Table 2 Therapeutic approaches targeting the lactate/lactylation axis
From: Post-translational protein lactylation modification in health and diseases: a double-edged sword
Target | Representative drugs | Research status | Example diseases | Effects | Ref/Trial No. |
|---|---|---|---|---|---|
MCT1 | AZD3965 | Clinical trial | Raji B cell lymphoma | Lactate uptake | NCT01791595 |
MCT1 | BAY8002 | Pre-clinical | Triple negative breast cancer | Lactate uptake | [118] |
MCT1 | SR13800 | Pre-clinical | Neuroblastoma, lyphoma, breast cancer | Lactate uptake | [119] |
MCT1 | AR-C155858 | Pre-clinical | Breast cancer, colorectal cancer | Lactate uptake | [116] |
MCT1 | 7ACC2 | Pre-clinical | Pancreatic cancer | Lactate uptake | [117] |
MCT4 | Syrosingopine | Pre-clinical | Myeloma | Lactate excretion | [115] |
LDHA | GSK2837808A | Pre-clinical | Liver cancer | Lactate production | [98] |
LDHA | Oxamate | Pre-clinical | Prostate and lung adenocarcinomas | Lactate production | [99] |
PDHK | Dichloroacetate | Clinical trial | Metastatic breast cancer, lung cancer, etc. | Lactate production | NCT01029925, NCT01386632, etc. |
Hexokinase | 2DG | Clinical trial | Prostate cancer, lung cancer, breast cancer, etc. | Lactate production | NCT00096707, NCT00588185, etc. |
Hexokinase | 3-BrPA | Pre-clinical | Breast cancer, liver cancer, bladder cancer, etc. | Lactate production | [122] |
Hexokinase | Tristetraprolin | Pre-clinical | Breast cancer | Lactate production | [123] |
Hexokinase | Lonidamine | Pre-clinical | Lung cancer, breast cancer, melanoma, etc. | Lactate production | [124] |
GPR81 | Curcumin | Clinical trial | Acute lymphoblastic leukemia, prostate cancer, etc. | Lactate uptake | NCT05045443, NCT04731844, etc. |
GPR81 | LRH7-G5 | Pre-clinical | Triple negative breast cancer | Lactate uptake | [118] |
HDAC | ITSA-1 | Pre-clinical | Nasopharynx cancer | Lactylation production | [126] |
HAT | Garcinol | Pre-clinical | Breast cancer, colon cancer, lung cancer, etc. | Lactylation production | [127] |
GCN5 | CPTH6 | Pre-clinical | Leukemia, lung cancer | Lactylation production | [128] |
p300/CBP | A-485 | Pre-clinical | Neovascularization, pituitary adenoma, melanoma, etc. | Lactylation production | [110] |