Aldehyde Dehydrogenase (ALDH) Inhibitor

Disulfiram (Tetraethylthiuram disulfide) is a specific inhibitor of aldehyde-dehydrogenase (ALDH1), used for the treatment of chronic alcoholism by producing an acute sensitivity to alcohol. Disulfiram inhibits gasdermin D (GSDMD) pore formation in liposomes and inflammasome-mediated pyroptosis and IL-1β secretion in human and mouse cells. Disulfiram, a copper ion carrier, with Cu²⁺ increases intracellular ROS levels and induces cuproptosis.

4-Hydroxynonenal (4-HNE) is an α,β unsaturated hydroxyalkenal and an oxidative/nitrosative stress biomarker. 4-Hydroxynonenal is a substrate and an inhibitor of acetaldehyde dehydrogenase 2 (ALDH2). 4-Hydroxynonenal can modulate a number of signaling processes mainly through forming covalent adducts with nucleophilic functional groups in proteins, nucleic acids, and membrane lipids. 4-Hydroxynonenal plays an important role in cancer through mitochondria.

Daidzin is an isoflavone with antioxidant, anticancer, and antiatherosclerotic activities. Daidzin is a potent and selective inhibitor of mitochondrial ALDH-2. Daidzin reduces ethanol consumption.

Win 18446 is an orally active testes-specific enzyme ALDH1a2 inhibitor, with an IC₅₀ of 0.3 μM. Win 18446 reversibly inhibits spermatogenesis in many species and inhibits Retinoic acid (HY-14649) biosynthesis from Retinol (HY-B1342) within the testes.

Cyanamide is a cell division and plant growth inhibitor, as well as an allelochemical derived from Vicia villosa. Cyanamide inhibits root growth and biomass accumulation in a dose-dependent manner by disrupting the formation of mitotic spindles and phragmoplast complexes, reducing the number of mitotic cells and blocking the cell cycle. The effects of Cyanamide are partially reversible after removal from low-concentration environments. Cyanamide is also a specific inhibitor of aldehyde dehydrogenase (ALDH). Although Cyanamide has no direct effect on tumor growth, it can significantly enhance the anti-tumor efficacy of Cyclophosphamide (HY-17420) at non-toxic doses by inhibiting the inactivation of Cyclophosphamide. Cyanamide enables Cyclophosphamide to exert equivalent therapeutic effects at lower doses, effectively inhibiting the growth of primary and metastatic tumors and prolonging the lifespan of tumor-bearing mice. Cyanamide is commonly used in studies related to ha-1 hepatoma and rls lymphosarcoma.

ALDH3A1-IN-4 is a selective ALDH3A1 inhibitor with an IC₅₀ of 0.2 μM. ALDH3A1-IN-4 binds to the aldehyde-binding pocket of ALDH3A1 via hydrophobic interactions and van der Waals forces. ALDH3A1-IN-4 acts as a chemosensitizer that sensitizes ALDH3A1-expressing cancer cells to the antiproliferative effect of mafosfamide, but does not produce a sensitizing effect on non-cancer cells that do not express ALDH3A1. ALDH3A1-IN-4 is applicable to research related to lung adenocarcinoma and glioblastoma.

4-Diethylaminobenzaldehyde is a reversible aldehyde dehydrogenases (ALDHs) inhibitor, with a K_i of 4 nM for ALDH1. 4-Diethylaminobenzaldehyde displays potent anti-androgenic effect (IC₅₀= 1.71μM).

NCT-501 is a reversible, non-competitive, selective, blood-brain barrier-permeable ALDH1A1 inhibitor with an IC₅₀ of 40 nM. NCT-501 inhibits the AKT-β-catenin signaling pathway, induces necroptosis in nasopharyngeal carcinoma cells, suppresses their proliferation and inhibits stem cell spheroid formation. NCT-501 can be used in research related to nasopharyngeal carcinoma, esophageal squamous cell carcinoma and malignant tumors.

Disulfiram (Standard) is the analytical standard of Disulfiram. This product is intended for research and analytical applications. Disulfiram (Tetraethylthiuram disulfide) is a specific inhibitor of aldehyde-dehydrogenase (ALDH1), used for the treatment of chronic alcoholism by producing an acute sensitivity to alcohol. Disulfiram inhibits gasdermin D (GSDMD) pore formation in liposomes and inflammasome-mediated pyroptosis and IL-1β secretion in human and mouse cells. Disulfiram + Cu²⁺ increases intracellular ROS levels triggering apoptosis of ovarian cancer stem cells^[1-6].

