INSM-18
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MedKoo CAT#: 201562

CAS#: 500-38-9

Description: INSM-18, also known as nordihydroguaiaretic acid, NDGA and masoprocol, is a naturally occurring antioxidant dicatechol originally derived from the creosote bush Larrea divaricatta with antipromoter, anti-inflammatory, and antineoplastic activities. NDGA directly inhibits activation of two receptor tyrosine kinases (RTKs), the insulin-like growth factor receptor (IGF-1R) and the c-erbB2/HER2/neu receptor, resulting in decreased proliferation of susceptible tumor cell populations.


Chemical Structure

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INSM-18
CAS# 500-38-9

Theoretical Analysis

MedKoo Cat#: 201562
Name: INSM-18
CAS#: 500-38-9
Chemical Formula: C18H22O4
Exact Mass: 302.15181
Molecular Weight: 302.36488
Elemental Analysis: C, 71.50; H, 7.33; O, 21.17

Price and Availability

Size Price Availability Quantity
1.0g USD 300.0 2 weeks
5.0g USD 780.0 2 weeks
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Synonym: INSM18; INSM-18, INSM 18, masoprocol, nordihydroguaiaretic acid, NDGA, actinex.

IUPAC/Chemical Name: 4,4'-((2R,3S)-2,3-dimethylbutane-1,4-diyl)bis(benzene-1,2-diol)

InChi Key: HCZKYJDFEPMADG-TXEJJXNPSA-N

InChi Code: 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/t11-,12+

SMILES Code: C[C@@H](CC1=CC=C(O)C(O)=C1)[C@H](C)CC2=CC=C(O)C(O)=C2

Appearance: Solid powder

Purity: >98%

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, not in water

Shelf Life: >5 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: 2934.99.9001

Product Data:

Certificate of Analysis:

Safety Data Sheet (SDS):

Biological target: Nordihydroguaiaretic acid is a 5-lipoxygenase (5LOX) (IC50=8 μM) and tyrosine kinase inhibitor.
In vitro activity: The present studies now demonstrate that NDGA inhibits androgen-stimulated growth of LAPC-4 prostate cancer cells by several potential mechanisms. One mechanism, as observed in other cells, is direct inhibition of IGF-1R tyrosine kinase activity. Another potential mechanism of NDGA inhibition is attenuation of androgen stimulation of IGF-1R expression. FRET analysis of the AR suggests that the NDGA effect on AR action occurs after androgen-induced conformational changes in the AR. These findings with NDGA and other IGF-1R inhibitors, support the hypothesis that inhibition of the IGF-1R tyrosine kinase can modulate the androgen response on prostate cancer cell proliferation. Reference: Prostate. 2008 Aug 1; 68(11): 1232–1240. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7305632/
In vivo activity: In conclusion, these studies suggest 16 weeks HTF (high trans-fat, high cholesterol and high fructose) diet fed mice exhibit obesity, insulin resistance, hepatic steatosis, fibrosis, inflammation, ER stress, oxidative stress, and liver injury (Fig. 7). These metabolic changes were significantly attenuated by simultaneous dietary administration of NDGA. This study further provides evidence that dietary administration of NDGA to HTF-fed mice improves hepatic dyslipidemia and NASH pathology by upregulating PPARα gene expression, increasing fatty acid oxidation via the peroxisomal β-oxidation pathway and attenuating ER stress, inflammation, fibrosis and progenitor cell activity. Thus, NDGA might have substantial therapeutic potential in the clinical management of NASH and associated fibrosis. Reference: Mol Cell Endocrinol. 2019 Dec 1; 498: 110538. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7273809/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 78.33 259.06
Ethanol 80.0 264.58

Preparing Stock Solutions

The following data is based on the product molecular weight 302.36488 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.

