Biological Activity

TH5487 is a selective 8-oxoguanine DNA glycosylase 1 (OGG1) inhibitor with an IC50 of 342 nM. TH5487 (5 μM; 1 hour) decreases TNFα- and LPS-induced proinflammatory gene expression to near pretreatment levels. TH5487 stops OGG1 from recognizing its DNA substrate, inhibits DNA repair and modifies OGG1 chromatin dynamics, which results in the inhibition of proinflammatory pathway genes.

In vivo, TH5487 (prophylactic intraperitoneally injection; 8-30 mg/kg; 1-9 hours) decreases TNFα or LPS induced the robust recruitment of neutrophils to the airways, and reduces the pulmonary neutrophil count in a time-dependent manner.

Chemical Information

Molecular Weight	541.18
Formula	C19H18BrIN4O2
CAS Number	2304947-71-3
Solubility (25°C)	DMSO ≥ 13 mg/mL
Storage	Powder          -20°C   3 years ;  4°C   2 years In solvent       -80°C   6 months ;  -20°C   1 month

Conversion of different model animals based on BSA (PMID: 27057123)

Species	Mouse	Rat	Rabbit	Guinea pig	Hamster	Dog
Weight (kg)	0.02	0.15	1.8	0.4	0.08	10
Body Surface Area (m2)	0.007	0.025	0.15	0.05	0.02	0.5
Km factor	3	6	12	8	5	20

Animal A (mg/kg) = Animal B (mg/kg) multiplied by	Animal B Km
	Animal A Km

For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the K_m factor for a mouse and then divide by the K_m factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.

References

[1] Visnes T, et al. Science. Small-molecule inhibitor of OGG1 suppresses proinflammatory gene expression and inflammation.