transactivation

EPI-001 is an androgen receptor N-terminal domain antagonist with IC50 of ～6 μM and a selective PPAR-gamma modulator.

Pifithrin-α hydrobromide (Pifithrin-α hydrobromide) is a p53 inhibitor, inhibiting p53-dependent transactivation of p53-responsive genes.

Tetramethylcurcumin is a novel curcumin analog, is an effective inhibitors of STAT3 phosphorylation, DNA binding activity, and transactivation in vitro.it also inhibits colony formation in soft agar, cell invasion, and exhibit synergy with the anti-cancer drug doxorubicin against breast cancer cells.

ORM-15341 is a potent and full antagonist for human AR (hAR)( with IC50 values of 38 nM as shown by transactivation assays in AR-HEK293 cells)

ZL0580 induces HIV suppression by inhibiting Tat transactivation and transcription elongation as well as by inducing repressive chromatin structure at the HIV promoter.

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.

NSC308848 is an effective apoptosis (cell death) inducer that operates in a Myc-dependent manner. It acts by inhibiting Myc transactivation and disrupting the DNA binding activity of Myc family proteins.

PPAR agonist6 (compound 5a) acts as an agonist for PPAR, exhibiting EC50 values of 3.6 μM and 2.6 μM for PPARα and PPARβ/δ respectively. Additionally, PPAR agonist6 inhibits the transactivation of a TNFα-dependent NF-κB-driven reporter gene in L929 cells [1].

PPARδ agonist10 (compound 7) is an orally active, selective partial agonist of PPARδ, with EC50 values of 0.053 μM for hPPARδ(LBD)-GAL4 and 0.30 µM for mPPARδ. In transactivation assays, it acts as a partial PPARδ agonist but fully stimulates muscle cell free fatty acid oxidation both in vitro and in vivo. PPARδ agonist10 can be utilized for dyslipidemia research.

CGP64222, a peptoid Tat/transactivation response element inhibitor, inhibits human immunodeficiency virus replication by blocking CXC-chemokine receptor 4-mediated virus entry.

UNBS-1450 is a sodium channel antagonist. UNBS-1450 is a hemi-synthetic cardenolide derived from 2″-oxovorusharin, it is effective against various cancer cell types with an excellent differential toxicity. At low nanomolar concentrations, UNBS-1450 induce

10058-F4 (c-Myc Inhibitor) is a cell-permeable thiazolidinone that specifically inhibits the c-Myc-Max interaction and prevents transactivation of c-Myc target gene expression; induces cell-cycle arrest and apoptosis.

BMS-695735, a benzimidazole inhibitor of insulin-like growth factor-1 receptor, has broad-spectrum antitumor activity in vivo. It was found that BMS-695735 had strong inhibition of CYP3A4, induction of CYP3A4 mediated by PXR transactivation, poor water so

Peroxisome proliferator-activated receptors (PPARs) α, δ, γ are ligand-activated nuclear transcription factors involved in the regulation of energy homeostasis as well as insulin sensitivity and glucose metabolism. Pharmacologies of PPARδ receptor agonists, though relatively obscure, have recently been reported to elevate high-density lipoprotein (HDL) cholesterol and lower plasma triglyceride (TG) levels in obese insulin resistant rhesus monkeys. CAY10592 is a full PPARδ agonist (EC50 = 30 nM) in a fatty acid oxidation assay of rat L6 muscle cells with desirable oral pharmacokinetic properties. In a transactivation assay using human PPAR receptors, CAY10592 acts as a selective partial PPARδ agonist (EC50 = 53 nM) with no effect on PPARα or PPARγ activity up to 30 μM. Chronic treatment of high fat fed ApoB100/CETP-transgenic mice with CAY10592 at a dose of 20 mg/kg increases HDL levels, decreases LDL and TG levels, and improves insulin sensitivity.

Bile acids are essential for solubilization and transport of dietary lipids, are the major products of cholesterol catabolism, and are physiological ligands for farnesoid X receptor (FXR), a nuclear receptor that regulates genes involved in lipid metabolism.1They are also inherently cytotoxic, as physiological imbalance contributes to increased oxidative stress.2,3Bile acid-controlled signaling pathways are promising novel targets to treat such metabolic diseases as obesity, type II diabetes, hyperlipidemia, and atherosclerosis.Guggulsterone, derived from resin of the guggul tree, is a competitive antagonist of FXR bothin vitroandin vivo.4Thecisstereoisomer of guggulsterone, (E)-guggulsterone, decreases chenodeoxycholic acid (CDCA)-induced FXR activation with an IC50value of 15 μM.5,6By inhibiting CDCA-induced transactivation of FXR, guggulsterone lowers low-density lipoprotein cholesterol and triglyceride levels in rodents fed a high cholesterol diet.4 1.Makishima, M., Okamoto, A.Y., Repa, J.J., et al.Identification of a nuclear receptor for bile acidsScience2841362-1365(1999) 2.Barbier, O., Torra, I.P., Sirvent, A., et al.FXR induces the UGT2B4 enzyme in hepatocytes: A potential mechanism of negative feedback control of FXR activityGastroenterology1241926-1940(2003) 3.Tan, K.P., Yang, M., and Ito, S.Activation of nuclear factor (erythroid-2 like) factor 2 by toxic bile acids provokes adaptive defense responses to enhance cell survival at the emergence of oxidative stressMol. Pharmacol.72(5)1380-1390(2007) 4.Urizar, N.L., Liverman, A.B., Dodds, D.T., et al.A natural product that lowers cholesterol as an anatagonist ligand for FXRScience296(5573)1703-1706(2002) 5.Cui, J., Huang, L., Zhao, A., et al.Guggulsterone is a farnesoid X receptor antagonist in coactivator association assays but acts to enhance transcription of bile salt export pumpThe Journal of Biological Chemisty278(12)10214-10220(2003) 6.Wu, J., Xia, C., Meier, J., et al.The hypolipidemic natural product guggulsterone acts as an antagonist of the bile acid receptorMolecular Endocrinology16(7)1590-1597(2002)

