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].
Click here for help
2D Structure
Click here for help
Click here for structure editor
Physico-chemical Properties
Click here for help
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
Click here for help
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+
Classification Click here for help
Compound class Synthetic organic
IUPAC Name Click here for help
Synonyms Click here for help
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