Compounds for regulating trained immunity, and their methods of use

A method for treating a cell-proliferation disorder in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of a nanobiologic composition comprising a high-density lipoprotein (HDL)-derived nanoparticle, wherein the nanoparticle comprises a compound of formula (I):

• or a pharmaceutically acceptable salt thereof,
• wherein:
• R1 is —H or —C(O)—RX;
• R2 and R3 are each independently selected from the group consisting of —H, alkyl, aryl, alkylene-aryl, —C(O)-alkyl, and —C(O)-aryl;
• R4, R5, and R5′ are each alkyl;
• R6 and R11 are each independently —H or alkyl;
• R7 is —Y-triazolyl-L;
• Y is alkylene;
• L is selected from the group consisting of a fatty acid chain, -alkylene-C(O)—W, -alkylene-O—C(O)—W, -alkylene-N-(alkylene-C(O)—NR11-alkylene-NR11—C(O)—W)2, and -alkylene-N-(alkylene-C(O)—W)2;
• W is a fatty acid chain, —O-alkylene-C(H)(OR8)-alkylene-OR9, a phospholipid, or a sterol;
• R8 and R9 are each independently RX or —C(O)—RX;
• R22, R33, R33′, R44, R44′, R55, and R55′ are each independently H or RA;
• RX is a fatty acid chain;
• wherein each aforementioned alkyl, alkylene, alkylene-aryl, aryl, and triazolyl is optionally substituted with one or more RA, wherein RA is independently selected for each occurrence from the group consisting of hydrogen, halo, alkoxy, haloalkoxy, cyano, hydroxyl, —N(RC)(RD), —C(O)N(RC)(RD), —N(RC)C(O)RB, —OC(O)NRCRD, —NRCC(O)ORB, —OC(O)RB, —C(O)ORB, —C(O)RB, —CO2H, —NO2, —SH, S(O)XRB (wherein X is 0, 1, or 2), aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, heterocycloalkyl, and RB;
• RC and RD are independently selected for each occurrence from the group consisting of hydrogen, alkyl, haloalkyl —C(O)RB, and —C(O)ORB;
• or RC and RD are taken together with the nitrogen to which they are attached to form a heterocyclic ring optionally substituted with RA;
• and
• RB is alkyl, alkenyl, or alkynyl optionally substituted with one or more fluoro.