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Purity: ≥98%
SB505124 (SB-505124; SB 505124) is a novel, potent and selective inhibitor of TGFβR (TGF-β Receptor type I receptor) for ALK4, ALK5 (activin receptor-like kinase) with potential antineoplastic activity. It inhibits ALK4 and ALK5 with IC50s of 129 nM and 47 nM in cell-free assays, respectively. SB505124 also inhibits ALK7, but does not inhibit ALK1, 2, 3, or 6 and has potential anticancer activity. 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.
| ln Vitro |
When SB-505124 is applied at concentrations up to 100 μM for 48 hours, renal epithelial A498 cells show no signs of toxicity. At dosages up to 10 μM, 505124 does not inhibit ALK2, but it does inhibit the closely related ALK4 with an IC50 value of 129±11 nM (about 2.5 times less sensitive than ALK5). In all three of these cell lines, TGF-β-induced phosphorylation of Smad2 is inhibited in a concentration-dependent manner by SB-505124 (1 μM). Despite the distinct patterns of activation in these cells, SB-505124 (1 or 5 μM) potently suppresses TGF-β-induced activation of JNK/SAP, extracellular signal-regulated kinase 1/2, and p38[1]. In vitro, SB-505124 (10 μM) inhibits CTGF and α-SMA expression, as well as Smad2 phosphorylation[2]. SB-505124 is shown to upregulate CTGF and α-SMA by immunofluorescence. Explants removed from eyes treated with SB-505124 during GFS exhibit robust cell outgrowth, but those treated with MMC exhibit weak outgrowth[3].
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| ln Vivo |
When administered in combination with a single dose of carboplatin (60 mg/kg), SB-505124 (5 mg/kg; ip) does not provide any impact in C57Bl6 mice bearing A549 xenografts. However, in five of these animals, this combination produces long-lasting responses that do not require maintenance therapy[4].
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| Animal Protocol |
Animal/Disease Models: C57Bl6 mice with A549 xenografts[4]
Doses: 5 mg/kg Route of Administration: Ip; daily Experimental Results: Had no effect alone, but administration with a single dose of carboplatin (60 mg/kg) resulted in durable responses without the need for maintenance therapy in five animals. |
| References |
[1]. DaCosta Byfield S, et al. SB-505124 is a selective inhibitor of transforming growth factor-beta type I receptors ALK4, ALK5, and ALK7. Mol Pharmacol. 2004 Mar;65(3):744-52.
[2]. Sutariya V, et al. Thermoreversible gel for delivery of receptor-like kinase 5 inhibitor SB-505124 for glaucoma filtration surgery. Pharm Dev Technol. 2013 Jul-Aug;18(4):957-62. [3]. Sapitro J, et al. Suppression of transforming growth factor-β effects in rabbit subconjunctival fibroblasts by receptor-like kinase 5 inhibitor. Mol Vis. 2010 Sep 16;16:1880-92. [4]. Marini KD, et al. Inhibition of activin signaling in lung adenocarcinoma increases the therapeutic index of platinum chemotherapy. Sci Transl Med. 2018 Jul 25;10(451). pii: eaat3504. |
| Molecular Formula |
C20H21N3O2
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| Molecular Weight |
335.4
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| CAS # |
694433-59-5
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| Related CAS # |
356559-13-2
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| SMILES |
O1C([H])([H])OC2C([H])=C([H])C(=C([H])C1=2)C1=C(C2=C([H])C([H])=C([H])C(C([H])([H])[H])=N2)N([H])C(C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H])=N1
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| Synonyms |
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.45 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (7.45 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. View More
Solubility in Formulation 3: 30% PEG400+0.5% Tween80+5% propylene glycol:10 mg/mL |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.9815 mL | 14.9076 mL | 29.8151 mL | |
| 5 mM | 0.5963 mL | 2.9815 mL | 5.9630 mL | |
| 10 mM | 0.2982 mL | 1.4908 mL | 2.9815 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
 Docking results of SB-505124 (atom colors) in the ALK-5 ATP-binding pocket.Mol Vis.2010 Sep 16;16:1880-92. |
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Effects of SB-505124 on cell density.Rabbit subconjunctival fibroblasts were incubated with 10 µM of SB-505124 or 0.04% MMC and then with or without TGF-β2 (2 ng/ml) in 12-well plates for 48 h (n=3).The number of cells was counted using a hemocytometer after trypsinization.Mol Vis.2010 Sep 16;16:1880-92. |
Western blotting for phosphorylated Smad2 (pSmad2), CTGF, and α-SMA.Rabbit subconjunctival fibroblasts were incubated with TGF-β2 and various concentrations of SB-505124. SB-505124 effectively reduced the pSmad2 level and the expression of CTGF and α-SMA induced by TGF-β2 in a concentration-dependent fashion.Mol Vis.2010 Sep 16;16:1880-92. |
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