SB525334 | CAS#356559-20-1 | ALK5 inhibitor | TGF-βRI inhibitor

MedKoo Cat#: 406415 | Name: SB525334

Description:

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

SB525334 is a potent and selective inhibitor of the transforming growth factor-beta1 (TGF-beta1) receptor, activin receptor-like kinase (ALK5). SB525334 inhibited ALK5 kinase activity with an IC(50) of 14.3 nM and was approximately 4-fold less potent as an inhibitor of ALK4 (IC(50) = 58.5 nM). SB-525334 was inactive as an inhibitor of ALK2, ALK3, and ALK6 (IC(50) > 10,000 nM). In cell-based assays, SB-525334 (1 microM) blocked TGF-beta1-induced phosphorylation and nuclear translocation of Smad2/3 in renal proximal tubule cells and inhibited TGF-beta1-induced increases in plasminogen activator inhibitor-1 (PAI-1) and procollagen alpha1(I) mRNA expression in A498 renal epithelial carcinoma cells.

Chemical Structure

SB525334

CAS#356559-20-1

Theoretical Analysis

MedKoo Cat#: 406415

Name: SB525334

CAS#: 356559-20-1

Chemical Formula: C21H21N5

Exact Mass: 343.1797

Molecular Weight: 343.42

Elemental Analysis: C, 73.44; H, 6.16; N, 20.39

Price and Availability

Size	Price	Availability
10mg	USD 110.00	Ready to ship
25mg	USD 220.00	Ready to ship
50mg	USD 385.00	Ready to ship
100mg	USD 650.00	Ready to ship
200mg	USD 1,050.00	Ready to ship
500mg	USD 2,250.00	Ready to ship
1g	USD 3,850.00	Ready to ship

Bulk Inquiry

Buy Now

Add to Cart

Related CAS #

No Data

Synonym

SB525334; SB-525334; SB 525334

IUPAC/Chemical Name

6-(2-(tert-butyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoxaline

InChi Key

DKPQHFZUICCZHF-UHFFFAOYSA-N

InChi Code

InChI=1S/C21H21N5/c1-13-6-5-7-16(24-13)19-18(25-20(26-19)21(2,3)4)14-8-9-15-17(12-14)23-11-10-22-15/h5-12H,1-4H3,(H,25,26)

SMILES Code

CC1=CC=CC(C2=C(C3=CC=C4N=CC=NC4=C3)N=C(C(C)(C)C)N2)=N1

Appearance

Yellow to orange 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, not in water

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#A23T03K02

View CoA: current batch, Lot#A21T04K07

QC Data

View QC data: current batch, Lot#A21T04K07

View QC data: current batch, Lot#A23T03K02

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

SB 525334 is a potent and selective transforming growth factor β1 receptor (ALK5) inhibitor with an IC50 of 14.3 nM.

In vitro activity:

The potent and selective ALK5 kinase inhibitor, SB52533413 was used to assess the contribution of ALK5 in mediating the abnormal TGF-β1 responses observed in familial iPAH PASMCs. Significantly, the TGF-β1-mediated proliferation of familial iPAH PASMCs is abolished by pre-incubation of cells with a potent ALK5 kinase inhibitor, SB525334 implying that ALK5 transduces the abnormal pro-proliferative signal after ligand addition to these cells in vitro (Figure 3). Consistent with previously published data,13 SB525334 inhibited TGF-β1-mediated proliferation of familial iPAH PASMCs at an IC50 of 295 nmol/L (data not shown). Reference: Am J Pathol. 2009 Feb;174(2):380-9. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19116361/

In vivo activity:

A rat MCT model of pulmonary hypertension was used to determine the effects of therapeutic ALK5 inhibition using SB525334 on the development and progression of PAH pathologies in vivo. Previous optimization studies in rats had provided a model, which, after subcutaneous injection of MCT, established hypertensive pathologies by day 17, which became progressively worse, peaking at days 28 to 35 (data not shown). RV pressure rose from 25 to 64 mmHg by day 17, at which point ALK5 was inhibited via oral dosing of SB525334. Vehicle-treated animals continued to worsen, with a mean RV pressure of 92 mmHg attained by day 35. This deterioration was abrogated by treatment with 3 mg/kg of SB525334 (62 mmHg), with a trend toward reversal observed in 30 mg/kg treated animals (53 mmHg) (Figure 6A). The progression of RV hypertrophy measured by the Fulton index (RV/LV + S) was more pronounced beyond day 17. Treatment of animals with SB525334 significantly inhibited RV hypertrophy as the Fulton index ratio was reduced from 0.45 in vehicle-treated animals compared with 0.37 in 30 mg/kg SB525334-treated animals (Figure 6B). Reference: Am J Pathol. 2009 Feb;174(2):380-9. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19116361/

	Solvent	mg/mL	mM
Solubility
	DMSO	30.0	87.36

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 343.42 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:

In vitro protocol:

1. Thomas M, Docx C, Holmes AM, Beach S, Duggan N, England K, Leblanc C, Lebret C, Schindler F, Raza F, Walker C, Crosby A, Davies RJ, Morrell NW, Budd DC. Activin-like kinase 5 (ALK5) mediates abnormal proliferation of vascular smooth muscle cells from patients with familial pulmonary arterial hypertension and is involved in the progression of experimental pulmonary arterial hypertension induced by monocrotaline. Am J Pathol. 2009 Feb;174(2):380-9. doi: 10.2353/ajpath.2009.080565. Epub 2008 Dec 30. PMID: 19116361; PMCID: PMC2630548. 2. Grygielko ET, Martin WM, Tweed C, Thornton P, Harling J, Brooks DP, Laping NJ. Inhibition of gene markers of fibrosis with a novel inhibitor of transforming growth factor-beta type I receptor kinase in puromycin-induced nephritis. J Pharmacol Exp Ther. 2005 Jun;313(3):943-51. doi: 10.1124/jpet.104.082099. Epub 2005 Mar 15. PMID: 15769863.

