Targeted intracellular delivery of dimeric MSA stinga by two phlip® peptides

Abstract

Compositions comprising two pHLIP® peptides linked to a STING agonist, which is a dimer with a carboxylic acid subsituent (carboxyl group) at the terminal position of both monomers of the dimer, pharmaceutical compositions thereof, and methods of treatment using such compositions are disclosed herein.

Description

TARGETED INTRACELLULAR DELIVERY OF DIMERIC MSA STINGA BY TWO PHLIP® PEPTIDESSTATEMENT AS TO FEDERALLY SPONSORED RESEARCH

[0001] This invention was made with government support under grant number R01 GM073857 awarded by the National Institutes of Health. The government has certain rights in the invention.REFERENCE TO RELATED APPLICATIONS

[0002] This application claims the priority benefit of U.S. Provisional Application No. 63 / 590,353, filed on October 13, 2023, which is incorporated herein by reference in its entirety.REFERENCE TO SEQUENCE LISTING SUBMITTED ELECTRONICALLY

[0003] The contents of the sequence listing text file named “5095_017PC01_SequenceListing_ST26”, which was created on October 10, 2024 and is 212,977 bytes in size, is hereby incorporated by reference in its entirety.FIELD OF THE INVENTION

[0004] Compositions comprising two pH low insertion peptides (pHLIP®) each of which is linked to a stimulator of interferon genes (STING) agonist, which is a dimer with a carboxylic acid subsituent (carboxyl group) at the terminal position of both monomers of the dimer, pharmaceutical compositions thereof, and methods of treatment using such compositions are disclosed herein.BACKGROUND

[0005] Immune evasion is a hallmark of cancer. Conventional methods of treating cancer employ toxic agents that do not distinguish between normal and tumor tissues very well. Therefore these methods are limited in their use because of their harmful side effects.

[0006] Thus, there remains a need for new methods of treating cancer and tumors.SUMMARY OF THE INVENTION

[0007] Compositions comprising a conjugate of Formula (I): Peptide-Linker-STING-Linker-Peptide (I) wherein Peptide is a pHLIP® peptide, wherein Linker is a cleavable linker bonded to a carboxyl group on “STING”; wherein “STING” is a STING agonist selected from the group consisting of (2S,2'S)-4,4'-[butane-l,4-diylbis(6-methoxy-l-benzothiene-5,2-diyl)]bis(2- methyl-4-oxobutanoic acid), (2S,2'S)-4,4'-[propane-l,3-diylbis(6-methoxy-l-benzothiene-5,2-diyl)]bis(2- methyl-4-oxobutanoic acid), (S)-4-(5-(3-(2-(3-carboxypropanoyl)-6-methoxybenzo[b]thiophen-5-yl)propoxy)- 6-methoxythieno[3,2-b]pyri din-2 -yl)-2-methyl-4-oxobutanoic acid, 4-(5-(3-((2-(3-carboxypropanoyl)-6-methoxythieno[3,2-b]pyridin-5- yl)oxy)propyl)benzo[b]thiophen-2-yl)-4-oxobutanoic acid, 4-(5-(3-(2-(3-carboxypropanoyl)-6-methoxybenzo[b]thiophen-5-yl)propoxy)-6- methoxybenzo[d]thiazol-2-yl)-4-oxobutanoic acid, 4-(5-(3-((2-(3-carboxypropanoyl)-6-methoxybenzo[b]thiophen-5-yl)oxy)propyl) benzo[b]thiophen-2-yl)-4-oxobutanoic acid, 4-(5-(2-((2-(3-carboxypropanoyl)-6-methoxybenzo[b]thiophen-5-yl)oxy)ethyl)-6- methoxythieno[3,2-b]pyridin-2-yl)-4-oxobutanoic acid, 4-(5-(2-(2-(3-carboxypropanoyl)-6-methoxythieno[3,2-b]pyridin-5-yl)ethoxy)-6- methoxythieno[3,2-b]pyridin-2-yl)-4-oxobutanoic acid, 4-(5-(2-((2-(3-carboxypropanoyl)-6-methoxybenzo[d]thiazol-5-yl)oxy)ethyl)-6- methoxythieno[3,2-b]pyridin-2-yl)-4-oxobutanoic acid, 4-(5-(3-(2-(3-carboxypropanoyl)-6-methoxybenzo[b]thiophen-5-yl)propoxy)-6- methoxythieno[3,2-b]pyridin-2-yl)-4-oxobutanoic acid, (S)-4-(5-(3-((2-(3-carboxypropanoyl)-6-methoxythieno[3,2-b]pyridin-5- yl)oxy)propoxy)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, 4-(5-(3-((2-(3-carboxypropanoyl)-6-methoxybenzo[b]thiophen-5-yl)oxy)propyl)- 6-methoxythieno[3,2-b]pyri din-2 -yl)-4-oxobutanoic acid,(S)-4-(5-(3-((2-(3-carboxypropanoyl)-6-methoxythieno[3,2-b]pyridin-5- yl)oxy)propyl)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-(2-(3-carboxypropanoyl)-6-methoxythieno[3,2-b]pyridin-5- yl)propoxy)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-(2-((S)-3-carboxybutanoyl)-6-methoxybenzo[b]thiophen-5- yl)propoxy)-6-methoxythieno[3,2-b]pyridin-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(2-((2-(3-carboxypropanoyl)-6-methoxybenzo[b]thiophen-5- yl)oxy)ethoxy)-6-methoxythieno[3,2-b]pyridin-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-(3-carboxypropanoyl)-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-6-methoxythieno[3,2-b]pyridin-2-yl)-2-methyl-4-oxobutanoic acid, rac-(R)-4-(5-(2-((2-((R)-3-carboxybutanoyl)-4-fluoro-6- methoxybenzo[b]thiophen-5-yl)oxy)ethoxy)-6-methoxythieno[3,2-b]pyri din-2 -yl)-2- methyl-4-oxobutanoic acid,(S)-4-(5-(2-((2-(3-carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)ethoxy)-6-methoxythieno[3,2-b]pyridin-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-(3-carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-6-methoxythieno[3,2-b]pyridin-2-yl)-2-methyl-4-oxobutanoic acid, rac-(R)-4-(5-(3-((2-((R)-3-carboxybutanoyl)-4-fluoro-6- methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6-methoxythieno[3,2-b]pyri din-2 -yl)-2- methyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-(3-carboxypropanoyl)-6-methoxythieno[3,2-b]pyridin-5- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,4-(4-(3-(2-(3-carboxypropanoyl)-5-methoxbenzo[b]thiophen-6-yl)propyl)-6- methoxybenzo[b]thiophen-2-yl)-4-oxobutanoic acid,4,4'-(propane-l,3-diylbis(6-methoxybenzo[d]thiazole-5,2-diyl))bis(4-oxobutanoic acid),4,4'-(propane-l,3-diylbis(6-methylbenzo[b]thiophene-5,2-diyl))bis(4-oxobutanoic acid),4-(5-(3-(2-(3-carboxypropanoyl)-6-methoxybenzo[b]thiophen-5-yl)propyl)-6- methoxythieno[3,2-b]pyridin-2-yl)-4-oxobutanoic acid,(S)-4-(5-(3-(2-(3-carboxybutyl)-6-methoxybenzo[b]thiophen-5-yl)propyl)-6- methoxybenzo[b]thiophen-2-yl)-4-oxobutanoic acid,4-(5-(3-((2-(3-carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propyl)-6-methoxybenzo[b]thiophen-2-yl)-4-oxobutanoic acid,(S)-4-(5-(3-(2-(3-carboxypropanoyl)-6-methoxybenzo[b]thiophen-5-yl)propoxy)- 4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(2-((2-(3-carboxypropanoyl)-6-methoxybenzo[b]thiophen-5- yl)oxy)ethoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-(3-carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propyl)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propyl)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-(3-carboxypropanoyl)-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(6-(3-(7-((S)-3-carboxybutanoyl)-4-methoxythieno[2',3':5,6]benzo[l,2- d]oxazol-2-yl)propoxy)-5-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(2S)-4-{5-[3-({2-[(3 S)-3-carboxybutanoyl]-6-methoxy-l-benzothiophen-5- yl } oxy)propyl]-6-m ethoxy- 1 -benzothiophen-2-yl } -2-methyl-4-oxobutanoic acid,(S)-4-(5-(2-(2-((S)-3-carboxybutanoyl)-6-methoxybenzo[b]thiophen-5-yl)ethoxy)- 6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-(3-carboxypropanoyl)benzo[b]thiophen-6-yl)oxy)propoxy)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(6-(3-((2-(3-carboxypropanoyl)benzo[b]thiophen-5-yl)oxy)propoxy)-5- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(2S,2'S)-4,4'-((propane-l,3-diylbis(oxy))bis(5-methoxybenzo[b]thiophene-6,2- diyl))bis(2-methyl-4-oxobutanoic acid),(2S,2'S)-4,4'-((ethane-l,2-diylbis(oxy))bis(4-fluoro-6-methoxybenzo[b]thiophene- 5,2-diyl))bis(2-methyl-4-oxobutanoic acid),(S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-5-methoxybenzo[b]thiophen-6- yl)oxypropoxy)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(2S,2'S)-4,4'-((propane-l,3-diylbis(oxy))bis(6-methoxybenzo[b]thiophene-5,2- diyl))bis(2-methyl-4-oxobutanoic acid),(S)-4-(6-(2-((2-(3-carboxypropanoyl)benzo[b]thiophen-5-yl)oxy)ethoxy)-5- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-(3-carboxypropanoyl)benzo[b]thiophen-5-yl)oxy)propoxy)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,rac-(R)-4-(5-(2-((2-((R)-3-carboxybutanoyl)-5-methoxybenzo[b]thiophen-6- yl)oxy)ethoxy)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-6-methoxythieno[3,2-b]pyridin-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-(3-carboxybutanoyl)-6-methoxythieno[3,2-b]pyridin-5- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2,2-dimethyl-4-oxobutanoic acid,(2S)-4-{5-[2-({2-[(3 S)-3-carboxybutanoyl]-6-methoxy-l-benzothiophen-5- yl}amino)ethyl]-6-methoxy-l-benzothiophen-2-yl}-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-6-methoxybenzo[b]thiophen-5- yl)amino)propyl)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(2-((2-(3-carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)ethoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-(3-carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(R)-4-(5-(2-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)ethoxy)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(2-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)ethoxy)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, rac-(lR,2R)-2-(5-(3-((2-((R)-3-carboxybutanoyl)-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-6-methoxybenzo[b]thiophene-2-carbonyl)cyclopropane-l-carboxylic acid,(S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(6-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-5-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-(3-carboxybutanoyl)-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2,2-dimethyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-(3-carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(6-(3-((2-(3-carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-5-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-6-methoxybenzo[b]thiophen-5- yl)amino)propoxy)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, 4-(5-((3-(2-(3-carboxypropanoyl)-6-methoxybenzo[b]thiophen-5- yl)propyl)amino)-6-methoxythieno[3,2-b]pyridin-2-yl)-4-oxobutanoic acid, (2S,2'S)-4,4'-((ethane-l,2-diylbis(oxy))bis(6-methoxybenzo[b]thiophene-5,2- diyl))bis(2-methyl-4-oxobutanoic acid), (2S,2'S)-4,4'-(7,8,17,18-tetrahydro-6H,16H-bis[l]benzothieno[5,6-b:6',5'- i] [ 1 ,4,8, 1 l]tetraoxacyclotetradecine-2, 12-diyl)bis(2-methyl-4-oxobutanoic acid), (2S,2'S)-4,4'-(7,8,17,18-tetrahydro-6H,16H-bis[l]benzothieno[5,6-b:5',6'- i] [ 1 ,4,8, 1 l]tetraoxacyclotetradecine-2, 12-diyl)bis(2-methyl-4-oxobutanoic acid), (2S,2'S)-4,4'-(l,3-propanediylbis{oxy[6-(difluoromethoxy)-l-benzothiene-5,2- diyl] })bis(2-methyl-4-oxobutanoic acid), 4-(5-(2-((2-(3-carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)ethoxy)-6-methoxythieno[3,2-b]pyridin-2-yl)-4-oxobutanoic acid, 4-(5-(3-((2-(3-carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-6-methoxythieno[3,2-b]pyridin-2-yl)-4-oxobutanoic acid, (S)-4-(5-(2-((2-(3-carboxypropanoyl)-6-methoxythieno[3,2-b]pyridin-5- yl)oxy)ethoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, trans-2-(5-(3-(2-((S)-3-carboxybutanoyl)-6-methoxybenzo[b]thiophen-5- yl)propoxy)-4-fluoro-6-methoxybenzo[b]thiophene-2-carbonyl)-cyclopropanecarboxylic acid, trans-2-(5-(3-(2-(3-carboxypropanoyl)-6-methoxybenzo[b]thiophen-5- yl)propoxy)-4-fluoro-6-methoxybenzo[b]thiophene-2-carbonyl)cyclopropanecarboxylic acid, trans-2-(5-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen- 5-yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophene-2- carbonyl)cyclopropanecarboxylic acid, trans-2-(5-(3-((2-((lR,2R)-2-carboxycyclopropanecarbonyl)-4-fluoro-6- methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophene-2- carbonyl)cyclopropanecarboxylic acid,trans-2-(5-(3-((2-(3-carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophene-2- carbonyl)cyclopropanecarboxylic acid, trans-2-(5-(3-((2-((S)-3-carboxybutanoyl)-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophene-2- carbonyl)cyclopropanecarboxylic acid, trans-2-(5-(3-((2-((S)-3-carboxybutanoyl)-5-methoxybenzo[b]thiophen-6- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophene-2- carbonyl)cyclopropanecarboxylic acid,(R)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propyl)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(2S,2'S)-4,4'-(5,5'-(butane-l,4-diylbis(oxy))bis(6-methoxybenzo[b]thiophene-5,2- diyl))bis(2-methyl-4-oxobutanoic acid),(S)-4-(5-(4-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)butoxy)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(4-((2-((S)-3-carboxybutanoyl)-5-methoxybenzo[b]thiophen-6- yl)oxy)butoxy)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, trans-2-(6-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen- 5-yl)oxy)propoxy)-4-fluoro-5-methoxybenzo[b]thiophene-2- carbonyl)cyclobutanecarboxylic acid, trans-2-(5-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen- 5-yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophene-2- carbonyl)cyclobutanecarboxylic acid,(S)-4-(5-(3-((2-((S)-3-carboxybutyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propyl)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-((S)-3-carboxybutyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(2S,2'S)-4,4'-(5, 5 '-(pentane- 1, 5-diylbis(oxy))bis(6-methoxybenzo[b]thi ophene- 5,2-diyl))bis(2-methyl-4-oxobutanoic acid),(S)-4-(5-((5-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)pentyl)oxy)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-((S)-3-carboxybutyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propyl)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, trans-2-(5-(3-(2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)propoxy)-4-fluoro-6-methoxybenzo[b]thiophene-2-carbonyl)cyclopropanecarboxylic acid, trans-2-(5-(3-(2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)propoxy)-4-fluoro-6-methoxybenzo[b]thiophene-2-carbonyl)cyclobutanecarboxylic acid,(R)-4-(5-(3-((2-((R)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propyl)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-((R)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propyl)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-((6-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)hexyl)oxy)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, trans-2-(5-(3-(2-((S)-3-carboxybutanoyl)-6-methoxybenzo[b]thiophen-5- yl)propoxy)-4-fluoro-6-methoxybenzo[b]thiophene-2-carbonyl)cyclobutanecarboxylic acid,(S)-4-(5-(3-((2-(3-carboxy-3-methylbutyl)-4-fluoro-6-methoxybenzo[b]thiophen- 5-yl)oxy)propyl)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, trans-2-(5-(3-((2-((S)-3-carboxybutyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophene-2- carbonyl)cyclobutanecarboxylic acid,4,4'-(5,5'-(pentane-l,5-diylbis(oxy))bis(4-fluoro-6-methoxybenzo[b]thiophene- 5,2-diyl))bis(4-oxobutanoic acid),(S)-4-(5-((5-((2-(3-carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yloxy)pentyloxy)-4-fluoro-6-methoxybenzo[b]thi ophen-2 -yl)-2-methyl-4-oxobutanoic acid,(2 S,2 ' S)-4,4 '-(5 , 5 '-(pentane- 1 , 5 -diylbi s(oxy))bi s(4-fluoro-6- methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4-oxobutanoic acid),(S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-chloro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-((4-bromo-2-((S)-3-carboxybutanoyl)-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(4-((2-((S)-3-carboxybutyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)butoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(4-((2-((S)-3-carboxybutanoyl)-4-chloro-6-methoxybenzo[b]thiophen-5- yl)oxy)butoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(4-((4-bromo-2-((S)-3-carboxybutanoyl)-6-methoxybenzo[b]thiophen-5- yl)oxy)butoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(2S, 2'S)-4,4'-(5, 5 '-(propane-1, 3-diylbis(oxy))bis(4-chloro-6- methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4-oxobutanoic acid),(S)-4-(5-(3-((4-bromo-2-((S)-3-carboxybutanoyl)-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-chloro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(2S, 2'S)-4,4'-(5, 5 '-(propane-1, 3-diylbis(oxy))bis(4-bromo-6- methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4-oxobutanoic acid),2-((5-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2- yl)methyl)cyclobutanecarboxylic acid,(S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4,7-dichloro-6- methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thi ophen-2- yl)-2-methyl-4-oxobutanoic acid,(2 S,2 ' S)-4,4 '-((butane- 1 , 3 -diylbi s(oxy))bi s(4-fluoro-6- methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4-oxobutanoic acid),(2S,2'S)-4,4'-((pentane-l,4-diylbis(oxy))bis(4-fluoro-6- methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4-oxobutanoic acid),(2 S,2 ' S)-4,4 '-((hexane-2, 5 -diylbi s(oxy))bi s(4-fluoro-6- methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4-oxobutanoic acid), trans-2-(5-(3-((2-(3-carboxy-3-methylbutyl)-4-fluoro-6- methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophene-2- carbonyl)cyclobutane- 1 -carboxylic acid,(2 S,2 ' S)-4,4 '-(((2-methylpropane- 1 , 3 -diy 1 )b i s(oxy))bi s(4-fluoro-6- methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4-oxobutanoic acid),(2S,2'S)-4,4'-(((2,2-dimethylpropane-l,3-diyl)bis(oxy))bis(4-fluoro-6- methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4-oxobutanoic acid),(2 S, 2 ' S)-4, 4 '-(((cyclopropane- 1 , 1 -diylbi s-(methylene))bi s(oxy))bi s(4-fluoro-6- methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4-oxobutanoic acid),(S)-4-(5-(3-((2-((S)-3-carboxybutyl)-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-chloro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(4-bromo-5-(3-((2-((S)-3-carboxybutyl)-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-((S)-3-carboxybutyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-chloro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(4-bromo-5-(3-((2-((S)-3-carboxybutyl)-4-fluoro-6- methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6-methoxybenzo[b]thi ophen-2 -yl)-2- methyl-4-oxobutanoic acid,4-(5-(3-((2-(3-carboxy-3-methylbutyl)-4-fluoro-6-methoxybenzo[b]thi ophen-5- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2,2-dimethyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-((S)-3-carboxybutyl)-4-chloro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-((S)-3-carboxybutyl)-4-chloro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(2 S,2 ' S)-4,4 '-((ethane- 1 ,2-diylbi s(oxy))bi s(4-chloro-6- methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4-oxobutanoic acid),(S)-4-(5-(2-((2-((S)-3-carboxybutyl)-4-chloro-6-methoxybenzo[b]thiophen-5- yl)oxy)ethoxy)-4-chloro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-chloro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(2 S,2 ' S)-4,4 '-((propane- 1 , 3 -diylbi s(oxy))bi s(4-fluoro-6- methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4-oxobutanoic acid),(S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-6-(methylamino)benzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-((S)-3-carboxybutyl)-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-(2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)propoxy)-6-methoxythieno[3,2-b]pyridin-2-yl)-2-methyl-4-oxobutanoic acid,(2S,2'S)-4,4'-(((2-methylpropane-l,3-diyl)bis(oxy))bis(6- methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4-oxobutanoic acid),(S)-4-(5-(3-((2-(3-carboxypropanoyl)-6-methoxybenzo[b]thiophen-5- yl)oxy)propyl)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-(2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)propoxy)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-(3-carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propyl)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propyl)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-5-methoxythieno[3,2-b]pyridin-6- yl)oxy)propoxy)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(6-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-5-methoxythieno[3,2-b]pyridin-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(6-(3-((2-(3-carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-5-methoxythieno[3,2-b]pyridin-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-((S)-3-carboxybutyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, trans-2-(5-(3-((2-((S)-3-carboxybutanoyl)-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophene-2- carbonyl)cyclobutanecarboxylic acid, trans-2-(5-(3-((2-((S)-3-carboxybutanoyl)-5-methoxybenzo[b]thiophen-6- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophene-2- carbonyl)cyclobutanecarboxylic acid,(2 S,2 ' S)-4,4 '-(5 , 5 '-(butane- 1 ,4-diylbi s(oxy))bi s(4-chloro-6- methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4-oxobutanoic acid), (4-(5-(3-((2-(3-carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propyl)-6-methoxythieno[3,2-b]pyridin-2-yl)-4-oxobutanoic acid,(S)-4-(5-(3-(2-(3-carboxypropanoyl)-6-methoxythieno[3,2-b]pyridin-5- yl)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-((3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo [b]thiophen-5- yl)oxy)propyl)amino)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-((3-(2-(3-carboxypropanoyl)-6-methoxybenzo[b]thiophen-5- yl)propyl)amino)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-6-hydroxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3-carboxybutyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-6-hydroxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-chloro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-6-hydroxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-chloro-6-hydroxybenzo[b]thiophen-5- yl)oxy)propoxy)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-chloro-6-hydroxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-((S)-3-carboxybutyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-chloro-6-hydroxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-chloro-6-hydroxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-chloro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-hydroxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-hydroxybenzo[b]thiophen-5- yl)oxy)propoxy)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-chloro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-fluoro-6-hydroxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,wherein eachis a covalent bond are described herein.

[0008] In some aspects, the pHLIP® peptide of the conjugate of Formula (I) has the following sequence: X„Ym; YmXn; XnYmXj; YmXnYi; YmXnYiXj; XnYmXjYi; YmXnYiXjYi; XnYmXjYiXi; YmXnYiXjYiXh; XnYmXjYiXhYg; YmXnYiXj YiXhYg; XnYmXjYiXhYgXf; (XY)n; (YX)n; (XY)nYm; (YX)nYm; (XY)nXm; (YX)nXm; Ym(XY)n; Ym(YX)n; Xn(XY)m; Xn(YX)m; (XY)nYm(XY)i; (YX)nYm(YX)i; (XY)nXm(XY)i; (YX)nXm(YX)i; Ym(XY)n; Ym(YX)n; Xn(XY)m; or Xn(YX)m, wherein,(i) each Y is, independently, a non-polar amino acid with solvation energy, DGxcor> +0.50, or Glycine;(ii) each X is, independently, a protonatable amino acid, and(iii) n, m, i, j, 1, h, g, f are each, independently, an integer from 1 to 8.

[0009] In some aspects, the pHLIP® peptide of the conjugate of Formula (I) comprises a sequence comprising the sequence ADDQNPWRAYLDLLFPTDTLLLDLLWXG (SEQ ID NO: 220), wherein “X” is a functional group for conjugation purposes, selected from lysine (Lys), cysteine (Cys), Azido-containing amino acid or other modified amino acids, such as described herein in Table 3. In some aspects, the pHLIP® peptide of the conjugate of Formula (I) comprises a sequence consisting of the sequence ADDQNPWRAYLDLLFPTDTLLLDLLWXG (SEQ ID NO: 220), wherein “X” is a functional group for conjugation purposes, selected from lysine (Lys), cysteine (Cys), Azido-containing amino acid or other modified amino acids, such as described herein in Table 3.

[0010] In some aspects, the pHLIP® peptide of the conjugate of Formula (I) comprises a sequence selected from the group consisting of any one of SEQ ID NOs. 1-219. In some aspects, the pHLIP® peptide of the conjugate of Formula (I) has a sequence selected from the group consisting of any one of SEQ ID NOs. 1-219. In some aspects, the pHLIP® peptide of the conjugate of Formula (I) has a sequence comprising the sequence ADQDNPWRAYLDLLFPTDTLLLDLLWCG (SEQ ID NO: 218). In some aspects, the pHLIP® peptide of the conjugate of Formula (I) has a sequence comprising the sequence ADDQNPWRAYLDLLFPTDTLLLDLLWCG (SEQ ID NO: 219). In some aspects, the pHLIP® peptide of the conjugate of Formula (I) has a sequence consisting of the sequenceADQDNPWRAYLDLLFPTDTLLLDLLWCG (SEQ ID NO: 218). In some aspects, the pHLIP® peptide of the conjugate of Formula (I) has a sequence consisting of the sequenceADDQNPWRAYLDLLFPTDTLLLDLLWCG (SEQ ID NO: 219).

[0011] In some aspects, the STING agonist of the conjugate of Formula (I) is selected from the group consisting of (S)-4-(5-(3-((2-((S)-3-carboxybutyl)-4-fluoro-6- methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2- methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6- methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6-(methylamino)benzo[b]thiophen-2-yl)-2-methyl- 4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3-carboxybutyl)-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)- 4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6- hydroxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3- carboxybutanoyl)-4-fluoro-6-hydroxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,

[0012] In some aspects, the STING agonist of the conjugate of Formula (I) is (S)-4-(5-(3- ((2-((S)-3-carboxybutyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid. In some aspects, the STING agonist of the conjugate of Formula (I) is (S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6- methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6-(methylamino)benzo[b]thiophen-2-yl)-2-methyl- 4-oxobutanoic acid. In some aspects, the STING agonist of the conjugate of Formula (I) is (S)-4- (5-(3-((2-((S)-3-carboxybutyl)-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid. In some aspects, the STING agonist of the conjugate of Formula (I) is(S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6- methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6-hydroxybenzo[b]thiophen-2-yl)-2-methyl-4- oxobutanoic acid. In some aspects, the STING agonist of the conjugate of Formula (I) is(S)-4-(5- (3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-hydroxybenzo[b]thiophen-5-yl)oxy)propoxy)-4- fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid. In some aspects, the STING agonist of the conjugate of Formula (I) isIn some aspects, the STING agonist of the conjugate of Formula (I) is

[0013] Compositions comprising a conjugate of Formula (II) Peptide-Linker-STING-Linker-Peptide (II) wherein Peptide is a pHLIP® peptide comprising the sequence ADQDNPWRAYLDLLFPTDTLLLDLLWCG (SEQ ID NO: 218) or ADDQNPWRAYLDLLFPTDTLLLDLLWCG (SEQ ID NO: 219); wherein Linker is a cleavable linker bonded to a carboxyl group on “STING”; wherein STING is a STING agonist, which is a dimer with a carboxylic acid subsituent (carboxyl group) at the terminal position of both monomers of the dimer; and wherein each is a covalent bond are also described herein.

[0014] In some aspects, the pHLIP® peptide of the conjugate of Formula (II) comprises the sequence ADQDNPWRAYLDLLFPTDTLLLDLLWCG (SEQ ID NO: 218). In some aspects, the pHLIP® peptide of the conjugate of Formula (II) comprises the sequence ADDQNPWRAYLDLLFPTDTLLLDLLWCG (SEQ ID NO: 219). In some aspects, the pHLIP® peptide of the conjugate of Formula (II) consists of the sequence ADQDNPWRAYLDLLFPTDTLLLDLLWCG (SEQ ID NO: 218) orADDQNPWRAYLDLLFPTDTLLLDLLWCG (SEQ ID NO: 219). In some aspects, the pHLIP® peptide of the conjugate of Formula (II) consists of the sequenceADQDNPWRAYLDLLFPTDTLLLDLLWCG (SEQ ID NO: 218). In some aspects, the pHLIP® peptide of the conjugate of Formula (II) consists of the sequenceADDQNPWRAYLDLLFPTDTLLLDLLWCG (SEQ ID NO: 219).

[0015] In some aspects, the STING agonist of the conjugate of Formula (II) is a STING agonist described in U.S. Patent No. 10,793,557, hereby incorporated by reference in its entirety.In some aspects, the STING agonist of the conjugate of Formula (II) is a STING agonist described in Pan, B.S. et al., Science 369:6506 (2020), hereby incorporated by reference in its entirety.

