AH10-7   

GtoPdb Ligand ID: 9899

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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Physico-chemical Properties
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
SMILES / InChI / InChIKey
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
Classification
Compound class Synthetic organic
IUPAC Name
N-[(2S,3R)-3-hydroxy-1-{[(2S,3R,4S,5R,6R)-3,4,5-trihydroxy-6-{[(4-phenylbut-1-en-2-yl)oxy]methyl}oxan-2-yl]oxy}octadecan-2-yl]hexacosanamide
Database Links
GtoPdb PubChem SID 363894193
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