In vivo protocol:

1. Thomas M, Docx C, Holmes AM, Beach S, Duggan N, England K, Leblanc C, Lebret C, Schindler F, Raza F, Walker C, Crosby A, Davies RJ, Morrell NW, Budd DC. Activin-like kinase 5 (ALK5) mediates abnormal proliferation of vascular smooth muscle cells from patients with familial pulmonary arterial hypertension and is involved in the progression of experimental pulmonary arterial hypertension induced by monocrotaline. Am J Pathol. 2009 Feb;174(2):380-9. doi: 10.2353/ajpath.2009.080565. Epub 2008 Dec 30. PMID: 19116361; PMCID: PMC2630548. 2. Laping NJ, Everitt JI, Frazier KS, Burgert M, Portis MJ, Cadacio C, Gold LI, Walker CL. Tumor-specific efficacy of transforming growth factor-beta RI inhibition in Eker rats. Clin Cancer Res. 2007 May 15;13(10):3087-99. doi: 10.1158/1078-0432.CCR-06-1811. PMID: 17505012.

1: Ramdas V, McBride M, Denby L, Baker AH. Canonical Transforming Growth Factor-β Signaling Regulates Disintegrin Metalloprotease Expression in Experimental Renal Fibrosis via miR-29. Am J Pathol. 2013 Dec;183(6):1885-96. doi: 10.1016/j.ajpath.2013.08.027. Epub 2013 Oct 6. PubMed PMID: 24103556. 2: Ying WZ, Aaron KJ, Sanders PW. Transforming growth factor-β regulates endothelial function during high salt intake in rats. Hypertension. 2013 Nov;62(5):951-6. doi: 10.1161/HYPERTENSIONAHA.113.01835. Epub 2013 Sep 16. PubMed PMID: 24041947. 3: Walshe TE, dela Paz NG, D'Amore PA. The role of shear-induced transforming growth factor-β signaling in the endothelium. Arterioscler Thromb Vasc Biol. 2013 Nov;33(11):2608-17. doi: 10.1161/ATVBAHA.113.302161. Epub 2013 Aug 22. PubMed PMID: 23968981. 4: Peng R, Sridhar S, Tyagi G, Phillips JE, Garrido R, Harris P, Burns L, Renteria L, Woods J, Chen L, Allard J, Ravindran P, Bitter H, Liang Z, Hogaboam CM, Kitson C, Budd DC, Fine JS, Bauer CM, Stevenson CS. Bleomycin induces molecular changes directly relevant to idiopathic pulmonary fibrosis: a model for "active" disease. PLoS One. 2013;8(4):e59348. doi: 10.1371/journal.pone.0059348. Epub 2013 Apr 2. PubMed PMID: 23565148; PubMed Central PMCID: PMC3614979. 5: Kim YJ, Hwang JS, Hong YB, Bae I, Seong YS. Transforming growth factor beta receptor I inhibitor sensitizes drug-resistant pancreatic cancer cells to gemcitabine. Anticancer Res. 2012 Mar;32(3):799-806. PubMed PMID: 22399597; PubMed Central PMCID: PMC3508670. 6: Le Roux-Goglin E, Varon C, Spuul P, Asencio C, MÃ©graud F, GÃ©not E. Helicobacter infection induces podosome assembly in primary hepatocytes in vitro. Eur J Cell Biol. 2012 Mar;91(3):161-70. doi: 10.1016/j.ejcb.2011.11.003. Epub 2012 Feb 3. PubMed PMID: 22306377. 7: Thomas M, Docx C, Holmes AM, Beach S, Duggan N, England K, Leblanc C, Lebret C, Schindler F, Raza F, Walker C, Crosby A, Davies RJ, Morrell NW, Budd DC. Activin-like kinase 5 (ALK5) mediates abnormal proliferation of vascular smooth muscle cells from patients with familial pulmonary arterial hypertension and is involved in the progression of experimental pulmonary arterial hypertension induced by monocrotaline. Am J Pathol. 2009 Feb;174(2):380-9. doi: 10.2353/ajpath.2009.080565. Epub 2008 Dec 30. PubMed PMID: 19116361; PubMed Central PMCID: PMC2630548. 8: Laping NJ, Everitt JI, Frazier KS, Burgert M, Portis MJ, Cadacio C, Gold LI, Walker CL. Tumor-specific efficacy of transforming growth factor-beta RI inhibition in Eker rats. Clin Cancer Res. 2007 May 15;13(10):3087-99. PubMed PMID: 17505012. 9: Higashiyama H, Yoshimoto D, Kaise T, Matsubara S, Fujiwara M, Kikkawa H, Asano S, Kinoshita M. Inhibition of activin receptor-like kinase 5 attenuates bleomycin-induced pulmonary fibrosis. Exp Mol Pathol. 2007 Aug;83(1):39-46. Epub 2006 Dec 24. PubMed PMID: 17274978. 10: Grygielko ET, Martin WM, Tweed C, Thornton P, Harling J, Brooks DP, Laping NJ. Inhibition of gene markers of fibrosis with a novel inhibitor of transforming growth factor-beta type I receptor kinase in puromycin-induced nephritis. J Pharmacol Exp Ther. 2005 Jun;313(3):943-51. Epub 2005 Mar 15. PubMed PMID: 15769863.