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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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.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. 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.

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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
SMILES / InChI / InChIKey
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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.

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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
InChI Key JYHSRMKXBAPFST-UHFFFAOYSA-N
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
Key to terms and symbols Click on species/strain names for details Click column headers to sort
MOA/likely target Sp. Assay description Type Action Value Parameter Concentration range (M) Reference
Unknown MOA Pf3D7

Plasmodium falciparum 3D7

P. falciparum strain 3D7 (Pf3D7) was derived from isolate NF54 by limiting dilution. The complete genome of Pf3D7 has been sequenced (GenBank: LN999946.1).
Pf3D7 can be obtained from the European Malaria Reagent Repository or the Malaria Research and Reference Reagent Resource Center (MR4) and is sensitive to a panel of antimalarial compounds including chloroquine and pyrimethamine.
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 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)