nuclear translocation

LY294002 (SF 1101) is a broad-spectrum inhibitor of PI3K, inhibiting PI3Kα, PI3Kδ, and PI3Kβ (IC50=0.5 0.57 0.97 μM). LY294002 is also an inhibitor of DNA-PK (IC50=1.4 μM) and an inhibitor of CK2 (IC50=98 nM). LY294002 activates apoptosis and autophagy.

GA-017 is a potent, selective inhibitor of LATS1 and LATS2 (large tumor suppressor kinase 1 2), exhibiting IC50 values of 4.10 and 3.92 nM, respectively. This compound simultaneously acts as an activator of cell proliferation by promoting YAP TAZ activation and their nuclear translocation. Additionally, GA-017 enhances cell growth in 3D culture conditions and augments the ex vivo formation of mouse intestinal organoids [1].

Stattic (STAT3 Inhibitor V) is a STAT3 inhibitor (IC50=5.1 μM) that selectively inhibits STAT3 activation, dimerization, and nuclear translocation. Stattic has antitumor activity and induces apoptosis.

LTβR-IN-1 is a potent and selective lymphin β receptor (LTβR) inhibitor with a selective inhibitory effect on the nuclear translocation of p52 of TNF12A, without affecting the nuclear translocation of p65 mediated by the TNF-α receptor. It inhibits p52 nuclear translocation stimulated by TWEAK or Anti-LTβR with an IC50 of 10 μM and regulates the NF-kB signaling pathway in a ligand-independent manner.

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.

PF-02413873 is a competitive antagonist of nonsteroidal progesterone receptor with a Ki of 2.6 nM. PF-02413873 can be used in studies about the treatment of gynecological conditions such as endometriosis.

TV 3279 is a novel ChE-MAI inhibitor , and the neuroprotective properties depend on their ability to induce the anti-apoptotic proteins PKC, Bcl-2, Bcl-x, and SOD, and to block the nuclear translocation of the pro-apoptotic enzyme glyceraldehyde phosphate dehydrogenase in PC-12 and neuroblastoma cells.

Isorhamnetin (3-methylquercetin) is the methylated metabolite of quercetin. Quercetin is an important dietary flavonoid with in vitro antioxidant activity. Isorhamnetin prevents endothelial cell injuries from oxidized LDL via inhibition of lectin-like ox-LDL receptor-1 upregulation, interference of ox-LDL-mediated intracellular signaling pathway (p38MAPK activation, NF-kappaB nuclear translocation, eNOS expression) and the antioxidant activity of isorhamnetin. Isorhamnetin prevents endothelial dysfunction, superoxide production, and overexpression of p47phox induced by angiotensin II. Isorhamnetin appears to be a potent drug against esophageal cancer due to it's in vitro potential to not only inhibit proliferation but also induce apoptosis of Eca-109 cells.

QS11 is a GTPase activating protein of ADP-ribosylation factor 1 (ARFGAP1) inhibitor. Modulates ARF-GTP levels and synergizes with the Wnt β-catenin signaling pathway to upregulate β-catenin nuclear translocation. Also reduces in vitro migration of metastatic human breast cancer cells.

WHI-P97 is a rationally designed potent inhibitor of JAK-3. IC50 value: Target: JAK3 Treatment of mast cells with WHI-P97 inhibited the translocation of 5-lipoxygenase (5-LO) from the nucleoplasm to the nuclear membrane and consequently 5-LO-dependent leukotriene (LT) synthesis after IgE receptor FcepsilonRI crosslinking by >90% at low micromolar concentrations. WHI-P97 did not directly inhibit the enzymatic activity of 5-LO, but prevented its translocation to the nuclear membrane without affecting the requisite calcium signal.

SC144 is an orally active small-molecule gp130 inhibitor.

Darolutamide (BAY-1841788) is an androgen receptor (AR) antagonist that blocks AR nuclear translocation (Ki: 11 nM).

KIN101 (3-(4-Bromophenyl)-7-[(methylsulfonyl)oxy]-4-oxo-4H-chromene), an isoflavone agonist of IRF-3 dependent signaling, induces IRF-3 nuclear translocation. KIN101 has antiviral activity against RNA viruses, HCV, and RSV.

Triamcinolone (Aristocort) is a synthetic glucocorticoid with anti-inflammatory and immunomodulating properties. Upon cell entry, triamcinolone binds to and activates the glucocorticoid receptor, which leads to translocation of the ligand-receptor complex to the nucleus and induces expression of glucocorticoid-responsive genes such as lipocortins. Lipocortins inhibit phospholipase A2, thereby blocking the release of arachidonic acid from membrane phospholipids and preventing the synthesis of prostaglandins and leukotrienes, both mediators of inflammation. In addition, pro-inflammatory cytokine production, including interleukin (IL)-1and IL-6, and the activation of cytotoxic T-lymphocytes is also inhibited. T-cells are prevented from making IL-2 and proliferating. This agent also decreases the number of circulating lymphocytes, induces cell differentiation, and stimulates apoptosis through increasing Ikappa-B expression and curtailing activation of nuclear factor (NF)kappa-B.

