AMPK Inhibitor

(R)-MRT199665 is an isomer of MRT199665 (HY-120877). MRT199665 is a potent and ATP-competitive, selective MARK/SIK/AMPK inhibitor with IC₅₀s of 2/2/3/2 nM, 10/10 nM, and 110/12/43 nM for MARK1/MARK2/MARK3/MARK14, AMPKα1/AMPKα2, and SIK1/SIK2/SIK3, respectively. MRT199665 causes apoptosis in MEF2C-activated human acute myeloid leukemias (AML) cells. MRT199665 inhibits the phosphorylation of SIK substrate CRTC3 at S370.

Doxorubicin (Hydroxydaunorubicin), a cytotoxic anthracycline antibiotic, is an anti-cancer chemotherapy agent. Doxorubicin is a potent human DNA topoisomerase I and topoisomerase II inhibitor with IC₅₀s of 0.8 μM and 2.67 μM, respectively. Doxorubicin reduces basal phosphorylation of AMPK and its downstream target acetyl-CoA carboxylase. Doxorubicin induces apoptosis and autophagy.

XY221 (Compound 16o) selectively inhibits BRD4 BD2, with an IC₅₀ of 5.8 nM. XY221 demonstrates high pan-BD2 selectivity (667-fold over BRD4 BD1) and BRD4 BD2 domain selectivity (9−32-fold over BRD2/3/T BD2). XY221 induce Apoptosis in MV4-11 cells and shows anticancer activity .

ULK1-IN-2 (compound 3s) is a potent ULK1 inhibitor. ULK1-IN-2 shows highest cytotoxic effect against cancer cell lines, with IC₅₀ of 1.94 μM in A549. ULK1-IN-2 can induce apoptosis and simultaneously block autophagy, and can be used to study NSCLC (Non-small cell lung cancer).

Perfluorotetradecanoic acid (PFTeDA) is an orally active perfluoroalkyl substance. Perfluorotetradecanoic acid directly binds to the ligand-binding domain of purified hPPARγ, with a K_d value of 157.8 μM. Perfluorotetradecanoic acid significantly reduces the activity of the SIRT1/PGC1α and AMPK signaling pathways while stimulating the activity of the AKT1/mTOR signaling pathway. Perfluorotetradecanoic acid significantly upregulates the expression of corticosterone biosynthesis genes. Perfluorotetradecanoic acid increases ROS levels and promotes Apoptosis. Perfluorotetradecanoic acid impairs Leydig cell function and male reproductive endocrine function in adult male rats.

Bempedoic acid-d₄ is the deuterium labeled Bempedoic acid. Bempedoic acid (ETC-1002) is an ATP-citrate lyase (ACL) inhibitor. Bempedoic acid (ETC-1002) activates AMPK.

STO-609 acetate is a selective and cell-permeable inhibitor of the Ca²⁺/calmodulin-dependent protein kinase kinase (CaM-KK), with K_i values of 80 and 15 ng/mL for recombinant CaM-KKα and CaM-KKβ, respectively. STO-609 acetate inhibits AMP-activated protein kinase kinase (AMPKK) activity in HeLa cell lysates with an IC₅₀ ~0.02 g/ml.

LRRK2-IN-8 is a LRRK2 inhibitor. LRRK2-IN-8 inhibits LRRK2 (wt) and LRRK2 (G2019) with IC₅₀s lower than 10 nM, and inhibits TYK2 and NUAK1 with IC₅₀s of 10-100 nM.

NUAK1-IN-3 is a potent and selective NUAK1 inhibitor with an IC₅₀ of 0.49 nM. NUAK1-IN-3 also inhibits NUAK2 and JAK3 with IC₅₀ values of 265 and 225 nM. NUAK1-IN-3 engages Glu139 of NUAK1, forms a salt bridge between its bicyclic ring nitrogen and Asp142, and uses a fluorine atom to enhance hydrophobic binding interactions. NUAK1-IN-3 attenuates MYPT1 phosphorylation, suppresses the NUAK1-MYPT1 signaling axis, and inhibits proliferation, migration, and invasion of triple-negative breast cancer cells. NUAK1-IN-3 reverses TGF-β1-induced epithelial-mesenchymal transition (EMT) marker alterations, downregulates Snail and N-cadherin, and upregulates E-cadherin in tumor tissues. NUAK1-IN-3 suppresses tumor growth in triple-negative breast cancer xenograft models. NUAK1-IN-3 can be used for the research of triple-negative breast cancer.

Amorphigenin is a trothotenone compound. Amorphigenin inhibits osteoclast differentiation by suppressing the expression of c-Fos and NFATc1 in activated T cells. Amorphigenin degrades melanosome proteins by activating the AMPK-dependent autophagy pathway, but not in dependence of the mTOR pathway. Amorphigenin significantly protects bone mass and reduces bone erosion in a mouse model of inflammatory bone loss. Amorphigenin can be used to study inflammatory bone diseases, postmenopausal osteoporosis, and skin pigmentation disorders.

sGC stimulator 1 is a carbonyl sulfide (COS)/H₂S-donor hybrid soluble guanylyl cyclase (sGC) stimulator (EC₅₀ = 496 nM). sGC stimulator 1 exhibits a well-characterized H₂S-releasing property. sGC stimulator 1 reduces fibrosis in TGF-β1-treated cardiac fibroblasts by increasing cGMP and H₂S levels. sGC stimulator 1 can exert anti-fibrotic effects by activating sGC and increasing H₂S. sGC stimulator 1 can be used for the study of heart failure (HF).

