STO-609 free base | CAS#52029-86-4 | CaM-KK inhibitor

MedKoo Cat#: 530469 | Name: STO-609 free base

Description:

WARNING: This product is for research use only, not for human or veterinary use.

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

STO-609 free base

CAS#52029-86-4 (free base)

Theoretical Analysis

MedKoo Cat#: 530469

Name: STO-609 free base

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

Chemical Formula: C19H10N2O3

Exact Mass: 314.0691

Molecular Weight: 314.30

Elemental Analysis: C, 72.61; H, 3.21; N, 8.91; O, 15.27

Price and Availability

Size	Price	Availability
10mg	USD 150.00	Ready to ship
25mg	USD 250.00	Ready to ship
50mg	USD 450.00	Ready to ship
100mg	USD 750.00	Ready to ship
200mg	USD 1,250.00	Ready to ship
500mg	USD 2,850.00	Ready to ship
1g	USD 3,850.00	Ready to ship
2g	USD 6,450.00	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

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#A8T08K14

QC Data

View QC data: current batch, Lot#A8T08K14

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

STO-609 is a CaMKK inhibitor (IC50s = 120 and 40 ng/ml for CaMKKα and CaMKKβ, respectively). It is selective for CaMKKs over CaMKI, CaMKII, CaMKIV, MLCK, PKC, PKA, and p42 MAPK (IC50s = ≥10,000 ng/ml for all).

In vitro activity:

STO-609, a CaMKK inhibitor, blocked MRS2957-induced AMPK activation in MIN6 cells. Silencing the CaMKKβ gene in MIN6 cells also reduced AMPK phosphorylation when treated with MRS2957, confirming that P2Y6R activates AMPK via the CaMKKβ pathway. Reference: Biochem Pharmacol. 2013 Apr 1; 85(7): 991–998. https://pubmed.ncbi.nlm.nih.gov/23333427/

In vivo activity:

STO-609 treatment to inhibit CaMKK2 function confers protection against non-alcoholic fatty liver disease. In a murine model, STO-609S treatment significantly improved hepatic steatosis. Prolonged STO-609S treatment had no effect on body weight but slightly improved glycemia, which is consistent with its acute effects. Reference: Sci Rep. 2017; 7: 11793. https://pubmed.ncbi.nlm.nih.gov/28924233/

	Solvent	mg/mL	mM
Solubility
	DMSO	4.9	15.43

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

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.

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. 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. 2. 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. 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:

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.

