Structure of Nordihydroguaiaretic acid
CAS No.: 500-38-9
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
Nordihydroguaiaretic Acid is a naturally occuring mTORC1 inhibitor.
Synonyms: NDGA; NSC 4291
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Wegner, Scott A ; Kim, Hahn ; Avalos, José L ;
Abstract: Lactate transport plays a crucial role in the metabolism, microenvironment, and survival of cancer cells. However, current drugs targeting either MCT1 or MCT4, which traditionally mediate lactate import or efflux respectively, show limited efficacy beyond in vitro models. This limitation partly arises from the existence of both isoforms in certain tumors, however existing high-affinity MCT1/4 inhibitors are years away from human testing. Therefore, we conducted an optogenetic drug screen in Saccharomyces cerevisiae on a subset of the FDA-approved drug library to identify existing scaffolds that could be repurposed as monocarboxylate transporter (MCT) inhibitors. Our findings show that several existing drug classes inhibit MCT1 activity, including non-steroidal estrogens, non-steroidal anti-inflammatory drugs (NSAIDs), and natural products (in total representing approximately 1% of the total library, 78 out of 6400), with a moderate affinity (IC50 1.8–21 μM). Given the well-tolerated nature of NSAIDs, and their known anticancer properties associated with COX inhibition, we chose to further investigate their MCT1 inhibition profile. The majority of NSAIDs in our screen cluster into a single large structural grouping. Moreover, this group is predominantly comprised of FDA-approved NSAIDs, with seven exhibiting moderate MCT1 inhibition. Since these molecules form a distinct structural cluster with known NSAID MCT4 inhibitors, such as diclofenac, ketoprofen, and indomethacin, we hypothesize that these newly identified inhibitors may also inhibit both transporters. Consequently, NSAIDs as a class, and piroxicam specifically (IC50 4.4 μM), demonstrate MCT1 inhibition at theoretically relevant human dosages, suggesting immediate potential for standalone MCT inhibition or combined anticancer therapy.
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Purchased from AmBeed: 61-68-7 ; 22071-15-4 ; 1448671-31-5 ; 169590-42-5 ; 71125-38-7 ; 29679-58-1 ; 42924-53-8 ; 162011-90-7 ; 500-38-9
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CAS No. : | 500-38-9 |
Formula : | C18H22O4 |
M.W : | 302.36 |
SMILES Code : | CC(CC1=CC=C(O)C(O)=C1)C(C)CC2=CC=C(O)C(O)=C2 |
Synonyms : |
NDGA; NSC 4291
|
MDL No. : | MFCD00002206 |
InChI Key : | HCZKYJDFEPMADG-UHFFFAOYSA-N |
Pubchem ID : | 4534 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302 |
Precautionary Statements: | P301+P312+P330 |
Target |
|
Clinical Trial:
NCT Number | Conditions | Phases | Recruitment | Completion Date | Locations |
NCT02575794 | High Grade Glioma (III or IV) | Phase 1 | Recruiting | December 15, 2022 | United States, Alabama ... More >> UAB Comprehensive Cancer Center Not yet recruiting Birmingham, Alabama, United States, 35294-3410 Contact: Thiru Pillay, RN 205-934-1842 thiru@uab.edu Principal Investigator: Burt Nabors, MD United States, California Jonsson Comprehensive Cancer Center at UCLA Not yet recruiting Los Angeles, California, United States, 90095 Contact: Timothy Cloughesy, MD 310-825-5321 TCloughesy@mednet.ucla.edu Principal Investigator: Timothy Cloughesy, MD United States, Maryland Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Recruiting Baltimore, Maryland, United States, 21231 Contact: Quinn qta@jhmi.edu, RN 410-955-8837 qta@jhmi.edu Contact: Trisha Surakus 410-502-9864 tsuraku1@jhmi.edu Sub-Investigator: Matthias Holdhoff, MD Principal Investigator: Stuart Grossman, MD United States, Massachusetts Dana Farber Cancer Institute Not yet recruiting Boston, Massachusetts, United States, 02215 Contact: Jennifer Barrs 617-632-6119 JenniferA_Barrs@DFCI.HARVARD.EDU Principal Investigator: Patrick Wen, MD United States, Michigan Josephine Ford Cancer Center at Henry Ford Hospital Recruiting Detroit, Michigan, United States, 48202 Contact: Amy Williamson, RN awillia12@hfhs.org Contact: Emily Krozek, MHSA Ekrozek1@hfhs.org Principal Investigator: Tobias Walbert, MD United States, North Carolina Wake Forest University Comprehensive Cancer Center Not yet recruiting Winston-Salem, North Carolina, United States, 27157 Contact: Clinical Trials Office 336-713-6771 Principal