Abstract:
Provided herein are methods, uses and compositions for treating a patient with cancer wherein the cancer is characterized by a PTEN gene mutation, hi particular embodiments, the methods comprise administering to the patient a composition comprising a therapeutically effective amount of a PLK4 antagonist, and identifying a patient that is likely to be responsive to PLK4 antagonist therapy, if PTEN gene mutation is present.
Abstract:
Provided herein are methods, uses and compositions for treating a patient with cancer wherein the cancer is characterized by a PTEN gene mutation. In particular embodiments, the methods comprise administering to the patient a composition comprising a therapeutically effective amount of a PLK4 antagonist, and identifying a patient that is likely to be responsive to PLK4 antagonist therapy, if PTEN gene mutation is present.
Abstract:
Provided herein are methods, uses and compositions for treating a patient with cancer wherein the cancer is characterized by a PTEN gene mutation. In particular embodiments, the methods comprise administering to the patient a composition comprising a therapeutically effective amount of a PLK4 antagonist, and identifying a patient that is likely to be responsive to PLK4 antagonist therapy, if PTEN gene mutation is present.
Abstract:
Disclosed herein is a method of treating a subject with aberrant cytokine release from a disease or condition or at risk of developing aberrant cytokine release from a disease or condition. The method comprises administering to the subject an effective amount of a compound represented by structural formula (I): (I) or a pharmaceutically acceptable salt thereof. The variables in structural formula (I) are as described herein.
Abstract:
Provided herein are methods, uses and compositions for treating a patient with cancer wherein the cancer is characterized by a PTEN gene mutation. In particular embodiments, the methods comprise administering to the patient a composition comprising a therapeutically effective amount of a PLK4 antagonist, and identifying a patient that is likely to be responsive to PLK4 antagonist therapy, if PTEN gene mutation is present.
Abstract:
The invention is related to a method of treating a subject with acute myeloid leukemia, acute lymphoblastic leukemia, non-Hodgkin's lymphoma, Burkitt lymphoma, or diffuse large B-cell lymphoma by administration of Compound (I), or a pharmaceutically acceptable salt thereof.
Abstract:
Un antagonista de PLK4 para su uso en un procedimiento para tratamiento de cáncer en un paciente con cáncer, en el que dicho cáncer se caracteriza por una mutación del gen PTEN, en el que la mutación del gen PTEN da como resultado una expresión reducida de PTEN en comparación con un control normal, la expresión de una proteína PTEN no funcional o de funcionamiento limitado, o una pérdida de la expresión de PTEN, en el que el antagonista de PLK4 está representado por la fórmula estructural (X): **Fórmula** o una sal farmacéuticamente aceptable del mismo, en la que Ra es halógeno, ciano, -NR1R2, -NR2C(O)R1, -C(O)OR1, -OC(O)R1, -N(R2)C(O)NR1R2, -OR1 o alquilo C1-6, en la que el alquilo C1-6 está opcionalmente sustituido con uno o más sustituyentes seleccionados del grupo que consiste en halógeno, -OH, -SH, -O(alquilo C1-6), -S(alquilo C1-6) y haloalcoxi C1-6; cada R1 es independientemente -H o alquilo C1-6, en la que el alquilo C1-6 está opcionalmente sustituido con uno o más sustituyentes seleccionados independientemente del grupo que consiste en halógeno, -OH, -SH, -O(alquilo C1-3), -S(alquilo C1-3) y haloalcoxi C1-6; cada R2 es independientemente -H o alquilo C1-6, o, tomado conjuntamente con NR1, forma un grupo heterocíclico no aromático opcionalmente sustituido con uno o más sustituyentes seleccionados del grupo que consiste en =O, =S, halógeno, nitro, ciano, hidroxi, alquilo C1-6, haloalquilo C1-6, hidroxialquilo C1-6, amino, alquilamino C1-6, dialquilamino C1-6, aminoalquilo C1-6, (alquilamino C1-6)alquilo C1-6, (dialquilamino C1-6)alquilo C1-6, (fenil)alquilo C1-6, (heteroaril de 5-6 miembros)alquilo C1-6, alcoxi C1-6, haloalcoxi C1 -6, alquilcarboniloxi C1-6, alcoxicarbonilo C1-6, alquilcarbonilo C1-6, fenilo y heteroarilo de 5-6 miembros; R4 es -H, alquilo C1-C6, fenilo, -C(O)(alquilo C1-6), -C(O)(fenilo), -C(O)O(alquilo C1-6), -C(O)O(fenilo), -S(O)2(alquilo C1-6) o -S(O)2(fenilo); y R6 es fenilo opcionalmente sustituido, heteroarilo de 5-12 miembros opcionalmente sustituido, -CH2-(fenilo opcionalmente sustituido), -CH2-(heteroarilo de 5-12 miembros opcionalmente sustituido), -CH2-CH2-(fenilo opcionalmente sustituido ), -CH2-CH2-(heteroarilo de 5-12 miembros opcionalmente sustituido), -CH=CH- (fenilo opcionalmente sustituido), -CH=CH-(heteroarilo de 5-12 miembros opcionalmente sustituido), -C≡C(fenilo opcionalmente sustituido) o -C≡C-(heteroarilo de 5-12 miembros opcionalmente sustituido).
Abstract:
Disclosed herein is a method of treating a subject with aberrant cytokine release from a disease or condition or at risk of developing aberrant cytokine release from a disease or condition. The method comprises administering to the subject an effective amount of a compound represented by structural formula (I): (I) or a pharmaceutically acceptable salt thereof. The variables in structural formula (I) are as described herein.