nur77

Nur77 modulator 1 is an effective Nur77 binder (KD = 3.58 μM) that up-regulates Nur77 expression, mediates its sub-cellular localization, induces Nur77-dependent ER stress and autophagy, and leads to cell apoptosis, demonstrating anti-hepatoma activity.

TMPA is a nuclear receptor Nur77 and LKB1 interaction antagonist.

Cytosporone B (Dothiorelone G) is a naturally occurring agonist of the nuclear orphan receptor Nur77/NR4A1 (EC50=0.278 nM).

DIM-C-pPhOCH3 (C-DIM5) is a Nerve Growth Factor-Induced Bα (NGFI-Bα, Nur77) agonist

DIM-C-pPhOH (CDIM8) is a nur77 (NR4A1) antagonist,inhibits TGF-β induced cell migration of breast cancer cell lines,promotes ROS/endoplasmic reticulum stress and proapoptotic pathways in pancreatic cancer cell lines,mimics effects of Nur77 RNAi silencing.

4-PQBH is a potent Nur77-binding agent with antitumour activity.4-PQBH inhibits xenograft tumours through Nur77-mediated endoplasmic stress and autophagy by broadly inducing cysteoaspartase-independent cytoplasmic vacuolisation and parapetaloid ptosis.4-PQBH is used in the study of hepatocellular carcinoma.4-PQBH is a potent Nur77-binding agent with antitumour activity.

Nur77 modulator 4 (Compound 15h) is a Nur77 inducer with a KD of 0.477 μM. It significantly promotes Nur77 expression and apoptosis, exhibiting excellent growth inhibitory effects on HepG2 and MCF-7 cells, with an IC50 of less than 5 μM. Nur77 modulator 4 activates Nur77-mediated ER stress through the PERK-ATF4 and IRE1 signaling pathways, leading to apoptosis. This compound is applicable in cancer research.

Nur77 agonist-1 (Compound 8f) is an orally active Nur77 agonist. It induces ferroptosis by upregulating Nur77 protein expression, increasing reactive oxygen species (ROS) and lipid peroxidation levels, while decreasing GPX4 protein expression. Nur77 agonist-1 binds with affinity to the ligand binding domain of Nur77, with a KD of 13.80 μM. It demonstrates significant antiproliferative activity against various breast cancer cells (IC50: 2.15-3.26 μM) and exhibits low cytotoxicity towards normal cells. This compound is useful for breast cancer research.

Nur77 modulator 2 is a Nur77 regulator with a Kd value of 0.35 μM. Nur77 modulator 2 is also a potent, orally active inhibitor of inflammation. nur77 modulator 2 regulates Nur77 co-localization in mitochondria.

Nur77 modulator 3 (9e) binds to Nur77 and inhibits TGF-β1-induced α-SMA and COLA1 expression in a Nur77-dependent manner. It induces Nur77 expression and enhances autophagic flux by inhibiting the mTORC1 signaling pathway in vitro and in vivo. Nur77 modulator 3 blocks the progression of hepatic fibrosis [1].

NR4A agonist-2, derived from the design of Vidofludimus, is a selective pan-NR4A agonist with a dissociation constant (Kd) of 0.10 μM for NR4A1 and half-maximal effective concentrations (EC50) of 0.098 μM, 0.092 μM, and 0.09 μM for Nur77, Nurr1, and NOR-1, respectively. It exhibits 47-fold selectivity for DHODH and demonstrates no cytotoxic activity at concentrations up to 10 μM. NR4A agonist-2 acts by binding to a specific surface pocket in the ligand-binding domain of Nurr1, inhibiting Nurr1 homodimer formation and activating response elements such as NBRE, NurRE, and DR5, thus robustly inducing the expression of neuroprotective genes like BDNF and SOD2. This compound holds potential for research in neurodegenerative diseases including Parkinson's disease, dementia, and multiple sclerosis.

Anticanceragent 258 is an imidazo[1,2-B][1,2,4]triazole derivative that modulates nuclear receptor activity. It exhibits an EC50 of 63 nM for Nurr in N2A cells and an IC50 of 0.1 pM for Nur77 in HEK293 cells. Anticanceragent 258 is applicable in studies related to cancer, metabolic disorders, and neurological diseases.

Anticanceragent 257 (compound of formula (I)) is an anticancer agent that regulates Nur77 and Nurr1.

