A134974 is a novel, potent and selective adenosine kinase (AK) inhibitor with IC50 of 60 pM. Systemic A-134974 (i.p.) dose dependently reduced hyperalgesia (ED(50) = 1 micromol/kg) and at higher doses, reduced locomotor activity (ED(50) = 16 micromol/kg). Administration of A-134974 intrathecally (i.t.) was more potent (ED(50) = 6 nmol) at producing antihyperalgesia than delivering the compound by intracerebralventricular (ED(50) = 100 nmol, i.c.v.) or intraplantar (ED(50) >300 nmol) routes. In contrast, i.c.v. administration of A-134974 was more effective in reducing locomotor activity than i.t. administration (ED(50) values were 1 and >100 nmol, respectively).

Physicochemical Properties

Molecular Formula	C11H14IN5O2
Molecular Weight	375.17
Exact Mass	375.019
CAS #	186141-75-3
Related CAS #	186141-75-3
PubChem CID	9885936
Appearance	Typically exists as solid at room temperature
Density	2.49±0.1 g/cm3(Predicted)
Boiling Point	469.8±45.0 °C(Predicted)
LogP	-1.1
Hydrogen Bond Donor Count	4
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	1
Heavy Atom Count	19
Complexity	349
Defined Atom Stereocenter Count	4
SMILES	C1[C@@H]([C@H]([C@H]([C@@H]1N2C=C(C3=C(N=CN=C32)N)I)O)O)N
InChi Key	NSXJHIFQIZKLGF-LWIVVEGESA-N
InChi Code	InChI=1S/C11H14IN5O2/c12-4-2-17(6-1-5(13)8(18)9(6)19)11-7(4)10(14)15-3-16-11/h2-3,5-6,8-9,18-19H,1,13H2,(H2,14,15,16)/t5-,6+,8+,9-/m0/s1
Chemical Name	(1S,2R,3S,5R)-3-amino-5-{4-amino-5-iodo-7H-pyrrolo[2,3-d]pyrimidin-7-yl}cyclopentane-1,2-diol
Synonyms	A134974;A 134974;A-134974
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

ln Vitro	In vitro activity: AK enzyme inhibition was assayed radiochemically as described byYamada et al. (1980) and McNally et al. (1997). The ability of A-134974 to inhibit AK activity in intact IMR-32 neuroblastoma cells (American Type Culture Collection, Gaithersburg, MD) carried out as previously described (Kowaluk and Cowart, 1994). Radioligand binding assay methodology for the A1, A2A, and A3 receptors was carried out as described by Jarvis et al. (2000). The ability of A-134974 to inhibit [3H]nitrobenzylthioinosine binding to the ADO transporter and to inhibit adenosine deaminase activity was also examined using previously described methodology (Parkinson and Geiger, 1996).
ln Vivo	Drugs administered to rats were A-134974 (Cowart, 1997, an AK inhibitor synthesized at Abbott Laboratories), morphine sulfate (Mallinckrodt, St. Louis, MO), and theophylline (a nonselective ADO receptor antagonist; Sigma Chemical Co., St. Louis, MO). All drugs were dissolved in sterile water for local (intraplantar, i.t., or i.c.v.) or systemic (i.p.) delivery. The drug administration procedures described below were followed for locomotor activity experiments as well as for hyperalgesia experiments. Each experimental group consisted of at least five animals.
Animal Protocol	Systemic Administration of A-134974: A-134974 (0.3–30 μmol/kg) or vehicle was administered i.p. 30 min before testing. Local Administration of A-134974: A-134974 (3–100 nmol) or vehicle was injected directly into 1) the lumbar spinal cord via indwelling intrathecal catheters, 2) the right lateral ventricle, or 3) the intraplantar region of a carrageenan-inflamed hindpaw (hyperalgesia experiments only). Male Sprague-Dawley rats (260–320 g)
References	J Pharmacol Exp Ther.2001 Feb;296(2):501-9.

Solubility Data

Solubility (In Vitro)

DMSO: 10 mM Water:N/A Ethanol:N/A

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.6655 mL	13.3273 mL	26.6546 mL
	5 mM	0.5331 mL	2.6655 mL	5.3309 mL
	10 mM	0.2665 mL	1.3327 mL	2.6655 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.