compound 10 [PMID: 34704759]   Click here for help

GtoPdb Ligand ID: 11802

Compound class: Synthetic organic
Comment: Compound 10 is a long-acting prodrug of the TGFβR inhibitor BMS-986260 [1]. It contains a matriptase peptide substrate domain, that is cleaved by the protease selectively in the tumour microenvironment. Compound 10 is sufficiently soluble to allow parenteral administration.
We generated the chemical structure shown here from the SMILES provided in the disclosure [1].
This prodrug approach is proposed to limit exposure of non-tumour tissue to the active parent molecule.
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 CDK toolkit. 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 38
Hydrogen bond donors 15
Rotatable bonds 79
Topological polar surface area 576.33
Molecular weight 1789.85
XLogP 3.63
No. Lipinski's rules broken 3
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.

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Canonical SMILES NCCCC[C@@H](C(=O)Nc1ccc(cc1)COC(=O)NCOCCn1cnc(c1c1ccc2n(n1)c(C#N)cn2)c1ccc(c(c1)Cl)F)NC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](NC(=O)COCCOCCNC(=O)COCCOCCNC(=O)CC[C@@H](C(=O)O)NC(=O)CC[C@@H](C(=O)O)NC(=O)CCCCCCCCCCCCCCCCC(=O)O)CC(C)C)CO
Isomeric SMILES Fc1ccc(cc1Cl)c1c(n(CCOCNC(=O)OCc2ccc(NC(=O)[C@@H](NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)COCCOCCNC(=O)COCCOCCNC(=O)CC[C@H](NC(=O)CC[C@H](NC(=O)CCCCCCCCCCCCCCCCC(=O)O)C(=O)O)C(=O)O)CO)CCCCN)cc2)cn1)c1ccc2n(n1)c(cn2)C#N
InChI InChI=1S/C84H121ClFN17O23/c1-56(2)45-67(99-75(110)53-124-44-42-122-39-36-90-74(109)52-123-43-41-121-38-35-89-70(105)32-29-65(82(116)117)98-72(107)33-30-66(83(118)119)97-71(106)20-15-13-11-9-7-5-3-4-6-8-10-12-14-16-21-76(111)112)81(115)100-68(50-104)79(113)92-49-73(108)96-64(19-17-18-34-87)80(114)95-59-25-22-57(23-26-59)51-126-84(120)94-55-125-40-37-102-54-93-77(58-24-27-62(86)61(85)46-58)78(102)63-28-31-69-91-48-60(47-88)103(69)101-63/h22-28,31,46,48,54,56,64-68,104H,3-21,29-30,32-45,49-53,55,87H2,1-2H3,(H,89,105)(H,90,109)(H,92,113)(H,94,120)(H,95,114)(H,96,108)(H,97,106)(H,98,107)(H,99,110)(H,100,115)(H,111,112)(H,116,117)(H,118,119)/t64-,65-,66-,67-,68-/m0/s1
InChI Key RRGOOOPOTXFKKZ-UNVBUFFDSA-N
References
1. Zhang Y, Parrish KE, Tortolani DR, Poss MA, Huang A, Wan H, Purandare AV, Donnell AF, Kempson J, Hou X et al.. (2021)
Long-Acting Tumor-Activated Prodrug of a TGFβR Inhibitor.
J Med Chem, 64 (21): 15787-15798. [PMID:34704759]