UNC4203   Click here for help

GtoPdb Ligand ID: 10131

Synonyms: MERTK inhibitor 19 [PMID: 30347155] | UNC4203A [US20150291606A1]
Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: The structure and activity of UNC4203 is disclosed in Zhao et al. (2018) [4] and we rendered the structure using the SMILES string provided therein. It is one of the chemical structures claimed in patent US20150291606A1 [3], with therapeutic uses of such compounds claimed in WO2015157125A1 [2].
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 6
Hydrogen bond donors 2
Rotatable bonds 8
Topological polar surface area 69.45
Molecular weight 504.36
XLogP 5.29
No. Lipinski's rules broken 1
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Canonical SMILES CCCC(Nc1ncc2c(n1)n(cc2c1ccc(cc1)CN1CCCN(CC1)C)C1CCC(CC1)O)C
Isomeric SMILES CCC[C@@H](Nc1ncc2c(n1)n(cc2c1ccc(cc1)CN1CCCN(CC1)C)[C@@H]1CC[C@H](CC1)O)C
InChI InChI=1S/C30H44N6O/c1-4-6-22(2)32-30-31-19-27-28(21-36(29(27)33-30)25-11-13-26(37)14-12-25)24-9-7-23(8-10-24)20-35-16-5-15-34(3)17-18-35/h7-10,19,21-22,25-26,37H,4-6,11-18,20H2,1-3H3,(H,31,32,33)/t22-,25-,26-/m0/s1
Immunopharmacology Comments
MERTK is one of the members of the TAM family of tyrosine kinases. It plays important roles in the innate immune system including the regulation of self-tolerance and inhibition of autoimmunity. In the tumour microenvironment TAM kinase activity (e.g. from tumour infiltrating macrophages) can undermine any antitumoral immune response and augment cancer progression. Subsequently, MERTK inhibition has been shown to inhibit tumour growth and metastasis in experimental models [1], and the development of MERTK inhibitors with potential as immuno-oncology therapeutics is underway. UNC4203 is a suitably selective pharmacological tool to examine the potential of MERTK inhibition as an immunomodulatory mechanism and to aid futher elucidation of MERTK's role in cancer immunology.