Compositions and methods for treating cancer

A method of treating colorectal cancer in a human subject with a K-Ras G12C-mutated colorectal cancer,

• the method comprising administering to said human subject with said K-Ras G12C-mutated colorectal cancer a therapeutically effective amount of a pharmaceutical composition for the treatment of said K-Ras G12C-mutated colorectal cancer, wherein the pharmaceutical composition comprises a pharmaceutically acceptable carrier and a compound having the formula:
• R1-L1-L2-L3-E,
• or a pharmaceutically acceptable salt, tautomer, or stereoisomer thereof, wherein
• R1 is a substituted phenyl having the formula
• wherein
• e5 is an integer from 1 to 4;
• each R3 is independently halogen, —CX3, —CN, —SO2NR7R8, —N(O)2, —NR7C(═O)R9, —NR7R8, —C(O)R9, —C(O)—OR9, —C(O)NR7R8, —OR10, substituted or unsubstituted alkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, wherein
• two adjacent R3 substituents are optionally joined to form a substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
• each R7, R8, R9, and R10 is independently hydrogen, or substituted or unsubstituted alkyl;
• R7 and R8 are optionally joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl;
• and
• X is —F;
• L1 is substituted or unsubstituted heteroarylene;
• L2 is a bond;
• L3 is
• wherein
• f8 is an integer from 0 to 8;
• each R2C is independently oxo, halogen, —CX3, —CN, —SO2Cl, —SOn3R10c, —SOv3NR7cR8c, —NHNH2, —ONR7CR8c, —NHC═(O)NHNH2, —NHC═(O)NR7cR8c, —N(O)m3, —NR7cR8c, —C(O)R9c, —C(O)—OR9c, —C(O)NR7cR8c, —OR10c, —NR7cSO2R10c, —NR7cC═(O)R9c, —NR7cC(O)—OR9c, —NR7cOR9c, —OCXc3, —OCHXc2, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
• wherein
• two adjacent R2C substituents are optionally joined to form a substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
• each R7c, R8c, R9c, and R10c is independently hydrogen, halogen, —CF3, —CN, —OH, —NH2, —COOH, —CONH2, —NO2, —SH, —SO2Cl, —SO3H, —SO4H, —SO2NH2, —NHNH2, —ONH2, —NHC═(O)NHNH2, —NHC═(O)NH2, —NHSO2H, —NHC═(O)H, —NHC(O)—OH, —NHOH, —OCF3, —OCHF2, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
• R7c and R8c are optionally joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl;
• m3 and v3 are independently an integer from 1 to 2;
• n3 is an integer from 0 to 4;
• Xc is independently —Cl, —Br, —I, or—F;
• and
• E is
• wherein each substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted heteroaryl, substituted aryl is independently substituted with a substituent group.