Orellanine 

Orellanine, a nephrotoxic alkaloid found in Cortinarius orellanus, is an orally active and selective non-competitive inhibitor of alkaline phosphatase. Orellanine chelates iron, generates reactive oxygen species (ROS), induces DNA scission, forms ortho-semiquinone radicals, downregulates antioxidant defenses, and inhibits mitochondrial function. Orellanine induces caspase 8/9-mediated apoptosis. Orellanine inhibits synthesis of proteins, RNA, DNA, and mitochondrial protein synthesis, with metabolic activation required for cell-free protein synthesis inhibition. Orellanine can be used for the research of metastatic clear cell renal cell carcinoma, acute renal failure, chronic renal insufficiency, and kidney damage^[1][2][3].

Orellanine inhibits local clear cell renal cell carcinoma cell cultures, while showing no major toxicity to HUVEC, HEPG2, or MDA cell lines at equivalent concentrations^[1].
Orellanine induces oxidative stress, mitochondrial dysfunction, and caspase 8/9-mediated apoptosis in SKRC-17, SKRC-52, and patient-derived metastatic clear cell renal cell carcinoma cell lines^[1].
Orellanine inhibits pinocytosis in Amoeba proteus and growth of Dictyostelium discoideum and Escherichia coli cells^[2].
Orellanine inhibits the DNA-dependent activity of both rat liver RNA polymerase B and Escherichia coli RNA polymerase^[2].
Orellanine noncompetitively inhibits alkaline phosphatase, γ-glutamyl transpeptidase, and leucine aminopeptidase, and interrupts adenosine triphosphatase production at the proximal tubular brush border^[2].
Orellanine (0.18 mM; 4-24 h) time-dependently inhibits protein, RNA, and DNA synthesis in Madin-Darby canine kidney (MDCK) cells without altering precursor uptake, reaching maximum inhibition of 73%, 80%, and 85% respectively after 24 h^[3].
Orellanine (0.1-0.6 mM; 90 min pre-incubation, 30 min synthesis) inhibits protein synthesis in purified rat liver mitochondria with an IC₅₀ of 0.3 mM, reaching a maximum inhibition of ~90% without altering leucine uptake into mitochondria^[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Orellanine exhibits dose-dependent lethal toxicity in male and female mice, with LD₅₀ values ranging from 8.3 mg/kg (s.c.) to 90 mg/kg (p.o.) and LD₁₀₀ values of 42 mg/kg (i.p.) and 109 mg/kg (p.o.)^[2].
Orellanine exhibits LD₅₀ values of 15 mg/kg (p.o.) in cats^[2].
Orellanine exhibits LD₅₀ values of 8 mg/kg (i.p.) in Guinea pig^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

252.18

C₁₀H₈N₂O₆

37338-80-0

Solid

Light yellow to yellow

[O-][N+]1=CC=C(O)C(O)=C1C2=C(O)C(O)=CC=[N+]2[O-]

Room temperature in continental US; may vary elsewhere.

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

• [1]. Lyons MJ, et al. Orellanine: From Fungal Origin to a Potential Future Cancer Treatment. J Nat Prod. 2023;86(6):1620-1631.  [Content Brief]

  [2]. Dinis-Oliveira RJ, et al. Human and experimental toxicology of orellanine. Hum Exp Toxicol. 2016;35(9):1016-1029.  [Content Brief]

  [3]. Richard JM, et al. Orellanine inhibits protein synthesis in Madin-Darby canine kidney cells, in rat liver mitochondria, and in vitro: indication for its activation prior to in vitro inhibition. Toxicology. 1991;67(1):53-62.  [Content Brief]