[0016] In some aspects, the STING agonist of the conjugate of Formula (II) is selected from the group consisting of (2S,2'S)-4,4'-[butane-l,4-diylbis(6-methoxy-l-benzothiene-5,2- diyl)]bis(2-methyl-4-oxobutanoic acid), (2S,2'S)-4,4'-[propane-l,3-diylbis(6-methoxy-l- benzothiene-5,2-diyl)]bis(2-methyl-4-oxobutanoic acid), (S)-4-(5-(3-(2-(3-carboxypropanoyl)-6- methoxybenzo[b]thiophen-5-yl)propoxy)-6-methoxythieno[3,2-b]pyridin-2-yl)-2-methyl-4- oxobutanoic acid, 4-(5-(3-((2-(3-carboxypropanoyl)-6-methoxythieno[3,2-b]pyridin-5- yl)oxy)propyl)benzo[b]thiophen-2-yl)-4-oxobutanoic acid, 4-(5-(3-(2-(3-carboxypropanoyl)-6- methoxybenzo[b]thiophen-5-yl)propoxy)-6-methoxybenzo[d]thiazol-2-yl)-4-oxobutanoic acid, 4-(5-(3-((2-(3-carboxypropanoyl)-6-methoxybenzo[b]thiophen-5-yl)oxy)propyl) benzo[b]thiophen- 2-yl)-4-oxobutanoic acid,4-(5-(2-((2-(3-carboxypropanoyl)-6-methoxybenzo[b]thiophen-5- yl)oxy)ethyl)-6-methoxythieno[3,2-b]pyridin-2-yl)-4-oxobutanoic acid, 4-(5-(2-(2-(3- carboxypropanoyl)-6-methoxythieno[3,2-b]pyridin-5-yl)ethoxy)-6-methoxythieno[3,2-b]pyridin- 2-yl)-4-oxobutanoic acid, 4-(5-(2-((2-(3-carboxypropanoyl)-6-methoxybenzo[d]thiazol-5- yl)oxy)ethyl)-6-methoxythieno[3,2-b]pyridin-2-yl)-4-oxobutanoic acid, 4-(5-(3-(2-(3- carboxypropanoyl)-6-methoxybenzo[b]thiophen-5-yl)propoxy)-6-methoxythieno[3,2-b]pyridin- 2-yl)-4-oxobutanoic acid, (S)-4-(5-(3-((2-(3-carboxypropanoyl)-6-methoxythieno[3,2-b]pyridin- 5-yl)oxy)propoxy)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, 4-(5-(3-((2- (3-carboxypropanoyl)-6-methoxybenzo[b]thiophen-5-yl)oxy)propyl)-6-methoxythieno[3,2- b]pyridin-2-yl)-4-oxobutanoic acid, (S)-4-(5-(3-((2-(3-carboxypropanoyl)-6-methoxythieno[3,2- b]pyridin-5-yl)oxy)propyl)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-(2-(3-carboxypropanoyl)-6-methoxythieno[3,2-b]pyridin-5-yl)propoxy)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-(2-((S)-3- carboxybutanoyl)-6-methoxybenzo[b]thiophen-5-yl)propoxy)-6-methoxythieno[3,2-b]pyridin-2- yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(2-((2-(3-carboxypropanoyl)-6- methoxybenzo[b]thiophen-5-yl)oxy)ethoxy)-6-methoxythieno[3,2-b]pyri din-2 -yl)-2-methyl-4- oxobutanoic acid, (S)-4-(5-(3-((2-(3-carboxypropanoyl)-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-6-methoxythieno[3,2-b]pyridin-2-yl)-2-methyl-4-oxobutanoic acid, rac-(R)-4- (5-(2-((2-((R)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)ethoxy)-6- methoxythieno[3,2-b]pyridin-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(2-((2-(3- carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)ethoxy)-6- methoxythieno[3,2-b]pyridin-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-(3- carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6- methoxythieno[3,2-b]pyridin-2-yl)-2-methyl-4-oxobutanoic acid, rac-(R)-4-(5-(3-((2-((R)-3- carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6- methoxythieno[3,2-b]pyridin-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-(3- carboxypropanoyl)-6-methoxythieno[3,2-b]pyridin-5-yl)oxy)propoxy)-4-fluoro-6- methoxybenzo[b]thi ophen-2 -yl)-2-methyl-4-oxobutanoic acid, 4-(4-(3-(2-(3-carboxypropanoyl)-5-methoxbenzo[b]thiophen-6-yl)propyl)-6-methoxybenzo[b]thiophen-2-yl)-4-oxobutanoic acid, 4,4'-(propane-l,3-diylbis(6-methoxybenzo[d]thiazole-5,2-diyl))bis(4-oxobutanoic acid), 4,4'- (propane-l,3-diylbis(6-methylbenzo[b]thiophene-5,2-diyl))bis(4-oxobutanoic acid), 4-(5-(3-(2- (3-carboxypropanoyl)-6-methoxybenzo[b]thiophen-5-yl)propyl)-6-methoxythieno[3,2-b]pyridin-2-yl)-4-oxobutanoic acid, (S)-4-(5-(3-(2-(3-carboxybutyl)-6-methoxybenzo[b]thiophen-5- yl)propyl)-6-methoxybenzo[b]thiophen-2-yl)-4-oxobutanoic acid, 4-(5-(3-((2-(3- carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propyl)-6- methoxybenzo[b]thiophen-2-yl)-4-oxobutanoic acid, (S)-4-(5-(3-(2-(3-carboxypropanoyl)-6- methoxybenzo[b]thiophen-5-yl)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl- 4-oxobutanoic acid, (S)-4-(5-(2-((2-(3-carboxypropanoyl)-6-methoxybenzo[b]thiophen-5- yl)oxy)ethoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4- (5-(3-((2-(3-carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propyl)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3- carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propyl)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-(3- carboxypropanoyl)-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(6-(3-(7-((S)-3- carboxybutanoyl)-4-methoxythieno[2',3':5,6]benzo[l,2-d]oxazol-2-yl)propoxy)-5- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (2S)-4-{5-[3-({2-[(3 S)-3- carboxybutanoyl]-6-methoxy-l-benzothiophen-5-yl}oxy)propyl]-6-methoxy-l-benzothi ophen-2- yl}-2-methyl-4-oxobutanoic acid, (S)-4-(5-(2-(2-((S)-3-carboxybutanoyl)-6- methoxybenzo[b]thiophen-5-yl)ethoxy)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4- oxobutanoic acid, (S)-4-(5-(3-((2-(3-carboxypropanoyl)benzo[b]thiophen-6-yl)oxy)propoxy)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(6-(3-((2-(3- carboxypropanoyl)benzo[b]thiophen-5-yl)oxy)propoxy)-5-methoxybenzo[b]thiophen-2-yl)-2- methyl-4-oxobutanoic acid, (2S,2'S)-4,4'-((propane-l,3-diylbis(oxy))bis(5- methoxybenzo[b]thiophene-6,2-diyl))bis(2-methyl-4-oxobutanoic acid), (2S,2'S)-4,4'-((ethane- l,2-diylbis(oxy))bis(4-fluoro-6-methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4-oxobutanoic acid), (S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-5-methoxybenzo[b]thiophen- 6-yl)oxypropoxy)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (2S,2'S)-4,4'-((propane-l,3- diylbis(oxy))bis(6-methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4-oxobutanoic acid), (S)-4- (6-(2-((2-(3-carboxypropanoyl)benzo[b]thiophen-5-yl)oxy)ethoxy)-5-methoxybenzo[b]thiophen- 2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-(3-carboxypropanoyl)benzo[b]thiophen-5- yl)oxy)propoxy)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, rac-(R)-4-(5- (2-((2-((R)-3-carboxybutanoyl)-5-methoxybenzo[b]thiophen-6-yl)oxy)ethoxy)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3- carboxybutanoyl)-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6-methoxythieno[3,2-b]pyridin-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-(3-carboxybutanoyl)-6- methoxythieno[3,2-b]pyridin-5-yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2,2- dimethyl-4-oxobutanoic acid, (2S)-4-{5-[2-({2-[(3S)-3-carboxybutanoyl]-6-methoxy-l- benzothiophen-5-yl}amino)ethyl]-6-methoxy-l-benzothiophen-2-yl}-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-6-methoxybenzo[b]thiophen-5-yl)amino)propyl)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(2-((2-(3- carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)ethoxy)-4-fluoro-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-(3- carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (R)-4-(5-(2-((2-((S)-3- carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)ethoxy)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(2-((2-((S)-3- carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)ethoxy)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, rac-(lR,2R)-2-(5-(3-((2-((R)-3- carboxybutanoyl)-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6-methoxybenzo[b]thiophene- 2-carbonyl)cyclopropane-l -carboxylic acid, (S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6- methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6-methoxybenzo[b]thi ophen-2 -yl)-2-methyl-4- oxobutanoic acid, (S)-4-(6-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-5-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3- ((2-(3-carboxybutanoyl)-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6- methoxybenzo[b]thiophen-2-yl)-2,2-dimethyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-(3- carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(6-(3-((2-(3- carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-5- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3- carboxybutanoyl)-6-methoxybenzo[b]thiophen-5-yl)amino)propoxy)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, 4-(5-((3-(2-(3-carboxypropanoyl)-6-methoxybenzo[b]thiophen-5-yl)propyl)amino)-6-methoxythieno[3,2-b]pyridin-2-yl)-4- oxobutanoic acid, (2S,2'S)-4,4'-((ethane-l,2-diylbis(oxy))bis(6-methoxybenzo[b]thiophene-5,2- diyl))bis(2-methyl-4-oxobutanoic acid), (2S,2'S)-4,4'-(7,8,17,18-tetrahydro-6H,16H- bis[l]benzothieno[5,6-b:6',5'-i][l,4,8,l l]tetraoxacyclotetradecine-2,12-diyl)bis(2-methyl-4- oxobutanoic acid), (2S,2'S)-4,4'-(7,8,17,18-tetrahydro-6H,16H-bis[l]benzothieno[5,6-b:5',6'- i] [ 1 ,4,8, 1 l]tetraoxacyclotetradecine-2, 12-diyl)bis(2-methyl-4-oxobutanoic acid), (2S,2'S)-4,4'-(l,3-propanediylbis{oxy[6-(difluoromethoxy)-l-benzothiene-5,2-diyl]})bis(2-methyl-4- oxobutanoic acid), 4-(5-(2-((2-(3-carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)ethoxy)-6-methoxythieno[3,2-b]pyridin-2-yl)-4-oxobutanoic acid, 4-(5-(3-((2-(3- carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6- methoxythieno[3,2-b]pyridin-2-yl)-4-oxobutanoic acid, (S)-4-(5-(2-((2-(3-carboxypropanoyl)-6- methoxythieno[3,2-b]pyridin-5-yl)oxy)ethoxy)-4-fluoro-6-methoxybenzo[b]thi ophen-2 -yl)-2- methyl-4-oxobutanoic acid, trans-2-(5-(3-(2-((S)-3-carboxybutanoyl)-6- methoxybenzo[b]thiophen-5-yl)propoxy)-4-fluoro-6-methoxybenzo[b]thiophene-2-carbonyl)- cyclopropanecarboxylic acid, trans-2-(5-(3-(2-(3-carboxypropanoyl)-6- methoxybenzo[b]thiophen-5-yl)propoxy)-4-fluoro-6-methoxybenzo[b]thiophene-2- carbonyl)cyclopropanecarboxylic acid, trans-2-(5-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6- methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophene-2- carbonyl)cyclopropanecarboxylic acid, trans-2-(5-(3-((2-((lR,2R)-2- carboxycyclopropanecarbonyl)-4-fluoro-6- methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4- fluoro-6-methoxybenzo[b]thiophene-2-carbonyl)cyclopropanecarboxylic acid, trans-2-(5-(3-((2- (3-carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6- methoxybenzo[b]thiophene-2-carbonyl)cyclopropanecarboxylic acid, trans-2-(5-(3-((2-((S)-3- carboxybutanoyl)-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6- methoxybenzo[b]thiophene-2-carbonyl)cyclopropanecarboxylic acid, trans-2-(5-(3-((2-((S)-3- carboxybutanoyl)-5-methoxybenzo[b]thiophen-6-yl)oxy)propoxy)-4-fluoro-6- methoxybenzo[b]thiophene-2-carbonyl)cyclopropanecarboxylic acid, (R)-4-(5-(3-((2-((S)-3- carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propyl)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (2S,2'S)-4,4'-(5,5'-(butane-l,4- diylbis(oxy))bis(6-methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4-oxobutanoic acid), (S)-4- (5-(4-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)butoxy)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(4-((2-((S)-3- carboxybutanoyl)-5-methoxybenzo[b]thiophen-6-yl)oxy)butoxy)-6-methoxybenzo[b]thiophen-2- yl)-2-methyl-4-oxobutanoic acid, trans-2-(6-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6- methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-5-methoxybenzo[b]thiophene-2- carbonyl)cyclobutanecarboxylic acid, trans-2-(5-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6- methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophene-2- carbonyl)cyclobutanecarboxylic acid, (S)-4-(5-(3-((2-((S)-3-carboxybutyl)-4-fluoro-6- methoxybenzo[b]thiophen-5-yl)oxy)propyl)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3-carboxybutyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (2S,2'S)-4,4'-(5,5'-(pentane-l,5-diylbis(oxy))bis(6-methoxybenzo[b]thiophene-5,2-diyl))bis(2- methyl-4-oxobutanoic acid), (S)-4-(5-((5-((2-((S)-3-carboxybutanoyl)-4-fluoro-6- methoxybenzo[b]thiophen-5-yl)oxy)pentyl)oxy)-6-methoxybenzo[b]thi ophen-2 -yl)-2-methyl-4- oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3-carboxybutyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propyl)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, trans-2- (5-(3-(2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)propoxy)-4-fluoro- 6-methoxybenzo[b]thiophene-2-carbonyl)cyclopropanecarboxylic acid, trans-2-(5-(3-(2-((S)-3- carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)propoxy)-4-fluoro-6- methoxybenzo[b]thiophene-2-carbonyl)cyclobutanecarboxylic acid, (R)-4-(5-(3-((2-((R)-3- carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propyl)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((R)-3- carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propyl)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-((6-((2-((S)-3- carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)hexyl)oxy)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, trans-2-(5-(3-(2-((S)-3- carboxybutanoyl)-6-methoxybenzo[b]thiophen-5-yl)propoxy)-4-fluoro-6- methoxybenzo[b]thiophene-2-carbonyl)cyclobutanecarboxylic acid, (S)-4-(5-(3-((2-(3-carboxy-3- methylbutyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propyl)-4-fluoro-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, trans-2-(5-(3-((2-((S)-3- carboxybutyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6- methoxybenzo[b]thiophene-2-carbonyl)cyclobutanecarboxylic acid, 4,4'-(5,5'-(pentane-l,5- diylbis(oxy))bis(4-fluoro-6-methoxybenzo[b]thiophene-5,2-diyl))bis(4-oxobutanoic acid), (S)-4- (5-((5-((2-(3-carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yloxy)pentyloxy)-4- fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (2S,2'S)-4,4'-(5,5'- (pentane-l,5-diylbis(oxy))bis(4-fluoro-6-methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4- oxobutanoic acid), (S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-chloro-6- methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2- methyl-4-oxobutanoic acid, (S)-4-(5-(3-((4-bromo-2-((S)-3-carboxybutanoyl)-6- methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2- methyl-4-oxobutanoic acid, (S)-4-(5-(4-((2-((S)-3-carboxybutyl)-4-fluoro-6- methoxybenzo[b]thiophen-5-yl)oxy)butoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(4-((2-((S)-3-carboxybutanoyl)-4-chloro-6- methoxybenzo[b]thiophen-5-yl)oxy)butoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2- methyl-4-oxobutanoic acid, (S)-4-(5-(4-((4-bromo-2-((S)-3-carboxybutanoyl)-6- methoxybenzo[b]thiophen-5-yl)oxy)butoxy)-4-fluoro-6-methoxybenzo[b]thi ophen-2 -yl)-2- methyl-4-oxobutanoic acid, (2S,2'S)-4,4'-(5,5'-(propane-l,3-diylbis(oxy))bis(4-chloro-6- methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4-oxobutanoic acid), (S)-4-(5-(3-((4-bromo-2- ((S)-3-carboxybutanoyl)-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-chloro-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (2S,2'S)-4,4'-(5,5'-(propane-l,3- diylbis(oxy))bis(4-bromo-6-methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4-oxobutanoic acid), 2-((5-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)methyl)cyclobutanecarboxylic acid, (S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4,7-dichloro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (2S,2'S)-4,4'-((butane-l,3-diylbis(oxy))bis(4-fluoro-6-methoxybenzo[b]thiophene-5,2- diyl))bis(2-methyl-4-oxobutanoic acid), (2S,2'S)-4,4'-((pentane-l,4-diylbis(oxy))bis(4-fluoro-6- methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4-oxobutanoic acid), (2S,2'S)-4,4'-((hexane- 2,5-diylbis(oxy))bis(4-fluoro-6-methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4-oxobutanoic acid), trans-2-(5-(3-((2-(3-carboxy- 3-methylbutyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophene-2-carbonyl)cyclobutane-l-carboxylic acid, (2S,2'S)-4,4'-(((2-methylpropane-l,3-diyl)bis(oxy))bis(4-fluoro-6- methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4-oxobutanoic acid), (2S,2'S)-4,4'-(((2,2- dimethylpropane-l,3-diyl)bis(oxy))bis(4-fluoro-6-methoxybenzo[b]thiophene-5,2-diyl))bis(2- methyl-4-oxobutanoic acid), (2S,2'S)-4,4'-(((cyclopropane-l,l-diylbis-(methylene))bis(oxy))bis(4-fluoro-6-methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4- oxobutanoic acid), (S)-4-(5-(3-((2-((S)-3-carboxybutyl)-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-chloro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4- (4-bromo-5-(3-((2-((S)-3-carboxybutyl)-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3- carboxybutyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-chl oro-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(4-bromo-5-(3-((2-((S)-3- carboxybutyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6-methoxy benzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, 4-(5-(3-((2-(3-carboxy-3-methylbutyl)-4- fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thi ophen-2-yl)-2,2-dimethyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3-carboxybutyl)-4-chloro-6- methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6-methoxybenzo[b]thi ophen-2 -yl)-2-methyl-4- oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3-carboxybutyl)-4-chloro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (2S,2'S)-4,4'-((ethane-l,2-diylbis(oxy))bis(4-chloro-6-methoxybenzo[b]thiophene-5,2- diyl))bis(2-methyl-4-oxobutanoic acid), (S)-4-(5-(2-((2-((S)-3-carboxybutyl)-4-chloro-6- methoxybenzo[b]thiophen-5-yl)oxy)ethoxy)-4-chloro-6-methoxybenzo[b]thiophen-2-yl)-2- methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-chloro-6- methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6-methoxybenzo[b]thi ophen-2 -yl)-2-methyl-4- oxobutanoic acid, (2 S,2 ' S)-4,4 '-((propane- 1 , 3 -diylbi s(oxy))bi s(4-fluoro-6- methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4-oxobutanoic acid), (S)-4-(5-(3-((2-((S)-3- carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6- (methylamino)benzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3- carboxybutyl)-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-(2-((S)-3- carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)propoxy)-6-methoxythieno[3,2- b]pyridin-2-yl)-2-methyl-4-oxobutanoic acid, (2S,2'S)-4,4'-(((2-methylpropane-l,3- diyl)bis(oxy))bis(6-methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4-oxobutanoic acid), (S)- 4-(5-(3-((2-(3-carboxypropanoyl)-6-methoxybenzo[b]thiophen-5-yl)oxy)propyl)-4-fluoro-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-(2-((S)-3- carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)propoxy)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-(3- carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propyl)-4-fluoro-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3- carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propyl)-4-fluoro-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3- carboxybutanoyl)-5-methoxythieno[3,2-b]pyridin-6-yl)oxy)propoxy)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(6-(3-((2-((S)-3- carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-5- methoxythieno[3,2-b]pyri din-2 -yl)-2-methyl-4-oxobutanoic acid, (S)-4-(6-(3-((2-(3- carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-5- methoxythieno[3,2-b]pyridin-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3- carboxybutyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, trans-2-(5-(3-((2-((S)-3- carboxybutanoyl)-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6- methoxybenzo[b]thiophene-2-carbonyl)cyclobutanecarboxylic acid, trans-2-(5-(3-((2-((S)-3- carboxybutanoyl)-5-methoxybenzo[b]thiophen-6-yl)oxy)propoxy)-4-fluoro-6- methoxybenzo[b]thiophene-2-carbonyl)cyclobutanecarboxylic acid, (2S,2'S)-4,4'-(5,5 '-(butane- l,4-diylbis(oxy))bis(4-chloro-6-methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4- oxobutanoic acid), (4-(5-(3-((2-(3-carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propyl)-6-methoxythieno[3,2-b]pyridin-2-yl)-4-oxobutanoic acid, (S)-4-(5-(3-(2-(3- carboxypropanoyl)-6-methoxythieno[3,2-b]pyridin-5-yl)propoxy)-4-fluoro-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-((3-((2-((S)-3- carboxybutanoyl)-4-fluoro-6-methoxybenzo [b]thiophen-5-yl)oxy)propyl)amino)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-((3-(2-(3- carboxypropanoyl)-6-methoxybenzo[b]thiophen-5-yl)propyl)amino)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3- carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6- hydroxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3- carboxybutyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6- hydroxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3- carboxybutanoyl)-4-chloro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6- hydroxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3- carboxybutanoyl)-4-chloro-6-hydroxybenzo[b]thiophen-5-yl)oxy)propoxy)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3- carboxybutanoyl)-4-chloro-6-hydroxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6- methoxybenzo[b]thiophen-2-yl)- 2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3- carboxybutyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-chl oro-6- hydroxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3- carboxybutanoyl)-4-chloro-6-hydroxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-chloro-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3- carboxybutanoyl)-4-fluoro-6-hydroxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3- carboxybutanoyl)-4-fluoro-6-hydroxybenzo[b]thiophen-5-yl)oxy)propoxy)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-chloro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6- hydroxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,

[0017] In some aspects, the STING agonist of the conjugate of Formula (II) is selected from the group consisting of (S)-4-(5-(3-((2-((S)-3-carboxybutyl)-4-fluoro-6- methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2- methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6- methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6-(methylamino)benzo[b]thiophen-2-yl)-2-methyl- 4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3-carboxybutyl)-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)- 4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6- hydroxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3- carboxybutanoyl)-4-fluoro-6-hydroxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,

[0018] In some aspects, the STING agonist of the conjugate of Formula (II) is (S)-4-(5-(3 - ((2-((S)-3-carboxybutyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid. In some aspects, the STING agonist of the conjugate of Formula (II) is (S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6- methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6-(methylamino)benzo[b]thiophen-2-yl)-2-methyl- 4-oxobutanoic acid. In some aspects, the STING agonist of the conjugate of Formula (II) is (S)-4- (5-(3-((2-((S)-3-carboxybutyl)-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid. In aspects, the STING agonist of the conjugate of Formula (II) is (S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6- methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6-hydroxybenzo[b]thiophen-2-yl)-2-methyl-4- oxobutanoic acid. In some aspects, the STING agonist of the conjugate of Formula (II) is (S)-4-(5- (3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-hydroxybenzo[b]thiophen-5-yl)oxy)propoxy)-4- fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid. In some aspects, the STING agonist of the conjugate of Formula (II) isIn some aspects, the STING agonist of the conjugate of Formula (II) is

[0019] In some aspects, all amino acids in the pHLIP® peptide of the conjugates of Formula(I) and Formula (II) are D-amino acids.

[0020] In some aspects, one or both Linkers of the conjugates of Formula (I) and Formula(II) comprise a disulfide bond or an acid-labile bond. In some aspects, one or both Linkers of the conjugates of Formula (I) and Formula (II) are self-immolative. In some aspects, one or both Linkers of the conjugates of Formula (I) and Formula (II) comprise a disulfide self-immolative bond. In some aspects the Linkers of the conjugate of Formula (I) or Formula (II) are the same or different.

[0021] In some aspects, pharmaceutical compositions comprising at least one of the compositions disclosed herein and one or more pharmaceutically excipients are provided.

[0022] In some aspects, methods of treating cancer in a subject in need thereof comprising administering a composition or a pharmaceutical composition disclosed herein to the subject are provided. In some aspects, the cancer is a solid tumor. In some aspects, a composition or pharmaceutical composition disclosed herein is injected directly into a tumor mass. In some aspects, a composition or pharmaceutical composition disclosed herein is administered systemically. In some aspects, the subject is a human.DESCRIPTION OF THE DRAWINGS

[0023] FIG. 1 shows schematic representation of 2pHLIP®-dMSA interaction with a membrane lipid bilayer. The chemical structure of dMSA and proposed interaction with 2 pHLIP® peptides are shown in FIG. 1A. FIG. IB shows schematics of 2pHLIP®-dMSA reversible interactions with the membranes of cells with normal surface pH (pHs = 7.2) in healthy tissue and membranes of acidic cells with surface pHs < 6.2 found in diseased tissues.

[0024] FIG. 2 shows the kinetics of self-immolation of 2pHLIP®-dMSA. HPLC chromatograms recorded at 280 nm and 325 nm for 2pHLIP®-dMSA treated with Dithiothreitol(DTT) dissolved in 50 mM phosphate buffer containing 150 mM NaCl pH 7.4 at different time points (0, 0.5, 1, 2, 4, 24, 48 hrs) after addition of DTT (FIGs. 2A-2G), and the retention time for dMSA (FIG. 2H) are shown.

[0025] FIG. 3 shows the interactions of 2pHLIP®-dMSA with liposome lipid bilayers. Fluorescence (FIG. 3A) and circular dichroism (CD) (FIG. 3B) spectra of 2pHLIP®-dMSA in solution at pH 7.4 (line 1), in the presence of l-palmitoyl-2-oleoyl-sn-glycero-3 -phosphocholine (POPC) liposomes at pH 7.4 (line 2) and in the presence of POPC liposomes at pH 3.5 (line 3) are shown. CD spectral signals were normalized per peptide and multiplied by (-1), since the D-amino acid pHLIP® peptides used in the study invert the usual CD spectrum. pH-dependent transitions monitored by changes of CD spectral signal in presence of POPC liposomes (experimental points and fitting curves with 95% confidence interval) are presented (FIG. 3C). Kinetics of fluorescence changes triggered by pH drops (FIGs. 3D-3E) and pH increases (FIG. 3F) in presence of POPC liposomes are shown.

[0026] FIG. 4 shows in vitro interferon (IFN) activations, biodistribution, pharmacokinetics (PK) and human serum albumin (HSA) binding induced by 2pHLIP®-dMSA. Activation of the IFN signaling pathway induced by 2pHLIP®-dMSA in THP-l-Blue-ISG (a human leukemia monocytic cell modified to express an interferon (IFN) regulatory factor (IRF)- inducible secreted embryonic alkaline phosphatase (SEAP) reporter construct) cells polarized by phorbol 12-myristate 13-acetate (PMA), Interleukin-4 (IL-4) / IL-13 into M2-type macrophages (alternatively activated macrophages) is shown (FIG. 4A). The results were normalized to the activity of dMSA alone at the maximum concentration tested, which was taken as 1. Kinetics of 2(ICG-pHLIP®)-dMSA targeting Colon Tumor #26 (CT26) tumor and clearance of the agent from major organs are shown (FIG. 4B). The mean fluorescence per area was calculated for each organ and tissue collected at different timepoints after single retro-orbital (RO) injection of 2(ICG- pHLIP®)-dMSA (50 pM 100 Ill). Normalized fluorescence recorded in blood, which was collected at different time points after single RO injection of 2(ICG-pHLIP®)-dMSA is shown (mean and Sd.). The data were fitted with an exponential function (FIG. 4C). Changes of Dansylamide (DNS A) (FIG. 4D) and Dansylglycine (DNSG) (FIG. 4E) fluorescence with increasing HSA concentration in absence (line 1) or presence of 5 pM (line 2) or 10 pM (line 3) of 2pHLIP®-dMSA are shown. The global fitting was performed with each set of data (FIG. 4D-4E) and the fitting curves are shown as lines 1-3.

[0027] FIG. 5 shows activation of cytokines after a single RO injection of 2pHLIP®- dMSA. Levels of tumor necrosis factor-a (TNF-a) (FIG. 5A-5B), IL-6 (FIG. 5C-5D), INF- (FIG. 5E-5F), IFN-y (FIG. 5G-5H) and INF-a (FIG. 5I-5J) cytokines are shown in tumors and serum as established by enzyme-linked immunosorbent assay (ELISA) at 6 and 24 hours after a single RO injection of 2pHLIP®-dMSA (300 pM 500 pl) in comparison to control mice (all points, mean and standard error (SE) are shown, * indicates that the / ?-level is <0.02 and ** indicates that the / ?-level is <0.002, otherwise differences are statistically insignificant, -levels were calculated using the Kolmogorov- Smirnov two-tailed nonparametric test).