Recalculate based on batch purity %
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
Formulation protocol: 1. Ryan CJ, Zavodovskaya M, Youngren JF, Campbell M, Diamond M, Jones J, Shiry L, Allan G, Maddux BA, Goldfine ID. Inhibitory effects of nordihydroguaiaretic acid (NDGA) on the IGF-1 receptor and androgen dependent growth of LAPC-4 prostate cancer cells. Prostate. 2008 Aug 1;68(11):1232-40. doi: 10.1002/pros.20789. PMID: 18491370; PMCID: PMC7305632. 2. Blecha JE, Anderson MO, Chow JM, Guevarra CC, Pender C, Penaranda C, Zavodovskaya M, Youngren JF, Berkman CE. Inhibition of IGF-1R and lipoxygenase by nordihydroguaiaretic acid (NDGA) analogs. Bioorg Med Chem Lett. 2007 Jul 15;17(14):4026-9. doi: 10.1016/j.bmcl.2007.04.092. Epub 2007 Apr 29. PMID: 17502145; PMCID: PMC2253493. 3. Han L, Bittner S, Dong D, Cortez Y, Dulay H, Arshad S, Shen WJ, Kraemer FB, Azhar S. Creosote bush-derived NDGA attenuates molecular and pathological changes in a novel mouse model of non-alcoholic steatohepatitis (NASH). Mol Cell Endocrinol. 2019 Dec 1;498:110538. doi: 10https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7273809/.1016/j.mce.2019.110538. Epub 2019 Aug 12. PMID: 31415794; PMCID: PMC7273809. 4. Zhang H, Shen WJ, Li Y, Bittner A, Bittner S, Tabassum J, Cortez YF, Kraemer FB, Azhar S. Microarray analysis of gene expression in liver, adipose tissue and skeletal muscle in response to chronic dietary administration of NDGA to high-fructose fed dyslipidemic rats. Nutr Metab (Lond). 2016 Sep 29;13:63. doi: 10.1186/s12986-016-0121-y. PMID: 27708683; PMCID: PMC5041401.
In vitro protocol: 1. Ryan CJ, Zavodovskaya M, Youngren JF, Campbell M, Diamond M, Jones J, Shiry L, Allan G, Maddux BA, Goldfine ID. Inhibitory effects of nordihydroguaiaretic acid (NDGA) on the IGF-1 receptor and androgen dependent growth of LAPC-4 prostate cancer cells. Prostate. 2008 Aug 1;68(11):1232-40. doi: 10.1002/pros.20789. PMID: 18491370; PMCID: PMC7305632. 2. Blecha JE, Anderson MO, Chow JM, Guevarra CC, Pender C, Penaranda C, Zavodovskaya M, Youngren JF, Berkman CE. Inhibition of IGF-1R and lipoxygenase by nordihydroguaiaretic acid (NDGA) analogs. Bioorg Med Chem Lett. 2007 Jul 15;17(14):4026-9. doi: 10.1016/j.bmcl.2007.04.092. Epub 2007 Apr 29. PMID: 17502145; PMCID: PMC2253493.
In vivo protocol: 1. Han L, Bittner S, Dong D, Cortez Y, Dulay H, Arshad S, Shen WJ, Kraemer FB, Azhar S. Creosote bush-derived NDGA attenuates molecular and pathological changes in a novel mouse model of non-alcoholic steatohepatitis (NASH). Mol Cell Endocrinol. 2019 Dec 1;498:110538. doi: 10https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7273809/.1016/j.mce.2019.110538. Epub 2019 Aug 12. PMID: 31415794; PMCID: PMC7273809. 2. Zhang H, Shen WJ, Li Y, Bittner A, Bittner S, Tabassum J, Cortez YF, Kraemer FB, Azhar S. Microarray analysis of gene expression in liver, adipose tissue and skeletal muscle in response to chronic dietary administration of NDGA to high-fructose fed dyslipidemic rats. Nutr Metab (Lond). 2016 Sep 29;13:63. doi: 10.1186/s12986-016-0121-y. PMID: 27708683; PMCID: PMC5041401.

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1: Díaz-Gerevini GT, Daín A, Pasqualini ME, López CB, Eynard AR, Repossi G. Diabetic encephalopathy: beneficial effects of supplementation with fatty acids ω3 and nordihydroguaiaretic acid in a spontaneous diabetes rat model. Lipids Health Dis. 2019 Feb 8;18(1):43. doi: 10.1186/s12944-018-0938-7. PubMed PMID: 30736810; PubMed Central PMCID: PMC6368734.

2: Awasthi S, Preethy R, Saraswathi NT. Nordihydroguaiaretic acid prevents glycation induced structural alterations and aggregation of albumin. Int J Biol Macromol. 2019 Feb 1;122:479-484. doi: 10.1016/j.ijbiomac.2018.10.173. Epub 2018 Oct 26. PubMed PMID: 30416092.