KIN1408 is an antiviral small molecule compound that is an agonist of the RIG-1-like receptor (RLR) pathway and is able to drive the activation of IRF3 (Interferon Regulatory Factor 3) to induce the expression of innate immunity genes (e.g., MDA5, RIG-1, Mx1, IRF7, and IFIT1), and to promote the nuclear translocation of IRF3 by targeting MAVS (Mitochondrial Antiviral Signaling Protein) or its upstream IRF3 nuclear translocation by targeting MAVS (mitochondrial antiviral signaling protein) or its upstream factors. KIN1400 is the parent, and KIN1409 is a derivative.

Ciglitazone (ADD 3878) is a potent and selective PPARγ agonist (EC50: 3 μM) and oral hypoglycemic agent. Ciglitazone inhibits proliferation and differentiation of th17 cells, decreases insulin levels, vascular endothelial growth factor production and blood pressure, and induces cell cycle arrest in gastric cancer cells. Selegiline induces apoptosis in opossum kidney epithelial cells and activates nuclear translocation of p38 MAPK and apoptosis-inducing factor (AIF). Ciglitazone exhibits hypoglycaemic activity in animal models of obesity and hyperglycaemia.

γ-Tocotrienol (Plastochromanol) is one of the four types of tocotrienol, a type of vitamin E. Itl is also a radioprotector, antioxidant. It shows antitumor and antihypertensive effects in vivo.

PMMB-187, a selective STAT3 inhibitor, exhibits an IC50 of 1.81 μM in MDA-MB-231 cells. This compound induces apoptosis in MDA-MB-231 cells by inhibiting STAT3 transcriptional activity and nuclear translocation, reducing mitochondrial membrane potential, increasing reactive oxygen species (ROS) production, and upregulating the expression of apoptosis-related proteins. PMMB-187 is useful for research in the field of cancer.

CXM102 is an activator of autophagy. This compound induces autophagy in aged BMSCs, rejuvenating them and promoting their preferential differentiation into osteoblasts. CXM102 enhances the nuclear translocation of transcription factor EB (TFEB) and the formation of osteoblasts. In middle-aged male mice, it stimulates bone anabolic metabolism, reduces marrow adipocytes, delays bone loss, lowers serum inflammation levels, reduces organ fibrosis, and extends lifespan.

SC428 acts as an inhibitor of the androgen receptor (AR), specifically targeting the N-terminal domain of AR. This compound effectively diminishes the transactivation of various AR forms, including AR-V7, ARv567es, full-length AR (AR-FL), and its LBD mutants. Additionally, SC428 significantly inhibits AR-FL nuclear translocation, chromatin binding, and AR-regulated gene transcription under androgen stimulation. In vitro, SC428 suppresses the proliferation of tumor cells. In vivo, it inhibits tumor growth in mice transplanted with 22Rv1 cells by inducing apoptosis.

STAT3-IN-34 (Compound 15E) acts as a STAT3 inhibitor, blocking both the nuclear translocation and the transcriptional regulator activity of STAT3. It effectively inhibits HaCaT cell proliferation with an IC50 value of 0.008 μM. Additionally, STAT3-IN-34 reduces IL-17A expression and mitigates Imiquimod-induced psoriasis in mouse models.

COX-2-IN-48 (5-25) serves as an inhibitor of COX-2, exhibiting an IC50 of 51.7 nM against human COX-2. It displays anti-inflammatory and analgesic effects in various rodent models through inhibition of the NF-κB pathway. COX-2-IN-48 (5-25) inhibits the degradation of IκB, phosphorylation and nuclear translocation of NF-κB p65, and the expression of COX-2 and iNOS.

OxLig-1 (7-Ketocholesteryl-9-carboxynonanoate) constitutes a lipid component of oxidized low-density lipoprotein (oxLDL) and serves as a critical ligand for β-glycoprotein I (β(2)-GPI). It induces nuclear translocation by activating the NF-κB pathway. Additionally, oxLig-1 is utilized in the study of atherosclerosis (AS).

Alkyne-P60 is an effective 15-peptide inhibitor of Foxp3. It binds with Foxp3, inhibiting its nuclear translocation and attenuating the suppression of NFKB and NFAT functions mediated by Foxp3. Furthermore, Alkyne-P60 serves as a ligand for PROTAC target proteins.