STO-609 free base
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Hodoodo CAT#: H530469

CAS#: 52029-86-4 (free base)

Description: STO-609 is a specific inhibitor of the Ca(2+)/calmodulin-dependent protein kinase kinase. STO-609 inhibits the activities of recombinant CaM-KK alpha and CaM-KK beta isoforms, with K(i) values of 80 and 15 ng/ml, respectively, and also inhibits their autophosphorylation activities. STO-609 is highly selective for CaM-KK without any significant effect on the downstream CaM kinases (CaM-KI and -IV), and the IC(50) value of the compound against CaM-KII is approximately 10 microg/ml. STO-609 is a selective and cell-permeable inhibitor of CaM-KK and that it may be a useful tool for evaluating the physiological significance of the CaM-KK-mediated pathway in vivo as well as in vitro.


Chemical Structure

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STO-609 free base
CAS# 52029-86-4 (free base)

Theoretical Analysis

Hodoodo Cat#: H530469
Name: STO-609 free base
CAS#: 52029-86-4 (free base)
Chemical Formula: C19H10N2O3
Exact Mass: 314.07
Molecular Weight: 314.300
Elemental Analysis: C, 72.61; H, 3.21; N, 8.91; O, 15.27

Price and Availability

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10mg USD 150 Ready to ship
25mg USD 250 Ready to ship
50mg USD 450 Ready to ship
100mg USD 750 Ready to ship
200mg USD 1250 Ready to ship
500mg USD 2850 Ready to ship
1g USD 3850 Ready to ship
2g USD 6450 Ready to ship
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Related CAS #: 52029-86-4 (free base)   1173022-21-3 (acetate)  

Synonym: STO-609; STO 609; STO609.

IUPAC/Chemical Name: 7-oxo-7H-benzo[de]benzo[4,5]imidazo[2,1-a]isoquinoline-3-carboxylic acid

InChi Key: MYKOWOGZBMOVBJ-UHFFFAOYSA-N

InChi Code: InChI=1S/C19H10N2O3/c22-18-13-5-3-4-10-11(19(23)24)8-9-12(16(10)13)17-20-14-6-1-2-7-15(14)21(17)18/h1-9H,(H,23,24)

SMILES Code: O=C1C2=CC=CC3=C(C(O)=O)C=CC(C4=NC(C=CC=C5)=C5N41)=C32

Appearance: Yellow solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info:

Biological target: STO-609 is a selective and cell-permeable inhibitor of the Ca2+/calmodulin-dependent protein kinase kinase (CaM-KK), with Ki values of 80 and 15 ng/mL for recombinant CaM-KKα and CaM-KKβ, respectively.
In vitro activity: STO-609, a specific cell permeable inhibitor of CaMKK (1 µg/mL) inhibited MRS2957-induced AMPK activation in MIN6 cells (Fig. 5B). Also, CaMKKβ siRNA was used to silence its expression in MIN6 cells. The CaMKKβ gene-silenced MIN6 cells showed decreased AMPK phosphorylation in comparison to wild type MIN6 cells when treated with MRS2957 (Fig. 5C). The results confirmed that P2Y6R-activated AMPK phosphorylation is mediated through the CaMKKβ pathway. Reference: Biochem Pharmacol. 2013 Apr 1; 85(7): 991–998. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3594329/
In vivo activity: In the first model, wild type C57BL/6 J male mice were maintained on HFD for 12 weeks to induce hepatic steatosis followed by daily injection of either DMSO (vehicle) or STO-609S (30 μM/kg) for 4 weeks (Fig. 5A). Macroscopic and histological analyses show that STO-609S treatment markedly improves hepatic steatosis as evidenced by H&E and Oil Red O staining (Fig. 5B). In a second murine model of NAFLD, wild type C57BL/6 J male mice were injected with streptozotocin (STZ) at postnatal day 2 and maintained on HFD for 7 weeks after weaning to induce hepatic steatosis as previously described. Macroscopic and histological analyses show that STO-609 treatment markedly improves hepatic steatosis as evidenced by H&E and Oil Red O staining (Fig. 5D). Prolonged treatment with STO-609S had no effect on body weight (Supplemental Fig. 4A, B), but showed a slight improvement in glycemia (Supplemental Fig. 4A, B), consistent with the acute effect on glycemia (Fig. 3E). Reference: Sci Rep. 2017; 7: 11793. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5603587/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 4.9 15.43