DdBIC is a pyroptosis inducer that associates with Nur77, facilitating its translocation to the mitochondria. This interaction activates the depletion of SDHA succinyl-CoA, disrupts hemeostasis, causes electron leakage, and stimulates mitochondrial ROS generation. Mitochondrial ROS, induced by DdBIC, oxidatively activates OMA1, leading to OPA1 cleavage and release into the cytoplasm, triggering the PERK-activated integrated stress response, ultimately activating granzyme B (granzyme B) to cleave GSDMC. DdBIC is applicable in melanoma research.

BI1071 is an orally active modulator of the Nur77-Bcl-2 apoptotic pathway. It binds to the Nur77-LBD protein with a Kd value of 0.17 μM. BI1071 activates the Nur77 signaling pathway and induces apoptosis by translocating to the mitochondria and interacting with Bcl-2. It inhibits tumor growth in SW620 xenograft mouse models and is applicable in colon cancer research.

THPN is a Nur77 agonist. It also induces autophagy in melanoma cell lines.

Teduglutide (ALX-0600) is a glucagon-like peptide-2 analog that increases intestinal absorption by promoting mucosal growth and reducing mucosal degradation, improving intestinal recovery. It is used in the study of short bowel syndrome (SBS). Teduglutide activates NR4a1/nur77 expression and FXR signaling, alleviating intestinal dysfunction in mice and improving lung injury, making it useful for studying metabolic and cardiovascular diseases.

1. Acetylshikonin exhibits weak cytotoxicity against human umbilical vein endothelial cells (HUVECs) with IC5 of over 2 microM, exhibits the antiangiogenic and antitumorigenic effects by suppressing proliferation and angiogenic factors. 2. Acetylshikonin inhibits the generation of NADPH oxidase complex in the activation of respiratory burst of PMNs, but does not directly inhibit the activity of NADPH oxidase already generated. 3. Certain shikonin derivatives(such as Acetylshikonin) act as modulators of the Nur77-mediated apoptotic pathway and identify a new shikonin-based lead that targets Nur77 for apoptosis induction. 4. Acetylshikonin, shikonin, and alkannin have accelerative effect on the proliferation of granulation tissue in rats. 5. Acetylshikonin has inhibitory effect on the edematous response is due neither to the release of steroid hormones from the adrenal gland nor to the glucocorticoid activity, but probably partly to the suppression of mast cell degranulation and partly to protection of the vasculature from mediator challenge. 6. Acetylshikonin induces apoptosis of hepatitis B virus X protein-expressing human hepatocellular carcinoma cells via endoplasmic reticulum stress.

SR10098 is a high-affinity ligand for the NR4A nuclear receptor family that exhibits significant activating activity toward Nurr1 (NR4A2) (EC₅₀ = 24 nM) and modulatory effects on other members of the NR4A family (Nur77, Nor1). Nurr1 is involved in regulating the development, survival, and maintenance of dopaminergic neurons. Therefore, SR10098 can be used in research on Parkinson’s disease (PD) and neurodegenerative disorders.

Dendrogenin A (DDA) is a compound acting as a selective liver X receptor (LXR) modulator, cholesterol epoxide hydrolase inhibitor (Ki = 120 nM), and a metabolic product of cholesterol, originating from 5,6α-epoxy cholesterol through histamine conjugation via DDA synthase. This compound is present in non-cancerous human mammary epithelial cells and melanocytes, but absent or minimally present in various breast carcinoma, melanoma cells, and isolated human breast tumor tissues. DDA impedes the activation of LXRβ and LXRα induced by 22(R)-hydroxy cholesterol (IC50s = 76 and 362 nM, respectively), yet it also functions as a partial LXR agonist, boosting the protein levels of Nur77, NOR-1, LC3-I, and LC3-II in B16/F10 murine melanoma cells. It shows a preference for LXRα and LXRβ modulation while displaying selectivity over other receptors including pregnane X receptor (PXR), and various others at a concentration of 2.5 µM. Moreover, DDA enhances LC3-II protein levels in cancer cells and prompts autophagic cell death at specific concentrations. Notably, DDA (0.37 µg/kg) has been shown to diminish tumor growth in melanoma and mammary cancer murine models and promotes cancer cell differentiation both in vitro and in vivo.

Tokinolide B, isolated from Ligusticum porter rhizomes, mediates anti-inflammatory effects via Nur77 binding.

ST-CY14 is an inhibitor of the Nur77-PPARγ interaction with an EC50 of 3.15 μM. It binds to Nur77 (Kd=32 nM) to prevent its ubiquitination and degradation by PPARγ, reducing fatty acid uptake and mitochondrial respiration, and inhibiting the transcription of CD36 and FABP4. ST-CY14 suppresses proliferation and migration of MCF7 and MDA-MB-231 cancer cells and impedes tumor growth and bone metastasis in mouse models.