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SB-505124 HCl, the hydrochloride salt of SB505124, is a selective inhibitor of TGFβR (TGF-β Receptor type I receptor) for ALK4, ALK5 (activin receptor-like kinase) with potential anticancer activity.
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| ln Vitro |
At concentrations up to 100 μM for 48 hours, SB-505124 shows no toxicity to renal epithelial A498 cells. With an IC50 value of 129±11 nM, which is approximately 2.5 times less sensitive than ALK5, 505124 inhibits the closely related ALK4, but not ALK2, even at concentrations up to 10 μM. In all three of these cell lines, SB-505124 (1 μM) inhibits the TGF-β-induced phosphorylation of Smad2 in a concentration-dependent manner. Even though these cells exhibit distinct patterns of activation, SB-505124 (1 or 5 μM) effectively suppresses TGF-β-induced activation of JNK/SAP, extracellular signal-regulated kinase 1/2, and p38[1]. In vitro, SB-505124 (10 µM) inhibits the phosphorylation of Smad2, as well as the expression of CTGF and α-SMA. By using immunofluorescence, SB-505124 is able to suppress CTGF and α-SMA. While cell outgrowth is poor from eyes treated with MMC, it is robust from explants dissected from eyes to which SB-505124 is applied during GFS[3].
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| ln Vivo |
In C57Bl6 mice bearing A549 xenografts, SB-505124 (5 mg/kg; i.p.) by itself showed no impact; however, when combined with a single carboplatin dose (60 mg/kg), SB-505124 caused long-lasting responses in five species, eliminating the need for 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: intraperitoneal (ip) injection; Daily Experimental Results: No effect alone, but a single dose of carboplatin (60 mg/kg) gave The drug produced durable responses in 5 animals, requiring no maintenance treatment. |
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| 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 |
C20H22CLN3O2
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|---|---|
| Molecular Weight |
371.860583782196
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| CAS # |
356559-13-2
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| Related CAS # |
SB-505124;694433-59-5
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| SMILES |
Cl.O1COC2=CC=C(C=C12)C1=C(C2C=CC=C(C)N=2)NC(C(C)(C)C)=N1
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| 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) |
MEthanol : ~125 mg/mL (~336.15 mM)
DMSO : ~50 mg/mL (~134.46 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.72 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 (6.72 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6892 mL | 13.4459 mL | 26.8918 mL | |
| 5 mM | 0.5378 mL | 2.6892 mL | 5.3784 mL | |
| 10 mM | 0.2689 mL | 1.3446 mL | 2.6892 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.
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