3: Nolte J, Pöttgen LA, Sperlich J, Grossert A, Kempa A, Teusch N, Schörken U. Glucansucrase catalyzed synthesis and functional characterization of nordihydroguaiaretic acid glucosides. Enzyme Microb Technol. 2019 Jan;120:69-76. doi: 10.1016/j.enzmictec.2018.10.002. Epub 2018 Oct 5. PubMed PMID: 30396401.

4: Singh M, Bittner S, Li Y, Bittner A, Han L, Cortez Y, Inayathullah M, Arif Z, Parthasarathi R, Rajadas J, Shen WJ, Nicolls MR, Kraemer FB, Azhar S. Anti-hyperlipidaemic effects of synthetic analogues of nordihydroguaiaretic acid in dyslipidaemic rats. Br J Pharmacol. 2019 Feb;176(3):369-385. doi: 10.1111/bph.14528. Epub 2018 Dec 10. PubMed PMID: 30374952; PubMed Central PMCID: PMC6329620.

5: Wang L, Li L, Quan MY, Wang D, Jia Z, Li ZF, Li B, Guo L, Tan GJ. Nordihydroguaiaretic acid can suppress progression of experimental autoimmune encephalomyelitis. IUBMB Life. 2018 May;70(5):432-436. doi: 10.1002/iub.1739. Epub 2018 Apr 10. PubMed PMID: 29637686.

6: Chan JKW, Bittner S, Bittner A, Atwal S, Shen WJ, Inayathullah M, Rajada J, Nicolls MR, Kraemer FB, Azhar S. Nordihydroguaiaretic Acid, a Lignan from Larrea tridentata (Creosote Bush), Protects Against American Lifestyle-Induced Obesity Syndrome Diet-Induced Metabolic Dysfunction in Mice. J Pharmacol Exp Ther. 2018 May;365(2):281-290. doi: 10.1124/jpet.117.243733. Epub 2018 Feb 22. PubMed PMID: 29472517; PubMed Central PMCID: PMC5878670.

7: Abbas MA, Badran D, Disi A. Effect of nordihydroguaiaretic acid on spermatogenesis and fertility in rats. Andrologia. 2018 Apr;50(3). doi: 10.1111/and.12916. Epub 2017 Nov 6. PubMed PMID: 29110321.

8: Bibikova MV, Spiridonova NA, Korystova AF, Kublik LN, Levitman MK, Shaposhnikova VV, Korystov YN. Lipoxygenase Inhibitors Nordihydroguaiaretic Acid and Fungus Lecanicillum lecanii Extract Induce Death of Lymphoid Leukemia Cells. Bull Exp Biol Med. 2017 Jul;163(3):330-333. doi: 10.1007/s10517-017-3796-9. Epub 2017 Jul 26. PubMed PMID: 28744653.

9: Merino-Ramos T, Jiménez de Oya N, Saiz JC, Martín-Acebes MA. Antiviral Activity of Nordihydroguaiaretic Acid and Its Derivative Tetra-O-Methyl Nordihydroguaiaretic Acid against West Nile Virus and Zika Virus. Antimicrob Agents Chemother. 2017 Jul 25;61(8). pii: e00376-17. doi: 10.1128/AAC.00376-17. Print 2017 Aug. PubMed PMID: 28507114; PubMed Central PMCID: PMC5527643.

10: Zhao QW, Lin Y, Xu CR, Yao YL, Cui YH, Zhang X, Bian XW. NDGA-P21, a novel derivative of nordihydroguaiaretic acid, inhibits glioma cell proliferation and stemness. Lab Invest. 2017 Oct;97(10):1180-1187. doi: 10.1038/labinvest.2017.46. Epub 2017 May 15. PubMed PMID: 28504686.

11: Siddique YH, Ali F. Protective effect of nordihydroguaiaretic acid (NDGA) on the transgenic Drosophila model of Alzheimer's disease. Chem Biol Interact. 2017 May 1;269:59-66. doi: 10.1016/j.cbi.2017.04.005. Epub 2017 Apr 6. PubMed PMID: 28392391.

