| Identification | Back Directory | [Name]
4-({4-[(2,6-dimethylpyridin-3-yl)oxy]pyridin-2-yl}amino)benzenesulfonamide | [CAS]
1117684-36-2 | [Synonyms]
AZ12799734
4-({4-[(2,6-dimethylpyridin-3-yl)oxy]pyridin-2-yl}amino)benzenesulfonamide
Benzenesulfonamide, 4-[[4-[(2,6-dimethyl-3-pyridinyl)oxy]-2-pyridinyl]amino]- | [Molecular Formula]
C18H18N4O3S | [MDL Number]
MFCD26397939 | [MOL File]
1117684-36-2.mol | [Molecular Weight]
370.43 |
| Hazard Information | Back Directory | [Uses]
AZ12799734 is a selective, orally active TGFBR1 kinase inhibitor with an IC50 of 47 nM. AZ12799734 is also a pan BMP and TGFβ inhibitor[1]. | [Biochem/physiol Actions]
AZ12799734 is an orally active TGF-β type I receptors active site inhibitor (ALK1/2/3/4/5/6 Kd = 7.1/6.2/40/1/0.74/0.017 μM) that inhibits ALK5-dependent Smad2 nuclear translocation upon TGF-β1 stimulation (IC50 = 17 nM; MDA-MB-468), as well as ALK1/2/3/6-mediated Smad1 and ALK4/5/7-mediated Smad2 phosphorylation (10 μM; NIH3T3 expressing respective constitutively active receptors). AZ12799734 oral administration in rats results in heart valve lesions (200 mg/kg/day for 5 days) and physeal dysplasia (400 mg/kg/day for 6 days), consistent with a critical role of ALK5 in maintaining the integrity of heart valve and physis. | [in vivo]
AZ12799734 (0-400 mg/kg/day; p.o.; 3-7 days) induces histopathologic heart valve lesions in rat[2].
AZ12799734 (50 mg/kg; p.o.; once) shows total and free pharmacokinetic (PK) levels in the nude mouse with time over in vitro IC50 of 0.01885 μM[1]. | Animal Model: | Ten-week-old female HsdHan:WIST rats[2] | | Dosage: | 200 and 400 mg/kg/day | | Administration: | Oral, 3-7 days | | Result: | Hemorrhage into the heart valves was evident at low magnification and the normal architecture of the leaflet was replaced by hemorrhage.
Increased valvular interstitial cells in size and number and shows increased cytoplasm, an enlarged round to spindeloid nucleus, and frequently undergoing mitosis.
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| Animal Model: | Female BALB/c mice[1] | | Dosage: | 50 mg/kg | | Administration: | Oral administration (Pharmacokinetic Analysis) | | Result: | Showed total and free pharmacokinetic (PK) levels with time over in vitro IC50 of 0.01885 μM. |
| [IC 50]
TGFBR1: 47 nM (IC50); ALK6: 0.017 μM (Kd); ALK5: 0.74 μM (Kd); ALK4: 1 μM (Kd); ACVR1: 6.2 μM (Kd); ALK1: 7.1 μM (Kd); BMPR1A: 40 μM (Kd); BMP | [storage]
Store at -20°C | [References]
[1] Spender LC, et al. Preclinical Evaluation of AZ12601011 and AZ12799734, Inhibitors of Transforming Growth Factor β Superfamily Type 1 Receptors. Mol Pharmacol. 2019 Feb;95(2):222-234. DOI:10.1124/mol.118.112946
[2] Anderton MJ, et al. Induction of heart valve lesions by small-molecule ALK5 inhibitors. Toxicol Pathol. 2011 Oct;39(6):916-24. DOI:10.1177/0192623311416259 |
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R&D Systems, Inc
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18003437475 18003437475 |
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www.rndsystems.com |
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Merck KGaA
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(+86) 21 2033 8288 |
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http://www.sigmaaldrich.cn |
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