SB505124

SB505124 is a selective inhibitor of transforming growth factor-β type I receptor (ALK5, ALK4 and ALK7) with potential anticancer activity. SB505124 selectively inhibits signaling from TGF-β and activin; does not inhibit other ALK family members. SB-505124 selectively and concentration-dependently inhibits ALK4-, ALK5-, and ALK 7-dependent activation of downstream cytoplasmic signal transducers, Smad2 and Smad3, and of TGF-beta-induced mitogen-activated protein kinase pathway components but does not alter ALK1, ALK2, ALK3 or ALK6-induced Smad signaling.

Product information

CAS Number: 694433-59-5

Molecular Weight: 335.40

Formula: C20H21N3O2

Synonym:

SB-505124

SB505124

SB 505124

Chemical Name: 2-(4-(benzo[d][1,3]dioxol-5-yl)-2-(tert-butyl)-1H-imidazol-5-yl)-6-methylpyridine

Smiles: CC1=CC=CC(=N1)C1NC(=NC=1C1=CC=C2OCOC2=C1)C(C)(C)C

InChiKey: WGZOTBUYUFBEPZ-UHFFFAOYSA-N

InChi: InChI=1S/C20H21N3O2/c1-12-6-5-7-14(21-12)18-17(22-19(23-18)20(2,3)4)13-8-9-15-16(10-13)25-11-24-15/h5-10H,11H2,1-4H3,(H,22,23)

Technical Data

Appearance: Solid Power.

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

Solubility: Soluble in DMSO, not in water

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

SB505124 demonstrates no toxicity to renal epithelial A498 cells at concentrations up to 100 μM for 48 h. 505124 inhibits the closely related ALK4 with an IC50 value of 129±11 nM (about 2.5-fold less sensitive than ALK5) but does not inhibit ALK2 at concentrations up to 10 μM. SB505124 (1 μM) inhibits the TGF-β-induced phosphorylation of Smad2 in all three of these cell lines in a concentration-dependent fashion. SB505124 (1 or 5 μM) potently inhibits TGF-β-induced activation of JNK/SAP, extracellular signal-regulated kinase 1/2, and p38 despite the different patterns of activation in these cells. SB505124 (10 µM) impairs Smad2 phosphorylation and CTGF and α-SMA expression in vitro. SB505124 susspresses CTGF and α-SMA observed by immunofluorescence. Cell outgrowth from explants dissected from eyes to which SB505124 is applied during GFS is robust while outgrowth is poor from those treated with MMC.

In Vivo:

SB505124 (5 mg/kg; i.p.) alone has no effect in C57Bl6 mice with A549 xenografts, but administration of SB-505124 with a single dose of Carboplatin (60 mg/kg) results in durable responses without the need for maintenance therapy in five animals.

References:

1. Onai T, Takai A, Setiamarga DH, Holland LZ. Essential role of Dkk3 for head formation by inhibiting Wnt/β-catenin and Nodal/Vg1 signaling pathways in the basal chordate amphioxus. Evol Dev. 2012 Jul;14(4):338-50. doi: 10.1111/j.1525-142X.2012.00552.x. PubMed PMID: 22765205.
2. Joseph C, Hunter MG, Sinclair KD, Robinson RS. The expression, regulation and function of secreted protein, acidic, cysteine-rich in the follicle-luteal transition. Reproduction. 2012 Sep;144(3):361-72. doi: 10.1530/REP-12-0099. Epub 2012 Jun 25. PubMed PMID: 22733805.
3. Kocic J, Bugarski D, Santibanez JF. SMAD3 is essential for transforming growth factor-β1-induced urokinase type plasminogen activator expression and migration in transformed keratinocytes. Eur J Cancer. 2012 Jul;48(10):1550-7. doi: 10.1016/j.ejca.2011.06.043. Epub 2011 Jul 26. PubMed PMID: 21798735.

Products are for research use only. Not for human use.