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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
Molecular Formula C13H20N4O3
Molecular Weight 280.3229
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Description

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

CNS Active
3913
Curator's Comment: Lisofylline is CNS active in animals. No human data available.

Originator

Approval Year

Unknown
139594
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
8297
Inhibitor
8297
Signal transducer and activator of transcription 4
1
Target ID: Q14765
Gene ID: 6775.0
Gene Symbol: STAT4
Target Organism: Homo sapiens (Human)
Inhibitor
8297
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Phase II
1132
Unknown

Approved Use

Unknown
Primary
Phase III
656
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
5698 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/9435196
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
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/9435196
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
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/10673700
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
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/9435196
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
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/9435196
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
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/9435196
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
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/9435196
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:
https://pubmed.ncbi.nlm.nih.gov/10673700
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:
https://pubmed.ncbi.nlm.nih.gov/10673700
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:
https://pubmed.ncbi.nlm.nih.gov/10673700
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:
https://pubmed.ncbi.nlm.nih.gov/10673700
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:
https://pubmed.ncbi.nlm.nih.gov/10673700
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:
https://pubmed.ncbi.nlm.nih.gov/10673700
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:
https://pubmed.ncbi.nlm.nih.gov/10673700
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:
https://pubmed.ncbi.nlm.nih.gov/10673700
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:
https://pubmed.ncbi.nlm.nih.gov/10673700
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:
https://pubmed.ncbi.nlm.nih.gov/10673700
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:
https://pubmed.ncbi.nlm.nih.gov/10673700
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:
https://pubmed.ncbi.nlm.nih.gov/10673700
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:
https://pubmed.ncbi.nlm.nih.gov/10673700
Page: p.286
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG
substrate
1737

OverviewOther

Other InhibitorOther SubstrateOther Inducer
CYP1A2
1054

HLM
31

CYP2E1
667

CYP2A6
543
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
CYP2E1
667
 unlikely
CYP2A6
543
 yes [Km 38 uM]
CYP3A4
1737
 yes [Km 603 uM]
CYP1A2
1054
 yes
HLM
31
 yes
PubMed

PubMed

TitleDatePubMed
Patents

Patents

US20130122050
1
US8481580
1
WO2007027719A3
1

Sample Use Guides

In Vivo Use Guide
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.
Substance Class Chemical
Created
by admin
on Sat Dec 16 17:24:20 GMT 2023
Edited
by admin
on Sat Dec 16 17:24:20 GMT 2023
Record UNII
L1F2Q2X956
Record Status Validated (UNII)
Record Version
  • Download
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
Related Record Type Details
CYTOCHROME P450 3A4
METABOLIC ENZYME -> SUBSTRATE
Related Record Type Details
Structure of PENTOXIFYLLINE
METABOLITE ACTIVE -> PARENT
Structure of PENTOXIFYLLINE
PARENT -> METABOLITE ACTIVE
MINOR
Related Record Type Details
Structure of LISOFYLLINE
ACTIVE MOIETY
NIH
NCATS
PRIVACY ACT
ACCESSIBILITY
DISCLAIMER
HHS VULNERABILITY DISCLOSURE
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