IACS-010759 HCl

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

Description: IACS-010759 or IACS-10759 is a potent inhibitor of complex I of OXPHOS. IACS-10759 effectively inhibits ATP production and oxygen consumption in isolated mitochondria, and inhibits the conversion of NADH to NAD+ in immunoprecipitated complex I in low nM range. IACS-10759 is orally bioavailable with excellent physicochemical properties in preclinical species, and shows significant efficacy in multiple tumor indications both in vitro and in vivo. IACS-10759 causes robust tumor regression, but has no effect in the same model when glycolysis is restored.

Price and Availability

IACS-010759 HCl is not in stock, may be available through custom synthesis. For cost-effective reason, minimum 1 gram order is requested. The product will be characterized by NMR, HPLC and MS analysis. Purity (HPLC) is usually >98%. CoA, QC data, MSDS will be provided when product is successfully made. The estimated lead time is 2-3 months. Please send email to sales@medkoo.com to inquire quote.

Related CAS #: 1807523-99-4 (HCl)   1570496-34-2 (free base)   1807524-00-0 (besylate)   1807524-01-1 (mesylate)   1807524-05-5 (tosylate)    

Synonym: IACS-010759 HCl; IACS-010759 hydrochloride; IACS-10759; IACS 10759; IACS10759; IACS-010759; IACS 010759; IACS010759.

IUPAC/Chemical Name: 5-(5-methyl-1-(3-(4-(methylsulfonyl)piperidin-1-yl)benzyl)-1H-1,2,4-triazol-3-yl)-3-(4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazole hydrochloride

InChi Key: LUSCFOVOISLXTM-UHFFFAOYSA-N

InChi Code: LUSCFOVOISLXTM-UHFFFAOYSA-N

SMILES Code: FC(F)(F)OC1=CC=C(C2=NOC(C3=NN(CC4=CC=CC(N5CCC(S(=O)(C)=O)CC5)=C4)C(C)=N3)=N2)C=C1.[H]Cl

Technical Data

References

1: An OXPHOS Inhibitor Has Antitumor Activity in Multiple Tumor Models. Cancer Discov. 2018 Aug;8(8):OF13. doi: 10.1158/2159-8290.CD-RW2018-106. Epub 2018 Jun 22. PubMed PMID: 29934314.

2: Molina JR, Sun Y, Protopopova M, Gera S, Bandi M, Bristow C, McAfoos T, Morlacchi P, Ackroyd J, Agip AA, Al-Atrash G, Asara J, Bardenhagen J, Carrillo CC, Carroll C, Chang E, Ciurea S, Cross JB, Czako B, Deem A, Daver N, de Groot JF, Dong JW, Feng N, Gao G, Gay J, Do MG, Greer J, Giuliani V, Han J, Han L, Henry VK, Hirst J, Huang S, Jiang Y, Kang Z, Khor T, Konoplev S, Lin YH, Liu G, Lodi A, Lofton T, Ma H, Mahendra M, Matre P, Mullinax R, Peoples M, Petrocchi A, Rodriguez-Canale J, Serreli R, Shi T, Smith M, Tabe Y, Theroff J, Tiziani S, Xu Q, Zhang Q, Muller F, DePinho RA, Toniatti C, Draetta GF, Heffernan TP, Konopleva M, Jones P, Di Francesco ME, Marszalek JR. An inhibitor of oxidative phosphorylation exploits cancer vulnerability. Nat Med. 2018 Jul;24(7):1036-1046. doi: 10.1038/s41591-018-0052-4. Epub 2018 Jun 11. PubMed PMID: 29892070.

3: Lissanu Deribe Y, Sun Y, Terranova C, Khan F, Martinez-Ledesma J, Gay J, Gao G, Mullinax RA, Khor T, Feng N, Lin YH, Wu CC, Reyes C, Peng Q, Robinson F, Inoue A, Kochat V, Liu CG, Asara JM, Moran C, Muller F, Wang J, Fang B, Papadimitrakopoulou V, Wistuba II, Rai K, Marszalek J, Futreal PA. Mutations in the SWI/SNF complex induce a targetable dependence on oxidative phosphorylation in lung cancer. Nat Med. 2018 Jul;24(7):1047-1057. doi: 10.1038/s41591-018-0019-5. Epub 2018 Jun 11. Erratum in: Nat Med. 2018 Aug 13;:. PubMed PMID: 29892061.

4: Vangapandu HV, Alston B, Morse J, Ayres ML, Wierda WG, Keating MJ, Marszalek JR, Gandhi V. Biological and metabolic effects of IACS-010759, an OxPhos inhibitor, on chronic lymphocytic leukemia cells. Oncotarget. 2018 May 18;9(38):24980-24991. doi: 10.18632/oncotarget.25166. eCollection 2018 May 18. PubMed PMID: 29861847; PubMed Central PMCID: PMC5982765.