RESUMO
TGF-ß signaling plays an extremely important role in the occurrence and development of type 2 diabetes mellitus (T2DM), and the blockade of TGF-ß/Smad3 pathway protests against the high-fat diet-induced obesity and diabetes. As a specific small molecule inhibitor of Smad3 protein, the biological activities of compound SIS3 were evaluated by high-fat diet-induced T2DM model mice. In vivo results indicated that SIS3 can not only significantly reduce the body weight, fat mass, and fasting blood glucose in high-fat diet-induced T2DM model mice, but also improve insulin sensitivity and oral glucose tolerance of high-fat diet-induced T2DM model mice after the injection of SIS3 with 5 mg/kg for 45 days.
Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Isoquinolinas/farmacologia , Piridinas/farmacologia , Pirróis/farmacologia , Animais , Glicemia/efeitos dos fármacos , Dieta Hiperlipídica , Modelos Animais de Doenças , Teste de Tolerância a Glucose , Masculino , Camundongos , Camundongos Endogâmicos C57BLRESUMO
A series of novel benzamide derivatives were prepared and evaluated using cell-based measurements. Among these compounds, 10f significantly inhibited Hedgehog signaling and showed equivalent or more potency than GDC-0449 in different tests. Furthermore, compound 10f potently inhibited the proliferation of Daoy, a medulloblastoma cell line that is reported to be resistant to GDC-0449, which indicated a promising prospect in the treatment of Hedgehog signaling pathway related cancer in clinical trial.
Assuntos
Benzamidas/síntese química , Benzamidas/farmacologia , Receptores Acoplados a Proteínas G/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Sulfonas/síntese química , Sulfonas/farmacologia , Animais , Benzamidas/química , Linhagem Celular Tumoral , Células HEK293 , Proteínas Hedgehog/metabolismo , Humanos , Receptores Acoplados a Proteínas G/metabolismo , Receptor Smoothened , Relação Estrutura-Atividade , Sulfonas/química , Peixe-ZebraRESUMO
In the title compound, C18H16N4, the dihedral angle between the benzene and phenyl rings is 61.40â (4)°. In the crystal, mol-ecules are linked by N-Hâ¯N(nitrile) hydrogen bonds, forming inversion dimers. The dimers are further linked by N-Hâ¯N(amine) hydrogen bonds, and both units are arranged almost perpendicular to each other [angle between dimer mean planes = 84.43â (12)°]. This arrangement is extended to form a ladder-like structure parallel to the c axis.
RESUMO
In the title compound, C(14)H(10)Cl(2)INO(3)S, the dihedral angle between the benzene rings is 52.13â (10)°. In the crystal, the components are linked by pairs of N-Hâ¯O(sulfon-yl) hydrogen bonds into centrosymmetric dimers.