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AH10-7   Click here for help

GtoPdb Ligand ID: 9899

Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: AH10-7 is a sphinganine α-galactosylceramide (or galactosylsphingamide) that has been designed for the potential to activate CD1d-restricted invariant natural killer T (iNKT) cells as a mechanism to augment immune responses against cancer and infections [1]. It is an analogue of KRN7000 (PubChem CID 2826713, a.k.a. α-GalCer) that was originally developed for its potent immunomodulatory effects, and which was investigated as an immuno-oncology agent [3,7]. However, KRN7000 induces both Th1 and Th2 cytokine production, and produces a suboptimal immune response, which likely accounts for its apparent limited efficacy in clinical trials [5,8]. AH10-7 overcomes KRN7000's unpredictable effects by promoting a Th1-biased immune response, which suggests that it will elicit more favorable results against cancer and infection (whereas a Th2-biased response would likely be of more benefit against autoimmune diseases). Both KRN7000 and AH10-7 are ligands for the lipid-binding MHC class I-like protein CD1d. Recognition of lipid-based antigens presented by CD1d sets iNKT cells apart from conventional T cells.
Van Kaer and Wu (2018) have published a review of the therapeutic potential of iNKT cells in autoimmune conditions [6] and the application of unconventional T cells in immuno-oncology is reviewed by Godfrey et al. (2018) [2] and Krijgsman et al. (2018) [4].
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 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.

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Hydrogen bond acceptors 9
Hydrogen bond donors 5
Rotatable bonds 50
Topological polar surface area 137.71
Molecular weight 971.82
XLogP 21.6
No. Lipinski's rules broken 2

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
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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.

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/)

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Canonical SMILES CCCCCCCCCCCCCCCCCCCCCCCCCC(=O)NC(C(CCCCCCCCCCCCCCC)O)COC1OC(COC(=C)CCc2ccccc2)C(C(C1O)O)O
Isomeric SMILES CCCCCCCCCCCCCCCCCCCCCCCCCC(=O)N[C@H]([C@@H](CCCCCCCCCCCCCCC)O)CO[C@H]1O[C@H](COC(=C)CCc2ccccc2)[C@@H]([C@@H]([C@H]1O)O)O
InChI InChI=1S/C60H109NO8/c1-4-6-8-10-12-14-16-18-19-20-21-22-23-24-25-26-27-29-31-33-35-37-42-46-56(63)61-53(54(62)45-41-36-34-32-30-28-17-15-13-11-9-7-5-2)49-68-60-59(66)58(65)57(64)55(69-60)50-67-51(3)47-48-52-43-39-38-40-44-52/h38-40,43-44,53-55,57-60,62,64-66H,3-37,41-42,45-50H2,1-2H3,(H,61,63)/t53-,54+,55+,57-,58-,59+,60-/m0/s1
InChI Key AACQUTZHAXVZEB-MMSUBXCOSA-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/)
Bioactivity Comments
No affinity value for the binding of AH10-7 to CD1d is provided in [1]. Mouse CD1d pre-loaded with AH10-7 binds to a ternary T cell receptor complex with an affinity (Kd) in the 100-110 nM range [1].
Selectivity at other protein targets
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
CD1d molecule Hs None Binding - - - 1
⤷ [1]