XMD-17-51 is a pyrimido-diazepinone compound that is able to modulate protein kinases.

VS-II-173 is a pan-Pim kinase inhibitor with IC₅₀ values ​​of 0.07 μM and 0.02 μM for Pim1 and Pim3, respectively, and a residual activity of 46% for Pim2 at 1 μM. VS-II-173 also inhibits kinases such as HIPK2, PRK2, RSK1, DYRK1a and AMPK_α1, selectively inhibiting acute myeloid leukemia (AML) cells with significantly lower toxicity to non-malignant cells (EC₅₀ > 30 μM). VS-II-173 weakens the phosphorylation of substrates such as Stat5 (Y694), MDM2 (S166), Bad (S112), and 4E-BP1 (T37/46) by inhibiting Pim kinase-mediated signaling pathways, blocking pro-survival signals in AML cells and inducing apoptosis. VS-II-173 synergistically enhances anti-AML activity when combined with Daunorubicin (HY-13062A). VS-II-173 can be used in AML research, especially for AML with FLT3-ITD mutations and NPM1 mutations .

Fenitrothion-d₆ is the deuterium labeled Fenitrothion (HY-B1885). Fenitrothion is a broad-spectrum and orally active insecticide/acaricide. Fenitrothion inhibits cholinesterase, AMPKα and IRS1/PI3K/AKT. Fenitrothion causes Apoptosis, reduces SOD activity. Fenitrothion shows insecticidal effect against Rhyzopertha dominica and Tribolium castaneum adults. Fenitrothion is widely used in cotton crops, vegetable crops, fruit crops and field crops, especially rice. Fenitrothion can be used for brain and spleen toxicology studies.

ADSS2-IN-1 is a ADSS2 inhibitor. ADSS2-IN-1 inhibits de novo AMP biosynthesis by targeting ADSS2, downregulates AMPK activity and promotes mitophagy in drug-resistant cells. ADSS2-IN-1 alone induces mild apoptosis in acute myeloid leukemia cells, and acts synergistically with BH3 mimetics to enhance the apoptotic effect. ADSS2-IN-1 restores the sensitivity of drug-resistant acute myeloid leukemia cells and reduces disease burden in immunocompetent mouse models. ADSS2 antagonist-1 can be used for the research of acute myeloid leukemia.

Kirenol (Standard) is the analytical standard of Kirenol (HY-N0559). This product is intended for research and analytical applications. Kirenol is a diterpenoid compound, an orally active apoptosis inducer and signaling pathway regulator, with a K_d value of 5.47 μM against the target CK2. Kirenol promotes the cleavage of Bid into tBid, regulates the protein levels/phosphorylation of Bax, Bcl-2, p53 and p21, and induces caspase-independent apoptosis, S-phase cell cycle arrest, ROS accumulation and cytotoxicity in cancer cells. Kirenol activates the CK2/AKT and AMPK-mTOR-ULK1 pathways, inhibits the signaling of NF-κB, TGF-β/Smads and NLRP3 inflammasome, and regulates the GSK3β, BMP and Wnt/β-catenin pathways. Kirenol induces autophagy, mitophagy and osteoblast differentiation, promotes mitochondrial fusion, and exerts antioxidant, anti-inflammatory, antifibrotic, renoprotective, cardioprotective, neuroprotective and analgesic effects. Kirenol is applicable to research related to chronic myeloid leukemia, ischemic stroke, diabetic nephropathy, heart failure, acute lung injury and osteoporosis.

Tanshinol borneol ester, an angiogenesis stimulator, promoted multiple key steps of angiogenesis through Akt and MAPK signalling pathways. Tanshinol borneol ester has anti-ischemic and anti-atherosclerosis activities.

ARUK2010489 (Compound 23) is a potent, selective and brain-penetrant NUAK1 inhibitor with a pIC₅₀ of 8.7. ARUK2010489 also inhibits CDK2, CDK4 and CDK6 activity, with inhibitory rate of 7%, 39% and 26% at 1 μM. ARUK2010489 can be used for the research of neurological disease, such as Alzheimer’s disease (AD).

LRRK2/NUAK1/TYK2-IN-1 (conpound 226) shows inhibitory activity toward LRRK2 (Wt), LRRK2 (G2019), TYK2 and NUAK1, with IC₅₀ values lower than 10 nM. LRRK2/NUAK1/TYK2-IN-1 can be used for autoimmune disease research.

OXPHOS-IN-2 is an orally active OXPHOS inhibitor. OXPHOS-IN-2 exhibits potent inhibitory activity in PC9 (IC₅₀ = 12.3 nM) and Bxpc-3 cells (IC₅₀ = 250 nM in glucose medium, IC₅₀ = 17.5 nM in galactose medium). OXPHOS-IN-2 decreases the NADH/NAD⁺ ratio and reduces ATP levels. OXPHOS-IN-2 induces tumor cells apoptosis by activating reactive oxygen species (ROS) and downregulating the level of Nrf2. OXPHOS-IN-2 can be used for research on cancer such as non-small cell lung cancer and pancreatic cancer.