[CAS NO. 1604810-83-4] THZ1

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Catalog:	HY-80013
Brand:	MCE
CAS:	1604810-83-4

Overview

MDL	MFCD28167785
Molecular Weight	566.05
Molecular Formula	C31H28ClN7O2
SMILES	ClC1=CN=C(NC2=CC(NC(C3=CC=C(NC(/C=C/CN(C)C)=O)C=C3)=O)=CC=C2)N=C1C4=CNC5=CC=CC=C54

For research use only. We do not sell to patients.

62 Publications Citing Use of MCE

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[2]Cell. 2018 Sep 20;175(1):171-185.e25.
[3]Cell. 2017 Sep 7;170(6):1209-1223.e20.
[4]Science. 2021 Apr 30;372(6541):eaba8490.
[5]Cancer Discov. 2019 Nov;9(11):1538-1555.
[6]Nat Cell Biol. 2020 Oct;22(10):1187-1196.
[7]Mol Cell. 2019 May 16;74(4):674-687.e11.
[8]Hepatology. 2019 Jun;69(6):2502-2517.
[9]Sci Adv. 2020 Jul 17;6(29):eaba1593.
[10]Nat Commun. 2019 Jul 25;10(1):3319.
[11]Nat Commun. 2018 Nov 19;9(1):4866.
[12]Nat Commun. 2018 Aug 23;9(1):3392.
[13]Clin Cancer Res. 2019 Oct 15;25(20):6195-6205.
[14]Autophagy. 2021 Jun;17(6):1426-1447.
[15]Cancer Res. 2021 Jun 1;81(11):3105-3120.
[16]Genes Dev. 2020 Jan 1;34(1-2):53-71.
[17]Proc Natl Acad Sci U S A. 2019 Jun 25;116(26):12986-12995.
[18]EMBO Mol Med. 2022 Mar 7;e14990.
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[21]Oncogene. 2022 Aug 30.
[22]Oncogene. 2019 May;38(20):3932-3945.
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[33]Chinese Medical Journal. 2022.
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[35]Oncogenesis. 2020 May 12;9(5):47.
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[41]Front Oncol. 2021 May 24;11:664848.
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[43]Cells. 2021 May 12;10(5):1182.
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[52]J Mol Neurosci. 2021 Aug 31.
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[61]TUMOR, 2017, 37(11): 1119-1127.
[62]Harvard Medical School LINCS LIBRARY

Summary

THZ1 is a selective and potent covalent CDK7 inhibitor with an IC ₅₀ of 3.2 nM. THZ1 also inhibits the closely related kinases CDK12 and CDK13 and downregulates MYC expression ^[1] ^[2] .

IC50 & Target

CDK7

3.2 nM (IC ₅₀ )

CDK12

CDK13

In Vitro

THZ1 inhibits Jurkat cell and Loucy cell with IC ₅₀ of 50 nM, and 0.55 nM, respectively. THZ1 (9, 27, 83, 250, 750, and 2500 nM) inhibits CDK12 but at higher concentrations compared to CDK7. THZ1 (1 μM) irreversibly inhibits RNAPII CTD and CAK phosphorylation. THZ1 (2.5 µM) irreversibly inhibits RNAPII CTD phosphorylation by covalently targeting a unique cysteine located outside the kinase domain of CDK7 in Hela S3 cells. THZ1 (250 nM) causes decreased cellular proliferation and an increase in apoptotic index with concomitant reduction in anti-apoptotic proteins, most notably MCL-1 and XIAP in T-ALL cell lines ^[1] .
All genotypically-distinct human (hSCLC) cell lines exhibit high sensitivity to THZ1, with an IC ₅₀ in the range of 5-20 nM ^[3] .

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

In Vivo

THZ1 (10 mg/kg) demonstrates potent killing of primary chronic lymphocytic leukemia (CLL) cells and anti-proliferative activity against primary TALL cells and in vivo against a human T-ALL xenograft ^[1] .
THZ1 (10 mg/kg, i.v.) inhibits tumor growth in a mouse model of human MYCN-amplified NB and shows no toxicity ^[4] .
THZ1 (10 mg/kg, i.p.) completely suppresses oesophageal squamous cell carcinoma tumour growth in vivo without loss of body weight or other common toxic effects ^[5] .

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Appearance

Solid

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

Solvent & Solubility

In Vitro:

DMSO : 100 mg/mL ( 176.66 mM ; Need ultrasonic)

Ethanol : < 1 mg/mL (insoluble)

Preparing
Stock Solutions

Concentration Solvent Mass	1 mg	5 mg	10 mg

1 mM	1.7666 mL	8.8331 mL	17.6663 mL
5 mM	0.3533 mL	1.7666 mL	3.5333 mL
10 mM	0.1767 mL	0.8833 mL	1.7666 mL

* Please refer to the solubility information to select the appropriate solvent.

In Vivo:

1.

Add each solvent one by one: 10% DMSO >> 90% saline

Solubility: 5 mg/mL (8.83 mM); Suspended solution; Need ultrasonic
2.

Add each solvent one by one: 10% DMSO >> 40% PEG300 >> 5% Tween-80 >> 45% saline

Solubility: ≥ 2.5 mg/mL (4.42 mM); Clear solution
3.

Add each solvent one by one: 10% DMSO >> 90% corn oil

Solubility: ≥ 2.5 mg/mL (4.42 mM); Clear solution
4.

Add each solvent one by one: 10% DMSO >> 90% (20% SBE-β-CD in saline)

Solubility: 2.08 mg/mL (3.67 mM); Suspended solution; Need ultrasonic

* All of the co-solvents are available by MCE.

References

[1] Kwiatkowski N, et al. Targeting transcription regulation in cancer with a covalent CDK7 inhibitor. Nature. 2014 Jul 31;511(7511):616-20.
[2] Zeng M, et al. Targeting MYC dependency in ovarian cancer through inhibition of CDK7 and CDK12/13. Elife. 2018 Nov 13;7. pii: e39030.
[3] Christensen CL, et al. Targeting transcriptional addictions in small cell lung cancer with a covalent CDK7 inhibitor. Cancer Cell. 2014 Dec 8;26(6):909-22.
[4] Chipumuro, et al. CDK7 inhibition suppresses super-enhancer-linked oncogenic transcription in MYCN-driven cancer. Cell. 2014 Nov 20;159(5):1126-39. ?
[5] Jiang YY, et al. Targeting super-enhancer-associated oncogenes in oesophageal squamous cell carcinoma. Gut. 2016 May 10. pii: gutjnl-2016-311818.

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