Triptolide conjugates and uses thereof

A compound of Formula I, or an enantiomer, an enantiomeric mixture, a diastereomer, a diastereomeric mixture, or a pharmaceutically acceptable salt thereof:

• wherein
• m1, m2, n1, n2 are each independently 0-15;
• R1, R2, and R3 each independently OH, H, halo, unsubstituted or substituted C1-C10 alkyl, unsubstituted or substituted C3-C10 cycloalkyl, unsubstituted or substituted C1-C10 acyl, unsubstituted or substituted C1-C10 carboxyl ester, unsubstituted or substituted C1-C10 alkyl ketone, or unsubstituted or substituted C1-C10 alkyl ether;
• M1 is selected from a bond, —C(═O)—, —OPO2—, —SO2—, —NH(CO)—, —(CO)NH—, —CH2OPO2—,
• —CH2—O—C(═O)—, and —CH2O—;
• M2 is selected from C and Si;
• X1, X2, X3, X4, and X5 are each independently a bond, —C(═O)—, (C═O)-L1-(C═O), (C═O)-L1, L1-(C═O), O(CO), (CO)O, O, S, S—S, Se—Se—, NH, NR, NH(CO), (CO)NH, L2-NH(CO), NH(CO)-L2, L2-(CO)NH, —(CO)NH-L2, (CO)NH-L2-NH(CO), NR-L2-NR, L2-O, O-L2, unsubstituted or substituted C1-C10 alkylene, unsubstituted or substituted C3-C10 cycloalkylene, unsubstituted or substituted arylene, unsubstituted or substituted heteroarylene, unsubstituted or substituted C1-C10 heterocyclylene, or unsubstituted or substituted peptide comprising 1-10 natural amino acids;
• each L1 is each independently unsubstituted or substituted arylene, unsubstituted or substituted heteroarylene, unsubstituted or substituted C1-C10 heterocyclylene;
• each L2 is each independently unsubstituted or substituted C1-C10 alkylene;
• each R is independently unsubstituted or substituted C1-C10 alkyl, unsubstituted or substituted C3-C10 cycloalkyl, unsubstituted or substituted C1-C10 acyl, unsubstituted or substituted C1-C10 carboxyl ester, unsubstituted or substituted C1-C10 alkyl ketone, or unsubstituted or substituted C1-C10 alkyl ether, unsubstituted or substituted aryl, unsubstituted or substituted heteroaryl, or unsubstituted or substituted C1-C10 heterocycyl;
• and
• X5 is attached to any one of R4, R5, R6, R7, and R8;
• the remaining R4, R5, R6, R7, and R8 that are not attached to X5 are each independently H, OH, O(CO)NH2, halo, NH(C1-C10 acyl), unsubstituted or substituted O(C1-C10 alkyl), unsubstituted or substituted O(C3-C10 cycloalkyl), unsubstituted or substituted O(C1-C10 acyl), unsubstituted or substituted C1-C10 carboxyl ester, unsubstituted or substituted C1-C10 alkyl ketone, or unsubstituted or substituted C1-C10 alkyl ether, unsubstituted or substituted aryl, unsubstituted or substituted heteroaryl, unsubstituted or substituted C1-C10 heterocycyl, unsubstituted or substituted peptide comprising 1-10 amino acids, or forms a glycosidic bond with a natural monosaccharide.