TL12-186   Click here for help

GtoPdb Ligand ID: 12147

Synonyms: TL 12-186
Compound class: Synthetic organic
Comment: TL12-186 is a PROTAC class molecule, that targets cyclin-dependent kinase (CDK) family proteins for ubiquitination and proteasomal degradation [1]. TL12-186 binds to the CDKs via the parental multi-kinase inhibitor NVP-TAE684 (TAE-684), and uses a pomalidomide moiety to engage cereblon (CRBN). In engineered cell lines expressing individual CDKs, all 16 kinases were degraded by TL12-186 [2]. Interestingly, cell cycle-associated CDKs 1, 2, 4, and 6 were less susceptible to TL12-186-promoted degradation than the other CDKs. Formation of the ternary complex of TL12-186 with CRBN is required for efficient CDK2 degradation.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 19
Hydrogen bond donors 5
Rotatable bonds 21
Topological polar surface area 241.98
Molecular weight 930.32
XLogP 3.72
No. Lipinski's rules broken 2
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Canonical SMILES O=C(CNc1cccc2c1C(=O)N(C2=O)C1CCC(=O)NC1=O)NCCOCCOCCN1CCN(CC1)c1ccc(cc1)Nc1ncc(c(n1)Nc1ccccc1S(=O)(=O)C(C)C)Cl
Isomeric SMILES O=C1C(CCC(=O)N1)N1C(=O)c2c(C1=O)cccc2NCC(=O)NCCOCCOCCN1CCN(CC1)c1ccc(cc1)Nc1nc(Nc2c(cccc2)S(=O)(=O)C(C)C)c(cn1)Cl
InChI InChI=1S/C44H51ClN10O9S/c1-28(2)65(61,62)36-9-4-3-7-33(36)50-40-32(45)26-48-44(52-40)49-29-10-12-30(13-11-29)54-19-17-53(18-20-54)21-23-64-25-24-63-22-16-46-38(57)27-47-34-8-5-6-31-39(34)43(60)55(42(31)59)35-14-15-37(56)51-41(35)58/h3-13,26,28,35,47H,14-25,27H2,1-2H3,(H,46,57)(H,51,56,58)(H2,48,49,50,52)
Classification Click here for help
Compound class Synthetic organic
Ligand families/groups PROTACs, molecular glues and other degraders
IUPAC Name Click here for help
Synonyms Click here for help
TL 12-186
Database Links Click here for help
CAS Registry No. 2250025-88-6 (source: PubChem)
GtoPdb PubChem SID 472319269
PubChem CID 134812843
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