Difelikefalin is a κ-opioid receptor (KOR) agonist.1It activates KOR in HEK293 cells expressing the human receptor (EC50= 0.16 nM in a transactivation assay) and inhibits forskolin-induced cAMP production in R1.G1 mouse thyoma cells (EC50= 0.048 nM). Difelikefalin is selective for KOR over the μ-opioid receptor (MOR; EC50= >1 μM in a transactivation assay). It reduces acetic acid-induced writhing, as well as scratching behavior induced by the KOR antagonist GNTI, in mice (ED50s = 0.07 and 0.05 mg/kg, respectively). 1.Schteingart, C.D., Menzaghi, F., Jiang, G., et al.Synthetic peptide amides(2008)

Ro5-3335 (CBFβ-Runx1 inhibitor II) is core binding factor (CBF) inhibitor; preferentially kills human leukemia cell lines with CBF fusion proteins (IC50 = 1.1 μM). Ro5-3335 represses RUNX1/CBFβ-dependent transactivation in reporter assays and inhibits transcriptional regulation by RUNX1 and CBFβ. Ro5-3335 also reduces the leukemia burden in a mouse model. Attenuates RUNX1-dependent hematopoiesis in zebrafish embryos. It also is a Tat antagonist and inhibits HIV-1 replication in vitro.

BMS-687453 is a potent and selective PPAR alpha agonist, demonstrating an EC(50) of 10 nM for human PPAR alpha and approximately 410-fold selectivity versus human PPAR gamma in PPAR-GAL4 transactivation assays.

Anticancer agent 73 is an anticancer agent which potently targets transactivation response(TAR) RNA-binding protein 2 (TRBP) and disrupts the TRBP-Dicer interaction. Anticancer agent 73 suppresses the growth and metastasis of HCC in vitro and in vivo by modulating expression profiles of miRNAome and proteome in HCC cells.

Ivaltinostat (CG-200745) formic is an orally active pan-HDAC inhibitor with an isohydroxamic acid component that binds zinc at the bottom of the catalytic pocket. Ivaltinostat formic inhibits the deacetylation of histone H3 and tubulin, promotes p53 accumulation, induces p53-dependent transactivation, and enhances MDM2 and p21 (Waf1/Cip1) protein expression. It increases the sensitivity of Gemcitabine-resistant cells to Gemcitabine and 5-Fluorouracil (5-FU), induces apoptosis, and has antitumor effects.

JTP-117968 is a selective glucocorticoid receptor modulator (non-steroidal SGRM with an IC50 value of 6.8 nM) that exhibits improved transcriptional inhibition/transactivation dissociation.

Difelikefalin TFA is a κ-opioid receptor (KOR) agonist. It activates KOR in HEK293 cells expressing the human receptor (EC50 = 0.16 nM in a transactivation assay) and inhibits forskolin-induced cAMP production in R1.G1 mouse thyoma cells (EC50 = 0.048 nM). Difelikefalin TFA is selective for KOR over the μ-opioid receptor (MOR; EC50 = >1 µM in a transactivation assay). It reduces acetic acid-induced writhing, as well as scratching behavior induced by the KOR antagonist GNTI, in mice (ED50s = 0.07 and 0.05 mg kg, respectively).

Difelikefalin HCl is a κ-opioid receptor (KOR) agonist. It activates KOR in HEK293 cells expressing the human receptor (EC50 = 0.16 nM in a transactivation assay) and inhibits forskolin-induced cAMP production in R1.G1 mouse thyoma cells (EC50 = 0.048 nM). Difelikefalin HCl is selective for KOR over the μ-opioid receptor (MOR; EC50 = >1 µM in a transactivation assay). It reduces acetic acid-induced writhing, as well as scratching behavior induced by the KOR antagonist GNTI, in mice (ED50s = 0.07 and 0.05 mg kg, respectively).

CCCTP is a potent inhibitor of the 11β-HSD-1 enzyme with reduced pregnane-X receptor (PXR) transactivation activity.