U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C13H20N4O3
Molecular Weight 280.3229
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of LISOFYLLINE

SMILES

C[C@@H](O)CCCCN1C(=O)N(C)C2=C(N(C)C=N2)C1=O

InChI

InChIKey=NSMXQKNUPPXBRG-SECBINFHSA-N
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

HIDE SMILES / InChI
Lisofylline [1-(5R-hydroxyhexyl)-3,7-dimethylxanthine] is a unique metabolite of pentoxifylline. Lisofylline inhibited the generation of phosphatidic acid and free fatty acids. Lisofylline blocked the release of pro-inflammatory cytokines in oxidative tissue injury, in response to cancer chemotherapy and in experimental sepsis. Lisofylline regulates immune cell function and autoimmune response by inhibition of IL-12 signalling and cytokine production. Lisofylline may have therapeutic value in the prevention of autoimmune disorders, including Type 1 diabetes, autoimmune recurrence following islet transplantation, and in preservation of beta cell functional mass during islet isolation.

CNS Activity

Curator's Comment: Lisofylline is CNS active in animals. No human data available.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
5698 ng/mL
3 mg/kg single, intravenous
dose: 3 mg/kg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
LISOFYLLINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
226 ng/mL
226 mg/kg single, oral
dose: 226 mg/kg
route of administration: Oral
experiment type: SINGLE
co-administered:
LISOFYLLINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
10.88 μM
3 mg/kg single, intravenous
dose: 3 mg/kg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
LISOFYLLINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
2756 ng × h/mL
3 mg/kg single, intravenous
dose: 3 mg/kg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
LISOFYLLINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
343 ng × h/mL
226 mg/kg single, oral
dose: 226 mg/kg
route of administration: Oral
experiment type: SINGLE
co-administered:
LISOFYLLINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
0.77 h
3 mg/kg single, intravenous
dose: 3 mg/kg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
LISOFYLLINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
0.9 h
226 mg/kg single, oral
dose: 226 mg/kg
route of administration: Oral
experiment type: SINGLE
co-administered:
LISOFYLLINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
Doses

Doses

DosePopulationAdverse events​
3 mg/kg 1 times / 6 hours multiple, intravenous
Studied dose
Dose: 3 mg/kg, 1 times / 6 hours
Route: intravenous
Route: multiple
Dose: 3 mg/kg, 1 times / 6 hours
Sources: Page: p.286
unhealthy, ADULT
n = 19
Health Status: unhealthy
Condition: Hematologic malignancy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 19
Sources: Page: p.286
Disc. AE: Feelings of weakness, Vasodilatation...
AEs leading to
discontinuation/dose reduction:
Feelings of weakness (5.3%)
Vasodilatation (5.3%)
Seizures (5.3%)
Nausea (10.5%)
Vomiting (10.5%)
Sources: Page: p.286
AEs

AEs

AESignificanceDosePopulation
Nausea 10.5%
Disc. AE
3 mg/kg 1 times / 6 hours multiple, intravenous
Studied dose
Dose: 3 mg/kg, 1 times / 6 hours
Route: intravenous
Route: multiple
Dose: 3 mg/kg, 1 times / 6 hours
Sources: Page: p.286
unhealthy, ADULT
n = 19
Health Status: unhealthy
Condition: Hematologic malignancy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 19
Sources: Page: p.286
Vomiting 10.5%
Disc. AE
3 mg/kg 1 times / 6 hours multiple, intravenous
Studied dose
Dose: 3 mg/kg, 1 times / 6 hours
Route: intravenous
Route: multiple
Dose: 3 mg/kg, 1 times / 6 hours
Sources: Page: p.286
unhealthy, ADULT
n = 19
Health Status: unhealthy
Condition: Hematologic malignancy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 19
Sources: Page: p.286
Feelings of weakness 5.3%
Disc. AE
3 mg/kg 1 times / 6 hours multiple, intravenous
Studied dose
Dose: 3 mg/kg, 1 times / 6 hours
Route: intravenous
Route: multiple
Dose: 3 mg/kg, 1 times / 6 hours
Sources: Page: p.286
unhealthy, ADULT
n = 19
Health Status: unhealthy
Condition: Hematologic malignancy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 19
Sources: Page: p.286
Seizures 5.3%
Disc. AE
3 mg/kg 1 times / 6 hours multiple, intravenous
Studied dose
Dose: 3 mg/kg, 1 times / 6 hours
Route: intravenous
Route: multiple
Dose: 3 mg/kg, 1 times / 6 hours
Sources: Page: p.286
unhealthy, ADULT
n = 19
Health Status: unhealthy
Condition: Hematologic malignancy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 19
Sources: Page: p.286
Vasodilatation 5.3%
Disc. AE
3 mg/kg 1 times / 6 hours multiple, intravenous
Studied dose
Dose: 3 mg/kg, 1 times / 6 hours
Route: intravenous
Route: multiple
Dose: 3 mg/kg, 1 times / 6 hours
Sources: Page: p.286
unhealthy, ADULT
n = 19
Health Status: unhealthy
Condition: Hematologic malignancy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 19
Sources: Page: p.286
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer




Drug as victim
PubMed

PubMed

TitleDatePubMed
Lisofylline: a potential lead for the treatment of diabetes.
2005 Jan 1
Pentoxifylline and its major oxidative metabolites exhibit different pharmacological properties.
2006 Mar 27
Pentoxifylline as an adjunct therapy in children with cerebral malaria.
2010 Dec 21
Patents

