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Details

Stereochemistry MIXED
Molecular Formula C23H25ClN2O
Molecular Weight 380.91
Optical Activity UNSPECIFIED
Defined Stereocenters 0 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of OPAGANIB

SMILES

ClC1=CC=C(C=C1)C23CC4CC(CC(C4)(C2)C(=O)NCC5=CC=NC=C5)C3

InChI

InChIKey=CAOTVXGYTWCKQE-UHFFFAOYSA-N
InChI=1S/C23H25ClN2O/c24-20-3-1-19(2-4-20)22-10-17-9-18(11-22)13-23(12-17,15-22)21(27)26-14-16-5-7-25-8-6-16/h1-8,17-18H,9-15H2,(H,26,27)

HIDE SMILES / InChI

Molecular Formula C23H25ClN2O
Molecular Weight 380.91
Charge 0
Count
Stereochemistry MIXED
Additional Stereochemistry No
Defined Stereocenters 0 / 2
E/Z Centers 0
Optical Activity UNSPECIFIED

ABC-294640 is an orally bioavailable and selective sphingosine kinase-2 (SphK2) inhibitor with IC50 of approximately 60 uM. ABC-294640 inhibits SK2, a lipid kinase that catalyzes formation of the lipid signaling molecule sphingosine 1-phosphate (S1P). S1P promotes cancer growth, and proliferation and pathological inflammation, including TNFα signaling and other inflammatory cytokine production. Specifically, by inhibiting the SK2 enzyme, ABC-294640 blocks the synthesis of S1P which regulates fundamental biological processes such as cell proliferation, migration, immune cell trafficking and angiogenesis, and are also involved in immune-modulation and suppression of innate immune responses from T cells. Preliminary evidence suggests that because of its specificity for targeting SK2, rather than SK1, ABC-294640 may have a better therapeutic ratio than nonspecific sphingosine kinase inhibitors or those targeting only SK1. Oral administration of ABC-294640 to mice bearing mammary adenocarcinoma xenografts results in dose-dependent antitumor activity associated with depletion of S1P levels in the tumors and progressive tumor cell apoptosis. Therefore, this newly developed SK2 inhibitor provides an orally available drug candidate for the treatment of cancer and other diseases. ABC-294640 has completed multiple successful pre-clinical studies in inflammatory, GI, radioprotection and oncology models, as well as a Phase I clinical study in cancer patients with advanced solid tumors.

Approval Year

Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
5.16 μg/mL
500 mg 1 times / day multiple, oral
dose: 500 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
ABC-294640 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
50.84 μg × h/mL
500 mg 1 times / day multiple, oral
dose: 500 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
ABC-294640 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
10 h
500 mg 1 times / day multiple, oral
dose: 500 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
ABC-294640 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer


Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
yes [IC50 2.76 uM]
yes [IC50 4.77 uM]
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Efficacy of a novel sphingosine kinase inhibitor in experimental Crohn's disease.
2010 Apr
Pharmacology and antitumor activity of ABC294640, a selective inhibitor of sphingosine kinase-2.
2010 Apr
A novel sphingosine kinase inhibitor induces autophagy in tumor cells.
2010 May
Antiestrogenic effects of the novel sphingosine kinase-2 inhibitor ABC294640.
2010 Nov
Suppression of colitis-driven colon cancer in mice by a novel small molecule inhibitor of sphingosine kinase.
2010 Oct
Patents

