THZ1   

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].
2D Structure
Click here for structure editor
Physico-chemical Properties
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
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
Compound class Synthetic organic
IUPAC Name
N-[3-[[5-chloro-4-(1H-indol-3-yl)pyrimidin-2-yl]amino]phenyl]-4-[[(E)-4-(dimethylamino)but-2-enoyl]amino]benzamide
Synonyms
HY-80013
Database Links
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
Search UniChem for chemical match using the InChIKey OBJNFLYHUXWUPF-IZZDOVSWSA-N
Search UniChem for chemicals with the same backbone OBJNFLYHUXWUPF