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Chemical Structure| 330161-87-0 Chemical Structure| 330161-87-0

Structure of SU6656
CAS No.: 330161-87-0

Chemical Structure| 330161-87-0

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SU6656 is an inhibitor of Src family kinases with IC50 values of 280, 20, 130, and 170 nM for Src, Yes, Lyn, and Fyn, respectively. It inhibits FAK phosphorylation at Y576/577, Y925, and Y861 sites, as well as p-AKT.

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Product Details of SU6656

CAS No. :330161-87-0
Formula : C19H21N3O3S
M.W : 371.45
SMILES Code : O=S(C1=CC2=C(NC(/C2=C\C(N3)=CC4=C3CCCC4)=O)C=C1)(N(C)C)=O
MDL No. :MFCD10565928
InChI Key :LOGJQOUIVKBFGH-YBEGLDIGSA-N
Pubchem ID :5312137

Safety of SU6656

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Related Pathways of SU6656

RTK
PI3K-AKT
cytoskeleton

Isoform Comparison

Biological Activity

Target
  • Fyn

    Fyn, IC50:170 nM

  • Src

    Src, IC50:280 nM

  • Yes

    YES, IC50:20 nM

  • Lyn

    Lyn, IC50:130 nM

In Vitro:

Cell Line
Concentration Treated Time Description References
A431-III cells 10 µM 24 hours Reduced invasive ability Antioxidants (Basel). 2019 Nov 15;8(11):557
SYF cells 100 µM 1 hour SU6656 still activates AMPK and increases Thr172 phosphorylation in SYF cells lacking Src family kinases Cell Chem Biol. 2017 Jul 20;24(7):813-824. e4
HeLa cells 100 µM 1 hour SU6656 activates AMPK in HeLa cells but does not activate any AMPK-related kinases (ARKs) Cell Chem Biol. 2017 Jul 20;24(7):813-824. e4
HEK293 cells 1-100 µM 1 hour SU6656 activates AMPK and increases Thr172 phosphorylation, along with increased phosphorylation of downstream target ACC but not Raptor Cell Chem Biol. 2017 Jul 20;24(7):813-824. e4
Bt-549 cells 10 µM 1 hour Inhibition of c-Src activity significantly enhanced microtentacle formation Oncogene. 2010 Dec 2;29(48):6402-8
MDA-MB-231 cells 10 µM 1 hour Inhibition of c-Src activity significantly enhanced microtentacle formation while suppressing invadopodia Oncogene. 2010 Dec 2;29(48):6402-8
Pulmonary artery smooth muscle cells (PASMCs) 3 µM and 30 µM 10 min Inhibited hypoxic pulmonary vasoconstriction, particularly the sustained phase Cardiovasc Res. 2008 Dec 1;80(3):453-62
Rat pulmonary artery smooth muscle cells 30 µM 10 minutes Inhibited PGF2α-induced rho-kinase (ROCK-2) translocation Cardiovasc Res. 2008 Feb 1;77(3):570-9
Human macrophages 10 µM 10 minutes Inhibited macropinocytosis but not micropinocytosis Arterioscler Thromb Vasc Biol. 2010 Oct;30(10):2022-31
C2C12 myotubes 10 µM 2 hours To investigate the effect of SU6656 on LKB1 subcellular localization, results showed that SU6656 treatment caused redistribution of LKB1 from the nucleus to the cytoplasm. Cell Metab. 2010 Feb 3;11(2):113-24
E13 rat commissural neurons 0.5, 1, 2 µM 2 hours SU6656 inhibits Netrin-1-induced tyrosine phosphorylation of DCC J Cell Biol. 2004 Nov 22;167(4):687-98.
Rat oligodendrocytes 20 µM 24 hours Inhibited Lyn kinase activity and restored apoptotic signaling in oligodendrocytes Glia. 2010 Nov 15;58(15):1782-93
A431-III cells 1, 5, 10 µM 24 hours Reduced protein levels of S100A7, p-Src, and p-Stat3 Antioxidants (Basel). 2019 Nov 15;8(11):557
Lung cancer cells 5 µM 24, 48, 72 hours Inhibition of Src activity increases FABP4 expression and reduces lipid droplet accumulation EBioMedicine. 2019 Mar;41:134-145
CD34+ HPCs 2.5 µM 4 days Increased megakaryocyte ploidy and size, reduced terminal injury and apoptosis Blood Adv. 2018 Mar 27;2(6):597-606
Endothelial progenitor cells (EPCs) 2 µM 4 hours Inhibited SDF-1-induced migration of EPCs J Mol Cell Cardiol. 2015 Apr;81:49-53
Bone marrow mononuclear cells (BM MNCs) 2 µM 4 hours Inhibited SDF-1-induced migration of BM MNCs J Mol Cell Cardiol. 2015 Apr;81:49-53
Primary hepatocytes from male Wistar rats 15 µM 4 hours To investigate the effect of SU6656 on fasting-induced triglyceride (TG) loss. Results showed that SU6656 significantly blocked fasting-induced TG loss in control hepatocytes but had minimal effect on hepatocytes from ethanol-fed rats, likely due to pre-existing impaired lipophagy. Hepatol Commun. 2017 Aug;1(6):501-512
Human macrophages 20 µM 5 hours Inhibited macrophage macropinocytosis, reducing LDL uptake and cholesterol accumulation by approximately 40% Arterioscler Thromb Vasc Biol. 2010 Oct;30(10):2022-31
Mouse posterior cerebral artery smooth muscle cells 10 µM 50 minutes Inhibition of Src kinases reduced SMC death from H2O2 exposure in PCAs from young males but had no significant effect in old males. Aging Cell. 2024 May;23(5):e14110.
Human pulmonary artery endothelial cells (HPAECs) 3-6 µM 6 hours SU6656 partially attenuated KOdiA-PC–induced NF-κB phosphorylation and ICAM-1 expression, but more complete inhibition was achieved in cells coincubated with L37pA. Am J Respir Cell Mol Biol. 2024 Jan;70(1):11-25

