(R)-Lisofylline ((R)-Lisophylline) is the (R)-enantiomer of the Pentoxifylline metabolite and has anti-inflammatory activities. (R)-Lisofylline is an inhibitor (blocker/antagonist) of lysophosphatidic acid acyltransferase with IC50 of 0.6 µM and can interrupt STAT4 activation mediated by IL-12 signaling. (R)-Lisofylline may be utilized in the research of type 1 diabetes and autoimmune diseases.

Physicochemical Properties

Molecular Formula	C13H20N4O3
Molecular Weight	280.32
Exact Mass	280.153
CAS #	100324-81-0
Related CAS #	(S)-Lisofylline;100324-80-9;(±)-Lisofylline;6493-06-7;(±)-Lisofylline-d6;1185995-26-9
PubChem CID	501254
Appearance	White to off-white solid powder
Density	1.3±0.1 g/cm3
Boiling Point	511.2±56.0 °C at 760 mmHg
Flash Point	263.0±31.8 °C
Vapour Pressure	0.0±1.4 mmHg at 25°C
Index of Refraction	1.621
LogP	0.34
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	5
Heavy Atom Count	20
Complexity	390
Defined Atom Stereocenter Count	1
SMILES	C[C@H](CCCCN1C(=O)C2=C(N=CN2C)N(C1=O)C)O
InChi Key	NSMXQKNUPPXBRG-SECBINFHSA-N
InChi Code	InChI=1S/C13H20N4O3/c1-9(18)6-4-5-7-17-12(19)10-11(14-8-15(10)2)16(3)13(17)20/h8-9,18H,4-7H2,1-3H3/t9-/m1/s1
Chemical Name	1-[(5R)-5-hydroxyhexyl]-3,7-dimethylpurine-2,6-dione
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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture.
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	IC50: 0.6 µM (Lysophosphatidic acid acyltransferase)[1] STAT4[1]
ln Vitro	(R)-Lisofylline has no effect on IL-12 release from APCs ex vivo or in vitro, but it inhibits IL-12-driven Th1 differentiation and T cell proliferation in vitro[3].
ln Vivo	(R)-Lisofylline enhances insulin response and lowers glucose levels in Streptozotocin-treated rats after the oral glucose tolerance test. It also lessens the impairment of insulin secretion induced by IL-1β in cultured rat islet cells, suppresses IFN-γ production, the onset of diabetes, and macrophage infiltration into islets from NOD mice[1]. (R)-Lisofylline inhibits STAT4 phosphorylation, which stops IL-12 signaling, preventing β cell dysfunction in NOD mice. In mice, (R)-Lisofylline reduces the symptoms of experimental allergic encephalomyelitis[1]. (R)-Lisofylline also lessens sepsis-induced lung damage in minipigs and increases survival in mice given a fatal dosage of LPS injections. While pretreatment with (R)-Lisofylline lowers lung leak in rats given IL-1 intratracheally, it does not lessen the concentration of neutrophils in the lungs[1]. (R)-Lisofylline also inhibits the release of TNF-α when endotoxins from Salmonella or Escherichia coli are triggered in vivo in mice and ex vivo in human blood[1].
ADME/Pharmacokinetics	Metabolism / Metabolites Lisofylline has known human metabolites that include pentoxifylline and lisofylline 4,5-diol.
References	[1]. Physiologically Based Modeling of Lisofylline Pharmacokinetics Following Intravenous Administration in Mice. Eur J Drug Metab Pharmacokinet. 2016 Aug;41(4):403-12. [2]. Lisofylline Prevents Leak, but Not Neutrophil Accumulation, in Lungs of Rats Given IL-1 Intratracheally. J Appl Physiol (1985). 1997 Jan;82(1):226-32. [3]. Prevention of Experimental Allergic Encephalomyelitis via Inhibition of IL-12 Signaling and IL-12-mediated Th1 Differentiation: An Effect of the Novel Anti-Inflammatory Drug Lisofylline. J Immunol. 1998 Dec 15;161(12):7015-22.
Additional Infomation	(R)-lisofylline is a 1-(5-hydroxyhexyl)-3,7-dimethyl-3,7-dihydro-1H-purine-2,6-dione that has (R)-configuration. A synthetic small molecule which was under development for the treatment of type 1 diabetes mellitus. It has a role as an anti-inflammatory agent and an immunomodulator. It is an enantiomer of a (S)-lisofylline. Lisofylline has been investigated for the treatment of Type 1 Diabetes Mellitus.

Solubility Data

Solubility (In Vitro)

DMSO: 100 mg/mL (356.74 mM)

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	3.5674 mL	17.8368 mL	35.6735 mL
	5 mM	0.7135 mL	3.5674 mL	7.1347 mL
	10 mM	0.3567 mL	1.7837 mL	3.5674 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.