Preparing Stock Solutions

The following data is based on the product molecular weight 314.30 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Balasubramanian R, Maruoka H, Jayasekara PS, Gao ZG, Jacobson KA. AMP-activated protein kinase as regulator of P2Y(6) receptor-induced insulin secretion in mouse pancreatic β-cells. Biochem Pharmacol. 2013 Apr 1;85(7):991-8. doi: 10.1016/j.bcp.2012.11.029. Epub 2013 Jan 17. PMID: 23333427; PMCID: PMC3594329. 2. Ma Z, Wen D, Wang X, Yang L, Liu T, Liu J, Zhu J, Fang X. Growth inhibition of human gastric adenocarcinoma cells in vitro by STO-609 is independent of calcium/calmodulin-dependent protein kinase kinase-beta and adenosine monophosphate-activated protein kinase. Am J Transl Res. 2016 Feb 15;8(2):1164-71. PMID: 27158402; PMCID: PMC4846959. 3. York B, Li F, Lin F, Marcelo KL, Mao J, Dean A, Gonzales N, Gooden D, Maity S, Coarfa C, Putluri N, Means AR. Pharmacological inhibition of CaMKK2 with the selective antagonist STO-609 regresses NAFLD. Sci Rep. 2017 Sep 18;7(1):11793. doi: 10.1038/s41598-017-12139-3. PMID: 28924233; PMCID: PMC5603587.
In vitro protocol: 1. Balasubramanian R, Maruoka H, Jayasekara PS, Gao ZG, Jacobson KA. AMP-activated protein kinase as regulator of P2Y(6) receptor-induced insulin secretion in mouse pancreatic β-cells. Biochem Pharmacol. 2013 Apr 1;85(7):991-8. doi: 10.1016/j.bcp.2012.11.029. Epub 2013 Jan 17. PMID: 23333427; PMCID: PMC3594329. 2. Ma Z, Wen D, Wang X, Yang L, Liu T, Liu J, Zhu J, Fang X. Growth inhibition of human gastric adenocarcinoma cells in vitro by STO-609 is independent of calcium/calmodulin-dependent protein kinase kinase-beta and adenosine monophosphate-activated protein kinase. Am J Transl Res. 2016 Feb 15;8(2):1164-71. PMID: 27158402; PMCID: PMC4846959.
In vivo protocol: 1. York B, Li F, Lin F, Marcelo KL, Mao J, Dean A, Gonzales N, Gooden D, Maity S, Coarfa C, Putluri N, Means AR. Pharmacological inhibition of CaMKK2 with the selective antagonist STO-609 regresses NAFLD. Sci Rep. 2017 Sep 18;7(1):11793. doi: 10.1038/s41598-017-12139-3. PMID: 28924233; PMCID: PMC5603587.

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1: Gerner L, Munack S, Temmerman K, Lawrence-Dörner AM, Besir H, Wilmanns M, Jensen JK, Thiede B, Mills IG, Morth JP. Using the fluorescent properties of STO-609 as a tool to assist structure-function analyses of recombinant CaMKK2. Biochem Biophys Res Commun. 2016 Jul 22;476(2):102-7. doi: 10.1016/j.bbrc.2016.05.045. PubMed PMID: 27178209.

2: Fujiwara Y, Hiraoka Y, Fujimoto T, Kanayama N, Magari M, Tokumitsu H. Analysis of Distinct Roles of CaMKK Isoforms Using STO-609-Resistant Mutants in Living Cells. Biochemistry. 2015 Jun 30;54(25):3969-77. doi: 10.1021/acs.biochem.5b00149. PubMed PMID: 26050738.

3: Ma Z, Wen D, Wang X, Yang L, Liu T, Liu J, Zhu J, Fang X. Growth inhibition of human gastric adenocarcinoma cells in vitro by STO-609 is independent of calcium/calmodulin-dependent protein kinase kinase-beta and adenosine monophosphate-activated protein kinase. Am J Transl Res. 2016 Feb 15;8(2):1164-71. PubMed PMID: 27158402; PubMed Central PMCID: PMC4846959.

4: Kukimoto-Niino M, Yoshikawa S, Takagi T, Ohsawa N, Tomabechi Y, Terada T, Shirouzu M, Suzuki A, Lee S, Yamauchi T, Okada-Iwabu M, Iwabu M, Kadowaki T, Minokoshi Y, Yokoyama S. Crystal structure of the Ca²⁺/calmodulin-dependent protein kinase kinase in complex with the inhibitor STO-609. J Biol Chem. 2011 Jun 24;286(25):22570-9. doi: 10.1074/jbc.M111.251710. PubMed PMID: 21504895; PubMed Central PMCID: PMC3121401.

5: Monteiro P, Gilot D, Langouet S, Fardel O. Activation of the aryl hydrocarbon receptor by the calcium/calmodulin-dependent protein kinase kinase inhibitor 7-oxo-7H-benzimidazo[2,1-a]benz[de]isoquinoline-3-carboxylic acid (STO-609). Drug Metab Dispos. 2008 Dec;36(12):2556-63. doi: 10.1124/dmd.108.023333. PubMed PMID: 18755850.

6: Tokumitsu H, Inuzuka H, Ishikawa Y, Kobayashi R. A single amino acid difference between alpha and beta Ca2+/calmodulin-dependent protein kinase kinase dictates sensitivity to the specific inhibitor, STO-609. J Biol Chem. 2003 Mar 28;278(13):10908-13. PubMed PMID: 12540834.

7: Tokumitsu H, Inuzuka H, Ishikawa Y, Ikeda M, Saji I, Kobayashi R. STO-609, a specific inhibitor of the Ca(2+)/calmodulin-dependent protein kinase kinase. J Biol Chem. 2002 May 3;277(18):15813-8. Erratum in: J Biol Chem. 2003 Feb 7;278(6):4368. PubMed PMID: 11867640.