[0028] FIG. 6 shows the reduction of size of CT26 tumors and development of immune memory following two intraperitoneal (IP) injections of 2pHLIP®-dMSA. The experimental design is presented (FIG. 6A). Right flank CT26 tumor growth curves in Bagg Albino (Balb / c) mice are shown after two IP injections of 2pHLIP®-dMSA (FIG. 6B), dMSA (FIG. 6D) at dose 300 pM 500 pl per injection, 2pHLIP®-dMSA at lower dose (l.d.) 100 pM 500 pl per injection (FIG. 6C), and vehicle (FIG. 6E) performed on days 1 and 3, when tumors had reached about 100-150 mm3in volume. The average changes of mouse body weights after two IP injections of 2pHLIP®-dMSA (FIG. 6F) and 2pHLIP®-dMSA at lower dose (FIG. 6G) are shown. Kaplan-Meier survival plots are shown (FIG. 6H).

[0029] FIG. 7 shows the results of a competitive binding assay. DNSA and DNSG fluorescent dye binding constants with HSA (KDNSA and KDNSG) in the absence and presence of pHLIP®, pHLIP®-mMSA, 2pHLIP®-dMSA, warfarin and ibuprophen are shown.

[0030] FIG. 8 shows the binding of constructs to STING protein. Binding of 2’ 3 ’-cyclic guanosine monophosphate-adenosine monophosphate (2’3’-cGAMP) (control) (FIG. 8 A), monomeric mMSA (FIG. 8B) and dimeric dMSA (FIG. 8C) with human STING wild-type (WT) protein was measured by the homogeneous time resolved fluorescence (HTRF) binding competitive assay which uses d2-labeled STING ligand, a 6His tagged human STING protein, and an anti 6His cryptate-labeled antibody. Investigated STING agonists (STINGa) were competing with the STING ligand-d2 and prevented fluorescence resonance energy transfer (FRET). Half- maximal inhibitory concentration (IC50) values are from curve fitting.

[0031] FIG. 9 shows a schematic representation of pHLIP®-mMSA interaction with a membrane. The chemical structure of mMSA is shown in FIG. 9A. FIG. 9B shows schematics of pHLIP®-mMSA interactions with a cell membrane with normal surface pH (pHs = 7.2) in healthytissues and membrane of acidic cells with surface pHs < 6.2 found in diseased tissues. The circular object on the end of the black line represents monomeric MSA.

[0032] FIG. 10 shows the kinetics of self-immolation of pHLIP®-mMSA. High- performance liquid chromatography (HPLC) chromatograms recorded at 280 nm and 325 nm for pHLIP®-mMSA treated with DTT dissolved in 50 mM phosphate buffer containing 150 mM NaCl pH 7.4 at different time points (0, 0.5, 1, 2, 4, 24 hrs) after addition of DTT (FIGs. 10A-10F) and the retention time for mMSA (FIG. 10G) and pHLIP® (FIG. 10H) are shown.

[0033] FIG. 11 shows the interaction of pHLIP®-mMSA with liposome lipid bilayers. Fluorescence (FIG. 11 A) and CD (FIG. 11B) spectra of pHLIP®-mMSA in solution at pH 7.4 (line 1), in the presence of POPC liposomes at pH 7.4 (line 2) and in the presence of POPC liposomes at pH 3.5 (line 3) are shown. CD spectral signals were multiplied by (-1), since D-amino acid pHLIP® peptides were used in the study. pH-dependent transitions monitored by changes of the CD spectral signal in the presence of POPC liposomes (experimental points and fitting curves with 95% confidence interval) is shown (FIG. 11C). Kinetics of fluorescence changes triggered by a pH drop (FIG. 11D-11E) or pH increase (FIG. HF) in the presence of POPC liposomes are shown.

[0034] FIG. 12 shows the biodistribution of 2(ICG-pHLIP®)-dMSA in organs and tissues. Mean fluorescence per area was calculated in tumor (FIG. 12A), liver (FIG. 12B), kidneys (FIG. 12C), lung (FIG. 12D), heart (FIG. 12E), spleen (FIG. 12F), pancreas (FIG. 12G), large intestine (FIG. 12H), small intestine (FIG. 121), bone (FIG. 12J), brain (FIG. 12K), and muscle (FIG. 12L) conditions at different time points after a single RO injection of the agent. All points, means and standard errors are shown.

[0035] FIG. 13 shows changes in DNS A and DNSG fluorescence in various experimental conditions. Changes of DNSA (FIG. 13A-13C) and DNSG (FIG. 13D-13F) fluorescence with increasing HSA concentration in absence (line 1) or presence of 5 pM (line 2) or 10 pM (line 3) of pHLIP® (FIG. 13A and 13D), pHLIP®-mMSA (FIG. 13B and 13E), warfarin (FIG. 13C) and ibuprofen (FIG. 13F) are shown. The global fitting was performed with each set of data and the fitting curves are shown as lines 1-3.DETAILED DESCRIPTION

[0036] Compositions comprising two pHLIP® peptides each of which is linked to a STING agonist, which is a dimer with a carboxylic acid subsituent (carboxyl group) at the terminal position of both monomers of the dimer, are described herein.

[0037] A pHLIP® peptide (pH Low Insertion Peptide) is a linear, water-soluble membrane peptide that interacts weakly with a cell membrane at neutral pH, without insertion into the lipid bilayer; however, at slightly acidic pH (<7.0), pHLIP® inserts into the cell membrane and forms a stable transmembrane alpha-helix. In addition to tumor cells characterized by low pH (<7.0), immune cells within a tumor mass are also characterized by low pH (<7.0). For example, the cells within the environment of a tumor mass, e.g., macrophages, are also characterized by low pH. By binding a pHLIP® to a STING agonist, the compositions and methods specifically deliver the drug directly to the cancerous and immune (macrophages) cells and into their cytosols due to their acidic cell surfaces. Delivering a STING agonist using pHLIP® peptides boosts the immune system, e.g., by stimulating the production of interferon-gamma, to mount and / or establish a tumor specific immune response and fight the cancer.Definitions

[0038] As used herein, “effective,” when referring to an amount of a composition, refers to the quantity of the composition that is sufficient to yield a desired response. For example, the amount of cargo, e.g., STING agonist yields a desired response, e.g., augmentation of an antitumor effect, without undue adverse side effects (such as toxicity, irritation, or allergic response) commensurate with a reasonable benefit / risk ratio when used in the manner of this disclosure.

[0039] In some embodiments, a subject is a mammal. In certain embodiments, the mammal is a rodent (e.g., a mouse or a rat), a primate (e.g., a chimpanzee, a gorilla, a monkey, a gibbon, a baboon), a cow, a camel, a dog, a cat, a horse, a llama, a sheep, a goat, or a pig. In some embodiments, the subject is a human.

[0040] The transitional term “comprising,” which is synonymous with “including,” “containing,” or “characterized by,” is inclusive or open-ended and does not exclude additional, unrecited elements or method steps. By contrast, the transitional phrase “consisting of’ excludes any element, step, or ingredient not specified in the claim. The transitional phrase “consisting essentially of’ limits the scope of a claim to the specified materials or steps “and those that do not materially affect the basic and novel characteristic(s)” of the claimed invention.

[0041] As used herein, the singular forms “a,” “an,” and “the” include the plural reference unless the context clearly dictates otherwise. Thus, for example, a reference to “a disease,” “a disease state”, or “an amino acid” is a reference to one or more such embodiments, and includes equivalents thereof known to those skilled in the art and so forth.

[0042] As used herein, the term "about," when used to modify an amount related to the invention, refers to variation in the numerical quantity that can occur, for example, through routine testing and handling; through inadvertent error in such testing and handling; through differences in the manufacture, source, or purity of ingredients employed in the invention; and the like. Whether or not modified by the term "about", numerical values recited herein, including in the claims, include equivalents of the recited quantities. In some aspects, the term "about" means plus or minus 10% of the reported numerical value.

[0043] As used herein, “treating” encompasses, e.g., inhibition, regression, or stasis of the progression of a disorder. Treating also encompasses the prevention or amelioration of any symptom or symptoms of the disorder. As used herein, “inhibition” of disease progression or a disease complication in a subject means preventing or reducing the disease progression and / or disease complication in the subject.

[0044] As used herein, “pharmaceutically acceptable” carrier or excipient refers to a carrier or excipient that is suitable for use with humans and / or animals without undue adverse side effects (such as toxicity, irritation, and allergic response) commensurate with a reasonable benefit / risk ratio. It can be, e.g., a pharmaceutically acceptable solvent, suspending agent or vehicle, for delivering the instant compounds to the subject.

[0045] As used herein, “MSA”, “mMSA”, and “monomeric MSA” refers to a compound of the following structure:

[0046] As used herein, “dMSA” and “dimeric MSA” refers to a compound of the following structure:

[0047] As used herein, “2pHLIP®-dMSA” refers to a structure as described in FIG. 1 where dMSA is linked to a pHLIP® of SEQ ID NO: 218 through the carboxylic acid subsituent (carboxyl group) at the terminal position of both monomers of the dimer.

[0048] As used herein, “2(ICG-pHLIP®)-dMSA” refers to a structure as described in FIG. 1 where dMSA is linked to a pHLIP® of SEQ ID NO: 221 through the carboxylic acid subsituent (carboxyl group) at the terminal position of both monomers of the dimer. Indocyanine green is conjugated with the lysine residue at the N-terminal end of the pHLIP®.

[0049] As used herein, “pHLIP®-mMSA” refers to a structure as described in FIG. 9 where mMSA is linked to a pHLIP® of SEQ ID NO: 218 through the carboxylic acid subsituent (carboxyl group) at the terminal position of the monomer.

[0050] Each embodiment disclosed herein is contemplated as being applicable to each of the other disclosed embodiments. Thus, all combinations of the various elements described herein are within the scope of the invention.

[0051] Other features and advantages of the invention will be apparent from the following description of the preferred embodiments thereof, and from the claims. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, suitable methods and materials are described below.STING agonists

[0052] In some aspects, the STING agonist of the conjugates of Formula (I) and Formula (II) is a STING agonist described in U.S. Patent No. 10,793,557, hereby incorporated by reference in its entirety. In some aspects, the STING agonist of the conjugates of Formula (I) and Formula (II) is a STING agonist described in Pan, B.S. etal., Science 369:6506 (2020), hereby incorporated by reference in its entirety.

[0053] Exemplary STING agonists of the conjugates of Formula (I) and Formula (II) include, but in relation to Formula (II), are not limited to, (2S,2'S)-4,4'-[butane-l,4-diylbis(6- methoxy-l-benzothiene-5,2-diyl)]bis(2-methyl-4-oxobutanoic acid), (2S,2'S)-4,4'-[propane-l,3- diylbis(6-methoxy-l-benzothiene-5,2-diyl)]bis(2-methyl-4-oxobutanoic acid), (S)-4-(5-(3-(2-(3- carboxypropanoyl)-6-methoxybenzo[b]thiophen-5-yl)propoxy)-6-methoxythieno[3,2-b]pyridin- 2-yl)-2-methyl-4-oxobutanoic acid, 4-(5-(3-((2-(3-carboxypropanoyl)-6-methoxythieno[3,2- b]pyridin-5-yl)oxy)propyl)benzo[b]thiophen-2-yl)-4-oxobutanoic acid, 4-(5-(3-(2-(3-carboxypropanoyl)-6-methoxybenzo[b]thiophen-5-yl)propoxy)-6-methoxybenzo[d]thiazol-2-yl)-4-oxobutanoic acid, 4-(5-(3-((2-(3-carboxypropanoyl)-6-methoxybenzo[b]thiophen-5- yl)oxy)propyl) benzo[b]thiophen-2-yl)-4-oxobutanoic acid,4-(5-(2-((2-(3-carboxypropanoyl)-6- methoxybenzo[b]thiophen-5-yl)oxy)ethyl)-6-methoxythieno[3,2-b]pyridin-2-yl)-4-oxobutanoic acid, 4-(5-(2-(2-(3-carboxypropanoyl)-6-methoxythieno[3,2-b]pyridin-5-yl)ethoxy)-6- methoxythieno[3,2-b]pyridin-2-yl)-4-oxobutanoic acid, 4-(5-(2-((2-(3-carboxypropanoyl)-6- methoxybenzo[d]thiazol-5-yl)oxy)ethyl)-6-methoxythieno[3,2-b]pyridin-2-yl)-4-oxobutanoic acid, 4-(5-(3-(2-(3-carboxypropanoyl)-6-methoxybenzo[b]thiophen-5-yl)propoxy)-6- methoxythieno[3,2-b]pyridin-2-yl)-4-oxobutanoic acid, (S)-4-(5-(3-((2-(3-carboxypropanoyl)-6- methoxythieno[3,2-b]pyridin-5-yl)oxy)propoxy)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4- oxobutanoic acid, 4-(5-(3-((2-(3-carboxypropanoyl)-6-methoxybenzo[b]thiophen-5- yl)oxy)propyl)-6-methoxythieno[3,2-b]pyridin-2-yl)-4-oxobutanoic acid, (S)-4-(5-(3-((2-(3- carboxypropanoyl)-6-methoxythieno[3,2-b]pyridin-5-yl)oxy)propyl)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-(2-(3- carboxypropanoyl)-6-methoxythieno[3,2-b]pyridin-5-yl)propoxy)-6-methoxybenzo[b]thiophen- 2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-(2-((S)-3-carboxybutanoyl)-6- methoxybenzo[b]thiophen-5-yl)propoxy)-6-methoxythieno[3,2-b]pyridin-2-yl)-2-methyl-4- oxobutanoic acid, (S)-4-(5-(2-((2-(3-carboxypropanoyl)-6-methoxybenzo[b]thiophen-5- yl)oxy)ethoxy)-6-methoxythieno[3,2-b]pyridin-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3- ((2-(3-carboxypropanoyl)-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6-methoxythieno[3,2- b]pyridin-2-yl)-2-methyl-4-oxobutanoic acid, rac-(R)-4-(5-(2-((2-((R)-3-carboxybutanoyl)-4- fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)ethoxy)-6-methoxythieno[3,2-b]pyridin-2-yl)-2- methyl-4-oxobutanoic acid, (S)-4-(5-(2-((2-(3-carboxypropanoyl)-4-fluoro-6- methoxybenzo[b]thiophen-5-yl)oxy)ethoxy)-6-methoxythieno[3,2-b]pyri din-2 -yl)-2-methyl-4- oxobutanoic acid, (S)-4-(5-(3-((2-(3-carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-6-methoxythieno[3,2-b]pyridin-2-yl)-2-methyl-4-oxobutanoic acid, rac-(R)-4- (5-(3-((2-((R)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6- methoxythieno[3,2-b]pyridin-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-(3- carboxypropanoyl)-6-methoxythieno[3,2-b]pyridin-5-yl)oxy)propoxy)-4-fluoro-6- methoxybenzo[b]thi ophen-2 -yl)-2-methyl-4-oxobutanoic acid, 4-(4-(3-(2-(3-carboxypropanoyl)-5-methoxbenzo[b]thiophen-6-yl)propyl)-6-methoxybenzo[b]thiophen-2-yl)-4-oxobutanoic acid, 4,4'-(propane-l,3-diylbis(6-methoxybenzo[d]thiazole-5,2-diyl))bis(4-oxobutanoic acid), 4,4'- (propane-l,3-diylbis(6-methylbenzo[b]thiophene-5,2-diyl))bis(4-oxobutanoic acid), 4-(5-(3-(2-(3-carboxypropanoyl)-6-methoxybenzo[b]thiophen-5-yl)propyl)-6-methoxythieno[3,2-b]pyridin- 2-yl)-4-oxobutanoic acid, (S)-4-(5-(3-(2-(3-carboxybutyl)-6-methoxybenzo[b]thiophen-5- yl)propyl)-6-methoxybenzo[b]thiophen-2-yl)-4-oxobutanoic acid, 4-(5-(3-((2-(3- carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propyl)-6- methoxybenzo[b]thiophen-2-yl)-4-oxobutanoic acid, (S)-4-(5-(3-(2-(3-carboxypropanoyl)-6- methoxybenzo[b]thiophen-5-yl)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl- 4-oxobutanoic acid, (S)-4-(5-(2-((2-(3-carboxypropanoyl)-6-methoxybenzo[b]thiophen-5- yl)oxy)ethoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4- (5-(3-((2-(3-carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propyl)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3- carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propyl)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-(3- carboxypropanoyl)-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(6-(3-(7-((S)-3- carboxybutanoyl)-4-methoxythieno[2',3':5,6]benzo[l,2-d]oxazol-2-yl)propoxy)-5- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (2S)-4-{5-[3-({2-[(3 S)-3- carboxybutanoyl]-6-methoxy-l-benzothiophen-5-yl}oxy)propyl]-6-methoxy-l-benzothi ophen-2- yl}-2-methyl-4-oxobutanoic acid, (S)-4-(5-(2-(2-((S)-3-carboxybutanoyl)-6- methoxybenzo[b]thiophen-5-yl)ethoxy)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4- oxobutanoic acid, (S)-4-(5-(3-((2-(3-carboxypropanoyl)benzo[b]thiophen-6-yl)oxy)propoxy)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(6-(3-((2-(3- carboxypropanoyl)benzo[b]thiophen-5-yl)oxy)propoxy)-5-methoxybenzo[b]thiophen-2-yl)-2- methyl-4-oxobutanoic acid, (2S,2'S)-4,4'-((propane-l,3-diylbis(oxy))bis(5- methoxybenzo[b]thiophene-6,2-diyl))bis(2-methyl-4-oxobutanoic acid), (2S,2'S)-4,4'-((ethane- l,2-diylbis(oxy))bis(4-fluoro-6-methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4-oxobutanoic acid), (S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-5-methoxybenzo[b]thiophen- 6-yl)oxypropoxy)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (2S,2'S)-4,4'-((propane-l,3- diylbis(oxy))bis(6-methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4-oxobutanoic acid), (S)-4- (6-(2-((2-(3-carboxypropanoyl)benzo[b]thiophen-5-yl)oxy)ethoxy)-5-methoxybenzo[b]thiophen- 2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-(3-carboxypropanoyl)benzo[b]thiophen-5- yl)oxy)propoxy)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, rac-(R)-4-(5- (2-((2-((R)-3-carboxybutanoyl)-5-methoxybenzo[b]thiophen-6-yl)oxy)ethoxy)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6-methoxythieno[3,2- b]pyridin-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-(3-carboxybutanoyl)-6- methoxythieno[3,2-b]pyridin-5-yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2,2- dimethyl-4-oxobutanoic acid, (2S)-4-{5-[2-({2-[(3S)-3-carboxybutanoyl]-6-methoxy-l- benzothiophen-5-yl}amino)ethyl]-6-methoxy-l-benzothiophen-2-yl}-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-6-methoxybenzo[b]thiophen-5-yl)amino)propyl)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(2-((2-(3- carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)ethoxy)-4-fluoro-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-(3- carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (R)-4-(5-(2-((2-((S)-3- carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)ethoxy)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(2-((2-((S)-3- carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)ethoxy)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, rac-(lR,2R)-2-(5-(3-((2-((R)-3- carboxybutanoyl)-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6-methoxybenzo[b]thiophene- 2-carbonyl)cyclopropane-l -carboxylic acid, (S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6- methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6-methoxybenzo[b]thi ophen-2 -yl)-2-methyl-4- oxobutanoic acid, (S)-4-(6-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-5-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3- ((2-(3-carboxybutanoyl)-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6- methoxybenzo[b]thiophen-2-yl)-2,2-dimethyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-(3- carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(6-(3-((2-(3- carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-5- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3- carboxybutanoyl)-6-methoxybenzo[b]thiophen-5-yl)amino)propoxy)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, 4-(5-((3-(2-(3-carboxypropanoyl)-6-methoxybenzo[b]thiophen-5-yl)propyl)amino)-6-methoxythieno[3,2-b]pyridin-2-yl)-4- oxobutanoic acid, (2S,2'S)-4,4'-((ethane-l,2-diylbis(oxy))bis(6-methoxybenzo[b]thiophene-5,2- diyl))bis(2-methyl-4-oxobutanoic acid), (2S,2'S)-4,4'-(7,8,17,18-tetrahydro-6H,16H- bis[l]benzothieno[5,6-b:6',5'-i][l,4,8,l l]tetraoxacyclotetradecine-2,12-diyl)bis(2-methyl-4- oxobutanoic acid), (2S,2'S)-4,4'-(7,8,17,18-tetrahydro-6H,16H-bis[l]benzothieno[5,6-b:5',6'-i] [ 1 ,4,8, 1 l]tetraoxacyclotetradecine-2, 12-diyl)bis(2-methyl-4-oxobutanoic acid), (2S,2'S)-4,4'- (l,3-propanediylbis{oxy[6-(difluoromethoxy)-l-benzothiene-5,2-diyl]})bis(2-methyl-4- oxobutanoic acid), 4-(5-(2-((2-(3-carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)ethoxy)-6-methoxythieno[3,2-b]pyridin-2-yl)-4-oxobutanoic acid, 4-(5-(3-((2-(3- carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6- methoxythieno[3,2-b]pyridin-2-yl)-4-oxobutanoic acid, (S)-4-(5-(2-((2-(3-carboxypropanoyl)-6- methoxythieno[3,2-b]pyridin-5-yl)oxy)ethoxy)-4-fluoro-6-methoxybenzo[b]thi ophen-2 -yl)-2- methyl-4-oxobutanoic acid, trans-2-(5-(3-(2-((S)-3-carboxybutanoyl)-6- methoxybenzo[b]thiophen-5-yl)propoxy)-4-fluoro-6-methoxybenzo[b]thiophene-2-carbonyl)- cyclopropanecarboxylic acid, trans-2-(5-(3-(2-(3-carboxypropanoyl)-6- methoxybenzo[b]thiophen-5-yl)propoxy)-4-fluoro-6-methoxybenzo[b]thiophene-2- carbonyl)cyclopropanecarboxylic acid, trans-2-(5-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6- methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophene-2- carbonyl)cyclopropanecarboxylic acid, trans-2-(5-(3-((2-((lR,2R)-2- carboxycyclopropanecarbonyl)-4-fluoro-6- methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4- fluoro-6-methoxybenzo[b]thiophene-2-carbonyl)cyclopropanecarboxylic acid, trans-2-(5-(3-((2- (3-carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6- methoxybenzo[b]thiophene-2-carbonyl)cyclopropanecarboxylic acid, trans-2-(5-(3-((2-((S)-3- carboxybutanoyl)-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6- methoxybenzo[b]thiophene-2-carbonyl)cyclopropanecarboxylic acid, trans-2-(5-(3-((2-((S)-3- carboxybutanoyl)-5-methoxybenzo[b]thiophen-6-yl)oxy)propoxy)-4-fluoro-6- methoxybenzo[b]thiophene-2-carbonyl)cyclopropanecarboxylic acid, (R)-4-(5-(3-((2-((S)-3- carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propyl)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (2S,2'S)-4,4'-(5,5'-(butane-l,4- diylbis(oxy))bis(6-methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4-oxobutanoic acid), (S)-4- (5-(4-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)butoxy)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(4-((2-((S)-3- carboxybutanoyl)-5-methoxybenzo[b]thiophen-6-yl)oxy)butoxy)-6-methoxybenzo[b]thiophen-2- yl)-2-methyl-4-oxobutanoic acid, trans-2-(6-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6- methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-5-methoxybenzo[b]thiophene-2- carbonyl)cyclobutanecarboxylic acid, trans-2-(5-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6- methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophene-2- carbonyl)cyclobutanecarboxylic acid, (S)-4-(5-(3-((2-((S)-3-carboxybutyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propyl)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4- oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3-carboxybutyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (2S,2'S)-4,4'-(5,5'-(pentane-l,5-diylbis(oxy))bis(6-methoxybenzo[b]thiophene-5,2-diyl))bis(2- methyl-4-oxobutanoic acid), (S)-4-(5-((5-((2-((S)-3-carboxybutanoyl)-4-fluoro-6- methoxybenzo[b]thiophen-5-yl)oxy)pentyl)oxy)-6-methoxybenzo[b]thi ophen-2 -yl)-2-methyl-4- oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3-carboxybutyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propyl)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, trans-2- (5-(3-(2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)propoxy)-4-fluoro- 6-methoxybenzo[b]thiophene-2-carbonyl)cyclopropanecarboxylic acid, trans-2-(5-(3-(2-((S)-3- carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)propoxy)-4-fluoro-6- methoxybenzo[b]thiophene-2-carbonyl)cyclobutanecarboxylic acid, (R)-4-(5-(3-((2-((R)-3- carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propyl)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((R)-3- carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propyl)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-((6-((2-((S)-3- carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)hexyl)oxy)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, trans-2-(5-(3-(2-((S)-3- carboxybutanoyl)-6-methoxybenzo[b]thiophen-5-yl)propoxy)-4-fluoro-6- methoxybenzo[b]thiophene-2-carbonyl)cyclobutanecarboxylic acid, (S)-4-(5-(3-((2-(3-carboxy-3- methylbutyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propyl)-4-fluoro-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, trans-2-(5-(3-((2-((S)-3- carboxybutyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6- methoxybenzo[b]thiophene-2-carbonyl)cyclobutanecarboxylic acid, 4,4'-(5,5'-(pentane-l,5- diylbis(oxy))bis(4-fluoro-6-methoxybenzo[b]thiophene-5,2-diyl))bis(4-oxobutanoic acid), (S)-4- (5-((5-((2-(3-carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yloxy)pentyloxy)-4- fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (2S,2'S)-4,4'-(5,5'- (pentane-l,5-diylbis(oxy))bis(4-fluoro-6-methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4- oxobutanoic acid), (S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-chloro-6- methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2- methyl-4-oxobutanoic acid, (S)-4-(5-(3-((4-bromo-2-((S)-3-carboxybutanoyl)-6- methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2- methyl-4-oxobutanoic acid, (S)-4-(5-(4-((2-((S)-3-carboxybutyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)butoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2- methyl-4-oxobutanoic acid, (S)-4-(5-(4-((2-((S)-3-carboxybutanoyl)-4-chloro-6- methoxybenzo[b]thiophen-5-yl)oxy)butoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2- methyl-4-oxobutanoic acid, (S)-4-(5-(4-((4-bromo-2-((S)-3-carboxybutanoyl)-6- methoxybenzo[b]thiophen-5-yl)oxy)butoxy)-4-fluoro-6-methoxybenzo[b]thi ophen-2 -yl)-2- methyl-4-oxobutanoic acid, (2S,2'S)-4,4'-(5,5'-(propane-l,3-diylbis(oxy))bis(4-chloro-6- methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4-oxobutanoic acid), (S)-4-(5-(3-((4-bromo-2- ((S)-3-carboxybutanoyl)-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-chloro-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (2S,2'S)-4,4'-(5,5'-(propane-l,3- diylbis(oxy))bis(4-bromo-6-methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4-oxobutanoic acid), 2-((5-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)methyl)cyclobutanecarboxylic acid, (S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4,7-dichloro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (2S,2'S)-4,4'-((butane-l,3-diylbis(oxy))bis(4-fluoro-6-methoxybenzo[b]thiophene-5,2- diyl))bis(2-methyl-4-oxobutanoic acid), (2S,2'S)-4,4'-((pentane-l,4-diylbis(oxy))bis(4-fluoro-6- methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4-oxobutanoic acid), (2S,2'S)-4,4'-((hexane- 2,5-diylbis(oxy))bis(4-fluoro-6-methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4-oxobutanoic acid), trans-2-(5-(3-((2-(3-carboxy- 3-methylbutyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophene-2-carbonyl)cyclobutane-l-carboxylic acid, (2S,2'S)-4,4'-(((2-methylpropane-l,3-diyl)bis(oxy))bis(4-fluoro-6- methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4-oxobutanoic acid), (2S,2'S)-4,4'-(((2,2- dimethylpropane-l,3-diyl)bis(oxy))bis(4-fluoro-6-methoxybenzo[b]thiophene-5,2-diyl))bis(2- methyl-4-oxobutanoic acid), (2S,2'S)-4,4'-(((cyclopropane-l,l-diylbis-(methylene))bis(oxy))bis(4-fluoro-6-methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4- oxobutanoic acid), (S)-4-(5-(3-((2-((S)-3-carboxybutyl)-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-chloro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4- (4-bromo-5-(3-((2-((S)-3-carboxybutyl)-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3- carboxybutyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-chl oro-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(4-bromo-5-(3-((2-((S)-3- carboxybutyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6-methoxy benzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, 4-(5-(3-((2-(3-carboxy-3-methylbutyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2- yl)-2,2-dimethyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3-carboxybutyl)-4-chloro-6- methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6-methoxybenzo[b]thi ophen-2 -yl)-2-methyl-4- oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3-carboxybutyl)-4-chloro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (2S,2'S)-4,4'-((ethane-l,2-diylbis(oxy))bis(4-chloro-6-methoxybenzo[b]thiophene-5,2- diyl))bis(2-methyl-4-oxobutanoic acid), (S)-4-(5-(2-((2-((S)-3-carboxybutyl)-4-chloro-6- methoxybenzo[b]thiophen-5-yl)oxy)ethoxy)-4-chloro-6-methoxybenzo[b]thiophen-2-yl)-2- methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-chloro-6- methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6-methoxybenzo[b]thi ophen-2 -yl)-2-methyl-4- oxobutanoic acid, (2 S,2 ' S)-4,4 '-((propane- 1 , 3 -diylbi s(oxy))bi s(4-fluoro-6- methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4-oxobutanoic acid), (S)-4-(5-(3-((2-((S)-3- carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6- (methylamino)benzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3- carboxybutyl)-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-(2-((S)-3- carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)propoxy)-6-methoxythieno[3,2- b]pyridin-2-yl)-2-methyl-4-oxobutanoic acid, (2S,2'S)-4,4'-(((2-methylpropane-l,3- diyl)bis(oxy))bis(6-methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4-oxobutanoic acid), (S)- 4-(5-(3-((2-(3-carboxypropanoyl)-6-methoxybenzo[b]thiophen-5-yl)oxy)propyl)-4-fluoro-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-(2-((S)-3- carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)propoxy)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-(3- carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propyl)-4-fluoro-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3- carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propyl)-4-fluoro-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3- carboxybutanoyl)-5-methoxythieno[3,2-b]pyridin-6-yl)oxy)propoxy)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(6-(3-((2-((S)-3- carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-5- methoxythieno[3,2-b]pyri din-2 -yl)-2-methyl-4-oxobutanoic acid, (S)-4-(6-(3-((2-(3- carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-5- methoxythieno[3,2-b]pyridin-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3-carboxybutyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, trans-2-(5-(3-((2-((S)-3- carboxybutanoyl)-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6- methoxybenzo[b]thiophene-2-carbonyl)cyclobutanecarboxylic acid, trans-2-(5-(3-((2-((S)-3- carboxybutanoyl)-5-methoxybenzo[b]thiophen-6-yl)oxy)propoxy)-4-fluoro-6- methoxybenzo[b]thiophene-2-carbonyl)cyclobutanecarboxylic acid, (2S,2'S)-4,4'-(5,5 '-(butane- l,4-diylbis(oxy))bis(4-chloro-6-methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4- oxobutanoic acid), (4-(5-(3-((2-(3-carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propyl)-6-methoxythieno[3,2-b]pyridin-2-yl)-4-oxobutanoic acid, (S)-4-(5-(3-(2-(3- carboxypropanoyl)-6-methoxythieno[3,2-b]pyridin-5-yl)propoxy)-4-fluoro-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-((3-((2-((S)-3- carboxybutanoyl)-4-fluoro-6-methoxybenzo [b]thiophen-5-yl)oxy)propyl)amino)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-((3-(2-(3- carboxypropanoyl)-6-methoxybenzo[b]thiophen-5-yl)propyl)amino)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3- carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6- hydroxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3- carboxybutyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6- hydroxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3- carboxybutanoyl)-4-chloro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6- hydroxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3- carboxybutanoyl)-4-chloro-6-hydroxybenzo[b]thiophen-5-yl)oxy)propoxy)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3- carboxybutanoyl)-4-chloro-6-hydroxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6- methoxybenzo[b]thiophen-2-yl)- 2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3- carboxybutyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-chl oro-6- hydroxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3- carboxybutanoyl)-4-chloro-6-hydroxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-chloro-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3- carboxybutanoyl)-4-fluoro-6-hydroxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3- carboxybutanoyl)-4-fluoro-6-hydroxybenzo[b]thiophen-5-yl)oxy)propoxy)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-chloro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6- hydroxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,

