- SB525334
- SD-208
- LY2157299
- SB 431542
- RepSox
- A 83-01
| GW788388ALK5 inhibitor,potent and selective |
Sample solution is provided at 25 µL, 10mM.
Nature.2017 Jan 19;541(7637):417-420.
Nature.2018 Nov;563(7731):407-411.Nature.2018 Jun 13.Nature.2018 Jun 27.Nature.2018 Mar 29;555(7698):673-677.Nature.2017 Sep 7;549(7670):96-100.Nature.2016 Apr 21;532(7599):398-401.
Science.2016 Aug 5;353(6299)594-8Nat Nanotechnol.2017 Dec;12(12):1190-1198.Nature Biotechnology.2017 Jun;35(6):569-576Nat Med.2018 Sep 17.Cell.2018 Dec 21. pii: S0092-8674(18)31561-7.Cell.Available online 25 October 2018.Cell.2018 Sep 27. pii: S0092-8674(18)31183-8.Cell.2018 Jun 28;174(1):172-186.e21.Cell.2018 Feb 22;172(5):1007-1021.e17.Cell.2017 Nov 30;171(6):1284-1300.e21.Cell.2017 Aug 17. pii: S0092-8674(17)30869-3.Cell.2017 Jul 13;170(2):312-323Nat Med.2018 Jan 29.Nat Med.2017 Nov;23(11):1342-1351.Cell.2017 Apr 6;169(2):286-300.Cell.2015 Aug 27;162(5):987-1002.Cell.2015 Feb 12;160(4):729-44.Nature Medicine.2017 Apr;23(4):493-500.Cancer Cell.2018 May 14;33(5):905-921.e5.Cancer Cell.2018 Apr 9;33(4):752-769.e8.Cancer Cell.2018 Mar 12;33(3):401-416.e8.Cancer Cell.2017 Aug 14;32(2):253-267.e5.Nat Methods.2018 Jul;15(7):523-526.Cell Stem Cell.2018 May 3;22(5):769-778.e4.Cell Stem Cell.2017 Nov 20. pii: S1934-5909(17)30375-2.Quality Control & MSDS
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- Purity = 98.05%
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- HPLC (Retest)
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- Datasheet
Chemical structure
| Description | GW788388 is a potent and selective inhibitor of ALK5 with an IC50 value of 18 nM. | |||||
| Targets | ALK5 | |||||
| IC50 | 18 nM | |||||
| Cell experiment [1]: | |
Cell lines | NMuMG and MDA-MD-231 cells |
Preparation method | The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20 °C for several months. |
Reaction Conditions | 1, 2.5, 5 or 10 μM; 1 hr |
Applications | In NMuMG and MDA-MD-231 cells, GW788388 dose-dependently inhibited TGF-β-induced Smad2 phosphorylation. In addition, TGF-β-mediated Smad1/5 phosphorylation, which requires ALK5 and TbRII, was also inhibited by GW788388. |
| Animal experiment [1]: | |
Animal models | A db/db mouse model of spontaneous diabetic nephropathy |
Dosage form | 2 mg/kg/day; p.o.; for 5 weeks |
Applications | In a db/db mouse model of spontaneous diabetic nephropathy, GW788388 significantly reduced collagen deposits, substantially improved glomerulopathy (marked by mesangial matrix expansion, mesangial hypertrophy, proliferation, and glomerular basement membrane thickening), as well as decreased urinary albumin concentrations. |
Other notes | Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
References: [1]. Petersen, M., et al., Oral administration of GW788388, an inhibitor of TGF-beta type I and II receptor kinases, decreases renal fibrosis. Kidney Int, 2008. 73(6): p. 705-15. | |
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| Cas No. | 452342-67-5 | SDF | Download SDF |
| Synonyms | N/A | ||
| Chemical Name | N-(oxan-4-yl)-4-[4-(5-pyridin-2-yl-1H-pyrazol-4-yl)pyridin-2-yl]benzamide | ||
| Canonical SMILES | C1COCCC1NC(=O)C2=CC=C(C=C2)C3=NC=CC(=C3)C4=C(NN=C4)C5=CC=CC=N5 | ||
| Formula | C25H23N5O2 | M.Wt | 425.49 |
| Solubility | ≥21.25mg/mL in DMSO | Storage | Store at -20°C |
| Physical Appearance | A solid | Shipping Condition | Evaluation sample solution : ship with blue ice.All other available size:ship with RT , or blue ice upon request |
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. | ||
GW788388 is a selective inhibitor of ALK5 with IC50 value of 18 nM [1].
Transforming growth factor beta (TGF-beta) type I receptor (ALK5) is the receptor of TGF-beta and plays an important role in transducing the TGF-beta signal from the cell surface to the cytoplasm [2 ].
GW788388 is a potent TGF-beta type I receptor inhibitor and has a much improved pharmacokinetic profile compared with the reported TGF-beta type I receptor inhibitor SB431542. When tested with human embryonic kidney 293T cells transfected with ALK5, TβRII, BMPRII or ActRII, GW788388 exhibited specific inhibitory function on the autophosphorylation of ALK5 and TβRII, while had some extent to ActRII and had no effect on BMPRII. Further, using Namrumurine mammary gland (NMuMG), MDA-MB-231, renal cell carcinoma (RCC)4 and U2OS cell lines, GW788388 treatment inhibited TGF-β-induced Smad2 phosphorylation, inhibited TGF-β-induced EMT and growth, and TGF-β-induced fibrotic responses [1]. In ESCC/fibroblast/HMVEC co-culture model, GW788388 treatment (1 μM) resulted in a complete reversal of vascular network formation that indicated GW788388 blocked ESCC-induced neoangiogenesis [3].
In 6-month-old db/db mouse model of spontaneous diabetic nephropathy, administration of GW788388 at the dose of 2 mg/kg/day orally for 5 weeks attenuated renal fibrosis without any side-effect [1]. In 10-week Sprague-Dawley rats model, oral administration of GW788388 (100-1000 mg/kg/day) for 4 days induced the thickness of femoral physis in a dose-dependent manner and severity of physeal changes , as well as subphyseal hyperostosis, increased with duration of dosing progressing from minimal to moderate in rats given 300 mg/kg/day for 10 days [2].
References: [1]. Petersen, M., et al., Oral administration of GW788388, an inhibitor of TGF-beta type I and II receptor kinases, decreases renal fibrosis. Kidney Int, 2008. 73(6): p. 705-15.[2]. Frazier, K., et al., Inhibition of ALK5 signaling induces physeal dysplasia in rats. Toxicol Pathol, 2007. 35(2): p. 284-95.[3]. Noma, K., et al., The essential role of fibroblasts in esophageal squamous cell carcinoma-induced angiogenesis. Gastroenterology, 2008. 134(7): p. 1981-93.
