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Details

Stereochemistry ACHIRAL
Molecular Formula C22H22ClN5O2S
Molecular Weight 455.96
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of APAFANT

SMILES

CC1=NN=C2CN=C(C3=C(SC(CCC(=O)N4CCOCC4)=C3)N12)C5=C(Cl)C=CC=C5

InChI

InChIKey=JGPJQFOROWSRRS-UHFFFAOYSA-N
InChI=1S/C22H22ClN5O2S/c1-14-25-26-19-13-24-21(16-4-2-3-5-18(16)23)17-12-15(31-22(17)28(14)19)6-7-20(29)27-8-10-30-11-9-27/h2-5,12H,6-11,13H2,1H3

HIDE SMILES / InChI
Molecular Formula C22H22ClN5O2S
Molecular Weight 455.96
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/25053619 | https://www.ncbi.nlm.nih.gov/pubmed/1671420 | https://www.ncbi.nlm.nih.gov/pubmed/12784066 | https://www.ncbi.nlm.nih.gov/pubmed/9131176

APAFANT is a platelet activating factor receptor (PAF-R) antagonist shown to have anticancer and cell differentiation effects. APAFANT has been found to be a specific PAF-R antagonist in pulmonary vasculature and when administered intratracheally in rats. APAFANT was observed to decrease lung nuclear factor-κB (NF-κB) activation, myeloperoxidase activity, and lavage neutrophil numbers. It has been shown to be a cytodifferentiating agent in murine erythroleukemia cells in vitro.

CNS Activity

Originator

Approval Year

Unknown
139594
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
8297
 40.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Not Provided
504
Unknown

Approved Use

Unknown
Primary
Not Provided
504
Unknown

Approved Use

Unknown
PubMed

PubMed

TitleDatePubMed
Effects of YM264, a novel PAF antagonist, on puromycin aminonucleoside-induced nephropathy in the rat.
1991 Apr 30
Molecular cloning and expression of platelet-activating factor receptor from human leukocytes.
1991 Oct 25
Evidence for the presence of specific high affinity cytosolic binding sites for platelet-activating factor in human neutrophils.
1993 Jan 15
In vitro modulation of interleukin-1 beta secretion by cultured rat doxorubicin-stimulated whole glomeruli and dissociated mesangial glomerular cells.
1994 Jan
Mechanisms for lipoxin A4-induced neutrophil-dependent cytotoxicity for human endothelial cells.
1995 Jul
A radioreceptor binding assay for platelet-activating factor (PAF) using membranes from CHO cells expressing human PAF receptor.
1995 Oct 26
Regulation of prostaglandin H synthase 2 expression in human monocytes by the marine natural products manoalide and scalaradial. Novel effects independent of inhibition of lipid mediator production.
1995 Sep 28
Mechanisms of platelet-activating factor-induced lipid body formation: requisite roles for 5-lipoxygenase and de novo protein synthesis in the compartmentalization of neutrophil lipids.
1996 Apr 1
Identification of transmembrane domain residues determinant in the structure-function relationship of the human platelet-activating factor receptor by site-directed mutagenesis.
1996 Sep 20
Oxidized low-density lipoprotein downregulates endothelial basic fibroblast growth factor through a pertussis toxin-sensitive G-protein pathway: mediator role of platelet-activating factor-like phospholipids.
2001 Jul 31
Single nucleotide polymorphism of human platelet-activating factor receptor impairs G-protein activation.
2001 Nov 16
Role of platelet-activating factor in phosphatidylcholine secretion in primary cultures of rat type II pneumocytes.
2002 Apr
Specific PAF antagonist WEB-2086 induces terminal differentiation of murine and human leukemia cells.
2002 May
Patents