[0054] In some aspects, the STING agonist of the conjugates of Formula (I) and Formula (II) is selected from the group consisting of (S)-4-(5-(3-((2-((S)-3-carboxybutyl)-4-fluoro-6- methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2- methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6- methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6-(methylamino)benzo[b]thiophen-2-yl)-2-methyl- 4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3-carboxybutyl)-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)- 4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6- hydroxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3- carboxybutanoyl)-4-fluoro-6-hydroxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,

[0055] In some aspects, the STING agonist of the conjugates of Formula (I) and Formula (II) is (S)-4-(5-(3-((2-((S)-3-carboxybutyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid. In some aspects, the STING agonist of the conjugates of Formula (I) and Formula (II) is (S)-4-(5-(3- ((2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6- (methylamino)benzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid. In some aspects, the STING agonist of the conjugates of Formula (I) and Formula (II) is (S)-4-(5-(3-((2-((S)-3-carboxybutyl)- 6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thi ophen-2 -yl)-2- methyl-4-oxobutanoic acid. In some aspects, the STING agonist of the conjugates of Formula (I) and Formula (II) is (S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6- methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6-hydroxybenzo[b]thiophen-2-yl)-2-methyl-4- oxobutanoic acid. In some aspects, the STING agonist of the conjugates of Formula (I) and Formula (II) is (S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-hydroxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid. In some aspects, the STING agonist of the conjugates of Formula (I) and Formula (II) issome aspects, the STING agonist of the conjugates of Formula (I) and Formula (II) ispHLIP® peptides

[0056] In some aspects, the pHLIP® peptide of the conjugate of Formula (I) has the following sequence: X„Ym; YmXn; XnYmXj; YmXnYi; YmXnYiXj; XnYmXjYi; YmXnYiXjYi; XnYmXjYiXi; YmXnYiXjYiXh; XnYmXjYiXhYg; YmXnYiXj YiXhYg; XnYmXjYiXhYgXf; (XY)n; (YX)n; (XY)nYm; (YX)nYm; (XY)nXm; (YX)nXm; Ym(XY)n; Ym(YX)n; Xn(XY)m; Xn(YX)m; (XY)nYm(XY)i; (YX)nYm(YX)i; (XY)nXm(XY)i; (YX)nXm(YX)i; Ym(XY)n; Ym(YX)n; Xn(XY)m; or Xn(YX)m, wherein,(i) each Y is, independently, a non-polar amino acid with solvation energy, DGxcor> +0.50, or Glycine;(ii) each X is, independently, a protonatable amino acid, and(iii) n, m, i, j, 1, h, g, f are each, independently, an integer from 1 to 8.

[0057] In some aspects, the pHLIP® peptide of the conjugate of Formula (I) comprises a sequence comprising the sequence ADDQNPWRAYLDLLFPTDTLLLDLLWXG (SEQ ID NO: 220), wherein “X” is a functional group for conjugation purposes, selected from lysine (Lys), cysteine (Cys), Azido-containing amino acid or other modified amino acids, such as described herein in Table 3. In some aspects, the pHLIP® peptide of the conjugate of Formula (I) comprises a sequence consisting of the sequence ADDQNPWRAYLDLLFPTDTLLLDLLWXG (SEQ ID NO: 220), wherein “X” is a functional group for conjugation purposes, selected from lysine (Lys),cysteine (Cys), Azido-containing amino acid or other modified amino acids, such as described herein in Table 3.

[0058] An example of a peptide isAEQNPIYWARYADWLFTTPLLLLDLALLVDADEGT (SEQ ID NO: 3) in which AEQNPIY (SEQ ID NO: 4) represents a flanking sequence, WARYADWLFTTPLLLLDLALLV (SEQ ID NO: 5) represents a membrane-inserting sequence, and DADEGT (SEQ ID NO: 6) represents a flanking sequence.

[0059] Other exemplary pHLIP® peptides of the conjugate of Formula (I) are shown in theTables below. The sequences are provided N-terminus to C-terminus.Table 1 : Non-limiting examples of pHLIP® sequences.Table 2: Non-limiting examples of pHLIP® sequences.* Ac means Acetylated N-terminus; and Am means Amidated C-terminusTable 3: Coded and exemplary non-coded amino acids including L-isomers, D-isomers, alpha-isomers, beta-isomers, glycol-, and methyl- modifications.Table 4: Non-limiting examples of protonatable residues and their substitutions including L-isomers, D- isomers, alpha-isomers, and beta-isomers.Table 5: Examples of coded amino acid substitutions.Table 6: Non-limiting examples of membrane-inserting sequences belonging to different groups of pHLIP® peptides.

[0060] Each protonatable residue (shown in bold) could be replaced by its substitution from Table 4. Each non-polar residue could be replaced by its coded amino acid substitution from Table 5, and / or non-coded amino acid substitutions from Table 3.Table 7: Non-limiting examples of pHLIP® sequences.

[0061] A cysteine, a lysine, an azido-modified amino acid, or an alkynyl modified amino acid can be incorporated at the N-terminal (first six residues) or C-terminal (last six residues) parts of the peptides for conjugation with a cargo, and a linker.

[0062] In some aspects, the pHLIP® peptide of the conjugate of Formula (I) comprises a sequence selected from the group consisting of any one of SEQ ID NOs. 1-219. In some aspects, the pHLIP® peptide of the conjugate of Formula (I) has a sequence selected from the group consisting of any one of SEQ ID NOs. 1-219. In some aspects, the pHLIP® peptide of the conjugates of Formula (I) and Formula (II) has a sequence comprising the sequence ADQDNPWRAYLDLLFPTDTLLLDLLWCG (SEQ ID NO: 218). In some aspects, the pHLIP® peptide of the conjugates of Formula (I) and Formula (II) has a sequence comprising the sequence ADDQNPWRAYLDLLFPTDTLLLDLLWCG (SEQ ID NO: 219). In some aspects, the pHLIP® peptide of the conjugates of Formula (I) and Formula (II) has a sequence consisting of the sequence ADQDNPWRAYLDLLFPTDTLLLDLLWCG (SEQ ID NO: 218). In some aspects, the pHLIP® peptide of the conjugates of Formula (I) and Formula (II) has a sequence consisting of the sequence ADDQNPWRAYLDLLFPTDTLLLDLLWCG (SEQ ID NO: 219).Linker

[0063] A Linker can be relatively small, e.g., only a few atoms, to a rather large polymer of 4-5 kDa. A Linker can react on one end with a free thiol to spontaneously form a disulfide bond, with thiopyridine as a leaving group, and on the other end reacts with activate amine or hydroxyl groups in the presence of DIPEA (N,N-Diisopropylethylamine), and in some cases DMAP (4- Dimethylaminopyridine) or other activator base, to form a carbamate or carbonate, respectively. This material can be used if pHLIP® is protected at its amino terminus, such as with N-acetylation. This material can also be reacted with pHLIP® bearing a cysteine residue or with a thiol-bearing linker for subsequent conjugation to pHLIP®, and forms a conjugate by disulfide exchange with thiopyridine as a leaving group. This material can be used to form a conjugate with pHLIP® bearing a lysine residue, if pHLIP® is protected at its amino terminus, such as with N-acetylation.

[0064] In some aspects, one or both Linkers of the conjugates of Formula (I) and Formula (II) comprise a disulfide bond or an acid-labile bond. In some aspects, one or both Linkers of the conjugates of Formula (I) and Formula (II) are self-immolative. In some aspects, one or bothLinkers of the conjugates of Formula (I) and Formula (II) comprise a disulfide self-immolative bond. In some aspects, the two Linkers of the conjugates of Formula (I) and Formula (II) are identical or different.

[0065] In some aspects, a succinimidyl 3-(2-pyridyldithio)propionate (SPDP) cross-linker is used. SPDP is a short-chain crosslinker for amine-to-sulfhydryl conjugation via NHS-ester and pyridyl di thiol reactive groups that form cleavable (reducible) disulfide bonds with cysteine sulfhydryls. SPDP is used to activate NH2 derivative of cCDN (of e.g., c[3'-AHC- G(2',5')pA(3',5')p], or c[G(2',5')p-2'-AHC-A(3',5')p]), purify and exchange disulfide with SH of single cysteine at the C-terminus of pHLIP® peptide to obtain pHLIP®-S-S-cCDN.

[0066] In some aspects, the following cross-linkers can be used: LC-SPDP (succinimidyl 6-(3(2-pyridyldithio)propionamido)hexanoate); Sulfo-LC-SPDP (sulfosuccinimidyl 6-(3'-(2- pyridyldithio)propionamido)hexanoate); PEG4-SPDP (PEGylated, long-chain SPDP crosslinker); PEG12-SPDP (PEGylated, long-chain SPDP crosslinker); SMCC (succinimidyl 4-(N- maleimidomethyl)cyclohexane-l -carboxylate); Sulfo-SMCC (sulfosuccinimidyl 4-(N- maleimidomethyl)cyclohexane-l -carboxylate); SMPT (4-succinimidyloxycarbonyl-alpha-methyl- a(2-pyridyldithio)toluene); DTME (dithiobismaleimidoethane).

[0067] In some aspects, one or both Linkers of the conjugates of Formula (I) and Formula (II) are attached to the C-terminus of the pHLIP® peptide.Compositions

[0068] Compositions comprising a conjugate of Formula (I) Peptide-Linker-STING-Linker-Peptide (I) wherein Peptide is a pHLIP® peptide, wherein Linker is a cleavable linker bonded to a carboxyl group on “STING”; wherein “STING” is a STING agonist selected from the group consisting of (2S,2'S)-4,4'-[butane-l,4-diylbis(6-methoxy-l-benzothiene-5,2-diyl)]bis(2- methyl-4-oxobutanoic acid), (2S,2'S)-4,4'-[propane-l,3-diylbis(6-methoxy-l-benzothiene-5,2-diyl)]bis(2- methyl-4-oxobutanoic acid), (S)-4-(5-(3-(2-(3-carboxypropanoyl)-6-methoxybenzo[b]thiophen-5-yl)propoxy)- 6-methoxythieno[3,2-b]pyri din-2 -yl)-2-methyl-4-oxobutanoic acid, 4-(5-(3-((2-(3-carboxypropanoyl)-6-methoxythieno[3,2-b]pyridin-5- yl)oxy)propyl)benzo[b]thiophen-2-yl)-4-oxobutanoic acid,4-(5-(3-(2-(3-carboxypropanoyl)-6-methoxybenzo[b]thiophen-5-yl)propoxy)-6- methoxybenzo[d]thiazol-2-yl)-4-oxobutanoic acid,4-(5-(3-((2-(3-carboxypropanoyl)-6-methoxybenzo[b]thiophen-5-yl)oxy)propyl) benzo[b]thiophen-2-yl)-4-oxobutanoic acid,4-(5-(2-((2-(3-carboxypropanoyl)-6-methoxybenzo[b]thiophen-5-yl)oxy)ethyl)-6- methoxythieno[3,2-b]pyridin-2-yl)-4-oxobutanoic acid,4-(5-(2-(2-(3-carboxypropanoyl)-6-methoxythieno[3,2-b]pyridin-5-yl)ethoxy)-6- methoxythieno[3,2-b]pyridin-2-yl)-4-oxobutanoic acid,4-(5-(2-((2-(3-carboxypropanoyl)-6-methoxybenzo[d]thiazol-5-yl)oxy)ethyl)-6- methoxythieno[3,2-b]pyridin-2-yl)-4-oxobutanoic acid,4-(5-(3-(2-(3-carboxypropanoyl)-6-methoxybenzo[b]thiophen-5-yl)propoxy)-6- methoxythieno[3,2-b]pyridin-2-yl)-4-oxobutanoic acid,(S)-4-(5-(3-((2-(3-carboxypropanoyl)-6-methoxythieno[3,2-b]pyridin-5- yl)oxy)propoxy)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,4-(5-(3-((2-(3-carboxypropanoyl)-6-methoxybenzo[b]thiophen-5-yl)oxy)propyl)- 6-methoxythieno[3,2-b]pyri din-2 -yl)-4-oxobutanoic acid,(S)-4-(5-(3-((2-(3-carboxypropanoyl)-6-methoxythieno[3,2-b]pyridin-5- yl)oxy)propyl)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-(2-(3-carboxypropanoyl)-6-methoxythieno[3,2-b]pyridin-5- yl)propoxy)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-(2-((S)-3-carboxybutanoyl)-6-methoxybenzo[b]thiophen-5- yl)propoxy)-6-methoxythieno[3,2-b]pyridin-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(2-((2-(3-carboxypropanoyl)-6-methoxybenzo[b]thiophen-5- yl)oxy)ethoxy)-6-methoxythieno[3,2-b]pyridin-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-(3-carboxypropanoyl)-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-6-methoxythieno[3,2-b]pyridin-2-yl)-2-methyl-4-oxobutanoic acid, rac-(R)-4-(5-(2-((2-((R)-3-carboxybutanoyl)-4-fluoro-6- methoxybenzo[b]thiophen-5-yl)oxy)ethoxy)-6-methoxythieno[3,2-b]pyri din-2 -yl)-2- methyl-4-oxobutanoic acid,(S)-4-(5-(2-((2-(3-carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)ethoxy)-6-methoxythieno[3,2-b]pyridin-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-(3-carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-6-methoxythieno[3,2-b]pyridin-2-yl)-2-methyl-4-oxobutanoic acid,rac-(R)-4-(5-(3-((2-((R)-3-carboxybutanoyl)-4-fluoro-6- methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6-methoxythieno[3,2-b]pyri din-2 -yl)-2- methyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-(3-carboxypropanoyl)-6-methoxythieno[3,2-b]pyridin-5- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,4-(4-(3-(2-(3-carboxypropanoyl)-5-methoxbenzo[b]thiophen-6-yl)propyl)-6- methoxybenzo[b]thiophen-2-yl)-4-oxobutanoic acid,4,4'-(propane-l,3-diylbis(6-methoxybenzo[d]thiazole-5,2-diyl))bis(4-oxobutanoic acid),4,4'-(propane-l,3-diylbis(6-methylbenzo[b]thiophene-5,2-diyl))bis(4-oxobutanoic acid),4-(5-(3-(2-(3-carboxypropanoyl)-6-methoxybenzo[b]thiophen-5-yl)propyl)-6- methoxythieno[3,2-b]pyridin-2-yl)-4-oxobutanoic acid,(S)-4-(5-(3-(2-(3-carboxybutyl)-6-methoxybenzo[b]thiophen-5-yl)propyl)-6- methoxybenzo[b]thiophen-2-yl)-4-oxobutanoic acid,4-(5-(3-((2-(3-carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propyl)-6-methoxybenzo[b]thiophen-2-yl)-4-oxobutanoic acid,(S)-4-(5-(3-(2-(3-carboxypropanoyl)-6-methoxybenzo[b]thiophen-5-yl)propoxy)- 4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(2-((2-(3-carboxypropanoyl)-6-methoxybenzo[b]thiophen-5- yl)oxy)ethoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-(3-carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propyl)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propyl)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-(3-carboxypropanoyl)-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(6-(3-(7-((S)-3-carboxybutanoyl)-4-methoxythieno[2',3':5,6]benzo[l,2- d]oxazol-2-yl)propoxy)-5-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(2S)-4-{5-[3-({2-[(3 S)-3-carboxybutanoyl]-6-methoxy-l-benzothiophen-5- yl } oxy)propyl]-6-m ethoxy- 1 -benzothiophen-2-yl } -2-methyl-4-oxobutanoic acid,(S)-4-(5-(2-(2-((S)-3-carboxybutanoyl)-6-methoxybenzo[b]thiophen-5-yl)ethoxy)- 6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-(3-carboxypropanoyl)benzo[b]thiophen-6-yl)oxy)propoxy)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(6-(3-((2-(3-carboxypropanoyl)benzo[b]thiophen-5-yl)oxy)propoxy)-5- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(2S,2'S)-4,4'-((propane-l,3-diylbis(oxy))bis(5-methoxybenzo[b]thiophene-6,2- diyl))bis(2-methyl-4-oxobutanoic acid),(2S,2'S)-4,4'-((ethane-l,2-diylbis(oxy))bis(4-fluoro-6-methoxybenzo[b]thiophene- 5,2-diyl))bis(2-methyl-4-oxobutanoic acid),(S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-5-methoxybenzo[b]thiophen-6- yl)oxypropoxy)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(2S,2'S)-4,4'-((propane-l,3-diylbis(oxy))bis(6-methoxybenzo[b]thiophene-5,2- diyl))bis(2-methyl-4-oxobutanoic acid),(S)-4-(6-(2-((2-(3-carboxypropanoyl)benzo[b]thiophen-5-yl)oxy)ethoxy)-5- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-(3-carboxypropanoyl)benzo[b]thiophen-5-yl)oxy)propoxy)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, rac-(R)-4-(5-(2-((2-((R)-3-carboxybutanoyl)-5-methoxybenzo[b]thiophen-6- yl)oxy)ethoxy)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-6-methoxythieno[3,2-b]pyridin-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-(3-carboxybutanoyl)-6-methoxythieno[3,2-b]pyridin-5- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2,2-dimethyl-4-oxobutanoic acid,(2S)-4-{5-[2-({2-[(3 S)-3-carboxybutanoyl]-6-methoxy-l-benzothiophen-5- yl}amino)ethyl]-6-methoxy-l-benzothiophen-2-yl}-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-6-methoxybenzo[b]thiophen-5- yl)amino)propyl)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(2-((2-(3-carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)ethoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-(3-carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(R)-4-(5-(2-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)ethoxy)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(2-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)ethoxy)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, rac-(lR,2R)-2-(5-(3-((2-((R)-3-carboxybutanoyl)-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-6-methoxybenzo[b]thiophene-2-carbonyl)cyclopropane-l-carboxylic acid,(S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(6-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-5-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-(3-carboxybutanoyl)-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2,2-dimethyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-(3-carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(6-(3-((2-(3-carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-5-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-6-methoxybenzo[b]thiophen-5- yl)amino)propoxy)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, 4-(5-((3-(2-(3-carboxypropanoyl)-6-methoxybenzo[b]thiophen-5- yl)propyl)amino)-6-methoxythieno[3,2-b]pyridin-2-yl)-4-oxobutanoic acid,(2S,2'S)-4,4'-((ethane-l,2-diylbis(oxy))bis(6-methoxybenzo[b]thiophene-5,2- diyl))bis(2-methyl-4-oxobutanoic acid),(2S,2'S)-4,4'-(7,8,17,18-tetrahydro-6H,16H-bis[l]benzothieno[5,6-b:6',5'- i] [ 1 ,4,8, 1 l]tetraoxacyclotetradecine-2, 12-diyl)bis(2-methyl-4-oxobutanoic acid), (2S,2'S)-4,4'-(7,8,17,18-tetrahydro-6H,16H-bis[l]benzothieno[5,6-b:5',6'- i] [ 1 ,4,8, 1 l]tetraoxacyclotetradecine-2, 12-diyl)bis(2-methyl-4-oxobutanoic acid), (2S,2'S)-4,4'-(l,3-propanediylbis{oxy[6-(difluoromethoxy)-l-benzothiene-5,2- diyl] })bis(2-methyl-4-oxobutanoic acid),4-(5-(2-((2-(3-carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)ethoxy)-6-methoxythieno[3,2-b]pyridin-2-yl)-4-oxobutanoic acid,4-(5-(3-((2-(3-carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-6-methoxythieno[3,2-b]pyridin-2-yl)-4-oxobutanoic acid,(S)-4-(5-(2-((2-(3-carboxypropanoyl)-6-methoxythieno[3,2-b]pyridin-5- yl)oxy)ethoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, trans-2-(5-(3-(2-((S)-3-carboxybutanoyl)-6-methoxybenzo[b]thiophen-5- yl)propoxy)-4-fluoro-6-methoxybenzo[b]thiophene-2-carbonyl)-cyclopropanecarboxylic acid, trans-2-(5-(3-(2-(3-carboxypropanoyl)-6-methoxybenzo[b]thiophen-5- yl)propoxy)-4-fluoro-6-methoxybenzo[b]thiophene-2-carbonyl)cyclopropanecarboxylic acid, trans-2-(5-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen- 5-yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophene-2- carbonyl)cyclopropanecarboxylic acid, trans-2-(5-(3-((2-((lR,2R)-2-carboxycyclopropanecarbonyl)-4-fluoro-6- methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophene-2- carbonyl)cyclopropanecarboxylic acid, trans-2-(5-(3-((2-(3-carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophene-2- carbonyl)cyclopropanecarboxylic acid, trans-2-(5-(3-((2-((S)-3-carboxybutanoyl)-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophene-2- carbonyl)cyclopropanecarboxylic acid, trans-2-(5-(3-((2-((S)-3-carboxybutanoyl)-5-methoxybenzo[b]thiophen-6- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophene-2- carbonyl)cyclopropanecarboxylic acid,(R)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propyl)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(2S,2'S)-4,4'-(5,5'-(butane-l,4-diylbis(oxy))bis(6-methoxybenzo[b]thiophene-5,2- diyl))bis(2-methyl-4-oxobutanoic acid),(S)-4-(5-(4-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)butoxy)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(4-((2-((S)-3-carboxybutanoyl)-5-methoxybenzo[b]thiophen-6- yl)oxy)butoxy)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, trans-2-(6-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen- 5-yl)oxy)propoxy)-4-fluoro-5-methoxybenzo[b]thiophene-2- carbonyl)cyclobutanecarboxylic acid, trans-2-(5-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen- 5-yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophene-2- carbonyl)cyclobutanecarboxylic acid,(S)-4-(5-(3-((2-((S)-3-carboxybutyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propyl)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-((S)-3-carboxybutyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(2S,2'S)-4,4'-(5, 5 '-(pentane- 1, 5-diylbis(oxy))bis(6-methoxybenzo[b]thi ophene- 5,2-diyl))bis(2-methyl-4-oxobutanoic acid),(S)-4-(5-((5-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)pentyl)oxy)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-((S)-3-carboxybutyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propyl)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, trans-2-(5-(3-(2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)propoxy)-4-fluoro-6-methoxybenzo[b]thiophene-2-carbonyl)cyclopropanecarboxylic acid, trans-2-(5-(3-(2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)propoxy)-4-fluoro-6-methoxybenzo[b]thiophene-2-carbonyl)cyclobutanecarboxylic acid,(R)-4-(5-(3-((2-((R)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propyl)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-((R)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propyl)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-((6-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)hexyl)oxy)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,trans-2-(5-(3-(2-((S)-3-carboxybutanoyl)-6-methoxybenzo[b]thiophen-5- yl)propoxy)-4-fluoro-6-methoxybenzo[b]thiophene-2-carbonyl)cyclobutanecarboxylic acid,(S)-4-(5-(3-((2-(3-carboxy-3-methylbutyl)-4-fluoro-6-methoxybenzo[b]thiophen- 5-yl)oxy)propyl)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, trans-2-(5-(3-((2-((S)-3-carboxybutyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophene-2- carbonyl)cyclobutanecarboxylic acid,4,4'-(5,5'-(pentane-l,5-diylbis(oxy))bis(4-fluoro-6-methoxybenzo[b]thiophene- 5,2-diyl))bis(4-oxobutanoic acid),(S)-4-(5-((5-((2-(3-carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yloxy)pentyloxy)-4-fluoro-6-methoxybenzo[b]thi ophen-2 -yl)-2-methyl-4-oxobutanoic acid,(2 S,2 ' S)-4,4 '-(5 , 5 '-(pentane- 1 , 5 -diylbi s(oxy))bi s(4-fluoro-6- methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4-oxobutanoic acid),(S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-chloro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-((4-bromo-2-((S)-3-carboxybutanoyl)-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(4-((2-((S)-3-carboxybutyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)butoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(4-((2-((S)-3-carboxybutanoyl)-4-chloro-6-methoxybenzo[b]thiophen-5- yl)oxy)butoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(4-((4-bromo-2-((S)-3-carboxybutanoyl)-6-methoxybenzo[b]thiophen-5- yl)oxy)butoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(2S, 2'S)-4,4'-(5, 5 '-(propane-1, 3-diylbis(oxy))bis(4-chloro-6- methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4-oxobutanoic acid),(S)-4-(5-(3-((4-bromo-2-((S)-3-carboxybutanoyl)-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-chloro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(2S, 2'S)-4,4'-(5, 5 '-(propane-1, 3-diylbis(oxy))bis(4-bromo-6- methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4-oxobutanoic acid),2-((5-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2- yl)methyl)cyclobutanecarboxylic acid,(S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4,7-dichloro-6- methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thi ophen-2- yl)-2-methyl-4-oxobutanoic acid,(2 S,2 ' S)-4,4 '-((butane- 1 , 3 -diylbi s(oxy))bi s(4-fluoro-6- methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4-oxobutanoic acid),(2S,2'S)-4,4'-((pentane-l,4-diylbis(oxy))bis(4-fluoro-6- methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4-oxobutanoic acid),(2 S,2 ' S)-4,4 '-((hexane-2, 5 -diylbi s(oxy))bi s(4-fluoro-6- methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4-oxobutanoic acid), trans-2-(5-(3-((2-(3-carboxy-3-methylbutyl)-4-fluoro-6- methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophene-2- carbonyl)cyclobutane- 1 -carboxylic acid,(2 S,2 ' S)-4,4 '-(((2-methylpropane- 1 , 3 -diy 1 )b i s(oxy))bi s(4-fluoro-6- methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4-oxobutanoic acid),(2S,2'S)-4,4'-(((2,2-dimethylpropane-l,3-diyl)bis(oxy))bis(4-fluoro-6- methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4-oxobutanoic acid),(2 S, 2 ' S)-4, 4 '-(((cyclopropane- 1 , 1 -diylbi s-(methylene))bi s(oxy))bi s(4-fluoro-6- methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4-oxobutanoic acid),(S)-4-(5-(3-((2-((S)-3-carboxybutyl)-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-chloro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(4-bromo-5-(3-((2-((S)-3-carboxybutyl)-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-((S)-3-carboxybutyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-chloro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(4-bromo-5-(3-((2-((S)-3-carboxybutyl)-4-fluoro-6- methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6-methoxybenzo[b]thi ophen-2 -yl)-2- methyl-4-oxobutanoic acid,4-(5-(3-((2-(3-carboxy-3-methylbutyl)-4-fluoro-6-methoxybenzo[b]thi ophen-5- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2,2-dimethyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-((S)-3-carboxybutyl)-4-chloro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-((S)-3-carboxybutyl)-4-chloro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(2 S,2 ' S)-4,4 '-((ethane- 1 ,2-diylbi s(oxy))bi s(4-chloro-6- methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4-oxobutanoic acid),(S)-4-(5-(2-((2-((S)-3-carboxybutyl)-4-chloro-6-methoxybenzo[b]thiophen-5- yl)oxy)ethoxy)-4-chloro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-chloro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(2 S,2 ' S)-4,4 '-((propane- 1 , 3 -diylbi s(oxy))bi s(4-fluoro-6- methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4-oxobutanoic acid),(S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-6-(methylamino)benzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3-carboxybutyl)-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-(2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)propoxy)-6-methoxythieno[3,2-b]pyridin-2-yl)-2-methyl-4-oxobutanoic acid,(2S,2'S)-4,4'-(((2-methylpropane-l,3-diyl)bis(oxy))bis(6- methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4-oxobutanoic acid),(S)-4-(5-(3-((2-(3-carboxypropanoyl)-6-methoxybenzo[b]thiophen-5- yl)oxy)propyl)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-(2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)propoxy)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-(3-carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propyl)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propyl)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-5-methoxythieno[3,2-b]pyridin-6- yl)oxy)propoxy)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(6-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-5-methoxythieno[3,2-b]pyridin-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(6-(3-((2-(3-carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-5-methoxythieno[3,2-b]pyridin-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-((S)-3-carboxybutyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, trans-2-(5-(3-((2-((S)-3-carboxybutanoyl)-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophene-2- carbonyl)cyclobutanecarboxylic acid, trans-2-(5-(3-((2-((S)-3-carboxybutanoyl)-5-methoxybenzo[b]thiophen-6- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophene-2- carbonyl)cyclobutanecarboxylic acid,(2 S,2 ' S)-4,4 '-(5 , 5 '-(butane- 1 ,4-diylbi s(oxy))bi s(4-chloro-6- methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4-oxobutanoic acid),(4-(5-(3-((2-(3-carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propyl)-6-methoxythieno[3,2-b]pyridin-2-yl)-4-oxobutanoic acid,(S)-4-(5-(3-(2-(3-carboxypropanoyl)-6-methoxythieno[3,2-b]pyridin-5- yl)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-((3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo [b]thiophen-5- yl)oxy)propyl)amino)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-((3-(2-(3-carboxypropanoyl)-6-methoxybenzo[b]thiophen-5- yl)propyl)amino)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-6-hydroxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-((S)-3-carboxybutyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-6-hydroxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-chloro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-6-hydroxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-chloro-6-hydroxybenzo[b]thiophen-5- yl)oxy)propoxy)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-chloro-6-hydroxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-((S)-3-carboxybutyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-chloro-6-hydroxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-chloro-6-hydroxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-chloro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-hydroxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-hydroxybenzo[b]thiophen-5- yl)oxy)propoxy)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-chloro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-fluoro-6-hydroxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoicwherein eachis a covalent bond are described herein.

