apilimod   Click here for help

GtoPdb Ligand ID: 9859

Synonyms: LAM-002A (apilimod dimesylate) | LAM002A | STA 5326 | STA-5326 | STA5326
Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: Apilimod was originally identified as an inhibitor of IL-12/IL-23 production [10], but the molecular mechanism behind this biological effect was undetermined. Inhibition of IL-12/IL-23 production has application for the treatment Th1-and Th17-mediated immunologic pathologies (which are driven by IL-12 and IL-23 respectively) [9-10]. Apilimod has subsequently been identified as a selective inhibitor of the type III phosphoinostol kinase, PIKfyve [3-4].
We provide structural details for the parent molecule, but some bioactivity data may relate to use of the mesylate salt form as stipulated by the compound's USAN (see PubChem CID 115273300).

PIKfyve has been reported as being required for Ebola virus (EBOV) infection of host cells [7], and indeed apilimod has anti-EBOV activity in vitro. More broad-spectrum antiviral activity against Lassa virus (LASV), Marburg virus (MARV) [6] and SARS-CoV-2 [5,8] is supported in the literature. Activity of PIKfyve is markedly modulated by SARS-CoV-2 infection in vitro, and indicates potential hijacking of phosphatidylinositol enzyme activities by the coronavirus [2]. Pharmacological inhibition of this kinase with apilimod has anti-SARS-CoV-2 activity in two model cells lines, A549-ACE2 cells (IC50 7 nM) and Vero E6 cells (IC50 80 nM) and in human iPSC-derived pneumocyte-like cells . One note of caution: PIKfyve has also been implicated as a key component of antigen presentation by dendritic cells [1]. So in respect of the investigation of apilimod in SARS-CoV-2 infection (NCT04446377), inhibition of antigen presentation, the immune response to new antigens, and T-cell activation, may not be ideal in this setting. Would this leave patients susceptible to other infections during apilimod treatment? Results from the apilomod clinical trials will be interesting.
Click here for help
2D Structure
Click here for help
Click here for structure editor
Physico-chemical Properties
Click here for help
Hydrogen bond acceptors 7
Hydrogen bond donors 1
Rotatable bonds 8
Topological polar surface area 84.76
Molecular weight 418.21
XLogP 5.22
No. Lipinski's rules broken 1
SMILES / InChI / InChIKey
Click here for help
Canonical SMILES Cc1cccc(c1)C=NNc1nc(OCCc2ccccn2)nc(c1)N1CCOCC1
Isomeric SMILES Cc1cccc(c1)/C=N/Nc1nc(OCCc2ccccn2)nc(c1)N1CCOCC1
InChI 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+
InChI Key HSKAZIJJKRAJAV-KOEQRZSOSA-N
Classification Click here for help
Compound class Synthetic organic
IUPAC Name Click here for help
N-[(3-methylphenyl)methylideneamino]-6-morpholin-4-yl-2-(2-pyridin-2-ylethoxy)pyrimidin-4-amine
International Nonproprietary Names Click here for help
INN number INN
8763 apilimod
Synonyms Click here for help
LAM-002A (apilimod dimesylate) | LAM002A | STA 5326 | STA-5326 | STA5326
Database Links Click here for help
CAS Registry No. 541550-19-0 (source: WHO INN record)
GtoPdb PubChem SID 363894153
PubChem CID 10173277
Search Google for chemical match using the InChIKey HSKAZIJJKRAJAV-KOEQRZSOSA-N
Search Google for chemicals with the same backbone HSKAZIJJKRAJAV
Search PubMed clinical trials apilimod
Search PubMed titles apilimod
Search PubMed titles/abstracts apilimod
Search UniChem for chemical match using the InChIKey HSKAZIJJKRAJAV-KOEQRZSOSA-N
Search UniChem for chemicals with the same backbone HSKAZIJJKRAJAV