Sample Use Guides

In Vivo Use Guide
Curator's Comment: Mice: in mice bearing mammary adenocarcinoma xenografts, ABC-294640 (100 mg/kg, p.o.) significantly reduces tumor growth, associated with depletion of S1P levels. https://www.ncbi.nlm.nih.gov/pubmed/20061445
Treating patients with advanced solid tumors: given PO starting dose of ABC-294640 250 mg once on day on Days 1-28 of each 28-day cycle. Subsequent cohort doses (if reached) are as follows: 250 BID, 500 BID, 750 BID, 1,000 BID, 1,500 BID, 2,000 BID, 2,500 BID
Route of Administration: Oral
Using recombinant human SK1 and SK2, ABC-294640 demonstrated dose-dependent inhibition of SK2 with an IC50 of approximately 60 uM without affecting the activity of SK1 at concentrations up to at least 100 uM. ABC-294640 inhibits tumor cell proliferation with IC50 values ranging from approximately 6 to 48 uM, and impairs tumor cell migration concomitant with loss of microfilaments.
Substance Class Chemical
Created
by admin
on Fri Dec 15 19:52:44 GMT 2023
Edited
by admin
on Fri Dec 15 19:52:44 GMT 2023
Record UNII
DRG21OQ517
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
OPAGANIB
INN  
Official Name English
opaganib [INN]
Common Name English
ABC294640
Common Name English
4-PYRIDINYLMETHYL 3(4-CHLOROPHENYL)ADAMANTINE CARBOXAMIDE
Common Name English
4-PYRIDINYLMETHYL-3-(4-CHLOROPHENYL) ADAMANTANE CARBOXAMIDE
Common Name English
TRICYCLO(3.3.1.13,7)DECANE-1-CARBOXAMIDE, 3-(4-CHLOROPHENYL)-N-(4-PYRIDINYLMETHYL)-
Systematic Name English
Opaganib [WHO-DD]
Common Name English
ABC 294640
Code English
ABC-294640
Common Name English
Classification Tree Code System Code
FDA ORPHAN DRUG 318110
Created by admin on Fri Dec 15 19:52:44 GMT 2023 , Edited by admin on Fri Dec 15 19:52:44 GMT 2023
NCI_THESAURUS C1404
Created by admin on Fri Dec 15 19:52:44 GMT 2023 , Edited by admin on Fri Dec 15 19:52:44 GMT 2023
FDA ORPHAN DRUG 559116
Created by admin on Fri Dec 15 19:52:44 GMT 2023 , Edited by admin on Fri Dec 15 19:52:44 GMT 2023
Code System Code Type Description
NCI_THESAURUS
C98278
Created by admin on Fri Dec 15 19:52:44 GMT 2023 , Edited by admin on Fri Dec 15 19:52:44 GMT 2023
PRIMARY
DRUG BANK
DB12764
Created by admin on Fri Dec 15 19:52:44 GMT 2023 , Edited by admin on Fri Dec 15 19:52:44 GMT 2023
PRIMARY
INN
10561
Created by admin on Fri Dec 15 19:52:44 GMT 2023 , Edited by admin on Fri Dec 15 19:52:44 GMT 2023
PRIMARY
WIKIPEDIA
Opaganib
Created by admin on Fri Dec 15 19:52:44 GMT 2023 , Edited by admin on Fri Dec 15 19:52:44 GMT 2023
PRIMARY
CAS
915385-81-8
Created by admin on Fri Dec 15 19:52:44 GMT 2023 , Edited by admin on Fri Dec 15 19:52:44 GMT 2023
PRIMARY
SMS_ID
300000021745
Created by admin on Fri Dec 15 19:52:44 GMT 2023 , Edited by admin on Fri Dec 15 19:52:44 GMT 2023
PRIMARY
MESH
C548780
Created by admin on Fri Dec 15 19:52:44 GMT 2023 , Edited by admin on Fri Dec 15 19:52:44 GMT 2023
PRIMARY
EPA CompTox
DTXSID801318727
Created by admin on Fri Dec 15 19:52:44 GMT 2023 , Edited by admin on Fri Dec 15 19:52:44 GMT 2023
PRIMARY
FDA UNII
DRG21OQ517
Created by admin on Fri Dec 15 19:52:44 GMT 2023 , Edited by admin on Fri Dec 15 19:52:44 GMT 2023
PRIMARY
PUBCHEM
15604015
Created by admin on Fri Dec 15 19:52:44 GMT 2023 , Edited by admin on Fri Dec 15 19:52:44 GMT 2023
PRIMARY
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COMPETITIVE INHIBITOR
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ACTIVE MOIETY