8: Pritchard ZJ, Cary RL, Yang C, Novack DV, Voor MJ, Sankar U. Inhibition of CaMKK2 reverses age-associated decline in bone mass. Bone. 2015 Jun;75:120-7. doi: 10.1016/j.bone.2015.01.021. PubMed PMID: 25724145; PubMed Central PMCID: PMC4737584.

9: Nguyen TM, Combarnous Y, Praud C, Duittoz A, Blesbois E. Ca2+/Calmodulin-Dependent Protein Kinase Kinases (CaMKKs) Effects on AMP-Activated Protein Kinase (AMPK) Regulation of Chicken Sperm Functions. PLoS One. 2016 Jan 25;11(1):e0147559. doi: 10.1371/journal.pone.0147559. PubMed PMID: 26808520; PubMed Central PMCID: PMC4726612.

10: Nanba K, Chen A, Nishimoto K, Rainey WE. Role of Ca(2+)/calmodulin-dependent protein kinase kinase in adrenal aldosterone production. Endocrinology. 2015 May;156(5):1750-6. doi: 10.1210/en.2014-1782. PubMed PMID: 25679868; PubMed Central PMCID: PMC4398758.

11: Yurimoto S, Fujimoto T, Magari M, Kanayama N, Kobayashi R, Tokumitsu H. In vitro substrate phosphorylation by Ca²⁺/calmodulin-dependent protein kinase kinase using guanosine-5'-triphosphate as a phosphate donor. BMC Biochem. 2012 Dec 5;13:27. doi: 10.1186/1471-2091-13-27. PubMed PMID: 23216827; PubMed Central PMCID: PMC3537517.

12: Tinsley CJ, Narduzzo KE, Brown MW, Warburton EC. A role for the CAMKK pathway in visual object recognition memory. Hippocampus. 2012 Mar;22(3):466-76. doi: 10.1002/hipo.20913. PubMed PMID: 21298728.

13: Thors B, Halldórsson H, Thorgeirsson G. eNOS activation mediated by AMPK after stimulation of endothelial cells with histamine or thrombin is dependent on LKB1. Biochim Biophys Acta. 2011 Feb;1813(2):322-31. doi: 10.1016/j.bbamcr.2010.12.001. PubMed PMID: 21145922.

14: Abbott MJ, Edelman AM, Turcotte LP. CaMKK is an upstream signal of AMP-activated protein kinase in regulation of substrate metabolism in contracting skeletal muscle. Am J Physiol Regul Integr Comp Physiol. 2009 Dec;297(6):R1724-32. doi: 10.1152/ajpregu.00179.2009. PubMed PMID: 19812359.

15: Cary RL, Waddell S, Racioppi L, Long F, Novack DV, Voor MJ, Sankar U. Inhibition of Ca²⁺/calmodulin-dependent protein kinase kinase 2 stimulates osteoblast formation and inhibits osteoclast differentiation. J Bone Miner Res. 2013 Jul;28(7):1599-610. doi: 10.1002/jbmr.1890. PubMed PMID: 23408651; PubMed Central PMCID: PMC3688641.

16: Souza MA, Magni DV, Guerra GP, Oliveira MS, Furian AF, Pereira L, Marquez SV, Ferreira J, Fighera MR, Royes LF. Involvement of hippocampal CAMKII/CREB signaling in the spatial memory retention induced by creatine. Amino Acids. 2012 Dec;43(6):2491-503. doi: 10.1007/s00726-012-1329-4. PubMed PMID: 22669403.

17: Fortin DA, Srivastava T, Dwarakanath D, Pierre P, Nygaard S, Derkach VA, Soderling TR. Brain-derived neurotrophic factor activation of CaM-kinase kinase via transient receptor potential canonical channels induces the translation and synaptic incorporation of GluA1-containing calcium-permeable AMPA receptors. J Neurosci. 2012 Jun 13;32(24):8127-37. doi: 10.1523/JNEUROSCI.6034-11.2012. PubMed PMID: 22699894; PubMed Central PMCID: PMC3390208.

18: Ma Y, Yang F, Wang Y, Du Z, Liu D, Guo H, Shen J, Peng H. CaMKKβ is involved in AMP-activated protein kinase activation by baicalin in LKB1 deficient cell lines. PLoS One. 2012;7(10):e47900. doi: 10.1371/journal.pone.0047900. PubMed PMID: 23110126; PubMed Central PMCID: PMC3478266.

19: Schmitt JM, Abell E, Wagner A, Davare MA. ERK activation and cell growth require CaM kinases in MCF-7 breast cancer cells. Mol Cell Biochem. 2010 Feb;335(1-2):155-71. doi: 10.1007/s11010-009-0252-9. PubMed PMID: 19763792.

20: Jensen TE, Rose AJ, Jørgensen SB, Brandt N, Schjerling P, Wojtaszewski JF, Richter EA. Possible CaMKK-dependent regulation of AMPK phosphorylation and glucose uptake at the onset of mild tetanic skeletal muscle contraction. Am J Physiol Endocrinol Metab. 2007 May;292(5):E1308-17. PubMed PMID: 17213473.