Western blot analysis of extracts from HT-1080 cells, untreated (-) or treated with Human Transforming Growth Factor β1 (hTGF-β1) #8915 (10 ng/ml, 30 min; +) with or without pretreating the cells with LY-364947 (1 μM, 1 hr; +), using Phospho-Smad2 (Ser465/467)/Smad3 (Ser423/425) (D27F4) Rabbit mAb #8828 (upper), Smad2/3 (D7G7) XP® Rabbit mAb #8685 (middle), and β-Actin (D6A8) Rabbit mAb #8457 (lower).
Chemical structure of LY-364947.
LY-364947 is supplied as a lyophilized powder. For a 15 mM stock, reconstitute 5 mg of powder in 1.22 ml of DMSO. Working concentrations and length of treatment can vary depending on the desired effect.
Store lyophilized at room temperature, desiccated. In lyophilized form, the chemical is stable for 24 months. Once in solution, store at -20ºC and use within 3 months to prevent loss of potency. Aliquot to avoid multiple freeze/thaw cycles.
Molecular Weight: 272.3 g/mol
Molecular Formula: C17H12N4
Solubility: Soluble in DMSO at 25 mg/ml.
LY-364947, also known as HTS-466284, is a potent and selective TGF-β type-I receptor (TGF-β RI, TGFR-I, TβR-I, ALK-5) inhibitor. This small molecule specifically targets TGF-β RI with an IC50 value of 59 nM and is less effective on TGF-β RII and MLK-7K (IC50 values of 400 nM and 1400 nM, respectively) (1). LY-364947 regulates MDA-MB-231 cell invasion by inhibiting autocrine TGF-β signaling (2). Patients in intensive care units (ICUs) that suffer from chronic sepsis can experience weakening of the diaphragm muscles caused by muscle wasting, requiring mechanical ventilation. Members of the TGF-β family can trigger the activation of protein breakdown. Inhibition of the TGF-β pathway can protect the diaphragm during chronic sepsis, making LY-364947 an interesting compound to study as it relates to effective ICU patient care (3).
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