synthetic lethality

Syrosingopine is a dual inhibitor of MCT1 and MCT4, 60 times more potent against MCT4, preventing lactate and H+ efflux. Syrosingopine is an orally available antihypertensive drug with potential for cancer research in combination with metformin.

AB25583 is a potent inhibitor of the Polθ helicase domain (Polθ-hel). It blocks MMEJ repair, leading to DNA damage accumulation and synthetic lethality in BRCA1/2-deficient cancer cells.

PARP/EZH2-IN-2 (compound 12e) functions as a dual inhibitor targeting both PARP1 and EZH2, with IC50 values of 6.89 and 27.34 nM, respectively. This compound exhibits anticancer activity without toxicity to normal cells, achieving synthetic lethality indirectly by increasing PARP1 sensitivity through EZH2 inhibition, and inducing cell death by modulating excessive autophagy.

WRN-IN-19 (Compound (S)-27) is a covalent WRN helicase inhibitor, with a pIC50 of 5.4 at 0 hours and 7.5 at 4 hours in a DNA-unwinding endpoint assay. It demonstrates synthetic lethality against MSI-H (high microsatellite instability) cancer cells.

Endotoxin Inhibitor TFA is a synthetic peptide that exhibits high-affinity binding to lipid A, effectively detoxifying LPS and impeding LPS-induced cytokine release in vivo. It also suppresses the febrile response to LPS while demonstrating minimal toxicity and lethality [1].

ATR-IN-23 (Compound 34), a potent and selective ATR inhibitor, exhibits an IC50 of 1.5 nM, has demonstrated antiproliferative effects on LoVo cells, and induces synthetic lethality in HT-29 cells, suggesting its utility in researching DNA damage response (DDR)-deficient cancers [1].

AZD5305 is a potent, selective and oral active PARP inhibitor.