MST3

MST3 (STK24) is a serine/threonine kinase in the germinal-center kinase III family, with an N-terminal kinase domain and C-terminal regulatory domain^[1]. Mechanistically, caspase cleavage activates MST3 kinase activity, promotes nuclear translocation, and induces apoptotic morphology in Jurkat-cell apoptosis models^[2]. MST3 also phosphorylates NDR1/2 at hydrophobic-motif sites and supports G1/S cell-cycle progression through the NDR-p21 axis^[3]^[4]. In neural models, MST3 phosphorylates TAO1/2 to enable Myosin Va-dependent dendritic localization and excitatory synapse development^[5]. Cdk5-dependent MST3 phosphorylation regulates neuronal migration by inhibiting RhoA activity^[6]. In immune-cell models, the CCM3-STK24 complex coordinates UNC13D-driven vesicle exocytosis in neutrophils^[7]. Compared with related isoforms, MST3/STK24 differs from MST1/2 in experimental inhibitor response, because MST3/4-selective inhibition causes G1 arrest, whereas MST1/2 inhibition causes G2/M accumulation^[8]. For experimental applications, MR24 and MR30 provide selective MST3/4 chemical tools for dissecting MST3-dependent cell-cycle biology^[8].- MST3 connects apoptosis, cell-cycle control, neuronal migration, synapse development, and neutrophil exocytosis.- MST3 differs from MST1/2 through distinct inhibitor-driven cell-cycle arrest phenotypes.- MST3/4 inhibitors support pathway dissection, but disease-translation claims require model-specific validation.

References:

[1]. Schinkmann K, et al. Cloning and characterization of a human STE20-like protein kinase with unusual cofactor requirements. J Biol Chem. 1997 Nov 7;272(45):28695-703. [Content Brief]

[2]. Huang CY, et al. Caspase activation of mammalian sterile 20-like kinase 3 (Mst3). Nuclear translocation and induction of apoptosis. J Biol Chem. 2002 Sep 13;277(37):34367-74. [Content Brief]

[3]. Hromatka BS, et al. Transcriptional response of Candida albicans to nitric oxide and the role of the YHB1 gene in nitrosative stress and virulence. Mol Biol Cell. 2005 Oct;16(10):4814-26. [Content Brief]

[4]. Cornils H, et al. Human NDR kinases control G(1)/S cell cycle transition by directly regulating p21 stability. Mol Cell Biol. 2011 Apr;31(7):1382-95. [Content Brief]

[5]. Ultanir SK, et al. MST3 kinase phosphorylates TAO1/2 to enable Myosin Va function in promoting spine synapse development. Neuron. 2014 Dec 3;84(5):968-82. [Content Brief]

[6]. Tang J, et al. Cdk5-dependent Mst3 phosphorylation and activity regulate neuronal migration through RhoA inhibition. J Neurosci. 2014 May 28;34(22):7425-36. [Content Brief]

[7]. Zhang Y, et al. A network of interactions enables CCM3 and STK24 to coordinate UNC13D-driven vesicle exocytosis in neutrophils. Dev Cell. 2013 Oct 28;27(2):215-226. [Content Brief]

[8]. Rak M, et al. Development of Selective Pyrido[2,3-d]pyrimidin-7(8H)-one-Based Mammalian STE20-Like (MST3/4) Kinase Inhibitors. J Med Chem. 2024 Mar 14;67(5):3813-3842. [Content Brief]

MST3 Inhibitors (4)

MST3 Related Products (4):

By Type:	Selective (4)

Cat. No.	Product Name	Effect	Purity

HY-164595

IHMT-MST1-39	Inhibitor	99.68%
IHMT-MST1-39 is an orally active inhibitor for MST kinase, with IC₅₀ of 42, 109, 286, 159 nM for MST1, MST2, MST3, MST4. IHMT-MST1-39 activates the AMPK signaling pathway in liver cells, reduces apoptosis of pancreatic β-cells. IHMT-MST1-39 can be used for the studies of type 1 diabetes (T1D) and type 2 diabetes (T2D).

HY-157932A

MR24 TFA	Inhibitor	99.13%
MR24 TFA, a G-5555 (HY-19635) derivative, is a mammalian STE20-like (MST) kinase inhibitor. MR24 TFA shows selectively to MST3/4 over MST1/2, with EC₅₀ values of 57 and 583 nM, respectively. MR24 TFA induces G1 phase cell cycle arrest. MR24 TFA can be used for cancer research, such as breast, liver and lung cancers.

HY-114804

BRD2577	Inhibitor
BRD2577 is a selective mercaptopyruvate sulfurtransferase (3-MST) inhibitor with an IC₅₀ of 9.9 μM. BRD2577 inhibits H₂S production in colon carcinoma cells. BRD2577 exhibits weak to no significant inhibitory effect on colon cancer cell proliferation and mitochondrial activity. BRD2577 can be used for the research of colon cancer.

HY-157932

MR24	Inhibitor
MR24, a G-5555 (HY-19635) derivative, is a mammalian STE20-like (MST) kinase inhibitor. MR24 shows selectively to MST3/4 over MST1/2, with EC₅₀ values of 57 and 583 nM, respectively. MR24 induces G1 phase cell cycle arrest. MR24 can be used for cancer research, such as breast, liver and lung cancers.

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