AMPK Inhibitor

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

Dorsomorphin (BML-275) is a selective and ATP-competitive AMPK inhibitor (K_i=109 nM in the absence of AMP). Dorsomorphin (BML-275) selectively inhibits BMP type I receptors ALK2, ALK3, and ALK6. Dorsomorphin can reverse autophagy activation and anti-inflammatory effect of Urolithin A (HY-100599).

Dorsomorphin (Compound C) dihydrochloride is a potent, selective and ATP-competitive AMPK inhibitor, with a K_i of 109 nM. Dorsomorphin dihydrochloride inhibits BMP pathway by targeting the type I receptors ALK2, ALK3, and ALK6. Dorsomorphin dihydrochloride can reverse autophagy activation and anti-inflammatory effect of Urolithin A (HY-100599).

RMC-7977 is an orally active triple-complex RAS inhibitor that can simultaneously bind to cyclophilin A (CYPA) (K_d = 195 nM) and KRAS (G12V) (K_d = 292 μM). It exhibits broad-spectrum inhibitory activity against KRAS, NRAS, and HRAS proteins and their various wild-type and mutant variants. RMC-7977 induces apoptosis by inhibiting the phosphorylation of ERK, CRAF, and RSK, as well as increasing PARP cleavage. This leads to tumor regression, reduces resistance in KRAS^G12C cancer models, and demonstrates good tolerability across various RAS cancer models.

SBI-0206965 is a potent, selective and cell permeable autophagy kinase ULK1 inhibitor with IC₅₀s of 108 nM for ULK1 kinase and 711 nM for the highly related kinase ULK2. SBI-0206965 is also an AMPK inhibitor that can paradoxically increase Thr172 phosphorylation.

BAY-3827, a chemical probe, is a potent and selective AMPK inhibitor with IC₅₀ values of 1.4 nM at low (10 μM ATP concentration) and 15 nM at high (2 mM ATP concentration). BAY-3827 shows over 500-fold selectivity for most of the 331 kinases. BAY-3827 prevents phosphorylation of acetyl-CoA carboxylase 1 and shows strongest anti-proliferative activity in androgen-dependent prostate cancer cell lines.

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

STO-609 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 inhibits AMP-activated protein kinase kinase (AMPKK) activity in HeLa cell lysates with an IC₅₀ ~0.02 g/ml.

GSK-690693 is an ATP-competitive pan-Akt inhibitor with IC₅₀s of 2 nM, 13 nM, 9 nM for Akt1, Akt2 and Akt3, respectively. GSK-690693 is also an AMPK inhibitor, affects Unc-51-like autophagy activating kinase 1 (ULK1) activity and robustly inhibits STING-dependent IRF3 activation.

AMPK-IN-3 (compound 67) is a potent and selective AMPK inhibitor with IC₅₀s of 60.7, 107 and 3820 nM for AMPK (α2), AMPK (α1) and KDR, respectively. AMPK-IN-3 inhibits AMPK does not affect cell viability or cause significant cytotoxicity in K562 cells. AMPK-IN-3 can be used in study of cancer.

HTH-01-015 is a selective NUAK1/ARK5 inhibitor (IC₅₀ is 100 nM). HTH-01-015 inhibits NUAK1 with >100-fold higher potency than NUAK2 (IC50 of >10 μM).

WZ4003 is the first potent and highly specific NUAK kinase inhibitor with IC₅₀ of 20 nM/100 nM for NUAK1 (ARK5)/NUAK2, without significant inhibition on other 139 kinases.

Wu-5 is a USP10 inhibitor that can inhibit FLT3 and AMPK pathways, induce FLT3-ITD degradation and induce apoptosis.

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.

Chromium(III) acetate (Chromic acetate) is an AMPK inhibitor that promotes lipogenesis by inhibiting AMPK phosphorylation. Chromium(III) acetate has low toxicity in mammals, with an LD₅₀ of 2365 mg/kg in rats.

Xanthoangelol, extracted from Angelica keiskei, suppresses obesity-induced inflammatory responses. Xanthoangelol possesses antibacterial activity. Xanthoangelol inhibits monoamine oxidases. Xanthoangelol induces apoptosis in neuroblastoma and leukemia cells.

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.

Narazaciclib (ON123300), a strong and brain-penetrant multi-kinase inhibitor, inhibits CDK4 (IC₅₀=3.9 nM), Ark5 (IC₅₀=5 nM), PDGFRβ (IC₅₀=26 nM), FGFR1 (IC₅₀=26 nM), RET (IC₅₀=9.2 nM), and FYN (IC₅₀=11 nM). Single agent Narazaciclib causes a dose-dependent suppression of phosphorylation of Akt as well as activation of Erk in brain tumors. Narazaciclib inhibits CDK6 with an IC₅₀ of 9.82 nM.

MARK-IN-2 is a potent microtubule affinity regulating kinase (MARK) inhibitor with an IC₅₀ of 5 nM.

HTH-02-006 is a NUAK2 inhibitor, with an IC₅₀ value of 126 nM. HTH-02-006 inhibits NUAK2-mediated signaling by reducing phosphorylation of its substrate MYPT1 at S445 and downstream MLC. HTH-02-006 shows growth inhibitory efficacy in YAP-high cancer cells (HuCCT-1, SNU475). HTH-02-006 significantly suppresses YAP-induced hepatomegaly (reduced liver/body weight ratio) in TetO-YAP S127A transgenic mice and demonstrates significant anti-tumor efficacy in mice bearing HMVP2 prostate cancer allografts. HTH-02-006 can be used for the study of liver cancer and prostate cancer.