[0069] In some aspects, the pHLIP® peptide of the conjugate of Formula (I) has the following sequence: X„Ym; YmXn; XnYmXj; YmXnYi; YmXnYiXj; XnYmXjYi; YmXnYiXjYi; XnYmXjYiXi; YmXnYiXjYiXh; XnYmXjYiXhYg; YmXnYiXj YiXhYg; XnYmXjYiXhYgXf; (XY)n; (YX)n; (XY)nYm; (YX)nYm; (XY)nXm; (YX)nXm; Ym(XY)n; Ym(YX)n; Xn(XY)m; Xn(YX)m; (XY)nYm(XY)i; (YX)nYm(YX)i; (XY)nXm(XY)i; (YX)nXm(YX)i; Ym(XY)n; Ym(YX)n; Xn(XY)m; or Xn(YX)m, wherein,(i) each Y is, independently, a non-polar amino acid with solvation energy, DGxcor> +0.50, or Glycine;(ii) each X is, independently, a protonatable amino acid, and(iii) n, m, i, j, 1, h, g, f are each, independently, an integer from 1 to 8.

[0070] In some aspects, the pHLIP® peptide of the conjugate of Formula (I) comprises a sequence comprising the sequence ADDQNPWRAYLDLLFPTDTLLLDLLWXG (SEQ ID NO: 220), wherein “X” is a functional group for conjugation purposes, selected from lysine (Lys), cysteine (Cys), Azido-containing amino acid or other modified amino acids, such as described herein in Table 3. In some aspects, the pHLIP® peptide of the conjugate of Formula (I) comprises a sequence consisting of the sequence ADDQNPWRAYLDLLFPTDTLLLDLLWXG (SEQ ID NO: 220), wherein “X” is a functional group for conjugation purposes, selected from lysine (Lys), cysteine (Cys), Azido-containing amino acid or other modified amino acids, such as described herein in Table 3.

[0071] In some aspects, the pHLIP® peptide of the conjugate of Formula (I) comprises a sequence selected from the group consisting of any one of SEQ ID NOs. 1-219. In some aspects, the pHLIP® peptide of the conjugate of Formula (I) has a sequence selected from the group consisting of any one of SEQ ID NOs. 1-219. In some aspects, the pHLIP® peptide of the conjugate of Formula (I) has a sequence comprising the sequence ADQDNPWRAYLDLLFPTDTLLLDLLWCG (SEQ ID NO: 218). In some aspects, the pHLIP® peptide of the conjugate of Formula (I) has a sequence comprising the sequenceADDQNPWRAYLDLLFPTDTLLLDLLWCG (SEQ ID NO: 219). In some aspects, the pHLIP® peptide of the conjugate of Formula (I) has a sequence consisting of the sequence ADQDNPWRAYLDLLFPTDTLLLDLLWCG (SEQ ID NO: 218). In some aspects, the pHLIP® peptide of the conjugate of Formula (I) has a sequence consisting of the sequence ADDQNPWRAYLDLLFPTDTLLLDLLWCG (SEQ ID NO: 219).

[0072] In some aspects, the STING agonist of the conjugate of Formula (I) is selected from the group consisting of (S)-4-(5-(3-((2-((S)-3-carboxybutyl)-4-fluoro-6- methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2- methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6- methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6-(methylamino)benzo[b]thiophen-2-yl)-2-methyl- 4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3-carboxybutyl)-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)- 4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6- hydroxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3- carboxybutanoyl)-4-fluoro-6-hydroxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,

[0073] In some aspects, the STING agonist of the conjugate of Formula (I) is (S)-4-(5-(3-((2-((S)-3-carboxybutyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid. In some aspects, the STING agonist of the conjugate of Formula (I) is (S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6- methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6-(methylamino)benzo[b]thiophen-2-yl)-2-methyl- 4-oxobutanoic acid. In some aspects, the STING agonist of the conjugate of Formula (I) is (S)-4- (5-(3-((2-((S)-3-carboxybutyl)-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid. In some aspects, the STING agonist of the conjugate of Formula (I) is (S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6- methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6-hydroxybenzo[b]thiophen-2-yl)-2-methyl-4- oxobutanoic acid. In some aspects, the STING agonist of the conjugate of Formula (I) is(S)-4-(5- (3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-hydroxybenzo[b]thiophen-5-yl)oxy)propoxy)-4- fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid. In some aspects, the STING agonist of the conjugate of Formula (I) isIn some aspects, the STING agonist of the conjugate of Formula (I) is

[0074] Compositions comprising a conjugate of Formula (II): Peptide-Linker-STING-Linker-Peptide (II) wherein Peptide is a pHLIP® peptide comprising the sequence ADQDNPWRAYLDLLFPTDTLLLDLLWCG (SEQ ID NO: 218) or ADDQNPWRAYLDLLFPTDTLLLDLLWCG (SEQ ID NO: 219), wherein Linker is a cleavable linker bonded to a carboxyl group on “STING”; wherein STING is a STING agonist, which is a dimer with a carboxylic acid subsituent (carboxyl group) at the terminal position of both monomers of the dimer; andwherein eachis a covalent bond are also described herein.

[0075] In some aspects, the pHLIP® peptide of the conjugate of Formula (II) comprises the sequence ADQDNPWRAYLDLLFPTDTLLLDLLWCG (SEQ ID NO: 218). In some aspects, the pHLIP® peptide of the conjugate of Formula (II) comprises the sequenceADDQNPWRAYLDLLFPTDTLLLDLLWCG (SEQ ID NO: 219). In some aspects, the pHLIP® peptide of the conjugate of Formula (II) consists of the sequenceADQDNPWRAYLDLLFPTDTLLLDLLWCG (SEQ ID NO: 218) orADDQNPWRAYLDLLFPTDTLLLDLLWCG (SEQ ID NO: 219).

[0076] In some aspects, the pHLIP® peptide of the conjugate of Formula (II) consists of the sequence ADQDNPWRAYLDLLFPTDTLLLDLLWCG (SEQ ID NO: 218). In some aspects, the pHLIP® peptide of the conjugate of Formula (II) consists of the sequence ADDQNPWRAYLDLLFPTDTLLLDLLWCG (SEQ ID NO: 219).

[0077] In some aspects, the STING agonist of the conjugate of Formula (II) comprises a STING agonist described in U.S. Patent No. 10,793,557, hereby incorporated by reference in its entirety.

[0078] In some aspects, the STING agonist of the conjugate of Formula (II) is a STING agonist described in Pan, B.S. et al., Science 369:6506 (2020), hereby incorporated by reference in its entirety.

[0079] In some aspects, the STING agonist of the conjugate of Formula (II) is selected from the group consisting of (2S,2'S)-4,4'-[butane-l,4-diylbis(6-methoxy-l-benzothiene-5,2- diyl)]bis(2-methyl-4-oxobutanoic acid), (2S,2'S)-4,4'-[propane-l,3-diylbis(6-methoxy-l- benzothiene-5,2-diyl)]bis(2-methyl-4-oxobutanoic acid), (S)-4-(5-(3-(2-(3-carboxypropanoyl)-6- methoxybenzo[b]thiophen-5-yl)propoxy)-6-methoxythieno[3,2-b]pyridin-2-yl)-2-methyl-4- oxobutanoic acid, 4-(5-(3-((2-(3-carboxypropanoyl)-6-methoxythieno[3,2-b]pyridin-5- yl)oxy)propyl)benzo[b]thiophen-2-yl)-4-oxobutanoic acid, 4-(5-(3-(2-(3-carboxypropanoyl)-6- methoxybenzo[b]thiophen-5-yl)propoxy)-6-methoxybenzo[d]thiazol-2-yl)-4-oxobutanoic acid, 4- (5-(3-((2-(3-carboxypropanoyl)-6-methoxybenzo[b]thiophen-5-yl)oxy)propyl) benzo[b]thiophen- 2-yl)-4-oxobutanoic acid,4-(5-(2-((2-(3-carboxypropanoyl)-6-methoxybenzo[b]thiophen-5- yl)oxy)ethyl)-6-methoxythieno[3,2-b]pyridin-2-yl)-4-oxobutanoic acid, 4-(5-(2-(2-(3- carboxypropanoyl)-6-methoxythieno[3,2-b]pyridin-5-yl)ethoxy)-6-methoxythieno[3,2-b]pyridin- 2-yl)-4-oxobutanoic acid, 4-(5-(2-((2-(3-carboxypropanoyl)-6-methoxybenzo[d]thiazol-5- yl)oxy)ethyl)-6-methoxythieno[3,2-b]pyridin-2-yl)-4-oxobutanoic acid, 4-(5-(3-(2-(3- carboxypropanoyl)-6-methoxybenzo[b]thiophen-5-yl)propoxy)-6-methoxythieno[3,2-b]pyridin-2-yl)-4-oxobutanoic acid, (S)-4-(5-(3-((2-(3-carboxypropanoyl)-6-methoxythieno[3,2-b]pyridin- 5-yl)oxy)propoxy)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, 4-(5-(3-((2- (3-carboxypropanoyl)-6-methoxybenzo[b]thiophen-5-yl)oxy)propyl)-6-methoxythieno[3,2- b]pyridin-2-yl)-4-oxobutanoic acid, (S)-4-(5-(3-((2-(3-carboxypropanoyl)-6-methoxythieno[3,2- b]pyridin-5-yl)oxy)propyl)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-(2-(3-carboxypropanoyl)-6-methoxythieno[3,2-b]pyridin-5-yl)propoxy)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-(2-((S)-3- carboxybutanoyl)-6-methoxybenzo[b]thiophen-5-yl)propoxy)-6-methoxythieno[3,2-b]pyridin-2- yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(2-((2-(3-carboxypropanoyl)-6- methoxybenzo[b]thiophen-5-yl)oxy)ethoxy)-6-methoxythieno[3,2-b]pyri din-2 -yl)-2-methyl-4- oxobutanoic acid, (S)-4-(5-(3-((2-(3-carboxypropanoyl)-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-6-methoxythieno[3,2-b]pyridin-2-yl)-2-methyl-4-oxobutanoic acid, rac-(R)-4- (5-(2-((2-((R)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)ethoxy)-6- methoxythieno[3,2-b]pyridin-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(2-((2-(3- carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)ethoxy)-6- methoxythieno[3,2-b]pyridin-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-(3- carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6- methoxythieno[3,2-b]pyridin-2-yl)-2-methyl-4-oxobutanoic acid, rac-(R)-4-(5-(3-((2-((R)-3- carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6- methoxythieno[3,2-b]pyridin-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-(3- carboxypropanoyl)-6-methoxythieno[3,2-b]pyridin-5-yl)oxy)propoxy)-4-fluoro-6- methoxybenzo[b]thi ophen-2 -yl)-2-methyl-4-oxobutanoic acid, 4-(4-(3-(2-(3-carboxypropanoyl)-5-methoxbenzo[b]thiophen-6-yl)propyl)-6-methoxybenzo[b]thiophen-2-yl)-4-oxobutanoic acid, 4,4'-(propane-l,3-diylbis(6-methoxybenzo[d]thiazole-5,2-diyl))bis(4-oxobutanoic acid), 4,4'- (propane-l,3-diylbis(6-methylbenzo[b]thiophene-5,2-diyl))bis(4-oxobutanoic acid), 4-(5-(3-(2- (3-carboxypropanoyl)-6-methoxybenzo[b]thiophen-5-yl)propyl)-6-methoxythieno[3,2-b]pyridin- 2-yl)-4-oxobutanoic acid, (S)-4-(5-(3-(2-(3-carboxybutyl)-6-methoxybenzo[b]thiophen-5- yl)propyl)-6-methoxybenzo[b]thiophen-2-yl)-4-oxobutanoic acid, 4-(5-(3-((2-(3- carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propyl)-6- methoxybenzo[b]thiophen-2-yl)-4-oxobutanoic acid, (S)-4-(5-(3-(2-(3-carboxypropanoyl)-6- methoxybenzo[b]thiophen-5-yl)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl- 4-oxobutanoic acid, (S)-4-(5-(2-((2-(3-carboxypropanoyl)-6-methoxybenzo[b]thiophen-5- yl)oxy)ethoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-(3-carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propyl)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3- carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propyl)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-(3- carboxypropanoyl)-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(6-(3-(7-((S)-3- carboxybutanoyl)-4-methoxythieno[2',3':5,6]benzo[l,2-d]oxazol-2-yl)propoxy)-5- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (2S)-4-{5-[3-({2-[(3 S)-3- carboxybutanoyl]-6-methoxy-l-benzothiophen-5-yl}oxy)propyl]-6-methoxy-l-benzothi ophen-2- yl}-2-methyl-4-oxobutanoic acid, (S)-4-(5-(2-(2-((S)-3-carboxybutanoyl)-6- methoxybenzo[b]thiophen-5-yl)ethoxy)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4- oxobutanoic acid, (S)-4-(5-(3-((2-(3-carboxypropanoyl)benzo[b]thiophen-6-yl)oxy)propoxy)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(6-(3-((2-(3- carboxypropanoyl)benzo[b]thiophen-5-yl)oxy)propoxy)-5-methoxybenzo[b]thiophen-2-yl)-2- methyl-4-oxobutanoic acid, (2S,2'S)-4,4'-((propane-l,3-diylbis(oxy))bis(5- methoxybenzo[b]thiophene-6,2-diyl))bis(2-methyl-4-oxobutanoic acid), (2S,2'S)-4,4'-((ethane- l,2-diylbis(oxy))bis(4-fluoro-6-methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4-oxobutanoic acid), (S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-5-methoxybenzo[b]thiophen- 6-yl)oxypropoxy)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (2S,2'S)-4,4'-((propane-l,3- diylbis(oxy))bis(6-methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4-oxobutanoic acid), (S)-4- (6-(2-((2-(3-carboxypropanoyl)benzo[b]thiophen-5-yl)oxy)ethoxy)-5-methoxybenzo[b]thiophen- 2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-(3-carboxypropanoyl)benzo[b]thiophen-5- yl)oxy)propoxy)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, rac-(R)-4-(5- (2-((2-((R)-3-carboxybutanoyl)-5-methoxybenzo[b]thiophen-6-yl)oxy)ethoxy)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3- carboxybutanoyl)-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6-methoxythieno[3,2- b]pyridin-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-(3-carboxybutanoyl)-6- methoxythieno[3,2-b]pyridin-5-yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2,2- dimethyl-4-oxobutanoic acid, (2S)-4-{5-[2-({2-[(3S)-3-carboxybutanoyl]-6-methoxy-l- benzothiophen-5-yl}amino)ethyl]-6-methoxy-l-benzothiophen-2-yl}-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-6-methoxybenzo[b]thiophen-5-yl)amino)propyl)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(2-((2-(3- carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)ethoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-(3- carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (R)-4-(5-(2-((2-((S)-3- carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)ethoxy)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(2-((2-((S)-3- carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)ethoxy)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, rac-(lR,2R)-2-(5-(3-((2-((R)-3- carboxybutanoyl)-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6-methoxybenzo[b]thiophene- 2-carbonyl)cyclopropane-l -carboxylic acid, (S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6- methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6-methoxybenzo[b]thi ophen-2 -yl)-2-methyl-4- oxobutanoic acid, (S)-4-(6-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-5-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3- ((2-(3-carboxybutanoyl)-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6- methoxybenzo[b]thiophen-2-yl)-2,2-dimethyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-(3- carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(6-(3-((2-(3- carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-5- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3- carboxybutanoyl)-6-methoxybenzo[b]thiophen-5-yl)amino)propoxy)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, 4-(5-((3-(2-(3-carboxypropanoyl)-6-methoxybenzo[b]thiophen-5-yl)propyl)amino)-6-methoxythieno[3,2-b]pyridin-2-yl)-4- oxobutanoic acid, (2S,2'S)-4,4'-((ethane-l,2-diylbis(oxy))bis(6-methoxybenzo[b]thiophene-5,2- diyl))bis(2-methyl-4-oxobutanoic acid), (2S,2'S)-4,4'-(7,8,17,18-tetrahydro-6H,16H- bis[l]benzothieno[5,6-b:6',5'-i][l,4,8,l l]tetraoxacyclotetradecine-2,12-diyl)bis(2-methyl-4- oxobutanoic acid), (2S,2'S)-4,4'-(7,8,17,18-tetrahydro-6H,16H-bis[l]benzothieno[5,6-b:5',6'- i] [ 1 ,4,8, 1 l]tetraoxacyclotetradecine-2, 12-diyl)bis(2-methyl-4-oxobutanoic acid), (2S,2'S)-4,4'- (l,3-propanediylbis{oxy[6-(difluoromethoxy)-l-benzothiene-5,2-diyl]})bis(2-methyl-4- oxobutanoic acid), 4-(5-(2-((2-(3-carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)ethoxy)-6-methoxythieno[3,2-b]pyridin-2-yl)-4-oxobutanoic acid, 4-(5-(3-((2-(3- carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6- methoxythieno[3,2-b]pyridin-2-yl)-4-oxobutanoic acid, (S)-4-(5-(2-((2-(3-carboxypropanoyl)-6- methoxythieno[3,2-b]pyridin-5-yl)oxy)ethoxy)-4-fluoro-6-methoxybenzo[b]thi ophen-2 -yl)-2- methyl-4-oxobutanoic acid, trans-2-(5-(3-(2-((S)-3-carboxybutanoyl)-6-methoxybenzo[b]thiophen-5-yl)propoxy)-4-fluoro-6-methoxybenzo[b]thiophene-2-carbonyl)- cyclopropanecarboxylic acid, trans-2-(5-(3-(2-(3-carboxypropanoyl)-6- methoxybenzo[b]thiophen-5-yl)propoxy)-4-fluoro-6-methoxybenzo[b]thiophene-2- carbonyl)cyclopropanecarboxylic acid, trans-2-(5-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6- methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophene-2- carbonyl)cyclopropanecarboxylic acid, trans-2-(5-(3-((2-((lR,2R)-2- carboxycyclopropanecarbonyl)-4-fluoro-6- methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4- fluoro-6-methoxybenzo[b]thiophene-2-carbonyl)cyclopropanecarboxylic acid, trans-2-(5-(3-((2- (3-carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6- methoxybenzo[b]thiophene-2-carbonyl)cyclopropanecarboxylic acid, trans-2-(5-(3-((2-((S)-3- carboxybutanoyl)-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6- methoxybenzo[b]thiophene-2-carbonyl)cyclopropanecarboxylic acid, trans-2-(5-(3-((2-((S)-3- carboxybutanoyl)-5-methoxybenzo[b]thiophen-6-yl)oxy)propoxy)-4-fluoro-6- methoxybenzo[b]thiophene-2-carbonyl)cyclopropanecarboxylic acid, (R)-4-(5-(3-((2-((S)-3- carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propyl)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (2S,2'S)-4,4'-(5,5'-(butane-l,4- diylbis(oxy))bis(6-methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4-oxobutanoic acid), (S)-4- (5-(4-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)butoxy)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(4-((2-((S)-3- carboxybutanoyl)-5-methoxybenzo[b]thiophen-6-yl)oxy)butoxy)-6-methoxybenzo[b]thiophen-2- yl)-2-methyl-4-oxobutanoic acid, trans-2-(6-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6- methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-5-methoxybenzo[b]thiophene-2- carbonyl)cyclobutanecarboxylic acid, trans-2-(5-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6- methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophene-2- carbonyl)cyclobutanecarboxylic acid, (S)-4-(5-(3-((2-((S)-3-carboxybutyl)-4-fluoro-6- methoxybenzo[b]thiophen-5-yl)oxy)propyl)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4- oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3-carboxybutyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (2S,2'S)-4,4'-(5,5'-(pentane-l,5-diylbis(oxy))bis(6-methoxybenzo[b]thiophene-5,2-diyl))bis(2- methyl-4-oxobutanoic acid), (S)-4-(5-((5-((2-((S)-3-carboxybutanoyl)-4-fluoro-6- methoxybenzo[b]thiophen-5-yl)oxy)pentyl)oxy)-6-methoxybenzo[b]thi ophen-2 -yl)-2-methyl-4- oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3-carboxybutyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propyl)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, trans-2-(5-(3-(2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)propoxy)-4-fluoro- 6-methoxybenzo[b]thiophene-2-carbonyl)cyclopropanecarboxylic acid, trans-2-(5-(3-(2-((S)-3- carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)propoxy)-4-fluoro-6- methoxybenzo[b]thiophene-2-carbonyl)cyclobutanecarboxylic acid, (R)-4-(5-(3-((2-((R)-3- carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propyl)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((R)-3- carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propyl)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-((6-((2-((S)-3- carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)hexyl)oxy)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, trans-2-(5-(3-(2-((S)-3- carboxybutanoyl)-6-methoxybenzo[b]thiophen-5-yl)propoxy)-4-fluoro-6- methoxybenzo[b]thiophene-2-carbonyl)cyclobutanecarboxylic acid, (S)-4-(5-(3-((2-(3-carboxy-3- methylbutyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propyl)-4-fluoro-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, trans-2-(5-(3-((2-((S)-3- carboxybutyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6- methoxybenzo[b]thiophene-2-carbonyl)cyclobutanecarboxylic acid, 4,4'-(5,5'-(pentane-l,5- diylbis(oxy))bis(4-fluoro-6-methoxybenzo[b]thiophene-5,2-diyl))bis(4-oxobutanoic acid), (S)-4- (5-((5-((2-(3-carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yloxy)pentyloxy)-4- fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (2S,2'S)-4,4'-(5,5'- (pentane-l,5-diylbis(oxy))bis(4-fluoro-6-methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4- oxobutanoic acid), (S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-chloro-6- methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2- methyl-4-oxobutanoic acid, (S)-4-(5-(3-((4-bromo-2-((S)-3-carboxybutanoyl)-6- methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2- methyl-4-oxobutanoic acid, (S)-4-(5-(4-((2-((S)-3-carboxybutyl)-4-fluoro-6- methoxybenzo[b]thiophen-5-yl)oxy)butoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2- methyl-4-oxobutanoic acid, (S)-4-(5-(4-((2-((S)-3-carboxybutanoyl)-4-chloro-6- methoxybenzo[b]thiophen-5-yl)oxy)butoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2- methyl-4-oxobutanoic acid, (S)-4-(5-(4-((4-bromo-2-((S)-3-carboxybutanoyl)-6- methoxybenzo[b]thiophen-5-yl)oxy)butoxy)-4-fluoro-6-methoxybenzo[b]thi ophen-2 -yl)-2- methyl-4-oxobutanoic acid, (2S,2'S)-4,4'-(5,5'-(propane-l,3-diylbis(oxy))bis(4-chloro-6- methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4-oxobutanoic acid), (S)-4-(5-(3-((4-bromo-2- ((S)-3-carboxybutanoyl)-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-chloro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (2S,2'S)-4,4'-(5,5'-(propane-l,3- diylbis(oxy))bis(4-bromo-6-methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4-oxobutanoic acid), 2-((5-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)methyl)cyclobutanecarboxylic acid, (S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4,7-dichloro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (2S,2'S)-4,4'-((butane-l,3-diylbis(oxy))bis(4-fluoro-6-methoxybenzo[b]thiophene-5,2- diyl))bis(2-methyl-4-oxobutanoic acid), (2S,2'S)-4,4'-((pentane-l,4-diylbis(oxy))bis(4-fluoro-6- methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4-oxobutanoic acid), (2S,2'S)-4,4'-((hexane- 2,5-diylbis(oxy))bis(4-fluoro-6-methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4-oxobutanoic acid), trans-2-(5-(3-((2-(3-carboxy- 3-methylbutyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophene-2-carbonyl)cyclobutane-l-carboxylic acid, (2S,2'S)-4,4'-(((2-methylpropane-l,3-diyl)bis(oxy))bis(4-fluoro-6- methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4-oxobutanoic acid), (2S,2'S)-4,4'-(((2,2- dimethylpropane-l,3-diyl)bis(oxy))bis(4-fluoro-6-methoxybenzo[b]thiophene-5,2-diyl))bis(2- methyl-4-oxobutanoic acid), (2S,2'S)-4,4'-(((cyclopropane-l,l-diylbis-(methylene))bis(oxy))bis(4-fluoro-6-methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4- oxobutanoic acid), (S)-4-(5-(3-((2-((S)-3-carboxybutyl)-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-chloro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4- (4-bromo-5-(3-((2-((S)-3-carboxybutyl)-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3- carboxybutyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-chl oro-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(4-bromo-5-(3-((2-((S)-3- carboxybutyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6-methoxy benzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, 4-(5-(3-((2-(3-carboxy-3-methylbutyl)-4- fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thi ophen-2- yl)-2,2-dimethyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3-carboxybutyl)-4-chloro-6- methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6-methoxybenzo[b]thi ophen-2 -yl)-2-methyl-4- oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3-carboxybutyl)-4-chloro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (2S,2'S)-4,4'-((ethane-l,2-diylbis(oxy))bis(4-chloro-6-methoxybenzo[b]thiophene-5,2- diyl))bis(2-methyl-4-oxobutanoic acid), (S)-4-(5-(2-((2-((S)-3-carboxybutyl)-4-chloro-6- methoxybenzo[b]thiophen-5-yl)oxy)ethoxy)-4-chloro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-chloro-6- methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6-methoxybenzo[b]thi ophen-2 -yl)-2-methyl-4- oxobutanoic acid, (2 S,2 ' S)-4,4 '-((propane- 1 , 3 -diylbi s(oxy))bi s(4-fluoro-6- methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4-oxobutanoic acid), (S)-4-(5-(3-((2-((S)-3- carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6- (methylamino)benzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3- carboxybutyl)-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-(2-((S)-3- carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)propoxy)-6-methoxythieno[3,2- b]pyridin-2-yl)-2-methyl-4-oxobutanoic acid, (2S,2'S)-4,4'-(((2-methylpropane-l,3- diyl)bis(oxy))bis(6-methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4-oxobutanoic acid), (S)- 4-(5-(3-((2-(3-carboxypropanoyl)-6-methoxybenzo[b]thiophen-5-yl)oxy)propyl)-4-fluoro-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-(2-((S)-3- carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)propoxy)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-(3- carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propyl)-4-fluoro-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3- carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propyl)-4-fluoro-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3- carboxybutanoyl)-5-methoxythieno[3,2-b]pyridin-6-yl)oxy)propoxy)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(6-(3-((2-((S)-3- carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-5- methoxythieno[3,2-b]pyri din-2 -yl)-2-methyl-4-oxobutanoic acid, (S)-4-(6-(3-((2-(3- carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-5- methoxythieno[3,2-b]pyridin-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3- carboxybutyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, trans-2-(5-(3-((2-((S)-3- carboxybutanoyl)-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6- methoxybenzo[b]thiophene-2-carbonyl)cyclobutanecarboxylic acid, trans-2-(5-(3-((2-((S)-3- carboxybutanoyl)-5-methoxybenzo[b]thiophen-6-yl)oxy)propoxy)-4-fluoro-6- methoxybenzo[b]thiophene-2-carbonyl)cyclobutanecarboxylic acid, (2S,2'S)-4,4'-(5,5 '-(butane- l,4-diylbis(oxy))bis(4-chloro-6-methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4- oxobutanoic acid), (4-(5-(3-((2-(3-carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propyl)-6-methoxythieno[3,2-b]pyridin-2-yl)-4-oxobutanoic acid, (S)-4-(5-(3-(2-(3- carboxypropanoyl)-6-methoxythieno[3,2-b]pyridin-5-yl)propoxy)-4-fluoro-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-((3-((2-((S)-3- carboxybutanoyl)-4-fluoro-6-methoxybenzo [b]thiophen-5-yl)oxy)propyl)amino)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-((3-(2-(3- carboxypropanoyl)-6-methoxybenzo[b]thiophen-5-yl)propyl)amino)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3- carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6- hydroxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3- carboxybutyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6- hydroxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3- carboxybutanoyl)-4-chloro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6- hydroxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3- carboxybutanoyl)-4-chloro-6-hydroxybenzo[b]thiophen-5-yl)oxy)propoxy)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3- carboxybutanoyl)-4-chloro-6-hydroxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6- methoxybenzo[b]thiophen-2-yl)- 2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3- carboxybutyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-chl oro-6- hydroxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3- carboxybutanoyl)-4-chloro-6-hydroxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-chloro-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3- carboxybutanoyl)-4-fluoro-6-hydroxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3- carboxybutanoyl)-4-fluoro-6-hydroxybenzo[b]thiophen-5-yl)oxy)propoxy)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3- carboxybutanoyl)-4-chloro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6- hydroxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,