Citral is an orally active monoterpene compound in lemon grass essential oil and a natural ALDH1A inhibitor, which can induce apoptosis and cycle arrest in breast cancer cell lines, and has analgesic, anti-injurious and anti-inflammatory effects^[2][3].

YG1702 is a potent ALDH18A1-specific inhibitor. YG1702 attenuates the growth of MYCN-amplified NB and down-regulates MYCN. YG1702 physically interacts with ALDH18A1 with a high affinity and might potentially affect its enzymatic activity.

CVT-10216 is a highly selective, reversible aldehyde dehydrogenase-2 (ALDH-2) inhibitor with an IC₅₀ of 29 nM. CVT-10216 also has inhibitory effect of ALDH-1 with an IC₅₀ of 1.3 μM. CVT-10216 can reduce excessive alcohol drinking in alcohol-preferring rats and exhibit anxiolytic effects.

KM04416, an isothiazolone derivative, is a potent glycerol-3-phosphate dehydrogenase (GPD2) inhibitor. KM04416 significantly inhibits PNT1A cell proliferation.

Prunetin, an O-methylated isoflavone, possesses anti-inflammatory activity. Prunetin is a potent human aldehyde dehydrogenases inhibitor.

ALDH3A1-IN-3 (CB29) is a selective inhibitor of ALDH3A1, with a K_i value of 4.7 μM and an IC₅₀ value of 16 μM. ALDH3A1-IN-3 has no inhibitory potential on the in vitro activity of ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, or ALDH2. ALDH3A1-IN-3 can be used in cellular oxidation and cancer research.

ALDH1A inhibitor 673A is an ALDH1A inhibitor with IC₅₀s of 246 nM (ALDH1A1), 230 nM (ALDH1A2), 348 nM (ALDH1A3), respectively. ALDH1A inhibitor 673A has little or no inhibitory effect on other ALDH family members. ALDH1A inhibitor 673A induces necroptotic ovarian cancer stem-like cells (CSCs) death. ALDH1A inhibitor 673A induces DNA double stand breaks in cancer cells. ALDH1A inhibitor 673A can be used for the study of ovarian cancer.

Dyclonine hydrochloride (Dyclocaine hydrochloride) is an orally active, blood-brain barrier-permeable piperidine phenylacetone small molecule commonly used as a local anesthetic. Dyclonine hydrochloride acts as a highly selective allosteric antagonist of TRPV3; it also reversibly inhibits G9a, ALDH2 and ALDH3A1, non-competitively blocks AChE. Dyclonine hydrochloride activates the Nrf2/ARE pathway, relieves the epigenetic silencing of FXN, blocks Aβ42 aggregation, and promotes remyelination and reparative polarization of microglia. Dyclonine hydrochloride alleviates pruritus via TRPV3 inhibition; it is used in studies of neurodegenerative disease models based on its AChE inhibitory, antioxidant and remyelinating effects; it sensitizes drug-resistant tumors through ALDH inhibition, and combined use with protease inhibitors induces more tumor cell apoptosis; it inhibits Candida albicans in vitro. Dyclonine hydrochloride can be used for research on multiple diseases including neurodegenerative diseases, cancer and pruritic dermatitis.

ALDH3A1-IN-1 (Compound 18) is a potent inhibitor of ALDH3A1 with an IC₅₀ of 1.61 μM. ALDH3A1-IN-1 is more potent than DEAB against patient-derived primary prostate tumor epithelial cells, as single agents or in combination research with docetaxel.

IGUANA-1 is a potent and selective ALDH1B1 inhibitor. IGUANA-1 shows no significant mitochondrial toxicity. IGUANA-1 has antitumor activity.

CM037 is a highly selective and competitive ALDH1A1 inhibitor (IC₅₀=4.6 μM). CM037 blocks the catalytic activity of ALDH1A1, thereby inhibiting the activation of the downstream HIF-1α/VEGF pathway. CM037 is mainly used to study the ALDH1A1-mediated regulation of cancer stem cells (CSCs) and angiogenesis, especially in breast cancer, showing the potential to inhibit tumor angiogenesis and stem cell characteristics.