Provided herein are compounds, compositions, and methods useful for modulating the integrated stress response (ISR) and for treating related diseases; disorders and conditions.

RhlR modulators including agonist and antagonists which are useful for modulating QS phenotypes in Gram-negative bacteria. Certain compounds of general formula A-W-HG having various carbocyclic ad heterocyclic head groups (HG) and various tail groups (A), where W is CONH, SO.sub.2NH, CONHCH.sub.2, or SO.sub.2NHCH.sub.2 are RhlR agonists or antagonists. The compounds are useful in methods of modulating quorum sensing in Gram-negative bacteria, particularly in Pseudomonas. Compositions including certain RhlR modulators are useful for decreasing the virulence of Gram-negative bacteria. Pharmaceutical compositions comprising certain RhlR modulators are useful for treatment of infections of Gram-negative bacteria.

RhlR modulators including agonist and antagonists which are useful for modulating QS phenotypes in Gram-negative bacteria. Certain compounds of general formula A-W-HG having various carbocyclic ad heterocyclic head groups (HG) and various tail groups (A), where W is CONH, SO.sub.2NH, CONHCH.sub.2, or SO.sub.2NHCH.sub.2 are RhlR agonists or antagonists. The compounds are useful in methods of modulating quorum sensing in Gram-negative bacteria, particularly in Pseudomonas. Compositions including certain RhlR modulators are useful for decreasing the virulence of Gram-negative bacteria. Pharmaceutical compositions comprising certain RhlR modulators are useful for treatment of infections of Gram-negative bacteria.

Provided herein are fatty acid amide (FAAH) cleavable prodrugs of thyromimetics and pharmaceutical compositions comprising these compounds with at least one pharmaceutically acceptable excipient further comprising a peripherally restricted FAAH inhibitor.

Provided herein are fatty acid amide (FAAH) cleavable prodrugs of thyromimetics and pharmaceutical compositions comprising these compounds with at least one pharmaceutically acceptable excipient further comprising a peripherally restricted FAAH inhibitor.

Provided herein are fatty acid amide (FAAH) cleavable prodrugs of compounds that modulate a target in the brain including sphingosine-1-phosphate receptor (S1P1), lysophosphatidic acid receptor 1 (LPA1), G-protein coupled receptor 120 (GPR120), prostacyclin (PGI2), and transthyretin (TTR). Pharmaceutical compositions comprising these prodrugs, including in combination with a peripherally restricted FAAH inhibitor, and at least one pharmaceutically acceptable excipient, are also provided, and the use of these compounds and compositions in the treatment of CNS diseases or disorders.

Provided herein, inter alia, are compounds and methods useful for modulating the translational effects of eIF2 phosphorylation, the Integrated Stress Response (ISR), and the unfolded protein response (UPR); for treating diseases; for increasing protein production, and for improving long-term memory.

Provided herein, inter alia, are compounds and methods useful for modulating the translational effects of eIF2 phosphorylation, the Integrated Stress Response (ISR), and the unfolded protein response (UPR); for treating diseases; for increasing protein production, and for improving long-term memory.

Provided herein, inter alia, are compounds and methods useful for modulating the translational effects of eIF2 phosphorylation, the Integrated Stress Response (ISR), and the unfolded protein response (UPR); for treating diseases; for increasing protein production, and for improving long-term memory.

Provided herein, inter alia, are compounds and methods useful for modulating the translational effects of eIF2 phosphorylation, the Integrated Stress Response (ISR), and the unfolded protein response (UPR); for treating diseases; for increasing protein production, and for improving long-term memory.