1: 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. doi: 10.1074/jbc.M201075200. Epub 2002 Feb 26. Erratum in: J Biol Chem. 2003 Feb 7;278(6):4368. PMID: 11867640. 2: 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. doi: 10.1074/jbc.M213183200. Epub 2003 Jan 22. PMID: 12540834. 3: Ishikawa Y, Tokumitsu H, Inuzuka H, Murata-Hori M, Hosoya H, Kobayashi R. Identification and characterization of novel components of a Ca2+/calmodulin- dependent protein kinase cascade in HeLa cells. FEBS Lett. 2003 Aug 28;550(1-3):57-63. doi: 10.1016/s0014-5793(03)00817-2. PMID: 12935886. 4: Wayman GA, Kaech S, Grant WF, Davare M, Impey S, Tokumitsu H, Nozaki N, Banker G, Soderling TR. Regulation of axonal extension and growth cone motility by calmodulin-dependent protein kinase I. J Neurosci. 2004 Apr 14;24(15):3786-94. doi: 10.1523/JNEUROSCI.3294-03.2004. PMID: 15084659; PMCID: PMC6729350. 5: Schmitt JM, Wayman GA, Nozaki N, Soderling TR. Calcium activation of ERK mediated by calmodulin kinase I. J Biol Chem. 2004 Jun 4;279(23):24064-72. doi: 10.1074/jbc.M401501200. Epub 2004 Mar 29. PMID: 15150258. 6: Schmitt JM, Guire ES, Saneyoshi T, Soderling TR. Calmodulin-dependent kinase kinase/calmodulin kinase I activity gates extracellular-regulated kinase- dependent long-term potentiation. J Neurosci. 2005 Feb 2;25(5):1281-90. doi: 10.1523/JNEUROSCI.4086-04.2005. PMID: 15689566; PMCID: PMC6725957. 7: Kupzig S, Walker SA, Cullen PJ. The frequencies of calcium oscillations are optimized for efficient calcium-mediated activation of Ras and the ERK/MAPK cascade. Proc Natl Acad Sci U S A. 2005 May 24;102(21):7577-82. doi: 10.1073/pnas.0409611102. Epub 2005 May 12. PMID: 15890781; PMCID: PMC1103707. 8: Hurley RL, Anderson KA, Franzone JM, Kemp BE, Means AR, Witters LA. The Ca2+/calmodulin-dependent protein kinase kinases are AMP-activated protein kinase kinases. J Biol Chem. 2005 Aug 12;280(32):29060-6. doi: 10.1074/jbc.M503824200. Epub 2005 Jun 24. PMID: 15980064. 9: Hawley SA, Pan DA, Mustard KJ, Ross L, Bain J, Edelman AM, Frenguelli BG, Hardie DG. Calmodulin-dependent protein kinase kinase-beta is an alternative upstream kinase for AMP-activated protein kinase. Cell Metab. 2005 Jul;2(1):9-19. doi: 10.1016/j.cmet.2005.05.009. PMID: 16054095. 10: Woods A, Dickerson K, Heath R, Hong SP, Momcilovic M, Johnstone SR, Carlson M, Carling D. Ca2+/calmodulin-dependent protein kinase kinase-beta acts upstream of AMP-activated protein kinase in mammalian cells. Cell Metab. 2005 Jul;2(1):21-33. doi: 10.1016/j.cmet.2005.06.005. PMID: 16054096. 11: Tamás P, Hawley SA, Clarke RG, Mustard KJ, Green K, Hardie DG, Cantrell DA. Regulation of the energy sensor AMP-activated protein kinase by antigen receptor and Ca2+ in T lymphocytes. J Exp Med. 2006 Jul 10;203(7):1665-70. doi: 10.1084/jem.20052469. Epub 2006 Jul 3. PMID: 16818670; PMCID: PMC2118355. 12: Stahmann N, Woods A, Carling D, Heller R. Thrombin activates AMP-activated protein kinase in endothelial cells via a pathway involving Ca2+/calmodulin- dependent protein kinase kinase beta. Mol Cell Biol. 2006 Aug;26(16):5933-45. doi: 10.1128/MCB.00383-06. PMID: 16880506; PMCID: PMC1592798. 13: 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. doi: 10.1152/ajpendo.00456.2006. Epub 2007 Jan 9. PMID: 17213473. 14: Reihill JA, Ewart MA, Hardie DG, Salt IP. AMP-activated protein kinase mediates VEGF-stimulated endothelial NO production. Biochem Biophys Res Commun. 2007 Mar 23;354(4):1084-8. doi: 10.1016/j.bbrc.2007.01.110. Epub 2007 Jan 29. PMID: 17276402; PMCID: PMC1828119. 15: Witczak CA, Fujii N, Hirshman MF, Goodyear LJ. Ca2+/calmodulin-dependent protein kinase kinase-alpha regulates skeletal muscle glucose uptake independent of AMP-activated protein kinase and Akt activation. Diabetes. 2007 May;56(5):1403-9. doi: 10.2337/db06-1230. Epub 2007 Feb 7. PMID: 17287469. 16: Jensen TE, Rose AJ, Hellsten Y, Wojtaszewski JF, Richter EA. Caffeine- induced Ca(2+) release increases AMPK-dependent glucose uptake in rodent soleus muscle. Am J Physiol Endocrinol Metab. 2007 Jul;293(1):E286-92. doi: 10.1152/ajpendo.00693.2006. Epub 2007 Apr 3. PMID: 17405829. 17: Weigert C, Düfer M, Simon P, Debre E, Runge H, Brodbeck K, Häring HU, Schleicher ED. Upregulation of IL-6 mRNA by IL-6 in skeletal muscle cells: role of IL-6 mRNA stabilization and Ca2+-dependent mechanisms. Am J Physiol Cell Physiol. 2007 Sep;293(3):C1139-47. doi: 10.1152/ajpcell.00142.2007. Epub 2007 Jul 5. PMID: 17615159. 18: Kamata A, Sakagami H, Tokumitsu H, Sanda M, Owada Y, Fukunaga K, Kondo H. Distinct developmental expression of two isoforms of Ca2+/calmodulin-dependent protein kinase kinases and their involvement in hippocampal dendritic formation. Neurosci Lett. 2007 Aug 16;423(2):143-8. doi: 10.1016/j.neulet.2007.07.003. Epub 2007 Jul 31. PMID: 17669591. 19: Shen QW, Zhu MJ, Tong J, Ren J, Du M. Ca2+/calmodulin-dependent protein kinase kinase is involved in AMP-activated protein kinase activation by alpha- lipoic acid in C2C12 myotubes. Am J Physiol Cell Physiol. 2007 Oct;293(4):C1395-403. doi: 10.1152/ajpcell.00115.2007. Epub 2007 Aug 8. PMID: 17687000. 20: Cheng PY, Lee YM, Law KK, Lin CW, Yen MH. The involvement of AMP-activated protein kinases in the anti-inflammatory effect of nicotine in vivo and in vitro. Biochem Pharmacol. 2007 Dec 15;74(12):1758-65. doi: 10.1016/j.bcp.2007.08.004. Epub 2007 Aug 9. PMID: 17869227.