Ascofuranone 

Ascofuranone is an orally active inhibitor of Trypanosoma brucei brucei (TAO) with a K_i value of 2.38 nM. Ascofuranone inhibits IGF-1-induced cancer cell migration, invasion, motility and actin cytoskeleton formation, and exerts anti-tumor effects. Ascofuranone can be used in research related to tumor metastasis, African trypanosomiasis, bacterial infections, lung cancer and hepatocellular carcinoma^[1][3][5].

Ascofuranone (1-20 μM; 24 h) reduces cell viability in a dose-dependent manner in A549, PC3, and MCF-7 cancer cells, but shows limited cytotoxicity in LL24 normal lung cells at concentrations up to 20 μM^[1].
Ascofuranone (10 μM; 24 h) reduces baseline and IGF-1-induced cell invasion in A549, PC3, and MCF-7 cancer cells by approximately 0.5-fold, but does not alter invasion in LL24 normal lung cells, when used at 10 μM for 24 h^[1].
Ascofuranone (0.1-10 μM; 1 h pre-incubation followed by 10 min co-incubation with IGF-1) dose-dependently inhibits IGF-1-induced mTOR phosphorylation, and suppresses IGF-1-induced phosphorylation of the downstream mTOR effectors p70S6K and 4EBP1, in A549, PC3, and MCF-7 cancer cells^[1].
Ascofuranone (10 μM; 1 h pre-incubation followed by 4 h co-incubation with IGF-1) activates AMPK and ACC phosphorylation in an IGF-1-independent manner in A549 and PC3 cancer cells, when used at 10 μM with a 1 h pre-incubation followed by 4 h co-incubation with IGF-1^[1].
Ascofuranone (10 μM; 1 h pre-incubation followed by 10 min co-incubation with IGF-1) inhibits mTORC1 activity by inducing Raptor phosphorylation at Ser792 and modulating TSC2 phosphorylation, in an IGF-1-independent manner in A549 and PC3 cancer cells, when used at 10 μM with a 1 h pre-incubation followed by 10 min co-incubation with IGF-1^[1].
Ascofuranone (1-10 μM; 1 h pre-incubation followed by 10 min co-incubation with IGF-1) dose-dependently inhibits IGF-1-induced FAK phosphorylation in A549 and PC3 cancer cells^[1].
Ascofuranone (3 μM; 20 h) activates PXR transcriptional activity in U2OS cells with a minimum effective concentration of 3 μM^[2].
Ascofuranone (IC₅₀ 3.2 μM; 48 h) inhibits U2OS cell proliferation with an IC₅₀ of 3.2 μM^[2].
Ascofuranone significantly induces adipocyte differentiation of C3H10T1/2 cells, independent of PPARγ activation^[2].
Ascofuranone (50 nM) inhibits the ubiquinol oxidase activity of TAO-expressing E. coli BL21(DE3)pLysS cytoplasmic membranes, reducing activity to 31.6% of the uninhibited control^[3].
Ascofuranone (50 nM) inhibits 23% of the succinate-dependent oxygen consumption activity of TAO-expressing E. coli BL21(DE3)pLysS cytoplasmic membranes when used alone, and completely inhibits the cyanide-insensitive portion of this activity when combined with 5 mM K⁺CN^[3].
Ascofuranone (4-32 μg/mL) exhibits potent antimicrobial activity against select Gram-positive bacteria, including S. aureus, methicillin-resistant S. aureus, S. epidermidis, and B. subtilis, with MIC values ranging from 4 to 32 μg/mL, and against C. albicans with an MIC of 32 μg/mL, but is inactive against vancomycin-resistant E. faecalis (MIC >128 μg/mL)^[5].

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

Ascofuranone (50 mg/kg; i.p.; once every two days; 28 days) administered significantly reduces subcutaneous A549 xenograft tumor weight by approximately 71% relative to vehicle control (p ≤ 0.05)^[1].
Ascofuranone (50 mg/kg; i.p.; once every two days; 6 weeks) administered significantly reduces A549 lung metastasis by approximately 80% relative to vehicle control, associated with inhibition of FAK and mTORC1 pathway activity in lung tissues^[1].

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

420.93

C₂₃H₂₉ClO₅

38462-04-3

Oil

Colorless to light pink

C/C([C@@H]1CC(C(C)(O1)C)=O)=C\CC/C(C)=C/CC2=C(C(C=O)=C(C(Cl)=C2O)C)O

Room temperature in continental US; may vary elsewhere.

• [1]. Jeong YJ, et al. Ascofuranone suppresses invasion and F-actin cytoskeleton organization in cancer cells by inhibiting the mTOR complex 1 signaling pathway. Cell Oncol (Dordr). 2020;43(5):793-805.  [Content Brief]

  [2]. Togashi M, et al. Ascochlorin derivatives as ligands for nuclear hormone receptors. J Med Chem. 2003;46(19):4113-4123.  [Content Brief]

  [3]. Fukai Y, et al. Functional expression of the ascofuranone-sensitive Trypanosoma brucei brucei alternative oxidase in the cytoplasmic membrane of Escherichia coli. Comp Biochem Physiol C Pharmacol Toxicol Endocrinol. 1999;124(2):141-148.  [Content Brief]

  [4]. Hao X, et al. Acremopeptaibols A-F, 16-Residue Peptaibols from the Sponge-Derived Acremonium sp. IMB18-086 Cultivated with Heat-Killed Pseudomonas aeruginosa. J Nat Prod. 2021 Nov 26;84(11):2990-3000.  [Content Brief]