INE963   Click here for help

GtoPdb Ligand ID: 11929

Synonyms: MMV1582617 | NVP-INE963
Antimalarial Ligand
Compound class: Synthetic organic
Comment: INE963 is a potent antimalarial compound identified by the Novartis Institute for Tropical Diseases (NITD) during an optimization study of a series of 5-aryl-2-amino-imidazothiadiazole (ITD) derivatives [1]. The compound has progressed to clinical evaluation and was awarded MMV Project of the Year (2019).

The Malaria tab on this ligand page provides additional curator comments of relevance to the Guide to MALARIA PHARMACOLOGY.
2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 6
Hydrogen bond donors 2
Rotatable bonds 5
Topological polar surface area 130.04
Molecular weight 402.18
XLogP 2.04
No. Lipinski's rules broken 0
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Canonical SMILES NCC1(O)CCN(CC1)c1nn2c(s1)ncc2c1ccc(nc1OC)C(C)C
Isomeric SMILES COc1nc(ccc1c1cnc2sc(nn12)N1CCC(O)(CN)CC1)C(C)C
InChI InChI=1S/C19H26N6O2S/c1-12(2)14-5-4-13(16(22-14)27-3)15-10-21-17-25(15)23-18(28-17)24-8-6-19(26,11-20)7-9-24/h4-5,10,12,26H,6-9,11,20H2,1-3H3
Bioactivity Comments
In addition to single digit nanomolar activity against the asexual blood stage of P. falciparum 3D7 (see table below), INE963 demonstrates potent activity against drug-resistant P. falciparum cell lines (EC50 of 0.5-15 nM) [1]. The same study reports potency against P. falciparum and P. vivax clinical isolates from Brazil and Uganda (EC50 of 0.01-7.0 nM).
Whole organism assay data
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MOA/likely target Sp. Assay description Type Action Value Parameter Concentration range (M) Reference
Unknown MOA Pf3D7 Parasite growth inhibition assay - - 8.2 – 8.5 pEC50 - 1
pEC50 8.5 (EC50 3x10-9 M) [3H]-hypoxanthine incorporation [1]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
pEC50 8.2 (EC50 6x10-9 M) SYBR green assay [1]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)