dorsomorphin (Compound C)

Pharmacological rescue experiments using dorsomorphin and TBHQ confirmed the involvement of the AMPK/mTOR/NCOA4 and Nrf2/SLC7A11/GPX4 pathways, respectively. Furthermore, GRk1 synergistically potentiated the cytotoxic effects of cisplatin. In a xenograft mouse model, GRk1 effectively inhibited tumor growth without inducing significant systemic toxicity. Collectively, these findings identify GRk1 as a potent natural ferroptosis inducer and support its potential development as a promising adjuvant therapeutic strategy for OS.

Furthermore, the present study identified high levels of BMP4 secretion from these four human GIC cell lines and demonstrated that an inhibitor of BMP receptor, dorsomorphin or abrogation of BMP4 by siRNA in the GIC cells restored myogenic differentiation in C2C12 cells. The present study uncovered, for the first time, that BMP4 derived from human GIC cells exogenously inhibited myoblast differentiation by activating the Smad1/5/8‑Id signaling axis. In the future, this in vitro study may help to elucidate the complicated mechanisms underlying cancer‑induced cachexia in humans.

Analysis of TCGA data showed that high TFAM-SIRT3 co-expression is associated with overall survival across cancers, particularly in Kidney Renal Clear Cell Carcinoma (KIRC), where TFAM is downregulated (whereas SIRT3 is not). Together, these findings demonstrate that TFAM promotes mitochondrial fission via direct interaction with Sirt3, thereby activating the AMPK/MFF/Drp1 pathway.

Mechanistic verification was carried out by using the AMPK inhibitor BML-275 and the PGC-1α inhibitor SR-18292...Its protective effect may be related to the activation of the AMPK/PGC-1α signaling pathway and the subsequent enhancement of autophagy. This study reveals for the first time the potential value of Gf1 in the treatment of NAFLD and its molecular mechanism, providing new experimental evidence for the development of NAFLD drugs targeting the AMPK/PGC-1α/autophagy axis.

Pre-administration of AM-630 (selective CB2R antagonist; 0.5 and 1 mg/kg;i.p.) and BML-275 i.e. AMP activated protein kinase (AMPK) mediated autophagy inhibitor; 1.5 and 3 mg/kg;i.p.) substantially abrogated the cardioprotective response of RIPC. The current findings highlight the pivotal role of CB2R activation and AMPK activated autophagy in cardioprotective mechanism of RIPC against MIRI.

Meanwhile, AMPK inhibitor Dorsomorphin overturned the protective effect of GLS2 downregulation on myocardial cells. GLS2 silencing repressed myocardial damage in vivo. SP1-activated GLS2 could aggravate H/R-induced cardiomyocyte injury and ferroptosis by inactivating the AMPK/mTOR pathway, providing a promising therapeutic target for MIRI treatment in the future.

Myocardial ischemia-reperfusion injury (MIRI) causes severe clinical complications in patients. Further analysis showed that GEM administration prevented the I/R-induced decrease in phospho-AMPK levels in ischemic cardiac tissue, and pharmacological inhibition of AMPK with dorsomorphin (DSMF) abolished all cardioprotective effects of GEM. Taken together, these results suggest that GEM mitigates MIRI-induced cardiac injury by inhibiting apoptosis and oxidative stress via modulation of AMPK, supporting its potential for reducing MIRI-related cardiac damage.

This was confirmed by pathway inhibitors (Dorsomorphin, ESI-09) and siRNA knockdown, which reversed cell cycle arrest and reduced cytotoxicity...Crucially, AMPK inhibition attenuated Ad-VT's antitumor effects. These results demonstrate that Ad-VT exerts potent, tumor-selective activity against bladder cancer by inducing cAMP-dependent AMPK-Raptor-mTOR signaling and G2/M arrest, supporting its therapeutic potential.

Specifically, AdipoRon preferentially suppressed ACC1 expression and subsequently downregulated CPT1A, indicating disruption of fatty acid metabolism. These findings establish that AdipoRon suppresses MM progression through AMPK-driven metabolic reprogramming and apoptosis induction, positioning adiponectin receptor agonism as a promising therapeutic strategy for multiple myeloma.

These changes were consistent with AMPK activation, and pharmacological inhibition of AMPK with dorsomorphin (compound C) abolished cytokine production in VPS34-IN1-treated cells. Together, these results indicate that differential cytokine responses to autophagy inhibition are driven primarily by metabolic rewiring rather than autophagic flux per se, highlighting the interplay between metabolism, mitochondrial ROS, and signaling pathways in pDC activation.

Interestingly, dorsomorphin inhibited the expression and nucleation of Gli1 and Gli3 but not affected the expression of Gli2. Thus, these findings reveal that the new mechanism of AMPK inhibitor dorsomorphin against prostate cancer metastasis is through synergistically antagonizing JAK2/STAT3 and Gli2-independent Shh activation.

CC abolished all DIM-induced molecular changes in vitro. Collectively, DIM alleviates hepatic lipid accumulation and oxidative stress in MASLD models through AMPK activation, subsequently modulating PPARα and SREBP1/ACC1 pathways.