Cycloleucine is a specific inhibitor of S-adenosylmethionine-mediated methylation. Cycloleucine is an antagonist of the glycine allosteric site of the NMDA receptor with a Ki of 600 μM. Cycloleucine is also a competitive inhibitor of ATP:L-methionine-S-adenosyltransferase in vitro. Cycloleucine has anxiolytic and cytostatic effects.

Physicochemical Properties

Molecular Formula	C6H11NO2
Molecular Weight	129.16
Exact Mass	129.078
CAS #	52-52-8
PubChem CID	2901
Appearance	White to off-white solid powder
Density	1.2±0.1 g/cm3
Boiling Point	256.1±23.0 °C at 760 mmHg
Melting Point	320 °C (dec.)(lit.)
Flash Point	108.7±22.6 °C
Vapour Pressure	0.0±1.1 mmHg at 25°C
Index of Refraction	1.522
LogP	-0.05
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	3
Rotatable Bond Count	1
Heavy Atom Count	9
Complexity	127
Defined Atom Stereocenter Count	0
InChi Key	NILQLFBWTXNUOE-UHFFFAOYSA-N
InChi Code	InChI=1S/C6H11NO2/c7-6(5(8)9)3-1-2-4-6/h1-4,7H2,(H,8,9)
Chemical Name	1-aminocyclopentane-1-carboxylic acid
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	NMDA Receptor
ln Vitro	Internal methylation of viral RNA in B77 transformed chick embryo fibroblasts is blocked by cycloleucine (4–40 mM; 3 h)[5]. More than 90% of B77 38S RNA subunits are prevented from forming the penultimate Gm and m6A by cycloleucine (40 mM; 24 h)[5]. ?The viability of human KB and mouse L1210s leukemia cell lines is inhibited by cytostatic (10 μg/mL)[5].
ln Vivo	In rats, cycloleucine (0.5–4 μg; intracerebroventricular injection) prolongs open arm entry, increases open arm duration, and causes severe arrivals[3]. In mice infected with the Semliki Forest virus (SFV) strain A7(74) and normal mice, cycloleucine lowers the weights of the spleen and thymus[6].
Animal Protocol	Animal/Disease Models: Male rats bilaterally cannulated into the nucleus accumbens septi (NAS)[3] Doses: 1 µL of 0.5, 1.0, 2.0, 4 µg/µL Route of Administration: Intracerebroventrical injection Experimental Results: Increased time spent in the open arms and extreme arrivals at all doses. Increased open arm entries at the dose of 4 μg.
ADME/Pharmacokinetics	Absorption, Distribution and Excretion LEVELS OF (14)C IN LIVER & PANCREAS WERE RESPECTIVELY EIGHTFOLD & TWOFOLD THOSE IN BLOOD, 15 MIN AFTER IV DOSE OF [(14)C]-1-AMINOCYCLOPENTANECARBOXYLIC ACID TO RHESUS MONKEYS. (14)C LEVELS IN THESE TISSUES WERE SIMILAR TO THOSE IN BLOOD AFTER 24 HR. WHEN ADMIN TO MICE CYCLOLEUCINE ACCUM IN TISSUES AT LEVELS BETWEEN 0.02 & 1.29 MG/ML. MOST OF REMAINING 2% WAS ASSOC WITH PROTEIN. ACCUM AGAINST CONCN GRADIENT OCCURRED IN KIDNEY, IN SPLEEN TO GREATER EXTENT & TO MUCH GREATER DEGREE IN PANCREAS. THE DISTRIBUTION RATIOS FOR CNS TISSUE, KIDNEY & SPLEEN DID NOT CHANGE AS FUNCTION OF PLASMA CYCLOLEUCINE CONCN OR OF TIME BETWEEN 4 & 40 DAYS AFTER ADMIN TO MICE. 5 DAYS AFTER ADMIN OF CYCLOLEUCINE TO MICE, HEPATIC CYCLOLEUCINE DISTRIBUTION RATIO WAS CONSIDERABLY GREATER THAN UNITY AT THE LOWEST DOSES & INCR VARIABLY WITH INCR CYCLOLEUCINE PLASMA LEVELS. Biological Half-Life AT 0.4-0.5 MG/G PLASMA LEVEL AT 24 DAYS WAS NOT SIGNIFICANTLY DIFFERENT FROM THAT AT 1 DAY. HIGHEST DOSES (1-3 MG/G) RESULTED IN NEARLY SIMILAR PLASMA LEVELS BY 4TH DAY. T/2 IN PLASMA WAS EXTREMELY LONG.