[0080] In some aspects, the STING agonist of the conjugate of Formula (II) is selected from the group consisting of (S)-4-(5-(3-((2-((S)-3-carboxybutyl)-4-fluoro-6- methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2- methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6- methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6-(methylamino)benzo[b]thiophen-2-yl)-2-methyl- 4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3-carboxybutyl)-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)- 4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6- hydroxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3- carboxybutanoyl)-4-fluoro-6-hydroxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,

[0081] In some aspects, the STING agonist of the conjugate of Formula (II) is (S)-4-(5-(3 - ((2-((S)-3-carboxybutyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid. In some aspects, the STING agonist of the conjugate of Formula (II) is (S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6- methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6-(methylamino)benzo[b]thiophen-2-yl)-2-methyl- 4-oxobutanoic acid. In some aspects, the STING agonist of the conjugate of Formula (II) is (S)-4- (5-(3-((2-((S)-3-carboxybutyl)-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid. In some aspects, the STING agonist of the conjugate of Formula (II) is(S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6- methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6-hydroxybenzo[b]thiophen-2-yl)-2-methyl-4- oxobutanoic acid. In some aspects, the STING agonist of the conjugate of Formula (II) is (S)-4-(5- (3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-hydroxybenzo[b]thiophen-5-yl)oxy)propoxy)-4- fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid. In some aspects, the STING agonist of the conjugate of Formula (II) issome aspects, the STING agonist of the conjugate of Formula (II) is

[0082] In some aspects, all amino acids in the pHLIP® peptide of the conjugates of Formula(I) and Formula (II) disclosed herein are D-amino acids.

[0083] In some aspects, one or both Linkers of the conjugates of Formula (I) and Formula(II) comprise a disulfide bond or an acid-labile bond. In some aspects, one or both Linkers of the conjugates of Formula (I) and Formula (II) are self-immolative. In some aspects, one or both Linkers of the conjugates of Formula (I) and Formula (II) comprise a disulfide self-immolative bond. In some aspects the Linkers of the conjugate of Formula (I) or Formula (II) are the same or different.Methods of Treatment

[0084] Methods of using the compositions described herein for treating cancer in a subject in need thereof comprising administering a composition or pharmaceutical composition disclosed herein are also provided. In some aspects, the cancer is a solid tumor. In some aspets, the composition or pharmaceutical composition disclosed herein is injected directly into a tumor mass. In some aspects, the subject is a human.

[0085] Examples are provided below to facilitate a more complete understanding of the invention. The following examples illustrate the exemplary modes of making and practicing the invention. However, the scope of the invention is not limited to specific embodiments disclosed in these Examples, which are for purposes of illustration only, since alternative methods can be utilized to obtain similar results.EXAMPLESEXAMPLE 1: Synthesis of pHLIP®-STINGa Compounds

[0086] Modified monomeric and dimeric STING agonists, mMSA-(p-aminobenzyl alcohol)-SS-Pyridine (Pyridine = Py; p-aminobenzyl alcohol = PAB) and Py-SS-ethyl-dMSA-ethyl-SS-Py (Et=ethyl), respectively, were synthesized and purified by Iris Biotech GmbH. pHLIP® peptides consisting of all D amino acids were synthesized and purified at CSBio and Biosynth. To prepare pHLIP®-mMSA and 2pHLIP®-dMSA, Var3 pHLIP® peptides were synthesized with a single Cys residue at the membrane-inserting end: ADQDNPWRAYLDLLFPTDTLLLDLLWCG (SEQ ID NO: 218). pHLIP® peptides were mixed with mMSA-PAB-SS-Py or Py-SS-Et-dMSA-Et-SS-Py in dimethyl sulfoxide (DMSO) at a molar ratios of 1 : 1 or 2: 1, respectively. Sodium phosphate buffer (100 mM) containing 150 mM NaCl at pH 7.4 saturated with argon was added to the reaction mix (1 / 10 of the total volume) and the reaction mixture was kept for 2 hours at room temperature (RT). pHLIP®-mMSA and 2pHLIP®- dMSA constructs were purified by reverse phase high-performance liquid chromatography (HPLC) using Zorbax SB-C18 or Zorbax SB-C8, 9.4^250 mm, 5 pm columns (Agilent Technology) with a gradient from 20% to 80% acetonitrile in water containing 0.05% trifluoroacetic acid (TFA). For the preparation of a fluorescent version of 2pHLIP®-dMSA (2(ICG- pHLIP®)-dMSA), an N-terminal acetylated version of the pHLIP® peptide with a lysine introduced near the N-terminus (AKDQDNPWRAYLDLLFPTDTLLLDLLWCG (SEQ ID NO: 221)) was used. First, pHLIP® was conjugated with Py-SS-Et-dMSA-Et-SS-Py, followed by purification. Then, Indocyanine green N-hydroxysuccinimide active ester (ICG-NHS ester) (Iris Biotech GmbH) was conjugated with the lysine residue at the N-terminal end of pHLIP® in DMSO at molar ratio of 2.5: 1. Sodium bicarbonate buffer (100 mM) at pH 8.3 was added to the reaction mix (1 / 10 of the total volume) and the reaction mixture was kept at RT until the conjugation was completed. The final purification was performed as described above. The products were lyophilized and characterized by matrix-assisted laser desorption / ionization-time of flight (MALDI-TOF) mass- spectrometry and analytical HPLC. The molecular weight of pHLIP®-mMSA and 2pHLIP®-dMSA are 3,781 Da and 7,574 Da, respectively. The concentration of pHLIP®-STINGa conjugates was determined by absorbance using the following molar extinction coefficients: for pHLIP®-mMSA £525=15,000 M-1cm-1; 525=30,000 M 'em1for 2pHLIP®-dMSA and a?oo=137,OOO M 'em1for 2(ICG-pHLIP®)-dMSA.

[0087] Schematic representation of an example conjugate is shown in FIG. 1 and FIG. 9.EXAMPLE 2: Stability in Mouse and Human Plasma

[0088] To establish the stability of agents (2pHLIP®-dMSA, pHLIP®-mMSA, dMSA, mMSA and pHLIP®) in plasma, each agent was mixed with single donor human or BALB / c mouseplasma (Innovative Research) at a concentration of 200 |1M, and kept in plasma for 0, 1, 2, 4 or 24 hours at 37°C. Plasma proteins were precipitated by methanol (1 :5 volume ratio of plasma to methanol) and centrifuged for 10 min at 13.4 rpm. The supernatant was collected and analyzed by HPLC using a Zorbax SB-C18 4.6 x 250 mm, 5 pm column with a gradient from 20% to 80% acetonitrile in water containing 0.05% TFA. Chromatograms were recorded at 220 nm, 280 nm and 325 nm.

[0089] The results indicated the stability of 2pHLIP®-dMSA in human plasma was very high. However, the stability of the agent in mouse plasma was low. The cargo, dMSA, was released from the agent and underwent degradation within 24 hours.EXAMPLE 3 : Self-immolation Kinetics

[0090] To trigger S-S cleavage and self-immolation of the linker connecting pHLIP® peptide and mMSA or dMSA payloads, solutions of pHLIP®-mMSA or 2pHLIP®-dMSA were treated with dithiothreitol (DTT). At different time points (from 30 min to 48 hours of treatment) the samples were analyzed by HPLC using a Zorbax SB-C18 (for pHLIP®-mMSA) or a Zorbax SB-C8 (for 2pHLIP®-dMSA) 4.6 x 250 mm, 5 pm columns with a gradient from 20% to 80% acetonitrile in water containing 0.05% TFA. The chromatograms were recorded at 220 nm, 280 nm and 325 nm. mMSA, dMSA and pHLIP® were used as controls at the same HPLC conditions.

[0091] The results are provided in FIG. 2 and FIG. 10.

[0092] The results indicated that the cleavage of S-S bonds in 2pHLIP®-dMSA is followed by the formation of multiple intermediates during the self-immolation process, which is mostly completed within 48 hours with the release of dMSA in its original form (FIG. 2).EXAMPLE 4: Biophysical Studies

[0093] The interactions of pHLIP®-mMSA and 2pHLIP®-dMSA with liposomes were investigated by recording the construct’s fluorescence and circular dichroism (CD) using a PCI photon-counting spectrofluorometer (ISS) and a MOS-450 spectrometer (Bio-Logic Science Instruments), respectively, with temperature control set to 25°C. Liposomes, constituting of large unilamellar vesicles were prepared by extrusion. l-palmitoyl-2-oleoyl- w-glycero-3- phosphocholine (POPC) lipids (Avanti Polar Lipids) in chloroform were desolvated on a rotary evaporator and dried under vacuum for a minimum of 2 hours. The phospholipid film wasrehydrated in 2 mM citrate phosphate buffer, pH 7.4, vortexed, and passed through the extruder (using a 50 nm membrane pore size) 21 times.

[0094] Fluorescence spectra were recorded from 310 nm to 390 nm at an excitation wavelength of 295 nm and 1.0 mm sized slits. The excitation polarizer was set to 54.7 degrees (“magic angle”) while the emission polarizer was set to 0 degrees in order to reduce Wood’s anomalies. CD spectra were recorded from 190 to 260 nm with a step size of 1 nm. The concentrations of pHLIP®-mMSA / 2pHLIP®-dMSA and POPC were 7 pM and 1.4 mM, respectively.

[0095] The pH-dependent insertion of pHLIP®-mMSA or 2pHLIP®-dMSA into the lipid bilayer of POPC liposomes was studied by monitoring changes in the molar ellipticity as a function of pH. After the addition of aliquots of citric acid, the pHs of solutions containing pHLIP®- mMSA / 2pHLIP®-dMSA and POPC liposomes were measured using an Orion PerHecT ROSS Combination pH Micro Electrode and an Orion Dual Star pH and ISE Benchtop Meter. The millidegree ellipticity values were plotted as a function of pH. The pH-dependence was fit with the Henderson-Hasselbach equation to determine the cooperativity (n) and the mid-point (pK) of transition. The fitting equation used was the following:single transition where SI represents CD signal of pHLIP®-mMSA or 2pHLIP®-dMSA in presence of POPC at pH 8.5, when pHLIP® peptides are adsorbed, but not inserted across lipid bilayer, and S2 represents CD signal of pHLIP®-mMSA or 2pHLIP®-dMSA in presence of POPC at pH 4.5, when pHLIP® peptides are inserted across lipid bilayer of membrane.

[0096] Fluorescence kinetics was measured using a SFM-300 mixing system (Bio-Logic Science Instruments) in combination with the MOS-450 spectrometer with the temperature control set to 25°C. All samples were degassed before measurement to minimize air bubbles in the samples. pHLIP®-mMSA / 2pHLIP®-dMSA and POPC samples were incubated overnight to reach equilibrium, when most of the agent was associated with liposome lipid bilayers. To follow insertion into a membrane, a solution containing 14 pM pHLIP®-mMSA / 2pHLIP®-dMSA and 2.8 mM POPC was mixed with citric acid to lower the pH from pH 7.4 to 4. To follow exit of pHLIP®- mMSA / 2pHLIP®-dMSA from the membrane, a low pH solution containing 14 pM pHLIP®- mMSA / 2pHLIP®-dMSA and 2.8 mM POPC was mixed with dibasic phosphate buffer to raise the pH from 4 to 7.4. To monitor the fluorescence intensity changes during pHLIP®-mMSA / 2pHLIP®-dMSA insertion induced by the pH change, the emission signal was observed through a cut-off 320 nm filter at an excitation of 295 nm.

[0097] All data were fit to the appropriate equations by nonlinear least squares curve fitting procedures employing the Levenberg Marquardt algorithm using Origin 8.5.

[0098] The results are provided in FIG. 3 and FIG. 11.

[0099] The results confirmed the pH-dependent interactions of 2pHLIP®-dMSA with the membrane lipid bilayer. Fluorescence (FIG. 3A) and circular dichroism (FIG. 3B) measurements reflect the partitioning of pHLIP® into the lipid bilayer accompanied by formation of helical structure in membrane at low pH. 2pHLIP®-dMSA is observed to insert into the POPC bilayer with a pK of 6.0 and cooperativity of 1.2 (FIG. 3C). Insertion of 2pHLIP®-dMSA into lipid bilayer triggered by a pH drop from pH 7.4 to pH 4 was fast (completed within 100 msec) and small conformational adjustments were observed for another 50 sec (FIG. 3D). The kinetics of membrane insertion of 2pHLIP®-dMSA resulting from a pH drop from pH 7.4 to pH 6 (FIG. 3E), which is more relevant for biological conditions, was more efficient and fast than the insertion of pHLIP®-mMSA (FIG. HE). We also followed the exit of the agents from lipid bilayer induced by a pH rise from pH 4 to pH 7.4 and from pH 4 to pH 5.5 (FIG. 3F and FIG. HF). The exit of 2pHLIP®-dMSA is slightly slower, which is better illustrated during the intermediate pH jump (FIG. 3F), compared to the exit of pHLIP®-mMSA (FIG. HF). The data indicate that 2 pHLIP® peptides trigger efficient partitioning of dMSA into a lipid bilayer as the result of a pH drop.EXAMPLE 5 : Activation of IFN in M2 Macrophages

[0100] THP-1-Blue™-ISG cells (Invivogen) expressing an interferon (IFN) regulatory factor (IRF)-inducible secreted embryonic alkaline phosphatase (SEAP) reporter construct were used. Cells were maintained in Roswell Park Memorial Institute (RPMI) growth medium supplemented with L-glutamine, sodium pyruvate, 10% fetal bovine serum (FBS), normocin and ciprofloxacin hydrochloride in a humidified atmosphere of 5% CO2 and 95% air at 37°C. Cells were seeded in 96-well plates at a density of 75,000 cells / well. To generate M2 polarized macrophages, cells were treated first with 185 ng / mL phorbol 12-myristate 13-acetate (PMA) for 6 hours and then 20 ng / mL of interleukin 4 (IL-4) and 20 ng / mL of interleukin 13 (IL- 13) (both from PeproTech) were added for another 16 hours of treatment. At the completion of polarization, the growth medium was replaced with Dulbecco's Modified Eagle Medium (DMEM) medium without FBS, pH 6.9, containing increasing amounts of 2pHLIP®-dMSA or dMSA (up to 10.0pM). After a two-hour incubation, an equal volume of RPMI supplemented with 20% heat- inactivated FBS was added, and cells were incubated for another 48 hours. SEAP activity was accessed using the QUANTI-Blue™ Solution (Invivogen) to evaluate type I interferon protein levels: 150 pl of the colorimetric reagent was added to 50 pl of cell supernatant for 30 min, 37°C, followed by absorption measurement at 655 nm.

[0101] The results are provided in FIG. 4.

[0102] The results indicated that THPl-Blue cells exhibited a concentration-dependent activation of IRF signaling when polarized by phorbol 12-myristate 13-acetate (PMA), interleukin 4 (IL-4) and interleukin 13 (IL- 13) into M2 -type macrophages and treated with 2pHLIP®-dMSA (FIG. 4A). EC50 for 2pHLIP®-dMSA was calculated to be 200 nM, while EC50 for mMSA was established to be 2200 nM. This result showed successful intracellular delivery and cytoplasmic release of dMSA by pHLIP® peptides, and showed that the dimeric construct is significantly more active than the monomeric construct.EXAMPLE 6: Treatment of Mice

[0103] All animal studies were conducted at the University of Rhode Island (URI) according to the approved by URI Institution Animal Care and Use Committee (IACUC) animal protocol AN04-12-011. The studies complied with the principles and procedures outlined by the National Institutes of Health for the care and use of animals.

[0104] For the treatment of CT26 tumors, 5xl04CT26 murine colorectal cancer cells (ATCC, CRL-2638) were injected subcutaneously (SQ) in 100 pl of growth medium into the right flank of female Balb / c mice ranging in age from 7 to 9 weeks (Envigo RMS, Inc). On day 1, when tumors reached a volume of 100-130 mm3, mice were randomized into groups, body weight was measured and agents, including 2pHLIP®-dMSA, dMSA, mMSA or vehicle, were given as the first intraperitoneal (IP) injection. The second IP injection was given after 48 hours. mMSA, dMSA and pHLIP®-mMSA were given as two IP injections of 300 pM 500 pl. 2pHLIP®-dMSA was given as two IP injections of 300 pM 500 pl or 100 pM 500 pl (low dose). The compounds were dissolved in DMSO as a stock solution and transferred to phosphate-buffered saline (PBS) (vehicle). The residual DMSO in the final solution injected into animals was less than 2%. Tumor volume and body weight were measured 3 times per week throughout the study. Measurements of tumors were performed using calipers, and the tumor volume (F) was calculated with the formula:V = 0.52 - L - W2where L is the length and W is the width of the measured tumor. Mice were removed from the study and euthanized when the tumor volume was greater than 2,000 mm3.

[0105] In the 2pHLIP®-dMSA treated groups the mice that stayed tumor-free were rechallenged with tumor cells injected into the tumor-free flank on day 65 after the first injection of 2pHLIP®-dMSA. Tumor-free mice were kept for an additional 40 days (total of 105 days after the treatment with 2pHLIP®-dMSA) and then were euthanized.

[0106] The results are provided in FIG. 6.

[0107] The results indicated that all animals in the control groups that received either dMSA alone at a dose level of 300 pM 500 pl per injection (FIG. 6D) or vehicle (FIG. 6E) developed tumors within 18-20 days post-injection. In the treated groups, the tumors disappeared in 7 mice out of 10 and in 4 mice out of 10 for the lower dose of 2pHLIP®-dMSA (FIG. 6B and FIG. 6C). 11 survivals were re-injected with cancer cells on day 65, and none of them developed tumors, indicating the development of robust immune memory. Treatment of mice led to temporary weight loss followed by complete recovery and regain of weight (FIG. 6F and FIG. 6G). The Kaplan-Meier survival plots demonstrate dramatic differences between the controls and 2pHLIP®- dMSA treated groups (FIG. 6H). When dMSA was conjugated with two pHLIP® peptides that target dMSA to a tumor microenvironment (TME) and administered to a subject with a tumor, dMSA reduced tumor size and developed immune memory. dMSA did not exhibit any therapeutic activity by itself (without conjugation with two pHLIP® peptides).EXAMPLE 7: ELISA on Blood and Tumor Samples

[0108] To establish levels of cytokines in blood and tumor samples, 5xl04CT26 cancer cells were injected SQ in 100 pl of growth medium into the right flank of female Balb / c mice. When tumors reached 250-500 mm3in volume, the mice received a single IP injection of 300 pM 500 pl 2pHLIP®-dMSA or no injections. Animals were euthanized at 6- and 24-hours postinjection, blood and tumors were collected. Blood samples were kept for 40 min at RT, centrifuged at 5000 g for 20 min at +4°C and supernatant (serum) was collected. Tumors were frozen in liquid nitrogen. Both the serum and the tumor tissue samples were kept at -80°C until further processing and analysis. The tumor samples were processed while on ice, using a bullet blender (Next Advance) with 1 mm diameter zirconium silicate beads (Next Advance). The supernatant of the processed tumors was used for enzyme-linked immunosorbent assay (ELISA) assays. Matched antibody pair kits for mouse TNF alpha (Sino- Biological), mouse IL-6 (Abeam), mouse IFNgamma (Invitrogen), mouse IFN beta (Bio-Techne), and a precoated mouse IFN alpha kit (Invitrogen) were used. For TNF alpha and IFN beta the capture antibodies were diluted in PBS (Cytiva), while the IL-6 and IFN gamma capture antibodies were diluted in their respective coating buffers. The diluted capture antibodies were incubated in the plates overnight at +4°C and washed the next day with PBS / Tween washing buffer (Sigma- Aldrich). The TNF alpha plate was blocked using 2% BSA (Thermo-Scientific) diluted in washing buffer, the IFN beta plate was blocked using 1% BSA diluted in PBS, while the IFN alpha, IFN gamma, and IL-6 plates were blocked using their respective dilution buffers. Blocking was done for 2 hours at RT on an orbital shaker at 200 rpm. After blocking, the plates were washed and then incubated with the diluted tumor and serum samples along with the corresponding standard solutions for each ELISA kit. The samples were incubated for 2 hours at RT on an orbital shaker at 200 rpm. The TNF alpha plate was incubated for 1 hour at RT with a diluted detection antibody conjugated with horseradish peroxidase (HRP). The IL-6, IFN alpha, IFN beta, and IFN gamma plates were incubated for 1 hour at RT with a diluted detection antibody conjugated with biotin followed by incubation for 1 hour at RT with their respective diluted HRP-streptavidin conjugates. All plates were washed and incubated with 3,3',5,5'-tetramethylbenzidine (TMB) (Invitrogen) and peroxide solution mixed at a ratio of 1 : 1 (Thermo Scientific) for up to 20 min, then a stop solution (10% H2SO4) was added to the plates. The signal from the wells was quantified by absorbance measured at 450 nm using a Bio-Rad iMark microplate reader. Antibody standards were used to plot calibration curves.

[0109] The results are provided in FIG. 5.

[0110] The results indicated that:In tumors, the level of TNF-a increased 23 fold 6-hours post-injection and then fell to a normal level at 24 hours (FIG. 5A), however in serum, the level of TNF-a did not significantly change from the control level following injection (FIG. 5B);In tumors, the level of IL-6 rose about 2.4 fold at 6-hours post-treatment (FIG. 5C) with a slight increase of its level in serum (FIG. 5D), which returned to its normal level at 24 hours. The level of IL-6 in serum was an order of magnitude lower compared to its level in tumors;In tumors, the levels of type I interferon, IFN-P, increased 8 fold in treated animals (FIG. 5E), accompanied by a slight increase in serum (two orders of magnitude lower than the level in tumors) (FIG. 5F); andIn tumors and serum, the levels of IFN-a and IFN-y showed minimal change (FIG. 5G- 5J).

[0111] Thus, 2pHLIP®-dMSA induced transient tumor-targeted increases of type I interferon, IFN-P, and the pro-inflammatory cytokines TNF-a and IL-6, indicating activation of the nuclear factor kappa light chain enhancer of activated B cells (NF-kB) and IRF3 signaling pathways, without systemic activation.EXAMPLE 8: Biodistribution, PK, and Imaging

[0112] For biodistribution studies 5xl04of CT26 cancer cells were injected SQ in 100 pl of growth medium into the right flank of female Balb / c mice and tumors were grown until they reached 150-250 mm3in volume. Then a single retro-orbital (RO) injection of 50 pM 100 pl of 2(ICG-pHLIP®)-dMSA was performed. Animals were euthanized at 5 min, 1, 4, 24, 48, 72, and 120 hours post-injection, blood was collected in K2 ethylenediaminetetraacetic acid (EDTA) vacutainer blood collection tubes (BD), and necropsy was performed immediately after euthanization. Blood, tumors and major organs (kidney, liver, spleen, pancreas, lung, heart, large and small intestines, bone, muscle, and brain) were collected, and imaged ex vivo immediately after necropsy. Blood (200 pl) was imaged in 96-well plates with black bottom and walls. The zerotime point (0 min) was obtained by imaging of 2(ICG-pHLIP®)-dMSA diluted in blood collected from a control mouse that did not receive any injection (the dilution was made based on the assumption that a mouse contains 80 ml / kg of blood).

[0113] The in vivo and ex vivo bright field and near-infrared fluorescent imaging employed a Stryker 1588 advanced imaging modalities (AIM) endoscopic system with L10 AIM Light Source (808 nm excitation and collection of light in the range of approximately of 815 to 850 nm), and a 1588 AIM Camera using a 10 mm scope. The lens was kept at a fixed distance from the surface of the organs, within an enclosed (light-protected) area. Calibration curves converting laser and gain setting was established by imaging of pHLIP®-ICG solution at different concentrations. The ex vivo fluorescence imaging of tissue specimens was performed using three different laser settings and six different gain settings. The digital fluorescence images were split into Red-Green- Blue (RGB) channels, with the green channel being analyzed using Imaged program to calculate the average fluorescence intensity. All average intensities were adjusted based on their capture settings using calibration curves to present fluorescence intensities corresponding to the unified (the same) settings.

[0114] The results are provided in FIG. 4 and FIG. 12.

[0115] The results indicated a significant accumulation of the agent in the tumor from 1 hour and up to 48 hours followed by a slight decrease of the signal at later time points (FIG. 4B). The organ and tissue clearances were slow, which is associated with slow blood clearance. Whole blood imaging was performed to establish clearance of the agent (FIG. 4C). The observed halflife of 2(ICG-pHLIP®)-dMSA is 32.2 hours, which is significantly longer compared to any previously investigated pHLIP®-cargo conjugate.EXAMPLE 9: Binding of mMSA and dMSA to STING Protein

[0116] Binding of mMSA and dMSA to STING protein was measured with human STING WT binding kit (Cisbio). Briefly: mMSA (MSA2, from MCE), dMSA (Iris Biotech GmbH) or 2’3’-cGAMP (Cisbio) control were added in increasing concentrations to the 96-well microplate (PerkinElmer), followed by addition of 6His-tagged human STING WT protein. STING WT ligand d2 reagent was premixed with 6His Tuberculosis (Tb) antibodies, and it was added to each well and the plate was incubated for 3 hours at RT. Fluorescence intensities at 620 nm and 665 nm excited at 450 nm were recorded on the SpectraMax ID5 plate reader (Molecular Devices). The homogeneous time resolved fluorescence (HTRF) ratio was calculated to establish the binding of each agent to the STING protein and to calculate EC50.