Sample Use Guides

A multicenter, randomized placebo-controlled trial was performed in patients with hematologic malignancies receiving bone marrow transplantation from HLA-identical sibling donors. Patients were randomized to receive either placebo, 2 mg/kg lisofylline or 3 mg/kg lisofylline every 6 h, beginning before conditioning and continuing to day 21 or hospital discharge.
Route of Administration: Intravenous
In Vitro Use Guide
Human blood was stimulated with various endotoxin preparations, zymosan, or protein A, and the levels of secreted monokines were measured by enzyme-linked immunosorbent assay. CT-1501R (lisofylline) inhibited tumor necrosis factor alpha (TNF-alpha), interleukin 1 beta (IL-1 beta), and IL-6 release in a dose-dependent manner and was active with all stimuli tested including Salmonella and Escherichia coli-derived endotoxin, endotoxin from both rough and smooth E. coli strains, as well as zymosan and protein A. CT-1501R inhibited monokine release by approximately 50% at 200 microM and 30% at 50 microM and was independent of the relative potency of stimulus. CT-1501R also inhibited IL-1 alpha or IL-1 beta induction of either TNF-alpha or IL-1 beta and inhibited the synergistic effects of stimulation with both human IL-1 beta and murine TNF-alpha on release of human TNF-alpha. Inhibition of monokine release following stimulation with monokine(s) was, in general, greater than that achieved with lipopolysaccharide (LPS) stimulation.
Name Type Language
LISOFYLLINE
INN   MI   USAN   WHO-DD  
INN   USAN  
Official Name English
LISOFYLLINE [MI]
Common Name English
1H-PURINE-2,6-DIONE, 3,7-DIHYDRO-1-(5-HYDROXYHEXYL)-3,7-DIMETHYL-, (R)-
Common Name English
LISOFYLLINE [USAN]
Common Name English
1-[(R)-5-Hydroxyhexyl]theobromine
Systematic Name English
lisofylline [INN]
Common Name English
CT1501R
Code English
LISOFYLLINE, (R)-
Common Name English
Lisofylline [WHO-DD]
Common Name English
PROTEC
Brand Name English
CT-1501R
Code English
Classification Tree Code System Code
NCI_THESAURUS C744
Created by admin on Sat Dec 16 17:24:21 GMT 2023 , Edited by admin on Sat Dec 16 17:24:21 GMT 2023
Code System Code Type Description
MERCK INDEX
m6843
Created by admin on Sat Dec 16 17:24:21 GMT 2023 , Edited by admin on Sat Dec 16 17:24:21 GMT 2023
PRIMARY Merck Index
CAS
100324-81-0
Created by admin on Sat Dec 16 17:24:21 GMT 2023 , Edited by admin on Sat Dec 16 17:24:21 GMT 2023
PRIMARY
CHEBI
143527
Created by admin on Sat Dec 16 17:24:21 GMT 2023 , Edited by admin on Sat Dec 16 17:24:21 GMT 2023
PRIMARY
WIKIPEDIA
Lisofylline
Created by admin on Sat Dec 16 17:24:21 GMT 2023 , Edited by admin on Sat Dec 16 17:24:21 GMT 2023
PRIMARY
MESH
C025189
Created by admin on Sat Dec 16 17:24:21 GMT 2023 , Edited by admin on Sat Dec 16 17:24:21 GMT 2023
PRIMARY
SMS_ID
100000082544
Created by admin on Sat Dec 16 17:24:21 GMT 2023 , Edited by admin on Sat Dec 16 17:24:21 GMT 2023
PRIMARY
DRUG BANK
DB12406
Created by admin on Sat Dec 16 17:24:21 GMT 2023 , Edited by admin on Sat Dec 16 17:24:21 GMT 2023
PRIMARY
EPA CompTox
DTXSID7058709
Created by admin on Sat Dec 16 17:24:21 GMT 2023 , Edited by admin on Sat Dec 16 17:24:21 GMT 2023
PRIMARY
EVMPD
SUB08534MIG
Created by admin on Sat Dec 16 17:24:21 GMT 2023 , Edited by admin on Sat Dec 16 17:24:21 GMT 2023
PRIMARY
PUBCHEM
501254
Created by admin on Sat Dec 16 17:24:21 GMT 2023 , Edited by admin on Sat Dec 16 17:24:21 GMT 2023
PRIMARY
USAN
FF-20
Created by admin on Sat Dec 16 17:24:21 GMT 2023 , Edited by admin on Sat Dec 16 17:24:21 GMT 2023
PRIMARY
NCI_THESAURUS
C1516
Created by admin on Sat Dec 16 17:24:21 GMT 2023 , Edited by admin on Sat Dec 16 17:24:21 GMT 2023
PRIMARY
INN
7322
Created by admin on Sat Dec 16 17:24:21 GMT 2023 , Edited by admin on Sat Dec 16 17:24:21 GMT 2023
PRIMARY
FDA UNII
L1F2Q2X956
Created by admin on Sat Dec 16 17:24:21 GMT 2023 , Edited by admin on Sat Dec 16 17:24:21 GMT 2023
PRIMARY
ChEMBL
CHEMBL1411
Created by admin on Sat Dec 16 17:24:21 GMT 2023 , Edited by admin on Sat Dec 16 17:24:21 GMT 2023
PRIMARY