BML-275

Biological Activity

BML-275 inhibits BMP signals required for embryogenesis and promoted significant neural differentiation from human pluripotent stem cell (hPSC) lines. BML-275 acts as a potent, selective, reversible, and ATP-competitive inhibitor of AMPK (AMP-activated protein kinase); Ki = 109 nM in the presence of 5 μM ATP and the absence of AMP). BML-275 inhibited the cell proliferation of 4 human pancreatic cancer cell lines (MIA PaCa-2, Panc-1, Colo-357 and AsPC-1). In addition, BML-275 significantly increased the generation of intracellular reactive oxygen species (ROS), followed by induction of DNA damage signaling and apoptosis. Furthermore, BML-275 induced cell cycle arrest in the G2/M phase. BML-275 exerts its antitumor effects by inducing ROS generation, DNA damage and apoptosis via inhibition of the AMPK pathway and by inducing G2/M arrest via a pathway independent of AMPK, implicating its potential application as an antitumor agent for pancreatic cancer.

Product Citations

• 

  Indian J Pharm Sci. 2022;2022:84(3)284-293.

  Gallic acid Inhibits M1 Macrophage Polarization via Adenosine 5'-Monophosphate-Activated Protein Kinase/Signal Transducers and Activators of
  BML-275 purchased from AbMole

• 

  Int J Mol Sci. 2023 Jan 5;24(2):1070.

  Sulforaphane Suppresses H2O2-Induced Oxidative Stress and Apoptosis via the Activation of AMPK/NFE2L2 Signaling Pathway in Goat Mammary Epithelial Cells
  BML-275 purchased from AbMole

• 

  Int J Biol Sci. 2022 Jan 31;18(4):1594-1611.

  Atractylenolide III ameliorates Non-Alcoholic Fatty Liver Disease by activating Hepatic Adiponectin Receptor 1-Mediated AMPK Pathway
  BML-275 purchased from AbMole

• 

  BMC Cancer. 2020 Aug.

  Blockage of AMPK-ULK1 pathway mediated autophagy promotes cell apoptosis to increase doxorubicin sensitivity in breast cancer (BC) cells: an in vitro study
  BML-275 purchased from AbMole

• 

  J Cell Physiol. 2021 Mar;236(3):1889-1902.

  Icariin ameliorates endothelial dysfunction in type 1 diabetic rats by suppressing ER stress via the PPARα/Sirt1/AMPKα pathway
  BML-275 purchased from AbMole

Chemical Information

Molecular Weight	399.49
Formula	C24H25N5O
CAS Number	866405-64-3
Solubility (25°C)	DMSO 3 mg/mL warming
Storage	2-8°C, protect from light

Conversion of different model animals based on BSA (PMID: 27057123)

Species	Mouse	Rat	Rabbit	Guinea pig	Hamster	Dog
Weight (kg)	0.02	0.15	1.8	0.4	0.08	10
Body Surface Area (m2)	0.007	0.025	0.15	0.05	0.02	0.5
Km factor	3	6	12	8	5	20

Animal A (mg/kg) = Animal B (mg/kg) multiplied by	Animal B Km
	Animal A Km

For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the K_m factor for a mouse and then divide by the K_m factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.

References

[1] Li X, et al. PLoS One. Acetic acid activates the AMP-activated protein kinase signaling pathway to regulate lipid metabolism in bovine hepatocytes.

[2] Duong HQ, et al. Int J Oncol. BML-275, an AMPK inhibitor, induces DNA damage, G2/M arrest and apoptosis in human pancreatic cancer cells.

[3] Vucicevic L, et al. Autophagy. Compound C induces protective autophagy in cancer cells through AMPK inhibition-independent blockade of Akt/mTOR pathway.

[4] Jin J, et al. J Lipid Res. AMPK inhibitor Compound C stimulates ceramide production and promotes Bax redistribution and apoptosis in MCF7 breast carcinoma cells.