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TNNI3K degrader   Click here for help

GtoPdb Ligand ID: 11807

Synonyms: compound 21 [WO2021053495A1]
Compound class: Synthetic organic
Comment: This compound is a bifunctional degrader of the cardiac-specific kinase TNNI3K protein, that is claimed in patent WO2021053495A1 [1]. It's kinase binding domain is derived from the quinazoline TNNI3K inhibitor GSK114 [2], and it contains a cereblon binding ligand to promote association with the protein-degrading E3 ubiquitin ligase complex.
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 16
Hydrogen bond donors 3
Rotatable bonds 15
Topological polar surface area 184.27
Molecular weight 851.39
XLogP 2.12
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 CNS(=O)(=O)c1ccc(c(c1)Nc1ncnc2c1ccc(c2)OCCCN1CCN(CC1)C(=O)N1CCN(CC1)CCC#Cc1ccc(cc1)N1CCC(=O)NC1=O)N(C)C
Isomeric SMILES CNS(=O)(=O)c1cc(Nc2ncnc3cc(OCCCN4CCN(CC4)C(=O)N4CCN(CCC#Cc5ccc(cc5)N5CCC(=O)NC5=O)CC4)ccc23)c(cc1)N(C)C
InChI InChI=1S/C43H53N11O6S/c1-44-61(58,59)35-13-15-39(49(2)3)38(30-35)47-41-36-14-12-34(29-37(36)45-31-46-41)60-28-6-18-51-22-26-53(27-23-51)43(57)52-24-20-50(21-25-52)17-5-4-7-32-8-10-33(11-9-32)54-19-16-40(55)48-42(54)56/h8-15,29-31,44H,5-6,16-28H2,1-3H3,(H,45,46,47)(H,48,55,56)
InChI Key OGZQGEDLXOIYFN-UHFFFAOYSA-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/)
References
1. Arista L, Broennimann V, D'Alessandro PL, Doumampoum-Metoul L, Goude M-L, Hebach C, Hollingworth GJ, Jeulin IKJ, Kirman LC, Lorber J et al.. (2021)
Bifunctional degraders and their methods of use.
Patent number: WO2021053495A1. Assignee: Novartis Ag. Priority date: 16/09/2019. Publication date: 25/03/2021.
2. Lawhorn BG, Philp J, Graves AP, Shewchuk L, Holt DA, Gatto Jr GJ, Kallander LS. (2016)
GSK114: A selective inhibitor for elucidating the biological role of TNNI3K.
Bioorg Med Chem Lett, 26 (14): 3355-3358. [PMID:27246618]