Cycloleucine

Biological Activity

Cycloleucine is antagonist of NMDA receptor associated glycine receptor, with a Ki of 600 μM. Cycloleucine is a specific inhibitor of S-adenosyl-methionine mediated methylation. Cycloleucine is also a competitive inhibitor of ATP: L-methionine-S-adenosyl transferase in vitro. Cycloleucine (4-40 mM) 3 hours blocks internal methylation of viral RNA in B77 transformed chick embryo fibroblasts. 

In vivo, Cycloleucine (0.5-4 µg; intracerebroventrical injection) increases time spent in open arms, open arm entries, and extreme arrivals in rats. Cycloleucine reduces thymus and spleen weights in Semliki Forest virus (SFV) strain A7(74) infected and control mice.

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

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.

Chemical Information

References

Effects of Cycloleucine in the Nucleus Accumbens Septi on the Elevated plus Maze Test in Rats
Augusto P I Gargiulo, et al. Neuropsychobiology. 2020;79(3):191-197. PMID: 31927553.

The effect of cycloleucine on SFV A7(74) infection in mice
S Amor, et al. Br J Exp Pathol. 1987 Apr;68(2):225-35. PMID: 3034321.

1-Aminocyclobutane-1-carboxylate (ACBC): a specific antagonist of the N-methyl-D-aspartate receptor coupled glycine receptor
W F Hood, et al. Eur J Pharmacol. 1989 Feb 28;161(2-3):281-2. PMID: 2542048.

Cycloleucine blocks 5'-terminal and internal methylations of avian sarcoma virus genome RNA
K Dimock, et al. Biochemistry. 1978 Aug 22;17(17):3627-32. PMID: 210799.