References	[1]. 1-Aminocyclobutane-1-carboxylate (ACBC): a specific antagonist of the N-methyl-D-aspartate receptor coupled glycine receptor. Eur J Pharmacol. 1989 Feb 28;161(2-3):281-2. [2]. RNA methylation and control of eukaryotic RNA biosynthesis. Effects of cycloleucine, a specific inhibitor of methylation, on ribosomal RNA maturation. Eur J Biochem. 1977 Mar 15;74(1):19-29. [3]. Effects of Cycloleucine in the Nucleus Accumbens Septi on the Elevated plus Maze Test in Rats. Neuropsychobiology. 2020;79(3):191-197. [4]. Cytostatic activity in vitro of cycloleucine, aspartic acid and glutamic acid phosphonic analogues. Arch Immunol Ther Exp (Warsz). 1980;28(3):433-8. [5]. Cycloleucine blocks 5'-terminal and internal methylations of avian sarcoma virus genome RNA. Biochemistry. 1978 Aug 22;17(17):3627-32. [6]. The effect of cycloleucine on SFV A7(74) infection in mice. Br J Exp Pathol. 1987 Apr;68(2):225-35.
Additional Infomation	1-aminocyclopentanecarboxylic acid is a non-proteinogenic alpha-amino acid that is cyclopentane substituted at position 1 by amino and carboxy groups. It has a role as an EC 2.5.1.6 (methionine adenosyltransferase) inhibitor. Cycloleucine is non-metabolisable amino acid formed by cyclization of leucine. It is also a specific and reversible inhibitor of nucleic acid methylation and widely used in biochemical experiments. Cycloleucine has been reported in Streptomyces hydrogenans with data available. Cycloleucine is a non-metabolizable synthetic amino acid, formed through the cyclization of the amino acid leucine, with immunosuppressive, antineoplastic, and cytostatic activities. Cycloleucine competitively inhibits the enzyme methionine adenosyltransferase, resulting in the inhibition of S-adenosylmethionine (SAM) synthesis from methionine and ATP, and subsequent nucleic acid methylation and polyamine production; RNA, and perhaps to a lesser extent, DNA biosyntheses and cell cycle progression are finally disrupted. This agent is also a competitive inhibitor at the glycine modulatory site of the N-methyl-D-aspartate (NMDA) receptor. An amino acid formed by cyclization of leucine. It has cytostatic, immunosuppressive and antineoplastic activities. Mechanism of Action SYNTHETIC AMINO ACID THOUGHT TO ACT AS VALINE ANTAGONIST. Therapeutic Uses EXPTL USE (VET): SINGLE DOSES OF ANTILYMPHOCYTE SERUM, CYCLOPHOSPHAMIDE, CYCLOLEUCINE DELAYED ONSET OF HYPERACUTE FORM OF EXPTL ALLERGIC ENCEPHALOMYELITIS IN RATS. CYCLOLEUCINE & TILORONE-HCL WERE PROVEN TO HAVE SYNERGISTIC RELATIONSHIP. EXPTL USE: (11)C-CYCLOLEUCINE WAS EVALUATED AS TUMOR SCANNING AGENT IN 38 PT. EXTRAPOLATION FROM ANIMAL DATA GIVES 0.01 RAD/UCI FOR WHOLE BODY & LESS THAN 0.06 RAD/UCI FOR PANCREAS. 33/38 HAS GALLIUM CITRATE (67)GA SCANS ALSO; RESULTS 19 POS FORMER & 24 POS (67)GA SCANS. MEDICATION (VET): CARBOXYL-LABELED (11)C-CYCLOLEUCINE WAS PREPD IN MULTIMILLICURIE AMT. TISSUE DISTRIBUTION (750 MICROCURIE, IV) IN MORRIS 5123 C HEPATOMA BEARING RATS INDICATED THE COMPD HAS POTENTIAL AS TUMOR-LOCALIZING AGENT FOR DETECTING CANCER IN HUMANS. MEDICATION (VET): CYCLOLEUCINE PROTECTED RATS AGAINST SEIZURES IN MAXIMAL ELECTROSHOCK TEST BUT OFFERED NO PROTECTION AGAINST METRAZOL-(PENTYLENETETRAZOL) INDUCED SEIZURES IN MICE. Pharmacodynamics Cycloleucine has cytostatic, immunosuppressive and antineoplastic activities.

Solubility Data

Solubility (In Vitro)	H2O: 20 mg/mL (154.85 mM) DMSO: < 1 mg/mL
Solubility (In Vivo)	Solubility in Formulation 1: 100 mg/mL (774.23 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	7.7423 mL	38.7117 mL	77.4234 mL
	5 mM	1.5485 mL	7.7423 mL	15.4847 mL
	10 mM	0.7742 mL	3.8712 mL	7.7423 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.