Patents

DE3502392
1

Sample Use Guides

In Vivo Use Guide
Curator's Comment: 40mg tablets of apafant and/or identical oral placebo tablets, patients who belonged to the low-dose (L) group were administered one active and one placebo tablet 3 times a day (after breakfast, after supper, and before going to bed). Patients who belonged to the high-dose (H) group were administered two active tablets in the same fashion. Patients who belonged to the placebo (P) group were administered two placebo tablets in the same fashion. These tablets were administered in a double-blind fashion.
40 or 80 mg during 8 wk-treatment period
Route of Administration: Oral
In Vitro Use Guide
The ATRA-sensitive APL cell line NB4 and ATRA-resistant NB4 subclones NB4-007-6 and NB4-MR4 (gift of C Gambacorti-Passerini and WH Miller, respectively) were used for activity evaluation. Cells (1x105/ml) were incubated for 5 days without and with 1mkM WEB-2086 (APAFANT) or 1mM ATRA. Cell densities were evaluated daily.
Substance Class Chemical
Created
by admin
on Fri Dec 15 15:51:15 UTC 2023
Edited
by admin
on Fri Dec 15 15:51:15 UTC 2023
Record UNII
J613NI05SV
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
APAFANT
INN   JAN   MART.   MI   USAN  
USAN   INN  
Official Name English
APAFANT [USAN]
Common Name English
APAFANT [JAN]
Common Name English
apafant [INN]
Common Name English
APAFANT [MI]
Common Name English
APAFANT [MART.]
Common Name English
WEB-2086-BS
Code English
WEB 2086 BS
Code English
Classification Tree Code System Code
NCI_THESAURUS C1327
Created by admin on Fri Dec 15 15:51:15 UTC 2023 , Edited by admin on Fri Dec 15 15:51:15 UTC 2023
Code System Code Type Description
SMS_ID
100000086955
Created by admin on Fri Dec 15 15:51:15 UTC 2023 , Edited by admin on Fri Dec 15 15:51:15 UTC 2023
PRIMARY
FDA UNII
J613NI05SV
Created by admin on Fri Dec 15 15:51:15 UTC 2023 , Edited by admin on Fri Dec 15 15:51:15 UTC 2023
PRIMARY
EVMPD
SUB05533MIG
Created by admin on Fri Dec 15 15:51:15 UTC 2023 , Edited by admin on Fri Dec 15 15:51:15 UTC 2023
PRIMARY
MERCK INDEX
m1979
Created by admin on Fri Dec 15 15:51:15 UTC 2023 , Edited by admin on Fri Dec 15 15:51:15 UTC 2023
PRIMARY Merck Index
EPA CompTox
DTXSID5048974
Created by admin on Fri Dec 15 15:51:15 UTC 2023 , Edited by admin on Fri Dec 15 15:51:15 UTC 2023
PRIMARY
ChEMBL
CHEMBL280164
Created by admin on Fri Dec 15 15:51:15 UTC 2023 , Edited by admin on Fri Dec 15 15:51:15 UTC 2023
PRIMARY
INN
6369
Created by admin on Fri Dec 15 15:51:15 UTC 2023 , Edited by admin on Fri Dec 15 15:51:15 UTC 2023
PRIMARY
USAN
JJ-91
Created by admin on Fri Dec 15 15:51:15 UTC 2023 , Edited by admin on Fri Dec 15 15:51:15 UTC 2023
PRIMARY
PUBCHEM
65889
Created by admin on Fri Dec 15 15:51:15 UTC 2023 , Edited by admin on Fri Dec 15 15:51:15 UTC 2023
PRIMARY
CAS
105219-56-5
Created by admin on Fri Dec 15 15:51:15 UTC 2023 , Edited by admin on Fri Dec 15 15:51:15 UTC 2023
PRIMARY
NCI_THESAURUS
C77989
Created by admin on Fri Dec 15 15:51:15 UTC 2023 , Edited by admin on Fri Dec 15 15:51:15 UTC 2023
PRIMARY
Related Record Type Details
PLATELET-ACTIVATING FACTOR RECEPTOR
TARGET -> INHIBITOR
Binding Assay
IC50
Related Record Type Details
Structure of APAFANT
ACTIVE MOIETY
NIH
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