[0117] The results are provided in FIG. 8.

[0118] The results indicated that the binding affinities were 7.5 pM for mMSA and 24 nM for dMSA, indicating that the dimer is much more potent than the monomer.EXAMPLE 10: Binding to Human Serum Albumin (HSA)

[0119] Binding affinities of pHLIP®-mMSA and 2pHLIP®-dMSA to human serum albumin (HSA) (MilliporeSigma) were investigated using a series of competitive fluorescence binding assays measured on a SpectraMax ID5 plate reader with SoftMax 7.1.2 software. HSA was initially dissolved to 500 pM in deionized water and further diluted using pH 7.6 phosphate buffer. Dansylamide (DNS A) or dansylglycine (DNSG) (both from Tokyo Chemical Industry) were used as fluorescent markers, which are known to bind to specific sites on HSA. Each well contained 100 pL of sample consisting of the fluorescent marker DNS A or DNSG (1 pM), with different concentrations of pHLIP® agents (0, 5, or 10 pM) and concentrations of HSA ranging from 0 pM to 100 pM. Samples were incubated for 2 hours at 37°C. As controls, warfarin and ibuprofen, drugs- I l l - known to bind different sites on HSA, were used instead of pHLIP® agents. Fluorescence measurements from each well were performed at 485 nm with excitation at 365 nm at 37°C. As a control, binding of DNSA and DNSG were probed with each agent in absence of HSA. Before the measurements a plate reader optimization test was run. Data were fitted individually and globally using the Michaelis-Menten equation. In global fits a common maximal reaction rate (Vmax) value was used, established for 0 pM of pHLIP® agents for both DNSA and DNSG. Data were fitted by nonlinear least squares curve fitting procedures employing the Levenberg Marquardt algorithm using Origin 8.5.

[0120] The results are provided in FIG. 4 and FIG. 13, binding constants are provided in FIG. 7

[0121] The results indicated the binding of DNSA to HSA was reduced about 2 fold in the presence of 2pHLIP®-dMSA, while warfarin at concentration of 10 pM reduced DNSA binding to HSA by 5.3 fold (FIG. 7). Additionally, the binding of DNSG to HSA was reduced 7.8 fold in the presence of 10 pM of 2pHLIP®-dMSA, while ibuprofen reduced DNSG binding to HSA by 5.3 fold (FIG. 7). The results indicated strong binding of 2pHLIP®-dMSA to HSA, especially its site II, which is known to interact with cyclic compounds including ibuprofen, tryptophan, and compounds with free carboxyl groups.EXAMPLE 11 : Statistical Analysis

[0122] The Kolmogorov-Smirnov two-tailed nonparametric test was used to establish p- levels.

[0123] The patent and scientific literature referred to herein establishes the knowledge that is available to those with skill in the art. All United States patents and published or unpublished United States patent applications cited herein are hereby incorporated by reference. All published foreign patents and patent applications cited herein are hereby incorporated by reference. All other published references, documents, manuscripts and scientific literature cited herein are hereby incorporated by reference.

[0124] While this invention has been particularly shown and described with references to preferred embodiments thereof, it will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the scope of the invention encompassed by the appended claims.

Claims

WHAT IS CLAIMED IS:

1. A composition comprising a conjugate of Formula (I): Peptide-Linker-STING-Linker-Peptide (I) wherein Peptide is a pHLIP® peptide, wherein Linker is a cleavable linker bonded to a carboxyl group on “STING”; wherein “STING” is a STING agonist selected from the group consisting of (2S,2'S)-4,4'-[butane-l,4-diylbis(6-methoxy-l-benzothiene-5,2-diyl)]bis(2- methyl-4-oxobutanoic acid), (2S,2'S)-4,4'-[propane-l,3-diylbis(6-methoxy-l-benzothiene-5,2-diyl)]bis(2- methyl-4-oxobutanoic acid), (S)-4-(5-(3-(2-(3-carboxypropanoyl)-6-methoxybenzo[b]thiophen-5-yl)propoxy)- 6-methoxythieno[3,2-b]pyri din-2 -yl)-2-methyl-4-oxobutanoic acid, 4-(5-(3-((2-(3-carboxypropanoyl)-6-methoxythieno[3,2-b]pyridin-5- yl)oxy)propyl)benzo[b]thiophen-2-yl)-4-oxobutanoic acid, 4-(5-(3-(2-(3-carboxypropanoyl)-6-methoxybenzo[b]thiophen-5-yl)propoxy)-6- methoxybenzo[d]thiazol-2-yl)-4-oxobutanoic acid, 4-(5-(3-((2-(3-carboxypropanoyl)-6-methoxybenzo[b]thiophen-5-yl)oxy)propyl) benzo[b]thiophen-2-yl)-4-oxobutanoic acid, 4-(5-(2-((2-(3-carboxypropanoyl)-6-methoxybenzo[b]thiophen-5-yl)oxy)ethyl)-6- methoxythieno[3,2-b]pyridin-2-yl)-4-oxobutanoic acid, 4-(5-(2-(2-(3-carboxypropanoyl)-6-methoxythieno[3,2-b]pyridin-5-yl)ethoxy)-6- methoxythieno[3,2-b]pyridin-2-yl)-4-oxobutanoic acid, 4-(5-(2-((2-(3-carboxypropanoyl)-6-methoxybenzo[d]thiazol-5-yl)oxy)ethyl)-6- methoxythieno[3,2-b]pyridin-2-yl)-4-oxobutanoic acid, 4-(5-(3-(2-(3-carboxypropanoyl)-6-methoxybenzo[b]thiophen-5-yl)propoxy)-6- methoxythieno[3,2-b]pyridin-2-yl)-4-oxobutanoic acid, (S)-4-(5-(3-((2-(3-carboxypropanoyl)-6-methoxythieno[3,2-b]pyridin-5- yl)oxy)propoxy)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, 4-(5-(3-((2-(3-carboxypropanoyl)-6-methoxybenzo[b]thiophen-5-yl)oxy)propyl)- 6-methoxythieno[3,2-b]pyri din-2 -yl)-4-oxobutanoic acid, (S)-4-(5-(3-((2-(3-carboxypropanoyl)-6-methoxythieno[3,2-b]pyridin-5- yl)oxy)propyl)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-(2-(3-carboxypropanoyl)-6-methoxythieno[3,2-b]pyridin-5- yl)propoxy)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-(2-((S)-3-carboxybutanoyl)-6-methoxybenzo[b]thiophen-5- yl)propoxy)-6-methoxythieno[3,2-b]pyridin-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(2-((2-(3-carboxypropanoyl)-6-methoxybenzo[b]thiophen-5- yl)oxy)ethoxy)-6-methoxythieno[3,2-b]pyridin-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-(3-carboxypropanoyl)-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-6-methoxythieno[3,2-b]pyridin-2-yl)-2-methyl-4-oxobutanoic acid, rac-(R)-4-(5-(2-((2-((R)-3-carboxybutanoyl)-4-fluoro-6- methoxybenzo[b]thiophen-5-yl)oxy)ethoxy)-6-methoxythieno[3,2-b]pyri din-2 -yl)-2- methyl-4-oxobutanoic acid,(S)-4-(5-(2-((2-(3-carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)ethoxy)-6-methoxythieno[3,2-b]pyridin-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-(3-carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-6-methoxythieno[3,2-b]pyridin-2-yl)-2-methyl-4-oxobutanoic acid, rac-(R)-4-(5-(3-((2-((R)-3-carboxybutanoyl)-4-fluoro-6- methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6-methoxythieno[3,2-b]pyri din-2 -yl)-2- methyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-(3-carboxypropanoyl)-6-methoxythieno[3,2-b]pyridin-5- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,4-(4-(3-(2-(3-carboxypropanoyl)-5-methoxbenzo[b]thiophen-6-yl)propyl)-6- methoxybenzo[b]thiophen-2-yl)-4-oxobutanoic acid,4,4'-(propane-l,3-diylbis(6-methoxybenzo[d]thiazole-5,2-diyl))bis(4-oxobutanoic acid),4,4'-(propane-l,3-diylbis(6-methylbenzo[b]thiophene-5,2-diyl))bis(4-oxobutanoic acid),4-(5-(3-(2-(3-carboxypropanoyl)-6-methoxybenzo[b]thiophen-5-yl)propyl)-6- methoxythieno[3,2-b]pyridin-2-yl)-4-oxobutanoic acid,(S)-4-(5-(3-(2-(3-carboxybutyl)-6-methoxybenzo[b]thiophen-5-yl)propyl)-6- methoxybenzo[b]thiophen-2-yl)-4-oxobutanoic acid,4-(5-(3-((2-(3-carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propyl)-6-methoxybenzo[b]thiophen-2-yl)-4-oxobutanoic acid,(S)-4-(5-(3-(2-(3-carboxypropanoyl)-6-methoxybenzo[b]thiophen-5-yl)propoxy)- 4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(2-((2-(3-carboxypropanoyl)-6-methoxybenzo[b]thiophen-5- yl)oxy)ethoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-(3-carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propyl)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propyl)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-(3-carboxypropanoyl)-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(6-(3-(7-((S)-3-carboxybutanoyl)-4-methoxythieno[2',3':5,6]benzo[l,2- d]oxazol-2-yl)propoxy)-5-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (2S)-4-{5-[3-({2-[(3 S)-3-carboxybutanoyl]-6-methoxy-l-benzothiophen-5- yl } oxy)propyl]-6-m ethoxy- 1 -benzothiophen-2-yl } -2-methyl-4-oxobutanoic acid,(S)-4-(5-(2-(2-((S)-3-carboxybutanoyl)-6-methoxybenzo[b]thiophen-5-yl)ethoxy)- 6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-(3-carboxypropanoyl)benzo[b]thiophen-6-yl)oxy)propoxy)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(6-(3-((2-(3-carboxypropanoyl)benzo[b]thiophen-5-yl)oxy)propoxy)-5- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(2S,2'S)-4,4'-((propane-l,3-diylbis(oxy))bis(5-methoxybenzo[b]thiophene-6,2- diyl))bis(2-methyl-4-oxobutanoic acid),(2S,2'S)-4,4'-((ethane-l,2-diylbis(oxy))bis(4-fluoro-6-methoxybenzo[b]thiophene- 5,2-diyl))bis(2-methyl-4-oxobutanoic acid),(S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-5-methoxybenzo[b]thiophen-6- yl)oxypropoxy)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(2S,2'S)-4,4'-((propane-l,3-diylbis(oxy))bis(6-methoxybenzo[b]thiophene-5,2- diyl))bis(2-methyl-4-oxobutanoic acid),(S)-4-(6-(2-((2-(3-carboxypropanoyl)benzo[b]thiophen-5-yl)oxy)ethoxy)-5- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-(3-carboxypropanoyl)benzo[b]thiophen-5-yl)oxy)propoxy)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,rac-(R)-4-(5-(2-((2-((R)-3-carboxybutanoyl)-5-methoxybenzo[b]thiophen-6- yl)oxy)ethoxy)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-6-methoxythieno[3,2-b]pyridin-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-(3-carboxybutanoyl)-6-methoxythieno[3,2-b]pyridin-5- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2,2-dimethyl-4-oxobutanoic acid,(2S)-4-{5-[2-({2-[(3 S)-3-carboxybutanoyl]-6-methoxy-l-benzothiophen-5- yl}amino)ethyl]-6-methoxy-l-benzothiophen-2-yl}-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-6-methoxybenzo[b]thiophen-5- yl)amino)propyl)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(2-((2-(3-carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)ethoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-(3-carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(R)-4-(5-(2-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)ethoxy)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(2-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)ethoxy)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, rac-(lR,2R)-2-(5-(3-((2-((R)-3-carboxybutanoyl)-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-6-methoxybenzo[b]thiophene-2-carbonyl)cyclopropane-l-carboxylic acid,(S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(6-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-5-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-(3-carboxybutanoyl)-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2,2-dimethyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-(3-carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(6-(3-((2-(3-carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-5-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-6-methoxybenzo[b]thiophen-5- yl)amino)propoxy)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, 4-(5-((3-(2-(3-carboxypropanoyl)-6-methoxybenzo[b]thiophen-5- yl)propyl)amino)-6-methoxythieno[3,2-b]pyridin-2-yl)-4-oxobutanoic acid, (2S,2'S)-4,4'-((ethane-l,2-diylbis(oxy))bis(6-methoxybenzo[b]thiophene-5,2- diyl))bis(2-methyl-4-oxobutanoic acid), (2S,2'S)-4,4'-(7,8,17,18-tetrahydro-6H,16H-bis[l]benzothieno[5,6-b:6',5'- i] [ 1 ,4,8, 1 l]tetraoxacyclotetradecine-2, 12-diyl)bis(2-methyl-4-oxobutanoic acid), (2S,2'S)-4,4'-(7,8,17,18-tetrahydro-6H,16H-bis[l]benzothieno[5,6-b:5',6'- i] [ 1 ,4,8, 1 l]tetraoxacyclotetradecine-2, 12-diyl)bis(2-methyl-4-oxobutanoic acid), (2S,2'S)-4,4'-(l,3-propanediylbis{oxy[6-(difluoromethoxy)-l-benzothiene-5,2- diyl] })bis(2-methyl-4-oxobutanoic acid), 4-(5-(2-((2-(3-carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)ethoxy)-6-methoxythieno[3,2-b]pyridin-2-yl)-4-oxobutanoic acid, 4-(5-(3-((2-(3-carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-6-methoxythieno[3,2-b]pyridin-2-yl)-4-oxobutanoic acid, (S)-4-(5-(2-((2-(3-carboxypropanoyl)-6-methoxythieno[3,2-b]pyridin-5- yl)oxy)ethoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, trans-2-(5-(3-(2-((S)-3-carboxybutanoyl)-6-methoxybenzo[b]thiophen-5- yl)propoxy)-4-fluoro-6-methoxybenzo[b]thiophene-2-carbonyl)-cyclopropanecarboxylic acid, trans-2-(5-(3-(2-(3-carboxypropanoyl)-6-methoxybenzo[b]thiophen-5- yl)propoxy)-4-fluoro-6-methoxybenzo[b]thiophene-2-carbonyl)cyclopropanecarboxylic acid, trans-2-(5-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen- 5-yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophene-2- carbonyl)cyclopropanecarboxylic acid, trans-2-(5-(3-((2-((lR,2R)-2-carboxycyclopropanecarbonyl)-4-fluoro-6- methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophene-2- carbonyl)cyclopropanecarboxylic acid,trans-2-(5-(3-((2-(3-carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophene-2- carbonyl)cyclopropanecarboxylic acid, trans-2-(5-(3-((2-((S)-3-carboxybutanoyl)-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophene-2- carbonyl)cyclopropanecarboxylic acid, trans-2-(5-(3-((2-((S)-3-carboxybutanoyl)-5-methoxybenzo[b]thiophen-6- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophene-2- carbonyl)cyclopropanecarboxylic acid,(R)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propyl)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(2S,2'S)-4,4'-(5,5'-(butane-l,4-diylbis(oxy))bis(6-methoxybenzo[b]thiophene-5,2- diyl))bis(2-methyl-4-oxobutanoic acid),(S)-4-(5-(4-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)butoxy)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(4-((2-((S)-3-carboxybutanoyl)-5-methoxybenzo[b]thiophen-6- yl)oxy)butoxy)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, trans-2-(6-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen- 5-yl)oxy)propoxy)-4-fluoro-5-methoxybenzo[b]thiophene-2- carbonyl)cyclobutanecarboxylic acid, trans-2-(5-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen- 5-yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophene-2- carbonyl)cyclobutanecarboxylic acid,(S)-4-(5-(3-((2-((S)-3-carboxybutyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propyl)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-((S)-3-carboxybutyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(2S,2'S)-4,4'-(5, 5 '-(pentane- 1, 5-diylbis(oxy))bis(6-methoxybenzo[b]thi ophene- 5,2-diyl))bis(2-methyl-4-oxobutanoic acid),(S)-4-(5-((5-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)pentyl)oxy)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-((S)-3-carboxybutyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propyl)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, trans-2-(5-(3-(2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)propoxy)-4-fluoro-6-methoxybenzo[b]thiophene-2-carbonyl)cyclopropanecarboxylic acid, trans-2-(5-(3-(2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)propoxy)-4-fluoro-6-methoxybenzo[b]thiophene-2-carbonyl)cyclobutanecarboxylic acid,(R)-4-(5-(3-((2-((R)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propyl)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-((R)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propyl)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-((6-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)hexyl)oxy)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, trans-2-(5-(3-(2-((S)-3-carboxybutanoyl)-6-methoxybenzo[b]thiophen-5- yl)propoxy)-4-fluoro-6-methoxybenzo[b]thiophene-2-carbonyl)cyclobutanecarboxylic acid,(S)-4-(5-(3-((2-(3-carboxy-3-methylbutyl)-4-fluoro-6-methoxybenzo[b]thiophen- 5-yl)oxy)propyl)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, trans-2-(5-(3-((2-((S)-3-carboxybutyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophene-2- carbonyl)cyclobutanecarboxylic acid,4,4'-(5,5'-(pentane-l,5-diylbis(oxy))bis(4-fluoro-6-methoxybenzo[b]thiophene- 5,2-diyl))bis(4-oxobutanoic acid),(S)-4-(5-((5-((2-(3-carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yloxy)pentyloxy)-4-fluoro-6-methoxybenzo[b]thi ophen-2 -yl)-2-methyl-4-oxobutanoic acid,(2 S,2 ' S)-4,4 '-(5 , 5 '-(pentane- 1 , 5 -diylbi s(oxy))bi s(4-fluoro-6- methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4-oxobutanoic acid),(S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-chloro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-((4-bromo-2-((S)-3-carboxybutanoyl)-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(4-((2-((S)-3-carboxybutyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)butoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(4-((2-((S)-3-carboxybutanoyl)-4-chloro-6-methoxybenzo[b]thiophen-5- yl)oxy)butoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(4-((4-bromo-2-((S)-3-carboxybutanoyl)-6-methoxybenzo[b]thiophen-5- yl)oxy)butoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(2S, 2'S)-4,4'-(5, 5 '-(propane-1, 3-diylbis(oxy))bis(4-chloro-6- methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4-oxobutanoic acid),(S)-4-(5-(3-((4-bromo-2-((S)-3-carboxybutanoyl)-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-chloro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(2S, 2'S)-4,4'-(5, 5 '-(propane-1, 3-diylbis(oxy))bis(4-bromo-6- methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4-oxobutanoic acid),2-((5-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2- yl)methyl)cyclobutanecarboxylic acid,(S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4,7-dichloro-6- methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thi ophen-2- yl)-2-methyl-4-oxobutanoic acid,(2 S,2 ' S)-4,4 '-((butane- 1 , 3 -diylbi s(oxy))bi s(4-fluoro-6- methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4-oxobutanoic acid),(2S,2'S)-4,4'-((pentane-l,4-diylbis(oxy))bis(4-fluoro-6- methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4-oxobutanoic acid),(2 S,2 ' S)-4,4 '-((hexane-2, 5 -diylbi s(oxy))bi s(4-fluoro-6- methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4-oxobutanoic acid), trans-2-(5-(3-((2-(3-carboxy-3-methylbutyl)-4-fluoro-6- methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophene-2- carbonyl)cyclobutane- 1 -carboxylic acid,(2 S,2 ' S)-4,4 '-(((2-methylpropane- 1 , 3 -diy 1 )b i s(oxy))bi s(4-fluoro-6- methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4-oxobutanoic acid),(2S,2'S)-4,4'-(((2,2-dimethylpropane-l,3-diyl)bis(oxy))bis(4-fluoro-6- methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4-oxobutanoic acid),(2 S, 2 ' S)-4, 4 '-(((cyclopropane- 1 , 1 -diylbi s-(methylene))bi s(oxy))bi s(4-fluoro-6- methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4-oxobutanoic acid),(S)-4-(5-(3-((2-((S)-3-carboxybutyl)-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-chloro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(4-bromo-5-(3-((2-((S)-3-carboxybutyl)-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-((S)-3-carboxybutyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-chloro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(4-bromo-5-(3-((2-((S)-3-carboxybutyl)-4-fluoro-6- methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6-methoxybenzo[b]thi ophen-2 -yl)-2- methyl-4-oxobutanoic acid,4-(5-(3-((2-(3-carboxy-3-methylbutyl)-4-fluoro-6-methoxybenzo[b]thi ophen-5- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2,2-dimethyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-((S)-3-carboxybutyl)-4-chloro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-((S)-3-carboxybutyl)-4-chloro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(2 S,2 ' S)-4,4 '-((ethane- 1 ,2-diylbi s(oxy))bi s(4-chloro-6- methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4-oxobutanoic acid),(S)-4-(5-(2-((2-((S)-3-carboxybutyl)-4-chloro-6-methoxybenzo[b]thiophen-5- yl)oxy)ethoxy)-4-chloro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-chloro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(2 S,2 ' S)-4,4 '-((propane- 1 , 3 -diylbi s(oxy))bi s(4-fluoro-6- methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4-oxobutanoic acid),(S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-6-(methylamino)benzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-((S)-3-carboxybutyl)-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-(2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)propoxy)-6-methoxythieno[3,2-b]pyridin-2-yl)-2-methyl-4-oxobutanoic acid,(2S,2'S)-4,4'-(((2-methylpropane-l,3-diyl)bis(oxy))bis(6- methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4-oxobutanoic acid),(S)-4-(5-(3-((2-(3-carboxypropanoyl)-6-methoxybenzo[b]thiophen-5- yl)oxy)propyl)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-(2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)propoxy)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-(3-carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propyl)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propyl)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-5-methoxythieno[3,2-b]pyridin-6- yl)oxy)propoxy)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(6-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-5-methoxythieno[3,2-b]pyridin-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(6-(3-((2-(3-carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-5-methoxythieno[3,2-b]pyridin-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-((S)-3-carboxybutyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, trans-2-(5-(3-((2-((S)-3-carboxybutanoyl)-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophene-2- carbonyl)cyclobutanecarboxylic acid, trans-2-(5-(3-((2-((S)-3-carboxybutanoyl)-5-methoxybenzo[b]thiophen-6- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophene-2- carbonyl)cyclobutanecarboxylic acid,(2 S,2 ' S)-4,4 '-(5 , 5 '-(butane- 1 ,4-diylbi s(oxy))bi s(4-chloro-6- methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4-oxobutanoic acid), (4-(5-(3-((2-(3-carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propyl)-6-methoxythieno[3,2-b]pyridin-2-yl)-4-oxobutanoic acid,(S)-4-(5-(3-(2-(3-carboxypropanoyl)-6-methoxythieno[3,2-b]pyridin-5- yl)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-((3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo [b]thiophen-5- yl)oxy)propyl)amino)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-((3-(2-(3-carboxypropanoyl)-6-methoxybenzo[b]thiophen-5- yl)propyl)amino)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-6-hydroxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3-carboxybutyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-6-hydroxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-chloro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-6-hydroxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-chloro-6-hydroxybenzo[b]thiophen-5- yl)oxy)propoxy)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-chloro-6-hydroxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-((S)-3-carboxybutyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-chloro-6-hydroxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-chloro-6-hydroxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-chloro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-hydroxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-hydroxybenzo[b]thiophen-5- yl)oxy)propoxy)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-chloro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-fluoro-6-hydroxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid,wherein each is a covalent bond.

2. The composition of claim 1, wherein the pHLIP® peptide of the conjugate of Formula (I) has the following sequence: XnYm; YmXn; XnYmXj; YmXnYi; YmXnYiXj; XnYmXjYi; YmXnYiXjYi; XnYmXjYiXi; YmXnYiXjYiXh; XnYmXjYiXhYg; YmXnYiXjYiXhYg; XnYmXjYiXhYgXf; (XY)n; (YX)n; (XY)nYm; (YX)nYm; (XY)nXm; (YX)nXm; Ym(XY)n; Ym(YX)n; Xn(XY)m; Xn(YX)m; (XY)nYm(XY)i; (YX)nYm(YX)i; (XY)nXm(XY)i; (YX)nXm(YX)i; Ym(XY)n; Ym(YX)n; Xn(XY)m; or Xn(YX)m, wherein,(i) each Y is, independently, a non-polar amino acid with solvation energy, DGxcor> +0.50, or Glycine;(ii) each X is, independently, a protonatable amino acid, and(iii) n, m, i, j, 1, h, g, f are each, independently, an integer from 1 to 8.

3. The composition of claim 1 or 2, wherein the pHLIP® peptide of the conjugate of Formula (I) comprises a sequence comprising the sequence ADDQNPWRAYLDLLFPTDTLLLDLLWXG (SEQ ID NO: 220), wherein “X” is a functional group for conjugation purposes, selected from lysine (Lys), cysteine (Cys), Azido-containing amino acid or other modified amino acids.

4. The composition of claim 1 or 2, wherein the pHLIP® peptide of the conjugate of Formula (I) comprises a sequence consisting of the sequence ADDQNPWRAYLDLLFPTDTLLLDLLWXG (SEQ ID NO: 220), wherein “X” is a functional group for conjugation purposes, selected from lysine (Lys), cysteine (Cys), Azido-containing amino acid or other modified amino acids.

5. The composition of claim 1 or 2, wherein the pHLIP® peptide of the conjugate of Formula (I) comprises a sequence selected from the group consisting of any one of SEQ ID NOs. 1- 219.

6. The composition of claim 1 or 2, wherein the pHLIP® peptide of the conjugate of Formula (I) has a sequence selected from the group consisting of any one of SEQ ID NOs. 1-219.

7. The composition of claim 1 or 2, wherein the pHLIP® peptide of the conjugate of Formula (I) has a sequence comprising the sequence ADQDNPWRAYLDLLFPTDTLLLDLLWCG (SEQ ID NO: 218).

8. The composition of claim 1 or 2, wherein the pHLIP® peptide of the conjugate of Formula (I) has a sequence comprising the sequence ADDQNPWRAYLDLLFPTDTLLLDLLWCG (SEQ ID NO: 219).

9. The composition of claim 1 or 2, wherein the pHLIP® peptide of the conjugate of Formula (I) has a sequence consisting of the sequence ADQDNPWRAYLDLLFPTDTLLLDLLWCG (SEQ ID NO: 218).

10. The composition of claim 1 or 2, wherein the pHLIP® peptide of the conjugate of Formula (I) has a sequence consisting of the sequence ADDQNPWRAYLDLLFPTDTLLLDLLWCG (SEQ ID NO: 219).

11. The composition of any one of claims 1-10, wherein all amino acids in the pHLIP® peptide of the conjugate of Formula (I) are D-amino acids.

12. The composition of any one of claims 1-11, wherein the STING agonist of the conjugate of Formula (I) is (S)-4-(5-(3-((2-((S)-3-carboxybutyl)-4-fluoro-6- methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thi ophen-2- yl)-2-methyl-4-oxobutanoic acid.

13. The composition of any one of claims 1-11, wherein the STING agonist of the conjugate of Formula (I) is (S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6- methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6-(methylamino)benzo[b]thi ophen-2 -yl)-2- methyl-4-oxobutanoic acid.

14. The composition of any one of claims 1-11, wherein the STING agonist of the conjugate of Formula (I) is (S)-4-(5-(3-((2-((S)-3-carboxybutyl)-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid.

15. The composition of any one of claims 1-11, wherein the STING agonist of the conjugate of Formula (I) is16. The composition of any one of claims 1-11, wherein the STING agonist of the conjugate of Formula (I) is (S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6- methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6-hydroxybenzo[b]thiophen-2-yl)-2- methyl-4-oxobutanoic acid.

17. The composition of any one of claims 1-11, wherein the STING agonist of the conjugate of Formula (I) is (S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-hydroxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)- 2-methyl-4-oxobutanoic acid.

18. The composition of any one of claims 1-11, wherein the STING agonist of the conjugate19. The composition of any one of claims 1-18, wherein one or both Linkers of the conjugate of Formula (I) comprise a disulfide bond or an acid-labile bond.

20. The composition of claim 19, wherein one or both Linkers of the conjugate of Formula (I) are self-immolative.

21. The composition of claim 19, wherein one or both Linkers of the conjugate of Formula (I) comprise a disulfide self-immolative bond.

22. The composition of claim 19, wherein both Linkers of the conjugate of Formula (I) are the same.

23. The composition of claim 19, wherein both Linkers of the conjugate of Formula (I) are different.

24. A pharmaceutical composition comprising the composition of any one of claims 1-23 and one or more pharmaceutically acceptable excipients.

25. A method of treating cancer in a subject in need thereof comprising administering the composition of any one of claims 1-23 or the pharmaceutical composition of claim 24 to the subject in need thereof.

26. The method of claim 25, wherein the cancer is a solid tumor.

27. The method of claim 25 or 26, wherein the composition of any one of claims 1-23 or the pharmaceutical composition of claim 24 is injected directly into a tumor mass.

