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

Details

Stereochemistry ACHIRAL
Molecular Formula C23H26N6O2
Molecular Weight 418.4915
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of APILIMOD

SMILES

CC1=CC=CC(\C=N\NC2=NC(OCCC3=NC=CC=C3)=NC(=C2)N4CCOCC4)=C1

InChI

InChIKey=HSKAZIJJKRAJAV-KOEQRZSOSA-N
InChI=1S/C23H26N6O2/c1-18-5-4-6-19(15-18)17-25-28-21-16-22(29-10-13-30-14-11-29)27-23(26-21)31-12-8-20-7-2-3-9-24-20/h2-7,9,15-17H,8,10-14H2,1H3,(H,26,27,28)/b25-17+

HIDE SMILES / InChI
Apilimod is a small molecule inhibitor of interleukin-12 and interleukin-23 synthesis thereby preventing IL-12/IL-23 mediated immune responses. Apilimod is also observed to inhibit the nuclear accumulation of NF-kappB protein family, and viral infections dependent on phosphatidylinositol-3-phosphate 5-kinase (PIKfyve). Apilimod has been investigated as a potential treatment for a number of autoimmune conditions.

CNS Activity

Curator's Comment: Maximum tolerable dose before experiencing adverse CNS effects is 70 mg per day.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: Q9Y2I7
Gene ID: 200576.0
Gene Symbol: PIKFYVE
Target Organism: Homo sapiens (Human)
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Doses

Doses

DosePopulationAdverse events​
150 mg 2 times / day multiple, oral
Highest studied dose
Dose: 150 mg, 2 times / day
Route: oral
Route: multiple
Dose: 150 mg, 2 times / day
Sources:
unhealthy, ADULT
n = 5
Health Status: unhealthy
Condition: B-cell lymphoma
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 5
Sources:
DLT: hyponatremia, diarrhea...
Dose limiting toxicities:
hyponatremia (20%)
diarrhea (20%)
vomiting (60%)
nausea (grade 1-3, 60%)
Sources:
100 mg 1 times / day multiple, oral
Studied dose
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Sources: Page: p.1752
unhealthy, ADULT
n = 9
Health Status: unhealthy
Condition: rheumatoid arthritis
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 9
Sources: Page: p.1752
Disc. AE: headache...
AEs leading to
discontinuation/dose reduction:
headache (severe, 11.1%)
Sources: Page: p.1752
100 mg 2 times / day multiple, oral
Studied dose
Dose: 100 mg, 2 times / day
Route: oral
Route: multiple
Dose: 100 mg, 2 times / day
Sources: Page: p.1752
unhealthy, ADULT
n = 5
Health Status: unhealthy
Condition: rheumatoid arthritis
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 5
Sources: Page: p.1752
AEs

AEs

AESignificanceDosePopulation
diarrhea 20%
DLT, Disc. AE
150 mg 2 times / day multiple, oral
Highest studied dose
Dose: 150 mg, 2 times / day
Route: oral
Route: multiple
Dose: 150 mg, 2 times / day
Sources:
unhealthy, ADULT
n = 5
Health Status: unhealthy
Condition: B-cell lymphoma
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 5
Sources:
hyponatremia 20%
DLT, Disc. AE
150 mg 2 times / day multiple, oral
Highest studied dose
Dose: 150 mg, 2 times / day
Route: oral
Route: multiple
Dose: 150 mg, 2 times / day
Sources:
unhealthy, ADULT
n = 5
Health Status: unhealthy
Condition: B-cell lymphoma
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 5
Sources:
vomiting 60%
DLT, Disc. AE
150 mg 2 times / day multiple, oral
Highest studied dose
Dose: 150 mg, 2 times / day
Route: oral
Route: multiple
Dose: 150 mg, 2 times / day
Sources:
unhealthy, ADULT
n = 5
Health Status: unhealthy
Condition: B-cell lymphoma
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 5
Sources:
nausea grade 1-3, 60%
DLT, Disc. AE
150 mg 2 times / day multiple, oral
Highest studied dose
Dose: 150 mg, 2 times / day
Route: oral
Route: multiple
Dose: 150 mg, 2 times / day
Sources:
unhealthy, ADULT
n = 5
Health Status: unhealthy
Condition: B-cell lymphoma
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 5
Sources:
headache severe, 11.1%
Disc. AE
100 mg 1 times / day multiple, oral
Studied dose
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Sources: Page: p.1752
unhealthy, ADULT
n = 9
Health Status: unhealthy
Condition: rheumatoid arthritis
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 9
Sources: Page: p.1752
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG



