TL13-112   Click here for help

GtoPdb Ligand ID: 10529

Compound class: Synthetic organic
Comment: TL13-112 is a PROTAC (proteolysis targeting chimera) [1]. It is a hybrid molecule that simultaneously inhibits ALK kinase activity and recruits E3 ligase CRL4CRBN to target ALK for destruction via E3 ligase-mediated ubiquitination and proteasomal degradation. The ALK targeting function is based on the ALK inhibitor NVP-TAE684, and the cereblon ligand component is derived from pomalidomide.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 18
Hydrogen bond donors 5
Rotatable bonds 23
Topological polar surface area 247.97
Molecular weight 1001.39
XLogP 5.27
No. Lipinski's rules broken 3
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Canonical SMILES O=C(CNc1cccc2c1C(=O)N(C2=O)C1CCC(=O)NC1=O)NCCOCCOCCN1CCC(CC1)c1cc(OC(C)C)c(cc1C)Nc1ncc(c(n1)Nc1ccccc1S(=O)(=O)C(C)C)Cl
Isomeric SMILES O=C(CNc1cccc2c1C(=O)N(C2=O)C1CCC(=O)NC1=O)NCCOCCOCCN1CCC(CC1)c1cc(OC(C)C)c(cc1C)Nc1ncc(c(n1)Nc1ccccc1S(=O)(=O)C(C)C)Cl
InChI InChI=1S/C49H60ClN9O10S/c1-29(2)69-40-26-34(31(5)25-38(40)55-49-53-27-35(50)45(57-49)54-36-10-6-7-12-41(36)70(65,66)30(3)4)32-15-18-58(19-16-32)20-22-68-24-23-67-21-17-51-43(61)28-52-37-11-8-9-33-44(37)48(64)59(47(33)63)39-13-14-42(60)56-46(39)62/h6-12,25-27,29-30,32,39,52H,13-24,28H2,1-5H3,(H,51,61)(H,56,60,62)(H2,53,54,55,57)
1. Powell CE, Gao Y, Tan L, Donovan KA, Nowak RP, Loehr A, Bahcall M, Fischer ES, Jänne PA, George RE et al.. (2018)
Chemically Induced Degradation of Anaplastic Lymphoma Kinase (ALK).
J Med Chem, 61 (9): 4249-4255. [PMID:29660984]