mocravimod   Click here for help

GtoPdb Ligand ID: 9727

Synonyms: compound 2 [PMID: 23124563] | KRP-203 | KRP203
Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: Mocravimod (KRP203) is a sphingosine 1-phosphate receptor type 1 (S1P1R) agonist with immunomodulatory potential [6]. Structurally mocravimod is a highly modified analogue of the approved multiple sclerosis drug fingolimod. Like fingolimod it is a prodrug that is phosphorylated in vivo by sphingosine kinase 2 (SPHK2), with mocravimod-phosphate (+KRP203-phosphate) being the active entity.
2D Structure
Click here for help

2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

✖
Click here for structure editor
Physico-chemical Properties
Click here for help

Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

✖
Hydrogen bond acceptors 3
Hydrogen bond donors 3
Rotatable bonds 10
Topological polar surface area 101.01
Molecular weight 443.13
XLogP 4.71
No. Lipinski's rules broken 0

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
SMILES / InChI / InChIKey
Click here for help

SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

✖
Canonical SMILES OCC(CCc1ccc(cc1Cl)Sc1cccc(c1)OCc1ccccc1)(CO)N
Isomeric SMILES OCC(CCc1ccc(cc1Cl)Sc1cccc(c1)OCc1ccccc1)(CO)N
InChI InChI=1S/C24H26ClNO3S/c25-23-14-22(10-9-19(23)11-12-24(26,16-27)17-28)30-21-8-4-7-20(13-21)29-15-18-5-2-1-3-6-18/h1-10,13-14,27-28H,11-12,15-17,26H2
InChI Key IINUNQPYJGJCJI-UHFFFAOYSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
No information available.
Summary of Clinical Use Click here for help
Preclinical evidence suggested efficacy in preventing graft rejection [4,6-7] and this led to the design of studies in patients undergoing stem cell transplant for hematological malignancies to evaluate efficacy as an adjunct therapy. Mocravimod was also tested in autoimmune indications (ulcerative colitis, subacute cutaneous Lupus erythematosus and Crohn's disease).
Mechanism Of Action and Pharmacodynamic Effects Click here for help
The structural similarity of mocravimod to that of fingolimod suggests that this compound may act via a similar mechanism to effectively sequester peripheral lymphocytes and accelerate lymphocyte homing into the secondary lymphoid organ.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT01375179 Efficacy & Safety in Moderately Active Refractory Ulcerative Colitis Patients Phase 2 Interventional Novartis
NCT01830010 A Two-part Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of KRP203 in Patients Undergoing Stem Cell Transplant for Hematological Malignancies Phase 1 Interventional Novartis 2-3
NCT01294774 Safety and Efficacy of KRP203 in Subacute Cutaneous Lupus Erythematosus Phase 2 Interventional Novartis
NCT05429632 Mocravimod as Adjunctive and Maintenance Treatment in AML Patients Undergoing Allo-HCT Phase 3 Interventional Priothera SAS