FOXO

BN201 (OCS-05) is a drug with neuroprotective and myelin repair effects, which acts mainly by activating serum glucocorticoid kinase-2 (SGK2), which in turn activates the FOXO3 pathway to promote neuronal survival and myelin repair. It is mainly used for the treatment of inflammatory neurological diseases such as multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE).BN201 is able to regulate multiple kinases in the insulin growth factor 1 (IGF1) pathway and cross the blood-brain barrier.

AS1842856 is a Foxo1 inhibitor (IC50=30 nM) that specifically blocks the transcriptional activity of Foxo1 and reduces its activity by directly binding to activated FoxO1. AS1842856 has autophagy inhibitory activity.

Dc-y13-27, a derivative of DC-Y13, is a potent YTHDF2 inhibitor (KD: 37.9 μM). DC-Y13-27 has antitumor activity that enhances the response of radiotherapy and immunotherapy to tumors.

Broussochalcone A is a natural antioxidant and xanthine oxidase inhibitor (IC50 = 2.21 μM) that scavenges free radicals, inhibits iron-induced lipid peroxidation, and reduces nitric oxide synthesis in LPS-activated macrophages. Broussochalcone A induces apoptosis in human renal carcinoma cells by increasing ROS levels and activating the FOXO3 signaling pathway. Broussochalcone A is also a novel NR4A1 inhibitor that induces apoptosis in pancreatic cancer cells through NR4A1-dependent pathways.

kaempferide (4'-Methylkaempferol) inhibits the proliferation of native and estrogen receptor beta overexpressing colon cancer cells through a mechanism not mediated by ligand binding dependent estrogen receptor activation.

Conessine (Conessinum), a steroidal alkaloid isolated from Holarrhena floribunda, interacts with the histamine H3 receptor and has anti-malarial activity.

Piperacetazine (Piperacetazinum), an antipsychotic prodrug, is used forschizophrenia.

LOM612 is a potent and specific FOXO relocator that induces nuclear translocation of the FOXO3a reporter protein as well as endogenous FOXO3a and FOXO1 in a dose-dependent manner in U2OS cells, down-regulates the expression of c-Myc and cyclin D1, and has anti-proliferative effects in human cancer cell lines.

RLX (PD 139530) is a PI3K/Akt/FoxO3a signal inhibitor with anticancer activity against tumour cell lines such as colon cancer, inducing sub-G1 arrest and mitochondrial potential loss, thereby inhibiting tumour growth. RLX also exhibits antitussive and anti-asthmatic activity, reducing eosinophils and total lymphocytes in bronchoalveolar lavage (BAL) fluid, and exhibits toxicity toward A549 cells.

SB 699551 dihydrochloride is a 5-ht5a receptor antagonist.

JY-2 is an orally active and selective forkhead transcription factor O1 (FoxO1) inhibitor with antidiabetic activity and inhibits FoxO1 transcription.JY-2 can be used to study psoriasis and diabetes.

anticancer

Chlorzoxazone (Chlorzoxazon) is a Muscle Relaxant. The physiologic effect of chlorzoxazone is by means of Centrally-mediated Muscle Relaxation.

D-chiro-Inositol (D-(+)-CHIRO-INOSITOL) is an epimer of myo-inositol that is found in certain mammalian glycosylphosphatidylinositol protein anchors and inositol phosphoglycans possessing insulin-like bioactivity.

RLX HCl is a narcissus ketone analogue with anticancer activity that inhibits tumour proliferation by suppressing the PI3K/Akt/FoxO3a signalling pathway in experimental colon cancer, downregulating the p110α and p85 subunits of PI3K in HCT-116 cells, and exhibiting antiproliferative effects.

FOXJ1 agonist 1 (compound 16c), an orally effective small molecule, effectively enhances FOXJ1 expression and acts on multiciliated cells (MCC) in the mammalian airway system to prevent chronic obstructive pulmonary disease (COPD). Foxj1-IN-1 induces motile cilia production in the respiratory system of both zebrafish and mammals and inhibits elastase-induced COPD in mouse models. Additionally, Foxj1-IN-1 demonstrates good liver microsomal stability and favorable in vivo pharmacokinetic (PK) curves and area under the curve (AUC). It exhibits negligible inhibition of CYP and hERG and lacks significant cytotoxicity.

FOXO1-IN-3 is a highly-selective, orally active inhibitor of FOXO1 that reduces hepatic glucose production and improves insulin sensitivity and glucose regulation in db/db mice, without causing weight gain [1].

Kihadanin B can repress the adipogenesis by decreasing lipid accumulation through the suppression of the Akt-FOXO1-PPARγ axis in 3T3-L1 adipocytes.

Euphjatrophane M (Compound 6) is a FOXO1 inhibitor that reduces NF-κBp65 phosphorylation and exhibits anti-inflammatory properties. It can inhibit the production of nitric oxide and also suppress the mRNA expression of IL-6, IL-1β, and TNFα in LPS-induced RAW 264.7 macrophages.

SB 699551 is a selective 5-HT5A antagonist (Ki=6.31 nM) that enhances 5-HT neuronal function. It inhibits SERT (Ki=25.12 nM), reduces phosphorylation levels of AKT and FOXO1, and exhibits inhibitory effects against breast cancer.

Anticancer agent 7 (Example 5) is a potent anti-cancer compound with an IC50 value of 5 μM against H1650 lung cancer cells.