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Sprague-Dawley rats Pressure-natriuresis model Intravenous infusion 10 µmol/kg/min 60 minutes SU6656 inhibited cGMP-induced natriuresis, indicating that Src-family kinase plays an important role in the signaling pathway of cGMP-induced natriuresis. Hypertension. 2011 Jul;58(1):107-13
Balb/c nude mice Lung cancer xenograft model Intraperitoneal injection 20 mg/kg Every other day for 23 days Inhibition of Src activity reduces tumor growth and lipid droplet accumulation EBioMedicine. 2019 Mar;41:134-145
C57BL/6J mice Silicosis model Intraperitoneal injection 3 mg/kg/day Once daily from day 8 to day 28 SU6656 attenuated the activation of the PI3K/AKT pathway by inhibiting the phosphorylation of c-Src, thereby suppressing fibrosis in the silicosis model. Int J Mol Sci. 2023 Jan 1;24(1):774
Rat Isolated pulmonary artery rings In vitro incubation 3 μM and 30 μM Single application, observed for 40-45 minutes Inhibited PGF2α-induced Ca2+-sensitized contraction Cardiovasc Res. 2008 Feb 1;77(3):570-9
Nude mice Subcutaneous xenograft tumor model of A431/H9 or CA46 cells Intraperitoneal injection 300 μg Three doses injected every other day SU6656 combined with SS1P or HA22 showed synergistic antitumor effects in mouse xenograft tumor models Mol Cancer Ther. 2014 Jan;13(1):82-9
C57BLK6/J mice Wild type mice Intraperitoneal injection 4 mg/kg Single injection, monitored for 12 hours To investigate the effect of SU6656 on energy expenditure and fatty acid oxidation, results showed that SU6656 treatment increased energy expenditure and fatty acid oxidation, leading to reduced fat mass. Cell Metab. 2010 Feb 3;11(2):113-24
Mice Myocardial infarction model Intraperitoneal injection 6 mg/kg Single dose Reduced recruitment of BM PCs to ischemic myocardium J Mol Cell Cardiol. 2015 Apr;81:49-53

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.69mL

0.54mL

0.27mL

13.46mL

2.69mL

1.35mL

26.92mL

5.38mL

2.69mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1

References

[1]McCarthy SD, Jung D, et al. c-Src and Pyk2 protein tyrosine kinases play protective roles in early HIV-1 infection of CD4+ T-cell lines. J Acquir Immune Defic Syndr. 2014 Jun 1;66(2):118-26.

[2]Blake RA, Broome MA, et al. SU6656, a selective src family kinase inhibitor, used to probe growth factor signaling. Mol Cell Biol. 2000 Dec;20(23):9018-27.

[3]Iwona Cicha,et al. Dual inhibition of Src family kinases and Aurora kinases by SU6656 modulates CTGF (connective tissue growth factor) expression in an ERK-dependent manner. Int J Biochem Cell Biol. 2014 Jan;46:39-48.

[4] S H Kim,et al. Inhibition of p21 and Akt potentiates SU6656-induced caspase-independent cell death in FRO anaplastic thyroid carcinoma cells. Horm Metab Res. 2013 Jun;45(6):408-14.

[5]Nathalie Dussault,et al. Human B lymphocytes and non-Hodgkin's lymphoma cells become polyploid in response to the protein kinase inhibitor SU6656. Blood Cells Mol Dis. Jul-Aug 2007;39(1):130-4.

[6]Cyril Thouverey,et al. Selective inhibition of Src family kinases by SU6656 increases bone mass by uncoupling bone formation from resorption in mice. Bone. 2018 Aug;113:95-104.

[7]Michelle A Hardyman,et al. TNF-α-mediated bronchial barrier disruption and regulation by src-family kinase activation. J Allergy Clin Immunol.2013 Sep;132(3):665-675.e8.

[8]Kumar A, et al. Pharmacological investigations on possible role of Src kinases in neuroprotective mechanism of ischemic postconditioning in mice. Int J Neurosci. 2014 Oct;124(10):777-86.

 

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