28. The method of claim 25 or 26, wherein the composition of any one of claims 1-23 or the pharmaceutical composition of claim 24 is systemically administered.

29. The method of any one of claims 25-28, wherein the subject is a human.

30. A composition comprising a conjugate of Formula (II)Peptide-Linker-STING-Linker-Peptide (II) wherein Peptide is a pHLIP® peptide comprising the sequence ADQDNPWRAYLDLLFPTDTLLLDLLWCG (SEQ ID NO: 218) or ADDQNPWRAYLDLLFPTDTLLLDLLWCG (SEQ ID NO: 219), wherein Linker is a cleavable linker bonded to a carboxyl group on “STING”; wherein STING is a STING agonist, which is a dimer with a carboxylic acid subsituent (carboxyl group) at the terminal position of both monomers of the dimer; and wherein each is a covalent bond.

31. The composition of claim 30, wherein the pHLIP® peptide of the conjugate of Formula (II) comprises the sequence ADQDNPWRAYLDLLFPTDTLLLDLLWCG (SEQ ID NO:

32. The composition of claim 30, wherein the pHLIP® peptide of the conjugate of Formula (II) comprises the sequence ADDQNPWRAYLDLLFPTDTLLLDLLWCG (SEQ ID NO: 219).

33. The composition of claim 30, wherein the pHLIP® peptide of the conjugate of Formula (II) consists of the sequence(a) ADQDNPWRAYLDLLFPTDTLLLDLLWCG (SEQ ID NO : 218) or(b) ADDQNPWRAYLDLLFPTDTLLLDLLWCG (SEQ ID NO: 219).

34. The composition of claim 33, wherein the pHLIP® peptide of the conjugate of Formula (II) consists of the sequence ADQDNPWRAYLDLLFPTDTLLLDLLWCG (SEQ ID NO:218).

35. The composition of claim 33, wherein the pHLIP® peptide of the conjugate of Formula (II) consists of the sequence ADDQNPWRAYLDLLFPTDTLLLDLLWCG (SEQ ID NO:219).

36. The composition of any one of claims 30-35, wherein all amino acids in the pHLIP® peptide of the conjugate of Formula (II) are D-amino acids.

37. The composition of any one of claims 30-36, wherein the STING agonist of the conjugate of Formula (II) is selected from the group consisting of (2S,2'S)-4,4'-[butane-l,4-diylbis(6- methoxy-l-benzothiene-5,2-diyl)]bis(2-methyl-4-oxobutanoic acid), (2S,2'S)-4,4'- [propane-l,3-diylbis(6-methoxy-l-benzothiene-5,2-diyl)]bis(2-methyl-4-oxobutanoic acid), (S)-4-(5-(3-(2-(3-carboxypropanoyl)-6-methoxybenzo[b]thiophen-5-yl)propoxy)-6- methoxythieno[3,2-b]pyridin-2-yl)-2-methyl-4-oxobutanoic acid, 4-(5-(3-((2-(3- carboxypropanoyl)-6-methoxythieno[3,2-b]pyridin-5-yl)oxy)propyl)benzo[b]thiophen-2- yl)-4-oxobutanoic acid, 4-(5-(3-(2-(3-carboxypropanoyl)-6-methoxybenzo[b]thiophen-5- yl)propoxy)-6-methoxybenzo[d]thiazol-2-yl)-4-oxobutanoic acid, 4-(5-(3-((2-(3- carboxypropanoyl)-6-methoxybenzo[b]thiophen-5-yl)oxy)propyl) benzo[b]thiophen-2- yl)-4-oxobutanoic acid,4-(5-(2-((2-(3-carboxypropanoyl)-6-methoxybenzo[b]thiophen-5- yl)oxy)ethyl)-6-methoxythieno[3,2-b]pyridin-2-yl)-4-oxobutanoic acid, 4-(5-(2-(2-(3-carboxypropanoyl)-6-methoxythieno[3,2-b]pyridin-5-yl)ethoxy)-6-methoxythieno[3,2- b]pyridin-2-yl)-4-oxobutanoic acid, 4-(5-(2-((2-(3-carboxypropanoyl)-6- methoxybenzo[d]thiazol-5-yl)oxy)ethyl)-6-methoxythieno[3,2-b]pyridin-2-yl)-4- oxobutanoic acid, 4-(5-(3-(2-(3-carboxypropanoyl)-6-methoxybenzo[b]thiophen-5- yl)propoxy)-6-methoxythieno[3,2-b]pyridin-2-yl)-4-oxobutanoic acid, (S)-4-(5-(3-((2-(3- carboxypropanoyl)-6-methoxythieno[3,2-b]pyridin-5-yl)oxy)propoxy)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, 4-(5-(3-((2-(3- carboxypropanoyl)-6-methoxybenzo[b]thiophen-5-yl)oxy)propyl)-6-methoxythieno[3,2- b]pyridin-2-yl)-4-oxobutanoic acid, (S)-4-(5-(3-((2-(3-carboxypropanoyl)-6- methoxythieno[3,2-b]pyridin-5-yl)oxy)propyl)-6-methoxybenzo[b]thi ophen-2 -yl)-2- methyl-4-oxobutanoic acid, (S)-4-(5-(3-(2-(3-carboxypropanoyl)-6-methoxythieno[3,2- b]pyridin-5-yl)propoxy)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-(2-((S)-3-carboxybutanoyl)-6-methoxybenzo[b]thiophen-5-yl)propoxy)-6- methoxythieno[3,2-b]pyridin-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(2-((2-(3- carboxypropanoyl)-6-methoxybenzo[b]thiophen-5-yl)oxy)ethoxy)-6-methoxythieno[3,2- b]pyridin-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-(3-carboxypropanoyl)-6- methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6-methoxythieno[3,2-b]pyri din-2 -yl)-2- methyl-4-oxobutanoic acid, rac-(R)-4-(5-(2-((2-((R)-3-carboxybutanoyl)-4-fluoro-6- methoxybenzo[b]thiophen-5-yl)oxy)ethoxy)-6-methoxythieno[3,2-b]pyri din-2 -yl)-2- methyl-4-oxobutanoic acid, (S)-4-(5-(2-((2-(3-carboxypropanoyl)-4-fluoro-6- methoxybenzo[b]thiophen-5-yl)oxy)ethoxy)-6-methoxythieno[3,2-b]pyri din-2 -yl)-2- methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-(3-carboxypropanoyl)-4-fluoro-6- methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6-methoxythieno[3,2-b]pyri din-2 -yl)-2- methyl-4-oxobutanoic acid, rac-(R)-4-(5-(3-((2-((R)-3-carboxybutanoyl)-4-fluoro-6- methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6-methoxythieno[3,2-b]pyri din-2 -yl)-2- methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-(3-carboxypropanoyl)-6-methoxythieno[3,2- b]pyridin-5-yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4- oxobutanoic acid, 4-(4-(3-(2-(3-carboxypropanoyl)-5-methoxbenzo[b]thiophen-6- yl)propyl)-6-methoxybenzo[b]thiophen-2-yl)-4-oxobutanoic acid, 4, 4 '-(propane- 1,3- diylbis(6-methoxybenzo[d]thiazole-5,2-diyl))bis(4-oxobutanoic acid), 4,4'-(propane-l,3- diylbis(6-methylbenzo[b]thiophene-5,2-diyl))bis(4-oxobutanoic acid), 4-(5-(3-(2-(3- carboxypropanoyl)-6-methoxybenzo[b]thiophen-5-yl)propyl)-6-methoxythieno[3,2- b]pyridin-2-yl)-4-oxobutanoic acid, (S)-4-(5-(3-(2-(3-carboxybutyl)-6-methoxybenzo[b]thiophen-5-yl)propyl)-6-methoxybenzo[b]thiophen-2-yl)-4-oxobutanoic acid, 4-(5-(3-((2-(3-carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propyl)-6-methoxybenzo[b]thiophen-2-yl)-4-oxobutanoic acid, (S)-4-(5-(3-(2-(3- carboxypropanoyl)-6-methoxybenzo[b]thiophen-5-yl)propoxy)-4-fluoro-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(2-((2-(3- carboxypropanoyl)-6-methoxybenzo[b]thiophen-5-yl)oxy)ethoxy)-4-fluoro-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-(3- carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propyl)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3- carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propyl)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-(3- carboxypropanoyl)-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(6-(3-(7-((S)-3- carboxybutanoyl)-4-methoxythieno[2',3':5,6]benzo[l,2-d]oxazol-2-yl)propoxy)-5- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (2S)-4-{5-[3-({2-[(3 S)-3- carboxybutanoyl]-6-methoxy-l-benzothiophen-5-yl}oxy)propyl]-6-methoxy-l- benzothiophen-2-yl}-2-methyl-4-oxobutanoic acid, (S)-4-(5-(2-(2-((S)-3- carboxybutanoyl)-6-methoxybenzo[b]thiophen-5-yl)ethoxy)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-(3- carboxypropanoyl)benzo[b]thiophen-6-yl)oxy)propoxy)-6-methoxybenzo[b]thiophen-2- yl)-2-methyl-4-oxobutanoic acid, (S)-4-(6-(3-((2-(3-carboxypropanoyl)benzo[b]thiophen- 5-yl)oxy)propoxy)-5-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (2S,2'S)-4,4'-((propane-l,3-diylbis(oxy))bis(5-methoxybenzo[b]thiophene-6,2- diyl))bis(2-methyl-4-oxobutanoic acid), (2S,2'S)-4,4'-((ethane-l,2-diylbis(oxy))bis(4- fluoro-6-methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4-oxobutanoic acid), (S)-4- (5-(3-((2-((S)-3-carboxybutanoyl)-5-methoxybenzo[b]thiophen-6-yl)oxypropoxy)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (2S,2'S)-4,4'-((propane- l,3-diylbis(oxy))bis(6-methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4-oxobutanoic acid), (S)-4-(6-(2-((2-(3-carboxypropanoyl)benzo[b]thiophen-5-yl)oxy)ethoxy)-5- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-(3- carboxypropanoyl)benzo[b]thiophen-5-yl)oxy)propoxy)-6-methoxybenzo[b]thiophen-2- yl)-2-methyl-4-oxobutanoic acid, rac-(R)-4-(5-(2-((2-((R)-3-carboxybutanoyl)-5- methoxybenzo[b]thiophen-6-yl)oxy)ethoxy)-6-methoxybenzo[b]thi ophen-2 -yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6-methoxythieno[3,2-b]pyridin-2-yl)-2-methyl-4-oxobutanoic acid,(S)-4-(5-(3-((2-(3-carboxybutanoyl)-6-methoxythieno[3,2-b]pyridin-5-yl)oxy)propoxy)- 4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2,2-dimethyl-4-oxobutanoic acid, (2S)-4-{5- [2-({2-[(3S)-3-carboxybutanoyl]-6-methoxy-l-benzothiophen-5-yl}amino)ethyl]-6- methoxy-l-benzothi ophen-2 -yl}-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3- carboxybutanoyl)-6-methoxybenzo[b]thiophen-5-yl)amino)propyl)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(2-((2-(3- carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)ethoxy)-4-fluoro-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-(3- carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (R)-4-(5-(2-((2-((S)-3- carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)ethoxy)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(2-((2-((S)-3- carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)ethoxy)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, rac-(lR,2R)-2-(5-(3-((2- ((R)-3-carboxybutanoyl)-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6- methoxybenzo[b]thiophene-2-carbonyl)cyclopropane-l -carboxylic acid, (S)-4-(5-(3-((2- ((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(6-(3-((2-((S)-3- carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-5- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-(3- carboxybutanoyl)-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6- methoxybenzo[b]thiophen-2-yl)-2,2-dimethyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-(3- carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(6-(3-((2-(3- carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-5- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3- carboxybutanoyl)-6-methoxybenzo[b]thiophen-5-yl)amino)propoxy)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, 4-(5-((3-(2-(3- carboxypropanoyl)-6-methoxybenzo[b]thiophen-5-yl)propyl)amino)-6- methoxythieno[3,2-b]pyridin-2-yl)-4-oxobutanoic acid, (2S,2'S)-4,4'-((ethane-l,2- diylbis(oxy))bis(6-methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4-oxobutanoicacid), (2S,2'S)-4,4'-(7,8,17,18-tetrahydro-6H,16H-bis[l]benzothieno[5,6-b:6',5'- i] [1 ,4,8, 1 l]tetraoxacyclotetradecine-2,12-diyl)bis(2-methyl-4-oxobutanoic acid), (2S,2'S)- 4,4'-(7,8,17,18-tetrahydro-6H,16H-bis[l]benzothieno[5,6-b:5',6'- i] [1 ,4,8, 1 l]tetraoxacyclotetradecine-2,12-diyl)bis(2-methyl-4-oxobutanoic acid), (2S,2'S)- 4,4'-(l,3-propanediylbis{oxy[6-(difluoromethoxy)-l-benzothiene-5,2-diyl]})bis(2- methyl-4-oxobutanoic acid), 4-(5-(2-((2-(3-carboxypropanoyl)-4-fluoro-6- methoxybenzo[b]thiophen-5-yl)oxy)ethoxy)-6-methoxythieno[3,2-b]pyri din-2 -yl)-4- oxobutanoic acid, 4-(5-(3-((2-(3-carboxypropanoyl)-4-fluoro-6- methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6-methoxythieno[3,2-b]pyri din-2 -yl)-4- oxobutanoic acid, (S)-4-(5-(2-((2-(3-carboxypropanoyl)-6-methoxythieno[3,2-b]pyridin-5-yl)oxy)ethoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, trans-2-(5-(3-(2-((S)-3-carboxybutanoyl)-6-methoxybenzo[b]thiophen-5- yl)propoxy)-4-fluoro-6-methoxybenzo[b]thiophene-2-carbonyl)-cyclopropanecarboxylic acid, trans-2-(5-(3-(2-(3-carboxypropanoyl)-6-methoxybenzo[b]thiophen-5-yl)propoxy)- 4-fluoro-6-methoxybenzo[b]thiophene-2-carbonyl)cyclopropanecarboxylic acid, trans-2- (5-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophene-2- carbonyl)cyclopropanecarboxylic acid, trans-2-(5-(3-((2-((lR,2R)-2- carboxycyclopropanecarbonyl)-4-fluoro-6- methoxybenzo[b]thiophen-5-yl)oxy)propoxy)- 4-fluoro-6-methoxybenzo[b]thiophene-2-carbonyl)cyclopropanecarboxylic acid, trans-2- (5-(3-((2-(3-carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)- 4-fluoro-6-methoxybenzo[b]thiophene-2-carbonyl)cyclopropanecarboxylic acid, trans-2- (5-(3-((2-((S)-3-carboxybutanoyl)-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4- fluoro-6-methoxybenzo[b]thiophene-2-carbonyl)cyclopropanecarboxylic acid, trans-2-(5- (3-((2-((S)-3-carboxybutanoyl)-5-methoxybenzo[b]thiophen-6-yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophene-2-carbonyl)cyclopropanecarboxylic acid, (R)-4-(5-(3-((2- ((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propyl)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (2S,2'S)-4,4'-(5,5'-(butane- l,4-diylbis(oxy))bis(6-methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4-oxobutanoic acid), (S)-4-(5-(4-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)butoxy)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5- (4-((2-((S)-3-carboxybutanoyl)-5-methoxybenzo[b]thiophen-6-yl)oxy)butoxy)-6- methoxybenzo[b]thi ophen-2 -yl)-2-methyl-4-oxobutanoic acid, trans-2-(6-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-5- methoxybenzo[b]thiophene-2-carbonyl)cyclobutanecarboxylic acid, trans-2-(5-(3-((2- ((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4- fluoro-6-methoxybenzo[b]thiophene-2-carbonyl)cyclobutanecarboxylic acid, (S)-4-(5-(3- ((2-((S)-3-carboxybutyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propyl)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3- carboxybutyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (2S,2'S)-4,4'-(5,5'- (pentane-l,5-diylbis(oxy))bis(6-methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4- oxobutanoic acid), (S)-4-(5-((5-((2-((S)-3-carboxybutanoyl)-4-fluoro-6- methoxybenzo[b]thiophen-5-yl)oxy)pentyl)oxy)-6-methoxybenzo[b]thiophen-2-yl)-2- methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3-carboxybutyl)-4-fluoro-6- methoxybenzo[b]thiophen-5-yl)oxy)propyl)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)- 2-methyl-4-oxobutanoic acid, trans-2-(5-(3-(2-((S)-3-carboxybutanoyl)-4-fluoro-6- methoxybenzo[b]thiophen-5-yl)propoxy)-4-fluoro-6-methoxybenzo[b]thiophene-2- carbonyl)cyclopropanecarboxylic acid, trans-2-(5-(3-(2-((S)-3-carboxybutanoyl)-4-fluoro- 6-methoxybenzo[b]thiophen-5-yl)propoxy)-4-fluoro-6-methoxybenzo[b]thiophene-2- carbonyl)cyclobutanecarboxylic acid, (R)-4-(5-(3-((2-((R)-3-carboxybutanoyl)-4-fluoro- 6-methoxybenzo[b]thiophen-5-yl)oxy)propyl)-6-methoxybenzo[b]thiophen-2-yl)-2- methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((R)-3-carboxybutanoyl)-4-fluoro-6- methoxybenzo[b]thiophen-5-yl)oxy)propyl)-6-methoxybenzo[b]thi ophen-2 -yl)-2-methyl- 4-oxobutanoic acid, (S)-4-(5-((6-((2-((S)-3-carboxybutanoyl)-4-fluoro-6- methoxybenzo[b]thiophen-5-yl)oxy)hexyl)oxy)-6-methoxybenzo[b]thiophen-2-yl)-2- methyl-4-oxobutanoic acid, trans-2-(5-(3-(2-((S)-3-carboxybutanoyl)-6- methoxybenzo[b]thiophen-5-yl)propoxy)-4-fluoro-6-methoxybenzo[b]thiophene-2- carbonyl)cyclobutanecarboxylic acid, (S)-4-(5-(3-((2-(3-carboxy-3-methylbutyl)-4-fluoro- 6-methoxybenzo[b]thiophen-5-yl)oxy)propyl)-4-fluoro-6-methoxybenzo[b]thi ophen-2- yl)-2-methyl-4-oxobutanoic acid, trans-2-(5-(3-((2-((S)-3-carboxybutyl)-4-fluoro-6- methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophene-2- carbonyl)cyclobutanecarboxylic acid, 4,4'-(5,5'-(pentane-l,5-diylbis(oxy))bis(4-fluoro-6- methoxybenzo[b]thiophene-5,2-diyl))bis(4-oxobutanoic acid), (S)-4-(5-((5-((2-(3- carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yloxy)pentyloxy)-4-fluoro-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (2S,2'S)-4,4'-(5,5'-(pentane-l,5-diylbis(oxy))bis(4-fluoro-6-methoxybenzo[b]thiophene-5,2-diyl))bis(2- methyl-4-oxobutanoic acid), (S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-chloro-6- methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thi ophen-2- yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((4-bromo-2-((S)-3-carboxybutanoyl)-6- methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thi ophen-2- yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(4-((2-((S)-3-carboxybutyl)-4-fluoro-6- methoxybenzo[b]thiophen-5-yl)oxy)butoxy)-4-fluoro-6-methoxybenzo[b]thi ophen-2 -yl)- 2-methyl-4-oxobutanoic acid, (S)-4-(5-(4-((2-((S)-3-carboxybutanoyl)-4-chloro-6- methoxybenzo[b]thiophen-5-yl)oxy)butoxy)-4-fluoro-6-methoxybenzo[b]thi ophen-2 -yl)- 2-methyl-4-oxobutanoic acid, (S)-4-(5-(4-((4-bromo-2-((S)-3-carboxybutanoyl)-6- methoxybenzo[b]thiophen-5-yl)oxy)butoxy)-4-fluoro-6-methoxybenzo[b]thi ophen-2 -yl)- 2-methyl-4-oxobutanoic acid, (2S,2'S)-4,4'-(5,5'-(propane-l,3-diylbis(oxy))bis(4-chloro- 6-methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4-oxobutanoic acid), (S)-4-(5-(3-((4- bromo-2-((S)-3-carboxybutanoyl)-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4- chloro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (2S,2'S)-4,4'- (5,5'-(propane-l,3-diylbis(oxy))bis(4-bromo-6-methoxybenzo[b]thiophene-5,2- diyl))bis(2-methyl-4-oxobutanoic acid), 2-((5-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6- methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thi ophen-2- yl)methyl)cyclobutanecarboxylic acid, (S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4,7- dichloro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (2S,2'S)-4,4'-((butane-l,3- diylbis(oxy))bis(4-fluoro-6-methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4- oxobutanoic acid), (2S,2'S)-4,4'-((pentane-l,4-diylbis(oxy))bis(4-fluoro-6- methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4-oxobutanoic acid), (2S,2'S)-4,4'- ((hexane-2, 5 -diylbi s(oxy))bi s(4-fluoro-6-methoxybenzo[b]thiophene-5 , 2 - diy 1 ))b i s(2- methyl-4-oxobutanoic acid), trans-2-(5-(3-((2-(3-carboxy- 3-methylbutyl)-4-fluoro-6- methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophene-2- carbonyl)cyclobutane-l -carboxylic acid, (2S,2'S)-4,4'-(((2-methylpropane-l,3- diyl)bis(oxy))bis(4-fluoro-6-methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4- oxobutanoic acid), (2S,2'S)-4,4'-(((2,2-dimethylpropane-l,3-diyl)bis(oxy))bis(4-fluoro-6- methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4-oxobutanoic acid), (2S,2'S)-4,4'- (((cy clopropane- 1 , 1 -diylbi s-(methylene))bi s(oxy))bi s(4-fluoro-6- methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4-oxobutanoic acid), (S)-4-(5-(3-((2-((S)-3-carboxybutyl)-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-chloro-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(4-bromo-5-(3-((2- ((S)-3-carboxybutyl)-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3- carboxybutyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-chl oro-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(4-bromo-5-(3-((2- ((S)-3-carboxybutyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6-methoxy benzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, 4-(5-(3-((2-(3-carboxy-3- methylbutyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6- methoxybenzo[b]thiophen-2-yl)-2,2-dimethyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3- carboxybutyl)-4-chloro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3- carboxybutyl)-4-chloro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (2S,2'S)-4,4'-((ethane-l,2- diylbis(oxy))bis(4-chloro-6-methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4- oxobutanoic acid), (S)-4-(5-(2-((2-((S)-3-carboxybutyl)-4-chloro-6- methoxybenzo[b]thiophen-5-yl)oxy)ethoxy)-4-chloro-6-methoxybenzo[b]thi ophen-2 -yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-chloro-6- methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6-methoxybenzo[b]thi ophen-2 -yl)-2- methyl-4-oxobutanoic acid, (2S,2'S)-4,4'-((propane-l,3-diylbis(oxy))bis(4-fluoro-6- methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4-oxobutanoic acid), (S)-4-(5-(3-((2- ((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6- (methylamino)benzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3-carboxybutyl)-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-(2-((S)-3- carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)propoxy)-6- methoxythieno[3,2-b]pyridin-2-yl)-2-methyl-4-oxobutanoic acid, (2S,2'S)-4,4'-(((2- methylpropane-l,3-diyl)bis(oxy))bis(6-methoxybenzo[b]thiophene-5,2-diyl))bis(2- methyl-4-oxobutanoic acid), (S)-4-(5-(3-((2-(3-carboxypropanoyl)-6- methoxybenzo[b]thiophen-5-yl)oxy)propyl)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)- 2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-(2-((S)-3-carboxybutanoyl)-4-fluoro-6- methoxybenzo[b]thiophen-5-yl)propoxy)-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4- oxobutanoic acid, (S)-4-(5-(3-((2-(3-carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propyl)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)- 2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6- methoxybenzo[b]thiophen-5-yl)oxy)propyl)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)- 2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-5- methoxythieno[3,2-b]pyridin-6-yl)oxy)propoxy)-6-methoxybenzo[b]thiophen-2-yl)-2- methyl-4-oxobutanoic acid, (S)-4-(6-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6- methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-5-methoxythieno[3,2-b]pyri din-2 -yl)-2- methyl-4-oxobutanoic acid, (S)-4-(6-(3-((2-(3-carboxypropanoyl)-4-fluoro-6- methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-5-methoxythieno[3,2-b]pyri din-2 -yl)-2- methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3-carboxybutyl)-4-fluoro-6- methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6-methoxybenzo[b]thi ophen-2 -yl)-2- methyl-4-oxobutanoic acid, trans-2-(5-(3-((2-((S)-3-carboxybutanoyl)-6- methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophene-2- carbonyl)cyclobutanecarboxylic acid, trans-2-(5-(3-((2-((S)-3-carboxybutanoyl)-5- methoxybenzo[b]thiophen-6-yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophene-2- carbonyl)cyclobutanecarboxylic acid, (2S,2'S)-4,4'-(5,5'-(butane-l,4-diylbis(oxy))bis(4- chloro-6-methoxybenzo[b]thiophene-5,2-diyl))bis(2-methyl-4-oxobutanoic acid), (4-(5- (3-((2-(3-carboxypropanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propyl)-6- methoxythieno[3,2-b]pyridin-2-yl)-4-oxobutanoic acid, (S)-4-(5-(3-(2-(3- carboxypropanoyl)-6-methoxythieno[3,2-b]pyridin-5-yl)propoxy)-4-fluoro-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-((3-((2-((S)-3- carboxybutanoyl)-4-fluoro-6-methoxybenzo [b]thiophen-5-yl)oxy)propyl)amino)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-((3-(2-(3- carboxypropanoyl)-6-methoxybenzo[b]thiophen-5-yl)propyl)amino)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3- carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6- hydroxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3- carboxybutyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6- hydroxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3- carboxybutanoyl)-4-chloro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6- hydroxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3- carboxybutanoyl)-4-chloro-6-hydroxybenzo[b]thiophen-5-yl)oxy)propoxy)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-chloro-6-hydroxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6- methoxybenzo[b]thiophen-2-yl)- 2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3- carboxybutyl)-4-fluoro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-chl oro-6- hydroxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3- carboxybutanoyl)-4-chloro-6-hydroxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-chloro-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3- carboxybutanoyl)-4-fluoro-6-hydroxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3- carboxybutanoyl)-4-fluoro-6-hydroxybenzo[b]thiophen-5-yl)oxy)propoxy)-6- methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid, (S)-4-(5-(3-((2-((S)-3- carboxybutanoyl)-4-chloro-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4-fluoro-6-38. The composition of claim 37, wherein the STING agonist of the conjugate of Formula (II) is (S)-4-(5-(3-((2-((S)-3-carboxybutyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid.

39. The composition of claim 37, wherein the STING agonist of the conjugate of Formula (II) is (S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-6-(methylamino)benzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid.

40. The composition of claim 37, wherein the STING agonist of the conjugate of Formula (II) is (S)-4-(5-(3-((2-((S)-3-carboxybutyl)-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-4- fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid.

41. The composition of claim 37, wherein the STING agonist of the conjugate of Formula (II) is42. The composition of claim 37, wherein the STING agonist of the conjugate of Formula (II) is (S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-methoxybenzo[b]thiophen-5- yl)oxy)propoxy)-6-hydroxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid.

43. The composition of claim 37, wherein the STING agonist of the conjugate of Formula (II) is (S)-4-(5-(3-((2-((S)-3-carboxybutanoyl)-4-fluoro-6-hydroxybenzo[b]thiophen-5- yl)oxy)propoxy)-4-fluoro-6-methoxybenzo[b]thiophen-2-yl)-2-methyl-4-oxobutanoic acid.

44. The composition of claim 37, wherein the STING agonist of the conjugate of Formula (II)45. The composition of any one of claims 30-44, wherein one or both Linkers of the conjugate of Formula (II) comprise a disulfide bond or an acid-labile bond.

46. The composition of claim 45, wherein one or both Linkers of the conjugate of Formula (II) are self-immolative.

47. The composition of claim 45, wherein one or both Linkers of the conjugate of Formula (II) comprise a disulfide self-immolative bond.

48. The composition of claim 45, wherein both Linkers of the conjugate of Formula (II) are the same.

49. The composition of claim 45, wherein both Linkers of the conjugate of Formula (II) are different.

50. A pharmaceutical composition comprising the composition of any one of claims 30-49 and one or more pharmaceutically acceptable excipients.

51. A method of treating cancer in a subject in need thereof comprising administering the composition of any one of claims 30-49 or the pharmaceutical composition of claim 50 to the subject in need thereof.

52. The method of claim 51, wherein the cancer is a solid tumor.

53. The method of claim 51 or 52, wherein the composition of any one of claims 30-49 or the pharmaceutical composition of claim 50 is injected directly into a tumor mass.

54. The method of claim 51 or 52, wherein the composition of any one of claims 30-49 or the pharmaceutical composition of claim 50 is systemically administered.

55. The method of any one of claims 51-54, wherein the subject is a human.

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