Last update 01 Nov 2024

FOXO3 x FOXO1

Last update 01 Nov 2024

Basic Info

Related Targets

FOXO3FOXO1

Drugs associated with FOXO3 x FOXO1

Anticancer therapeutics(Demuris Ltd.)

Target

FOXO1 x FOXO3

Mechanism

FOXO1 inhibitors [+1]

Active Org.-

Originator Org.

Demuris Ltd.

Active Indication-

Inactive Indication

Acute Myeloid Leukemia

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with FOXO3 x FOXO1

100 Translational Medicine associated with FOXO3 x FOXO1

0 Patents (Medical) associated with FOXO3 x FOXO1

620

Literatures (Medical) associated with FOXO3 x FOXO1

01 Oct 2024·The Ocular Surface

Cytarabine chemotherapy induces meibomian gland dysfunction

Article

Author: Han, Jiaxu ; Liang, Lingyi ; Xiao, Bing ; Tu, Mengqian ; Xue, Jianwen ; Qian, Xiaobing ; Chen, Ziyan ; Wang, Wenhui ; Liu, Ren

PURPOSECytarabine (Ara-C) chemotherapy causes symptoms resembling meibomian gland dysfunction (MGD), suggesting potential associations between Ara-C and MGD. In this study, the pathological effects of Ara-C on MGD were investigated in a rodent model.METHODSMice received Ara-C with or without rosiglitazone (PPARγ agonist) for 7 consecutive days. Slit-lamp biomicroscope was used for ocular examinations. Immunofluorescence detected acinar cell proliferation, differentiation, and ductal keratinization in the meibomian gland (MG). Lipid accumulation was evaluated by Oil Red O and LipidTox staining. Lipogenic status, FoxO1/FoxO3a cellular localization, and oxidative stress were visualized via immunohistochemistry. Western blotting assessed relative protein expression and AKT/FoxO1/FoxO3a pathway phosphorylation.RESULTSAra-C (50 mg/kg) did not affect mouse survival but induced damage to ocular surface microenvironment, including corneal epithelial defects, MG orifice plugging and acinar dropout, and lacrimal gland (LG) dysfunction. Ara-C intervention inhibited proliferation and caused progenitor loss in the MG, as evidenced by reduced PCNA+ labeling and P63+/Lrig1+ basal cell numbers. The MG ducts of Ara-C-treated mice exhibited marked dilatation, lipid deposition, and hyperkeratinization (K1/K10 overexpression). Ara-C disrupted MG lipid metabolism by downregulating PPARγ and its downstream lipogenic targets AWAT2/SOAT1/ELOVL4 and upregulating HMGCR. Dephosphorylation of AKT and the subsequent nuclear translocation of FoxO1/FoxO3a contributed to Ara-C-induced PPARγ downregulation. Ara-C triggered oxidative stress with increases in 4-HNE and 8-OHdG and Keap1/Nrf2/HO-1/SOD1 axis dysregulation. Rosiglitazone treatment ameliorated MGD-associated pathological manifestations, LG function, MG lipid metabolism, and oxidative stress in Ara-C-exposed mice.CONCLUSIONSSystemic Ara-C chemotherapy exerted topical cytotoxic effects on the ocular surface, and PPARγ restoration by rosiglitazone mitigated Ara-C-induced MGD alterations.

01 Oct 2024·Pharmaceutical Nanotechnology

An Oxidative Stress Study on Curcumin and NanoCurcumin against Aluminum Phosphide-induced Kidney Injury in Rats: The Role of SIRT1/FOXO3 Signaling Pathway in Nephrotoxicity

Article

Author: Abdolvahab, Mohadeseh Haji ; Kheiripour, Nejat ; Jouzdani, Ali Fathi ; Ranjbar, Akram ; Asl, Sara Soleimani ; Ghasemi, Hassan ; Manesh, Seyde Farnaz Motevali

Introduction:In this study, we have investigated the aluminium phosphide (ALP) toxicity on Renal Function and oxidative stress in kidney tissue of male rats and the possible protective role of Curcumin and nanoCurcumin against ALP-induced nephrotoxicity.Methods:Thirty-six adult male rats were divided into 6 groups (n=6). ALP (2 mg/kg oral administration) and control groups received Curcumin and nanoCurcumin (oral administration 100 mg/kg) or without it. After seven days of treatment, kidney parameters, oxidative stress biomarkers, and expression level of sirtuins1 (SIRT1)/Forkhead box protein O1 (FoxO1) pathway genes were evaluated in kidney tissue. In addition, histopathological changes in the kidney tissues were assayed.Results:In the ALP group, compared to the control group, lipid peroxidation levels, urea, and creatinine were increased, and total antioxidant capacity and thiol groups decreased significantly p < 0.05. In Curcumin and nanoCurcumin groups compared to the ALP group, lipid peroxidation and creatinine decreased significantly p < 0.05. Also, Curcumin and nanoCurcumin improved the tissue damage caused by ALP. NanoCurcumin modulated the effect of ALP on the gene expression levels in SIRT1/FoxO1.Conclusion:The present study showed that ALP intoxication in kidney tissue can induce oxidative damage. Moreover, Curcumin and nanocurcumin, as potential antioxidants, can be effective therapeutics in ALP-induced nephrotoxicity.

01 Oct 2024·Journal of Biochemical and Molecular Toxicology

The protective effects of esculetin against Doxorubicin‐Induced hepatotoxicity in rats: Insights into the modulation of Caspase, FOXOs, and heat shock protein pathways

Article

Author: Karadaş, Habibe ; Karaman, Melike ; Karağaç, Medine Sibel ; Isıyel, Murat ; Kizir, Duygu ; Tosun, Hilal ; Demir, Yeliz ; Öztürk, Neslihan ; Ceylan, Hamid ; Yeşilkent, Esra Nur

AbstractDoxorubicin (DOX) is an anthracycline antibiotic widely employed to treat carcinoma. Nevertheless, severe cardiotoxic side effects restrict its clinical use. Esculetin, a natural flavonoid, is found abundantly in plants. This study evaluated the protective effects of esculetin against DOX‐induced hepatotoxicity in rat livers. Forty‐eight rats were randomly divided into six groups with eight rats in each group: control (I), DOX (II), esculetin (III, 50 mg/kg), esculetin (IV, 100 mg/kg), DOX+esculetin 50 (V, DOX+esculetin 50 mg/kg), and DOX+esculetin 100 (VI, DOX+esculetin 100 mg/kg). The administration of esculetin effectively mitigated alterations in the measured biochemical parameters induced by DOX. Gene expression analyses demonstrated that esculetin treatment significantly reduced the DOX‐induced expression of Foxo1, Hspa1a, Hsp4a, Hsp5a, Casp3, and Casp9 while increasing the DOX‐induced expression of Foxo3. These findings suggest that esculetin, with its antioxidant and anti‐inflammatory effects, might be a therapeutic option for protecting against DOX‐induced hepatotoxicity.

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