APILIMOD

Investigational

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 Search

SMILES

CC1=CC(\C=N\NC2=NC(OCCC3=CC=CC=N3)=NC(=C2)N4CCOCC4)=CC=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

Description
Sources: http://adisinsight.springer.com/drugs/800018099 | https://www.cancer.gov/publications/dictionaries/cancer-drug?cdrid=780441 | https://www.ncbi.nlm.nih.gov/pubmed/17187316 | https://www.ncbi.nlm.nih.gov/pubmed/18847496 | https://clinicaltrials.gov/ct2/show/NCT02594384

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

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
NF-kappaB complex 2 Target ID: GO:0071159 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21141074	Interacts 323
1-phosphatidylinositol 3-phosphate 5-kinase 2 Target ID: Q9Y2I7 Gene ID: 200576.0 Gene Symbol: PIKFYVE Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/28104689	Inhibitor 8504
cytokine secretion involved in immune response 5 Target ID: GO:0002374 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22493730	Inhibitor 8504

Conditions

Condition	Modality	Highest Phase	Product
Rheumatoid arthritis 320 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22170479	Primary	Phase II 1147	Unknown Approved Use Unknown
Crohn's disease 64 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16804392	Primary	Phase II 1147	Unknown Approved Use Unknown
Experimental autoimmune uveoretinitis 2 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18847496	Primary	Basic research	Unknown Approved Use Unknown
Non-Hodgkin's lymphoma 81 Sources: https://clinicaltrials.gov/ct2/show/NCT02594384	Primary	Phase I 438	Unknown Approved Use Unknown
Psoriasis 87 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22493730	Primary	Phase II 1147	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
274 ng/mL EXPERIMENT https://assets.website-files.com/5bd270b2e599946e65c2ff05/5bd3e30af2904427b3a4e03b_LAM-Therapeutics_ASH_2017.pdf	100 mg 2 times / day multiple, oral dose: 100 mg route of administration: Oral experiment type: MULTIPLE co-administered:		APILIMOD plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
511 ng × h/mL EXPERIMENT https://assets.website-files.com/5bd270b2e599946e65c2ff05/5bd3e30af2904427b3a4e03b_LAM-Therapeutics_ASH_2017.pdf	100 mg 2 times / day multiple, oral dose: 100 mg route of administration: Oral experiment type: MULTIPLE co-administered:		APILIMOD plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
3.9 h EXPERIMENT https://assets.website-files.com/5bd270b2e599946e65c2ff05/5bd3e30af2904427b3a4e03b_LAM-Therapeutics_ASH_2017.pdf	100 mg 2 times / day multiple, oral dose: 100 mg route of administration: Oral experiment type: MULTIPLE co-administered:		APILIMOD plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse 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: https://assets.website-files.com/5bd270b2e599946e65c2ff05/5bd3e30af2904427b3a4e03b_LAM-Therapeutics_ASH_2017.pdf	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://assets.website-files.com/5bd270b2e599946e65c2ff05/5bd3e30af2904427b3a4e03b_LAM-Therapeutics_ASH_2017.pdf	DLT: nausea, vomiting... Dose limiting toxicities: nausea (grade 1-3, 60%) vomiting (60%) diarrhea (20%) hyponatremia (20%) Sources: https://assets.website-files.com/5bd270b2e599946e65c2ff05/5bd3e30af2904427b3a4e03b_LAM-Therapeutics_ASH_2017.pdf
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: https://pubmed.ncbi.nlm.nih.gov/22170479	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/22170479	Disc. AE: headache... AEs leading to discontinuation/dose reduction: headache (severe, 11.1%) Sources: https://pubmed.ncbi.nlm.nih.gov/22170479
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: https://pubmed.ncbi.nlm.nih.gov/22170479	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/22170479	Sources: https://pubmed.ncbi.nlm.nih.gov/22170479

AEs

AE	Significance	Dose	Population
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: https://assets.website-files.com/5bd270b2e599946e65c2ff05/5bd3e30af2904427b3a4e03b_LAM-Therapeutics_ASH_2017.pdf	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://assets.website-files.com/5bd270b2e599946e65c2ff05/5bd3e30af2904427b3a4e03b_LAM-Therapeutics_ASH_2017.pdf
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: https://assets.website-files.com/5bd270b2e599946e65c2ff05/5bd3e30af2904427b3a4e03b_LAM-Therapeutics_ASH_2017.pdf	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://assets.website-files.com/5bd270b2e599946e65c2ff05/5bd3e30af2904427b3a4e03b_LAM-Therapeutics_ASH_2017.pdf
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: https://assets.website-files.com/5bd270b2e599946e65c2ff05/5bd3e30af2904427b3a4e03b_LAM-Therapeutics_ASH_2017.pdf	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://assets.website-files.com/5bd270b2e599946e65c2ff05/5bd3e30af2904427b3a4e03b_LAM-Therapeutics_ASH_2017.pdf
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: https://assets.website-files.com/5bd270b2e599946e65c2ff05/5bd3e30af2904427b3a4e03b_LAM-Therapeutics_ASH_2017.pdf	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://assets.website-files.com/5bd270b2e599946e65c2ff05/5bd3e30af2904427b3a4e03b_LAM-Therapeutics_ASH_2017.pdf
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: https://pubmed.ncbi.nlm.nih.gov/22170479	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/22170479

