supratinib   Click here for help

GtoPdb Ligand ID: 10015

Compound class: Synthetic organic
Comment: Supratinib is an amphiphilic molecular analogue of the MEK inhibitor selumetinib [2]. Structurally it is selumetinib linked to a cholesterol-based tether that ficilitates its assembly into a stable supramolecular lipid bilayer nanoparticle. Supratinib was designed to form lipid nanoparticles which would deliver improved MEK-driven anti-cancer activity compared to the parent molecule. It is predicted that such a supramolecular therapeutic could be designed to include immune check point T cell activating biologics (e.g. anti-PD-1 or anti-PD-L1 monoclonal antibodies) which could ultimately be used to enhance cancer immunotherapy.
This same strategy of derivatizing a kinase inhibitor with a cholesterol anchor (in this case creating an analogue of the CSF1R inhibitor sotuletinib) and assembling it in a supramolecular structure with a macrophage-targeting anti-SIRPα mAb (which blocks the SIRPα/CD47 anti-phagocytic signal that is exploited by some cancer cells to avoid immune destruction) has been reported to enhance phagocytosis and removal of melanoma cancer cells by tumour associated macrophages in vitro and in vivo [1].
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 7
Hydrogen bond donors 2
Rotatable bonds 19
Topological polar surface area 120.78
Molecular weight 924.36
XLogP 15.14
No. Lipinski's rules broken 2
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 CC(CCCC(C1CCC2C1(C)CCC1C2CC=C2C1(C)CCC(C2)OC(=O)CCC(=O)OCCONC(=O)c1cc2n(C)cnc2c(c1Nc1ccc(cc1Cl)Br)F)C)C
Isomeric SMILES CC(CCC[C@@H]([C@H]1CC[C@H]2[C@]1(C)CC[C@@H]1[C@H]2CC=C2[C@]1(C)CCC(C2)OC(=O)CCC(=O)OCCONC(=O)c1cc2n(C)cnc2c(c1Nc1ccc(cc1Cl)Br)F)C)C
InChI InChI=1S/C48H63BrClFN4O6/c1-28(2)8-7-9-29(3)35-13-14-36-33-12-10-30-24-32(18-20-47(30,4)37(33)19-21-48(35,36)5)61-42(57)17-16-41(56)59-22-23-60-54-46(58)34-26-40-45(52-27-55(40)6)43(51)44(34)53-39-15-11-31(49)25-38(39)50/h10-11,15,25-29,32-33,35-37,53H,7-9,12-14,16-24H2,1-6H3,(H,54,58)/t29-,32?,33-,35+,36+,37+,47-,48+/m0/s1
InChI Key QUBHCPBWMPEXQW-NPAZBBTKSA-N
Classification Click here for help
Compound class Synthetic organic
Database Links Click here for help
GtoPdb PubChem SID 375973205
PubChem CID 134813900
Search Google for chemical match using the InChIKey QUBHCPBWMPEXQW-NPAZBBTKSA-N
Search Google for chemicals with the same backbone QUBHCPBWMPEXQW
UniChem Compound Search for chemical match using the InChIKey QUBHCPBWMPEXQW-NPAZBBTKSA-N
UniChem Connectivity Search for chemical match using the InChIKey QUBHCPBWMPEXQW-NPAZBBTKSA-N