12: Dain A, Repossi G, Diaz-Gerevini GT, Vanamala J, Das UN, Eynard AR. 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). Lipids Health Dis. 2016 Nov 25;15(1):205. PubMed PMID: 27884155; PubMed Central PMCID: PMC5123226.

13: Li X, Fan S, Pan X, Xiaokaiti Y, Duan J, Shi Y, Pan Y, Tie L, Wang X, Li Y, Li X. Nordihydroguaiaretic acid impairs prostate cancer cell migration and tumor metastasis by suppressing neuropilin 1. Oncotarget. 2016 Dec 27;7(52):86225-86238. doi: 10.18632/oncotarget.13368. PubMed PMID: 27863391; PubMed Central PMCID: PMC5349909.

14: Nusrat S, Zaidi N, Zaman M, Islam S, Ajmal MR, Siddiqi MK, Santra MK, Khan RH. Repositioning nordihydroguaiaretic acid as a potent inhibitor of systemic amyloidosis and associated cellular toxicity. Arch Biochem Biophys. 2016 Dec 15;612:78-90. doi: 10.1016/j.abb.2016.10.014. Epub 2016 Oct 24. PubMed PMID: 27789205.

15: Bergren DR, Valentine JL. Anti-anaphylactic action of nordihydroguaiaretic acid in antigen sensitized guinea pigs. Respir Physiol Neurobiol. 2016 Dec;234:26-31. doi: 10.1016/j.resp.2016.09.003. Epub 2016 Sep 3. PubMed PMID: 27595978.

16: Choi YS, Jung MY. Kinetic study on the singlet oxygen quenching activity of nordihydroguaiaretic acid (NDGA) using methylene blue sensitized photooxidation of α-terpinene. Food Sci Biotechnol. 2016 Oct 31;25(5):1333-1336. doi: 10.1007/s10068-016-0209-1. eCollection 2016. PubMed PMID: 30263413; PubMed Central PMCID: PMC6049261.

17: Leon D, Parada D, Vargas-Uribe M, Perez AA, Ojeda L, Zambrano A, Reyes AM, Salas M. Effect of nordihydroguaiaretic acid on cell viability and glucose transport in human leukemic cell lines. FEBS Open Bio. 2016 Aug 23;6(10):1000-1007. eCollection 2016 Oct. PubMed PMID: 27761359; PubMed Central PMCID: PMC5055036.

18: Nusrat S, Siddiqi MK, Zaman M, Zaidi N, Ajmal MR, Alam P, Qadeer A, Abdelhameed AS, Khan RH. Correction: A Comprehensive Spectroscopic and Computational Investigation to Probe the Interaction of Antineoplastic Drug Nordihydroguaiaretic Acid with Serum Albumins. PLoS One. 2016 Oct 13;11(10):e0164927. doi: 10.1371/journal.pone.0164927. eCollection 2016. PubMed PMID: 27736985; PubMed Central PMCID: PMC5063339.

19: Nusrat S, Siddiqi MK, Zaman M, Zaidi N, Ajmal MR, Alam P, Qadeer A, Abdelhameed AS, Khan RH. A Comprehensive Spectroscopic and Computational Investigation to Probe the Interaction of Antineoplastic Drug Nordihydroguaiaretic Acid with Serum Albumins. 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. PubMed PMID: 27391941; PubMed Central PMCID: PMC4938263.

20: Kimura K, Huang RC. Tetra-O-Methyl Nordihydroguaiaretic Acid Broadly Suppresses Cancer Metabolism and Synergistically Induces Strong Anticancer Activity in Combination with Etoposide, Rapamycin and UCN-01. PLoS One. 2016 Feb 17;11(2):e0148685. doi: 10.1371/journal.pone.0148685. eCollection 2016. PubMed PMID: 26886430; PubMed Central PMCID: PMC4757551.



Additional Information

This agent may induce apoptosis in susceptible tumor cell populations as a result of disruption of the actin cytoskeleton in association with the activation of stress activated protein kinases (SAPKs). In addition, NDGA inhibits arachidonic acid 5-lipoxygenase (5LOX), resulting in diminished synthesis of inflammatory mediators such as prostaglandins and leukotrines; it may prevent leukocyte infiltration into tissues and the release of reactive oxygen species and, at higher concentrations, may also inhibit cyclooxygenase.