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2252	inhibitor 2438	inhibitor 2507

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1741

Drug as perpetrator

Target	Modality	Activity
P-gp 1932	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346987#sid=137275937	inconclusive [IC50 20.931 uM]
CYP3A4 2633	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645841#sid=440681412	yes [IC50 1.6933 uM]
CYP2D6 2546	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645840#sid=440681412	yes [IC50 10.684 uM]
CYP2C9 2497	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645842#sid=440681412	yes [IC50 7.5637 uM]

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY559447	https://www.001chemical.com/chem/541550-19-0
Aaron Chemicals	AR00DE2F	http://www.aaronchem.com/541550-19-0
Active Biopharma	ABP000484	http://www.activebiopharma.com/541550-19-0
Adooq BioScience	A13794	https://www.adooq.com/apilimod.html
Ambinter	Amb22054351	http://www.ambinter.com/reference/22054351
Ark Pharm	AK546760	http://www.arkpharminc.com/products/541550-19-0.html
Ark Pharma Scientific Limited	A-0878	http://www.arkpharmtech.com/product/32829.html
AvaChem Scientific	6099	https://www.avachem.com/productSearch.asp?6099
Axon MedChem	1369	https://www.axonmedchem.com/product/1369
BioChemPartner	BCP27874	http://www.biochempartner.com/541550-19-0-BCP27874
BioCrick	BCC5286	http://www.biocrick.com/Apilimod-BCC5286.html
BOC Sciences	541550-19-0	https://www.bocsci.com/apilimod-cas-541550-19-0-item-54955.html
Chem Scene	CS-2341	http://www.chemscene.com/541550-19-0.html
ChemMol	49410299	http://www.chemmol.com/chemmol/49410299.html
ChemMol	97900147	http://www.chemmol.com/chemmol/97900147.html
ChemShuttle	153169	https://www.chemshuttle.com/catalogsearch/result/?q=541550-19-0&cat=
Chemspace	CSSB00020618405	https://chem-space.com/CSSB00020618405
Chemspace	CSSB00020676078	https://chem-space.com/CSSB00020676078
Combi-Blocks	QJ-6371	http://www.combi-blocks.com/cgi-bin/find.cgi?QJ-6371
DC Chemicals	DC8275	http://www.dcchemicals.com/product_show-Apilimod.html
Excenen	EX-A908	http://www.excenen.com/searchresultlist.php?id=541550-19-0
Finetech	FT-0700482	http://www.finetechnology-ind.com/prod/detail/pub/541550-19-0.html
Hairui	HR143463	http://www.hairuichem.com/en/product/541550-19-0.html
iChemical	EBD16453	http://www.ichemical.com/chemicals/cas-541550-19-0
Lab Network	LN01282301	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01282301
MedChem Express	HY-14644	https://www.medchemexpress.com/Apilimod.html
Molcore	MC559447	https://www.molcore.com/product/541550-19-0
MolPort	MolPort-039-337-258	https://www.molport.com/shop/molecule-link/MolPort-039-337-258
MuseChem	I011642	https://www.musechem.com/product/I011642.html
Selleck Chemicals	S6414	http://www.selleckchem.com/products/apilimod.html
Smolecule	S519123	http://www.smolecule.com/products/s519123
THE BioTek	bt-259503	https://www.thebiotek.com/product/inhibitors/bt-259503

PubMed

Title	Date	PubMed
		252160088
Brief report: a phase IIa, randomized, double-blind, placebo-controlled trial of apilimod mesylate, an interleukin-12/interleukin-23 inhibitor, in patients with rheumatoid arthritis.	2012 Jun	22170479
The phosphatidylinositol-3-phosphate 5-kinase inhibitor apilimod blocks filoviral entry and infection.	2017 Apr	28403145

Patents

Sample Use Guides

In Vivo Use Guide

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

In Vitro Use Guide

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

STA 5326

Preferred Name

English

APILIMOD

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

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