LY364947

• CAT Number: I003448
• CAS Number: 396129-53-6
• Molecular Formula: C17H12N4
• Molecular Weight: 272.31
• Purity: ≥95%
• Target: SMAD
• Solubility: DMSO: ≥ 25 mg/mL
• Storage: 3 years -20C powder
• IC50: 59 nM [1]
• IUPAC Name: 4-(5-pyridin-2-yl-1H-pyrazol-4-yl)quinoline
• InChI: InChI=1S/C17H12N4/c1-2-6-15-13(5-1)12(8-10-19-15)14-11-20-21-17(14)16-7-3-4-9-18-16/h1-11H,(H,20,21)
• InChIKey: IBCXZJCWDGCXQT-UHFFFAOYSA-N
• SMILES: C1=CC=C2C(=C1)C(=CC=N2)C3=C(NN=C3)C4=CC=CC=N4

LY364947 (CAT: I003448) is a potent ATP-competitive inhibitor of transforming growth factor beta receptor type I (TGFβR-I). It specifically targets and inhibits the activity of TGFβR-I, which is a key receptor involved in the TGF-β signaling pathway. By blocking the activity of TGFβR-I, LY364947 disrupts the signaling cascade mediated by TGF-β, a cytokine that plays a crucial role in regulating various cellular processes including cell growth, differentiation, and immune response. LY364947 demonstrates an inhibitory concentration (IC50) of 59 nM against TGFβR-I and exhibits 7-fold selectivity over TGFβR-II, another receptor involved in TGF-β signaling. This selectivity allows for specific targeting of TGFβR-I activity, potentially modulating TGF-β signaling pathways in various biological contexts.

Reference

1:Curr Drug Targets. 2013 Aug;14(9):1061-9. Validated RP-HPLC method for the simultaneous analysis of gemcitabine and LY-364947 in liposomal formulations.Bansal SS,Celia C,Ferrati S,Zabre E,Ferrari M,Palapattu G,Grattoni A, PMID: 23721184
Abstract: Combined use of gemcitabine (Gem) and LY-364947 (LY), a TGF-β1 receptor inhibitor, has shown promise for the treatment of fibrotic pancreatic cancer, by reducing collagen production and improving tumor drug penetration. The preparation and optimization of novel Gem and LY formulations, including co-encapsulation in liposomes, require a validated method for the simultaneous quantification of both drugs, a method that had yet to be developed. Here we demonstrate an RP-HPLC protocol for the simultaneous detection of Gem and LY at 266 and 228 nm with retention times of 3.37 and 11.34 mins, respectively. The method, which uses a C18 column and a KH2PO4 (10 mM)-methanol mobile phase, was validated for linearity, precision, accuracy, limits of detection, and robustness. Co-loaded liposomes with both Gem and LY (Gem/LY liposomes) were developed to investigate the protocol applicability to pharmacokinetic analysis and formulation characterization. The method specificity was evaluated in presence of liposomal components in fetal bovine serum (FBS). Finally, the method was demonstrated by quantifying Gem/LY liposomal encapsulation efficiency and concentration liposomes-spiked FBS.