocytes. The fatty acid transport proteins (FATP), when localized to the plasma membrane or at intracellular membrane junctions with the endoplasmic reticulum, function as a gate in the regulated transport of fatty acids and thus represent a therapeutic target to delimit the acquisition of fatty acids that contribute to disease as in the case of fatty acid overload, such as obesity, Typ 2 diabetes or cancers.
Lipofermata prevented palmitate-mediated oxidative stress, induction of BiP and CHOP and cell death in a dose-dependent manner in hsHepG2 and mINS-1E cells suggesting utility in preventing fatty acid-mediated cell death pathways and lipotoxic disease.
FATP2 selectively allows for the accumulation of arachidonic acid, which is needed for the cells to make prostaglandin E2 (PGE2), a potent inflammatory molecule that is also implicated in the immunosuppressive activity of MDSCs in cancer. Pharmacologic blockade of FATPs with the small molecule inhibitor Lipofermata abrogates lipid transport into melanoma cells and reduces melanoma growth and invasion. In combination with checkpoint inhibitors, FATP2 inhibition blocked tumor progression in mice.
Lipofermata also shows inhibitory activity against ADAMTS-5 (Aggrecanase-2) with potential use in osteoarthritis.

Product References

5'-Phenyl-3'H-spiro[indoline-3,2'-[1,3,4]thiadiazol]-2-one inhibitors of ADAMTS-5 (Aggrecanase-2): M.G. Bursavich, et al.; Bioorg. Med. Chem. Lett. 17, 5630 (2007)
Identification and characterization of small compound inhibitors of human FATP2: A. Sandoval, et al.; Biochem. Pharmacol. 79, 990 (2010)
Chemical inhibition of fatty acid absorption and cellular uptake limits lipotoxic cell death: C. Ahowesso, et al.; Biochem. Pharmacol. 98, 167 (2015)
Fatty Acid Transport Proteins: Targeting FATP2 as a Gatekeeper Involved in the Transport of Exogenous Fatty Acids: P.N. Black, et al.; Medchemcomm. 7, 612 (2016)
Adipocyte-derived lipids mediate melanoma progression via FATP proteins; M. Zhang, et al.; Cancer Discov. 8, 1006 (2018)
Fatty acid transport protein 2 reprograms neutrophils in cancer: F. Veglia, et al.; Nature 569, 73 (2019)
Deletion of fatty acid transport protein 2 (FATP2) in the mouse liver changes the metabolic landscape by increasing the expression of PPARα-regulated genes: V.M. Perez, et al.; Genomics Proteomics 295, P5737 (2020)
Regulation of ROS in myeloid-derived suppressor cells through targeting fatty acid transport protein 2 enhanced anti-PD-L1 tumor immunotherapy: A.O. Adeshakin, et al.; Cell Immunol. 362, 104286 (2021)
Multiple myeloma cells induce lipolysis in adipocytes and uptake fatty acids through fatty acid transporter proteins: C. Panaroni, et al.; Blood (Epub ahead of print) (2021)

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