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Chemical Structure| 2095433-94-4 Chemical Structure| 2095433-94-4

Structure of (E/Z)-THZ1 2HCl
CAS No.: 2095433-94-4

Chemical Structure| 2095433-94-4

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THZ1 2HCl is a Cdk7 inhibitor (IC50s = 3.2-15.6 nM in vitro) that selectively targets a remote cysteine residue located outside of the classic kinase domain. THZ1 2HCl also targets Cdk12 kinase activity although at a higher concentration (IC50 = 250 nM).

Synonyms: THZ1 Dihydrochloride; THZ1 2HCl

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Product Details of (E/Z)-THZ1 2HCl

CAS No. :2095433-94-4
Formula : C31H30Cl3N7O2
M.W : 638.97
SMILES Code : O=C(NC1=CC=CC(NC2=NC=C(Cl)C(C3=CNC4=C3C=CC=C4)=N2)=C1)C5=CC=C(NC(/C=C/CN(C)C)=O)C=C5.[H]Cl.[H]Cl
Synonyms :
THZ1 Dihydrochloride; THZ1 2HCl
MDL No. :N/A
InChI Key :AJTGQOACYBCREM-QVLKBJGCSA-N
Pubchem ID :129896819

Safety of (E/Z)-THZ1 2HCl

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Related Pathways of (E/Z)-THZ1 2HCl

Hedgehog

Isoform Comparison

Biological Activity

Target
  • CDK7

    CDK7, IC50:3.2 nM

In Vitro:

Cell Line
Concentration Treated Time Description References
NSCLC cells 50 nM 48 h THZ1 promotes apoptosis and suppresses NSCLC growth PMC7370470
Kasumi-1 cells 400 nM 1 h THZ1 treatment affects RNA polymerase dynamics and induces rapid apoptosis. PMC6486546
NPC cells 200 nM 6 h To assess the dose response and anti-cancer effects of THZ1, showing significant inhibition of cell growth and induction of apoptosis. PMC6637769
PancVH1 cells 500 nM 24 hours induces caspase-8 dependent apoptosis PMC9481717
HPNE cells 500 nM 24 hours no significant apoptosis observed PMC9481717
H4 cells 150 nM 72 hours To evaluate the effect of THZ1 on the viability of H4 cells, results showed that THZ1 significantly inhibited the viability of H4 cells. PMC10768977
U87 cells 38.29 nM 72 hours To evaluate the effect of THZ1 on the viability of U87 cells, results showed that THZ1 significantly inhibited the viability of U87 cells. PMC10768977
U251 cells 38.29 nM 72 hours To evaluate the effect of THZ1 on the viability of U251 cells, results showed that THZ1 significantly inhibited the viability of U251 cells. PMC10768977
HeLa cells 0.03 - 0.3 μM 30 minutes To investigate the effects of THZ1 on Pol II phosphorylation, co-transcriptional capping, promoter proximal pausing, and productive elongation. THZ1 does not affect initiation but blocks essentially all Pol II large subunit C-terminal domain (CTD) phosphorylation. PMC4546572
U266 cells 50-400 nM 24 hours THZ1 significantly reduced phosphorylation of RNA Pol II, indicating inhibition of transcription PMC6801078

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Mice Lewis lung carcinoma model Intraperitoneal injection 10 mg/kg twice daily enhanced anti-PD-1 therapy efficacy PMC7370470
Mice Xenograft model Intraperitoneal injection 10 mg/kg twice daily for 4 weeks To evaluate tumor growth inhibition and assess the tumor-suppressive function of THZ1. PMC6637769
Mice U251-luc orthotopic xenograft model IntratumOral injection 10 mg/kg Continuous infusion for 4 weeks To evaluate the effect of SNS032 on the growth of orthotopic U251-luc tumors, results showed that SNS032 significantly inhibited tumor growth and extended the survival of mice. PMC10768977
NOD/SCID-γ mice systemic U266 xenograft model Intraperitoneal injection 10 mg/kg once daily, 5 days/week for 4 weeks THZ1 significantly reduced tumor burden and prolonged survival with minimal toxicity PMC6801078

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

1.56mL

0.31mL

0.16mL

7.83mL

1.56mL

0.78mL

15.65mL

3.13mL

1.56mL

References

 

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