THZ1   Click here for help

GtoPdb Ligand ID: 8052

Synonyms: HY-80013
Compound class: Synthetic organic
Comment: THZ1 is a covalent inhibitor of the cyclin-dependent kinase, CDK7 [1]. The compound achieves CDK7 specificity by targeting a remote cysteine residue located outside of the canonical kinase domain. It was a preclinical lead compound.

CDK7 inhibition by THZ1 has been demonstrated to overcome tumour resistance (primary or acquired) to smoothened inhibitor drugs (such as sonidegib, vismodegib and glasdegib), principally via suppressed synthesis of two core transcription factors belonging to the hedgehog pathway (the glioma-associated oncogenes GLI1 and GLI2) [2]. This effect was detected in vitro and in vivo.
CDK7 inhibition has been shown to overcome resistance to HER2-targeted inhibitors in HER2 +ve breast cancer cells and in xenograft models [3].
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species
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 8
Hydrogen bond donors 4
Rotatable bonds 11
Topological polar surface area 115.04
Molecular weight 565.2
XLogP 4.75
No. Lipinski's rules broken 0
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 CN(CC=CC(=O)Nc1ccc(cc1)C(=O)Nc1cccc(c1)Nc1ncc(c(n1)c1c[nH]c2c1cccc2)Cl)C
Isomeric SMILES CN(C/C=C/C(=O)Nc1ccc(cc1)C(=O)Nc1cccc(c1)Nc1ncc(c(n1)c1c[nH]c2c1cccc2)Cl)C
InChI InChI=1S/C31H28ClN7O2/c1-39(2)16-6-11-28(40)35-21-14-12-20(13-15-21)30(41)36-22-7-5-8-23(17-22)37-31-34-19-26(32)29(38-31)25-18-33-27-10-4-3-9-24(25)27/h3-15,17-19,33H,16H2,1-2H3,(H,35,40)(H,36,41)(H,34,37,38)/b11-6+
InChI Key OBJNFLYHUXWUPF-IZZDOVSWSA-N
Classification Click here for help
Compound class Synthetic organic
IUPAC Name Click here for help
N-[3-[[5-chloro-4-(1H-indol-3-yl)pyrimidin-2-yl]amino]phenyl]-4-[[(E)-4-(dimethylamino)but-2-enoyl]amino]benzamide
Synonyms Click here for help
HY-80013
Database Links Click here for help
CAS Registry No. 1604810-83-4
GtoPdb PubChem SID 249565732
PubChem CID 73602827
Search Google for chemical match using the InChIKey OBJNFLYHUXWUPF-IZZDOVSWSA-N
Search Google for chemicals with the same backbone OBJNFLYHUXWUPF
UniChem Compound Search for chemical match using the InChIKey OBJNFLYHUXWUPF-IZZDOVSWSA-N
UniChem Connectivity Search for chemical match using the InChIKey OBJNFLYHUXWUPF-IZZDOVSWSA-N