OverviewOther

Other InhibitorOther SubstrateOther Inducer

Drug as perpetrator​
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
The phosphatidylinositol-3-phosphate 5-kinase inhibitor apilimod blocks filoviral entry and infection.
2017 Apr
Patents

Sample Use Guides

In a phase IIa clinical trial for rheumatoid arthritis Apilimod mesylate was administered orally at a dose of 100 mg/day or 100 mg twice per day for up to 12 weeks.
Route of Administration: Oral
Apilimod was tested for inhibition of EBOV infection in three cell lines: Vero E6, Huh 7, and hMDM cells. For each cell type, cells were plated in 1 black opaque 96-well plate, for the evaluation of drug cytotoxicity, and 2 clear-bottom, 96-well Operetta plates, for the evaluation of drug efficacy. Apilimod was dissolved in dimethyl sulfoxide (DMSO) and diluted in DMEM with 10% FBS with the final DMSO concentration not exceeding 0.05%. The Apilimod solution was diluted two-fold in an 8-point dilution series and transferred to cell plates 1 h prior to virus infection.
Name Type Language
APILIMOD
INN  
INN  
Official Name English
N-(3-METHYL-BENZYLIDENE)-N'-(6-MORPHOLIN-4-YL-2-(2-PYRIDIN-2-YL-ETHOXY)-PYRIMIDIN-4-YL)-HYDRAZINE
Systematic Name English
apilimod [INN]
Common Name English
BENZALDEHYDE, 3-METHYL-, (6-(4-MORPHOLINYL)-2-(2-(2-PYRIDINYL)ETHOXY)-4-PYRIMIDINYL)HYDRAZONE
Common Name English
STA 5326
Code English
Apilimod [WHO-DD]
Common Name English
BENZALDEHYDE, 3-METHYL-, 2-(6-(4-MORPHOLINYL)-2-(2-(2-PYRIDINYL)ETHOXY)-4-PYRIMIDINYL)HYDRAZONE
Common Name English
STA-5326
Code English
Classification Tree Code System Code
NCI_THESAURUS C129820
Created by admin on Fri Dec 15 16:15:41 UTC 2023 , Edited by admin on Fri Dec 15 16:15:41 UTC 2023
Code System Code Type Description
INN
8763
Created by admin on Fri Dec 15 16:15:41 UTC 2023 , Edited by admin on Fri Dec 15 16:15:41 UTC 2023
PRIMARY
EPA CompTox
DTXSID101025733
Created by admin on Fri Dec 15 16:15:41 UTC 2023 , Edited by admin on Fri Dec 15 16:15:41 UTC 2023
PRIMARY
FDA UNII
GFW2K84S4L
Created by admin on Fri Dec 15 16:15:41 UTC 2023 , Edited by admin on Fri Dec 15 16:15:41 UTC 2023
PRIMARY
CAS
541550-19-0
Created by admin on Fri Dec 15 16:15:41 UTC 2023 , Edited by admin on Fri Dec 15 16:15:41 UTC 2023
PRIMARY
WIKIPEDIA
Apilimod
Created by admin on Fri Dec 15 16:15:41 UTC 2023 , Edited by admin on Fri Dec 15 16:15:41 UTC 2023
PRIMARY
DRUG BANK
DB05611
Created by admin on Fri Dec 15 16:15:41 UTC 2023 , Edited by admin on Fri Dec 15 16:15:41 UTC 2023
PRIMARY
PUBCHEM
10173277
Created by admin on Fri Dec 15 16:15:41 UTC 2023 , Edited by admin on Fri Dec 15 16:15:41 UTC 2023
PRIMARY
SMS_ID
300000034076
Created by admin on Fri Dec 15 16:15:41 UTC 2023 , Edited by admin on Fri Dec 15 16:15:41 UTC 2023
PRIMARY
NCI_THESAURUS
C90808
Created by admin on Fri Dec 15 16:15:41 UTC 2023 , Edited by admin on Fri Dec 15 16:15:41 UTC 2023
PRIMARY