Abstract: The present application relates to a pharmaceutical combination comprising a phosphoinositide 3-kinase (PI3K) inhibitor and a second therapeutic agent, wherein the second therapeutic agent is an immune checkpoint inhibitor, a TGF? inhibitor, a bifunctional immune checkpoint/TGF? inhibitors or combinations thereof. The present application also provides a method of treatment comprising administering the combination, and the use of the drug combination for treating tumors.

Abstract: The present invention is directed to compositions and methods for modulating c-Rel-dependent cytokine production without materially altering the level of expression of NF?B and/or the amount of I?B. The present invention is also directed to screening for modulators of c-Rel activity as determined by assaying for altered subcellular localization of c-Rel but where the level of expression of NF?B and/or the amount of I?B is materially unaltered.

Abstract: The present invention is directed to compositions and methods for modulating c-Rel-dependent cytokine production without materially altering the level of expression of NF?B and/or the amount of I?B. The present invention is also directed to screening for modulators of c-Rel activity as determined by assaying for altered subcellular localization of c-Rel but where the level of expression of NF?B and/or the amount of I?B is materially unaltered.

Abstract: The present invention is directed to compositions and methods for modulating c-Rel-dependent cytokine production without materially altering the level of expression of NF?B and/or the amount of I?B. The present invention is also directed to screening for modulators of c-Rel activity as determined by assaying for altered subcellular localization of c-Rel but where the level of expression of NF?B and/or the amount of I?B is materially unaltered.

Abstract: The present invention is directed to compositions and methods for modulating c-Rel-dependent cytokine production without materially altering the level of expression of NF?B and/or the amount of I?B. The present invention is also directed to screening for modulators of c-Rel activity as determined by assaying for altered subcellular localization of c-Rel but where the level of expression of NF?B and/or the amount of I?B is materially unaltered.

Abstract: The present invention is directed to compositions and methods for modulating c-Rel-dependent cytokine production without materially altering the level of expression of NF?B and/or the amount of I?B. The present invention is also directed to screening for modulators of c-Rel activity as determined by assaying for altered subcellular localization of c-Rel but where the level of expression of NF?B and/or the amount of I?B is materially unaltered.

Abstract: This invention features pyrimidine compounds of formula (I): Rt is aryl, or heteroaryl; each of R2 and R4, independently, is halogen, nitro, cyano, isothionitro, SRc, or ORc; or R2 and R4, taken together, is carbonyl; R3 is Rc, alkenyl, alkynyl, ORc, OC(O)Rc, SO2Rc, S(O)Rc, S(O2)NRcRd, NRcRd, NRcCORd, NRcC(O)ORd, NRcC(O)NRcRd, NRcSO2Rd, CORc, C(O)ORc, or C(O)NRcRd; R5 is H or alkyl; n is 0, 1, 2, 3, 4, 5, or 6; X is O, S, S(O), S(O2), or NRc; Y is a covalent bond, CH2, C(O), C?N—Rc, C?N—ORc, C?N—SRc, O, S, S(O), S(O2), or NRc; Z is N or CH; one of U and V is N, and the other is CRc; and W is O, S, S(O), S(O2), NRc, or NC(O)Rc; in which each of Ra and Rb, independently, is H, alkyl, aryl, heteroaryl; and each of Rc and Rd, independently, is H, alkyl, aryl, heteroaryl, cyclyl, heterocyclyl, or alkylcarbonyl.

Abstract: This invention features pyrimidine compounds of formula (I): aryl, or heteroaryl; each of R2 and R4, independently, is Rc, halogen, nitro, cyano, isothionitro, SRc, or ORc; or R2 and R4, taken together, is carbonyl; R3 is Rc, alkenyl, alkynyl, ORc, OC(O)Rc, SO2Rc, S(O)Rc, S(O2)NRcRd, SRc, NRcRd, NRcCORd, NRcC(O)ORd, NRcC(O)NRcRd, NRcSO2Rd, CORc, C(O)ORc, or C(O)NRcRd; R5 is H or alkyl; n is 0, 1, 2, 3, 4, 5, or 6; X is O, S, S(O), S(O2), or NRc; Y is a covalent bond, CH2, C(O), C?N—Rc, C?N—ORc, C?N—SRc, O, S, S(O), S(O2), or NRc; Z is N or CH; one of U and V is N, and the other is CRc; and W is O, S, S(O), S(O2), NRc, or NC(O)Rc; in which each of Ra and Rb, independently, is H, alkyl, aryl, heteroaryl; and each of Rc and Rd, independently, is H, alkyl, aryl, heteroaryl, cyclyl, heterocyclyl, or alkylcarbonyl.

Abstract: The present invention is directed to compositions and methods for modulating c-Rel-dependent cytokine production without materially altering the level of expression of NF?B and/or the amount of I?B. The present invention is also directed to screening for modulators of c-Rel activity as determined by assaying for altered subcellular localization of c-Rel but where the level of expression of NF?B and/or the amount of I?B is materially unaltered.

Abstract: This invention features pyrimidine compounds of formula (I): aryl, or heteroaryl; each of R2 and R4, independently, is Rc, halogen, nitro, cyano, isothionitro, SRc, or ORc; or R2 and R4, taken together, is carbonyl; R3 is Rc, alkenyl, alkynyl, ORc, OC(O)Rc, SO2Rc, S(O)Rc, S(O2)NRcRd, SRc, NRcRd, NRcCORd, NRcC(O)ORd, NRcC(O)NRcRd, NRcSO2Rd, CORc, C(O)ORc, or C(O)NRcRd; R5 is H or alkyl; n is 0, 1, 2, 3, 4, 5, or 6; X is O, S, S(O), S(O2), or NRc; Y is a covalent bond, CH2, C(O), C?N—Rc, C?N—ORc, C?N—SRc, O, S, S(O), S(O2), or NRc; Z is N or CH; one of U and V is N, and the other is CRc; and W is O, S, S(O), S(O2), NRc, or NC(O)Rc; in which each of Ra and Rb, independently, is H, alkyl, aryl, heteroaryl; and each of Rc and Rd, independently, is H, alkyl, aryl, heteroaryl, cyclyl, heterocyclyl, or alkylcarbonyl.

Abstract: The present invention is directed to compositions and methods for modulating c-Rel-dependent cytokine production without materially altering the level of expression of NF?B and/or the amount of I?B. The present invention is also directed to screening for modulators of c-Rel activity as determined by assaying for altered subcellular localization of c-Rel but where the level of expression of NF?B and/or the amount of I?B is materially unaltered.

Abstract: This invention relates to indolizine compounds having formula 1

Abstract: This invention relates to compounds of Formula (I) 1