Investigator: Glenn Lesser, MD United States, Ohio Cleveland Clinic Taussig Cancer Center Not yet recruiting Cleveland, Ohio, United States, 44195 Contact: Cancer Center-Cares 216-444-7923 Sub-Investigator: David Peereboom, MD United States, Pennsylvania Abrams Cancer Center of the University of Pennsylvania Not yet recruiting Philadelphia, Pennsylvania, United States, 19104 Contact: Clinical Trials Office-Abrams Cancer Center 800-474-9892 Principal Investigator: Arati Desai, MD Hillman Cancer Center at University of Pittsburgh Cancer Institute Not yet recruiting Pittsburgh, Pennsylvania, United States, 15232 Contact: Clinical Trials Office - UPMC Cancer Centers 412-647-8073 Principal Investigator: Frank Lieberman, MD Less << |
NCT00664677 | Leukemias Acu... More >>te Myeloid Leukemia (AML) Acute Lymphocytic Leukemia (ALL) Adult T Cell Leukemia (ATL) Chronic Myeloid Leukemia (CML-BP) Chronic Lymphocytic Leukemia (CLL) Myelodysplastic Syndrome (MDS) Chronic Myelomonocytic Leukemia (CMML) Less << | Phase 1 | Terminated(Funding constraints... More >>) Less << | - | United States, North Carolina ... More >> UNC, Lineberger Comprehensive Cancer Center Chapel Hill, North Carolina, United States, 27599 Less << |
NCT00664586 | Refractory Solid Tumors ... More >> Lymphoma Less << | Phase 1 | Terminated(Funding constraints... More >>) Less << | - | United States, Tennessee ... More >> The Sarah Cannon Cancer Center Nashville, Tennessee, United States, 37203 Less << |
NCT00259818 | Cancer | Phase 1 | Completed | - | United States, Arizona ... More >> Premiere Oncology of Arizona Scottsdale, Arizona, United States United States, New York Albert Einstein College of Medicine Bronx, New York, United States United States, Tennessee Sarah Cannon Cancer Center Nashville, Tennessee, United States Less << |
NCT00057512 | Head and Neck Neoplasms | Phase 1 | Completed | - | United States, South Carolina ... More >> MUSC Charleston, South Carolina, United States, 29475 Less << |
NCT00313534 | Prostate Cancer | Phase 1 | Terminated(Ran out of drug) | - | United States, California ... More >> UCSF Comprehensive Cancer Center San Francisco, California, United States, 94115 Less << |
NCT00404248 | Brain and Central Nervous Syst... More >>em Tumors Less << | Phase 1 Phase 2 | Completed | - | United States, Alabama ... More >> UAB Comprehensive Cancer Center Birmingham, Alabama, United States, 35294-3410 United States, Florida H. Lee Moffitt Cancer Center and Research Institute at University of South Florida Tampa, Florida, United States, 33612-9497 United States, Georgia Winship Cancer Institute of Emory University Atlanta, Georgia, United States, 30322 United States, Maryland Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Baltimore, Maryland, United States, 21231 United States, Massachusetts Massachusetts General Hospital Boston, Massachusetts, United States, 02114 United States, Michigan Josephine Ford Cancer Center at Henry Ford Hospital Detroit, Michigan, United States, 48202 United States, North Carolina Wake Forest University Comprehensive Cancer Center Winston-Salem, North Carolina, United States, 27157-1096 United States, Ohio Cleveland Clinic Taussig Cancer Center Cleveland, Ohio, United States, 44195 United States, Pennsylvania Abramson Cancer Center of the University of Pennsylvania Philadelphia, Pennsylvania, United States, 19104-4283 Less << |
NCT00678015 | Prostate Cancer | Phase 2 | Terminated(Per protocol - inte... More >>rim analysis showed no significant PSA declines among the first 12 patients after 3 cycles of treatment) Less << | - | United States, California ... More >> UCSF Helen Diller Family Comprehensive Cancer Center San Francisco, California, United States, 94115 Less << |
NCT00154089 | Cervical Intraepithelial Neopl... More >>asia Less << | Phase 1 Phase 2 | Completed | - | United States, Maryland ... More >> University of Maryland, Dept. of Family Medicine Baltimore, Maryland, United States, 21201 Less << |
NCT00678015 | - | Terminated(Per protocol - inte... More >>rim analysis showed no significant PSA declines among the first 12 patients after 3 cycles of treatment) Less << | - | - | |
NCT00404248 | - | Completed | - | - |
Tags: Nordihydroguaiaretic acid | NDGA | Lipoxygenase Inhibitor | mTOR | PI3K/AKT/mTOR | Exosome | Tumor Growth, Proliferation and Apoptosis | Enzyme Inhibitors | 500-38-9
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