UNC8969   Click here for help

GtoPdb Ligand ID: 13302

Synonyms: compound 43 [PMID: 38556760] | UNC-8969
Compound class: Synthetic organic
Comment: UNC8969 is reported as a macrocyclic dual MERTK and AXL receptor tyrosine kinases (RTK) inhibitor [1]. It was designed to induce tumour cell killing in malignancies such as non-small cell lung cancer (NSCLC).
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 10
Hydrogen bond donors 4
Rotatable bonds 10
Topological polar surface area 119.45
Molecular weight 535.68
XLogP 2.15
No. Lipinski's rules broken 1

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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Canonical SMILES CCN(CC)CCNC(=O)[C@H]1CC[C@@H](CC1)NC(=O)C2=C3NC4=CC=C(C)C(=C4)OC/C=C\CNC(=N3)N=C2
Isomeric SMILES O=C(N[C@@H]1CC[C@@H](C(NCCN(CC)CC)=O)CC1)C2=C3NC4=CC=C(C)C(OC/C=C\CNC(=N3)N=C2)=C4
InChI InChI=1S/C29H41N7O3/c1-4-36(5-2)16-15-30-27(37)21-9-12-22(13-10-21)34-28(38)24-19-32-29-31-14-6-7-17-39-25-18-23(11-8-20(25)3)33-26(24)35-29/h6-8,11,18-19,21-22H,4-5,9-10,12-17H2,1-3H3,(H,30,37)(H,34,38)(H2,31,32,33,35)/b7-6-/t21-,22-
InChI Key UEMPFKOYBHCUIG-QVIWBNHYSA-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
Exhibits ~10-fold selectivity for MERTK and AXL compared to the other TAM family (Type XI) RTK TYRO3 and the Type III RTK FLT3 in vitro [1].
Selectivity at catalytic receptors
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
MER proto-oncogene, tyrosine kinase Hs Inhibitor Inhibition 9.0 pIC50 - 1
pIC50 9.0 (IC50 1.1x10-9 M) [1]
AXL receptor tyrosine kinase Hs Inhibitor Inhibition 8.3 pIC50 - 1
pIC50 8.3 (IC50 5.3x10-9 M) [1]
TYRO3 protein tyrosine kinase Hs Inhibitor Inhibition 7.2 pIC50 - 1
pIC50 7.2 (IC50 6.6x10-8 M) [1]
fms related receptor tyrosine kinase 3 Hs Inhibitor Inhibition 7.2 pIC50 - 1
pIC50 7.2 (IC50 7x10-8 M) [1]