NDGA

• CAT Number: I003757
• CAS Number: 500-38-9
• Molecular Formula: C₁₈H₂₂O₄
• Molecular Weight: 302.4
• Purity: ≥95%
• Target: mTOR
• Solubility: DMSO: 43 mg/mL
• Storage: Store at -20°C
• InChI: InChI=1S/C18H22O4/c1-11(7-13-3-5-15(19)17(21)9-13)12(2)8-14-4-6-16(20)18(22)10-14/h3-6,9-12,19-22H,7-8H2,1-2H3
• InChIKey: HCZKYJDFEPMADG-UHFFFAOYSA-N
• SMILES: CC(CC1=CC(=C(C=C1)O)O)C(C)CC2=CC(=C(C=C2)O)O

Nordihydroguaiaretic acid (NDGA) is a natural phenolic compound isolated from the creosote bush Larrea divaricata, which has anti-tumor activities both in vitro and in vivo. Its analogs are in clinical development for use in refractory solid tumors.IC50 Value:Target: mTORin vitro: NDGA may also direct target mTORC1 complex because NDGA suppressed amino acids- and insulin-stimulated mTORC1 and acted like rapamycin to disrupt mTOR-Raptor interaction [1]. NDGA increased PPARα promoter activity in AML12 hepatocytes and also prevented the fatty acid suppression of PPARα expression. In contrast, PPARα siRNA abrogated the stimulatory effect of NDGA on fatty acidcatabolism [2].in vivo: NDGA was able to induce Nrf2 translocation in vivo in kidneys of rats submitted to both U-NX and I/R injury and to protect against renal histological damage and apoptosis [3]. Comparison of the proportion of live mice at the age of 90% mortality was used as a surrogate for measurement of maximum lifespan;neither NDGA (p=0.12) nor aspirin (p=0.16) had a significant effect in this test. Measures of blood levels of NDGA or aspirin and its salicylicacid metabolite suggest that the observed lack of effects of NDGA or aspirin on life span in females could be related to gender differences in drug disposition or metabolism [4].Clinical trial: Nordihydroguaiaretic Acid in Treating Patients With Nonmetastatic Relapsed Prostate Cancer . Phase 1

Reference

1:Antiviral activity of nordihydroguaiaretic acid and its derivative tetra-O-methyl nordihydroguaiaretic acid against West Nile virus and Zika virus. Merino-Ramos T, Jiménez de Oya N, Saiz JC, Martín-Acebes MA.Antimicrob Agents Chemother. 2017 May 15. pii: AAC.00376-17. doi: 10.1128/AAC.00376-17. [Epub ahead of print] PMID: 28507114 2:NDGA-P21, a novel derivative of nordihydroguaiaretic acid, inhibits glioma cell proliferation and stemness. Zhao QW, Lin Y, Xu CR, Yao YL, Cui YH, Zhang X, Bian XW.Lab Invest. 2017 May 15. doi: 10.1038/labinvest.2017.46. [Epub ahead of print] PMID: 28504686 3:Protective effect of nordihydroguaiaretic acid (NDGA) on the transgenic Drosophila model of Alzheimer/’s disease. Siddique YH, Ali F.Chem Biol Interact. 2017 May 1;269:59-66. doi: 10.1016/j.cbi.2017.04.005. Epub 2017 Apr 6. No abstract available. PMID: 28392391 4:Long chain polyunsaturated fatty acids (LCPUFAs) and nordihydroguaiaretic acid (NDGA) modulate metabolic and inflammatory markers in a spontaneous type 2 diabetes mellitus model (Stillman Salgado rats). Dain A, Repossi G, Diaz-Gerevini GT, Vanamala J, Das UN, Eynard AR.Lipids Health Dis. 2016 Nov 25;15(1):205. PMID: 27884155 Free PMC Article5:Nordihydroguaiaretic acid impairs prostate cancer cell migration and tumor metastasis by suppressing neuropilin 1. Li X, Fan S, Pan X, Xiaokaiti Y, Duan J, Shi Y, Pan Y, Tie L, Wang X, Li Y, Li X.Oncotarget. 2016 Dec 27;7(52):86225-86238. doi: 10.18632/oncotarget.13368. PMID: 27863391 Free PMC Article6:Repositioning nordihydroguaiaretic acid as a potent inhibitor of systemic amyloidosis and associated cellular toxicity. Nusrat S, Zaidi N, Zaman M, Islam S, Ajmal MR, Siddiqi MK, Santra MK, Khan RH.Arch Biochem Biophys. 2016 Dec 15;612:78-90. doi: 10.1016/j.abb.2016.10.014. Epub 2016 Oct 24. PMID: 27789205 7:Anti-anaphylactic action of nordihydroguaiaretic acid in antigen sensitized guinea pigs. Bergren DR, Valentine JL.Respir Physiol Neurobiol. 2016 Dec;234:26-31. doi: 10.1016/j.resp.2016.09.003. Epub 2016 Sep 3. PMID: 27595978 8:Effect of nordihydroguaiaretic acid on cell viability and glucose transport in human leukemic cell lines. Leon D, Parada D, Vargas-Uribe M, Perez AA, Ojeda L, Zambrano A, Reyes AM, Salas M.FEBS Open Bio. 2016 Aug 23;6(10):1000-1007. eCollection 2016 Oct. PMID: 27761359 Free PMC Article9:Correction: A Comprehensive Spectroscopic and Computational Investigation to Probe the Interaction of Antineoplastic Drug Nordihydroguaiaretic Acid with Serum Albumins. Nusrat S, Siddiqi MK, Zaman M, Zaidi N, Ajmal MR, Alam P, Qadeer A, Abdelhameed AS, Khan RH.PLoS One. 2016 Oct 13;11(10):e0164927. doi: 10.1371/journal.pone.0164927. eCollection 2016. PMID: 27736985 Free PMC Article10:A Comprehensive Spectroscopic and Computational Investigation to Probe the Interaction of Antineoplastic Drug Nordihydroguaiaretic Acid with Serum Albumins. Nusrat S, Siddiqi MK, Zaman M, Zaidi N, Ajmal MR, Alam P, Qadeer A, Abdelhameed AS, Khan RH.PLoS One. 2016 Jul 8;11(7):e0158833. doi: 10.1371/journal.pone.0158833. eCollection 2016. Erratum in: PLoS One. 2016 Oct 13;11(10 ):e0164927. PMID: 27391941 Free PMC Article