THZ1 2HCl - Moligand™, 10mM in DMSO , Inhibitor of cyclin dependent kinase 7, CAS No.1604810-83-4(freebase), Inhibitor of cyclin dependent kinase 7

CAS: 1604810-83-4(freebase) Cat. No.: T408846 Molecular Weight: 638.97

GRADE & PURITY Moligand™, 10mM in DMSO

Synonyms

N-​[3-​[[5-​chloro-​4-​(1H-​indol-​3-​yl)​-​2-​pyrimidinyl]​amino]​phenyl]​-​4-​[[(2E)​-​4-​(dimethylamino)​-​1-​oxo-​2-​buten-​1-​yl]​amino]​-Benzamide dihydrochloride

Storage

Store at -80°C

Shipped In

Dry ice packs + Cold packs

Overview

Information

THZ1 is a covalentCDK7inhibitor which has the unprecedented ability to target a remote cysteine residue located outside of the canonical kinase domain, providing an unanticipated means of achieving selectivity for CDK7.
In vitro

THZ1 uses a unique mechanism, combining ATP-site and allosteric covalent binding, as a means of attaining potency and selectivity for CDK7. THZ1 irreversibly inhibits RNAPII CTD phosphorylation by covalently targeting a unique cysteine located outside the kinase domain of CDK7. THZ1, but not THZ1-R, completely inhibits the phosphorylation of the established intracellular CDK7 substrate RNAPII CTD at Ser\u20095 and Ser\u20097, with concurrent loss of Ser\u20092 phosphorylation at 250\u2009nM in Jurkat cells. THZ1 exhibits strong antiproliferative effects across a broad range of cancer cell lines from various cancer types. In Jurkat cells, low-dose THZ1 has a profound effect on a small subset of genes, including the key regulator RUNX1, thus contributing to subsequent loss of the greater gene expression program and cell death. THZ1 causes defects in Pol II(polymerase II) phosphorylation, co-transcriptional capping, promoter proximal pausing, and productive elongation.

In vivo

THZ1 reduces the proliferation of KOPTK1 T-ALL cells in a human xenograft mouse model. THZ1 is well tolerated at 10 mg/kg with no observable body weight loss or behavioural changes, suggesting that it causes no overt toxicity in the animals.
Cell Data

cell lines：

Concentrations：0-10 μM

Incubation Time：4 h

Powder Purity:≥97%

Specifications

Synonyms

N-​[3-​[[5-​chloro-​4-​(1H-​indol-​3-​yl)​-​2-​pyrimidinyl]​amino]​phenyl]​-​4-​[[(2E)​-​4-​(dimethylamino)​-​1-​oxo-​2-​buten-​1-​yl]​amino]​-Benzamide dihydrochloride

Specifications & Purity

Moligand™, 10mM in DMSO

Biochemical and Physiological Mechanisms

THZ1 is a covalent CDK7 inhibitor which has the unprecedented ability to target a remote cysteine residue located outside of the canonical kinase domain, providing an unanticipated means of achieving selectivity for CDK7.

Storage

Store at -80°C

Shipped In

Dry ice packs + Cold packs

This product requires cold chain shipping. Ground and other economy services are not available.

Grade

Moligand™

Action Type

INHIBITOR

Mechanism of action

Inhibitor of cyclin dependent kinase 7

Names and Identifiers

• Molecular Weight: 638.97

Associated Targets(Human)

CDK7 Tchem Cyclin-dependent kinase 7 (1 Activities)

Discover Target: CDK7

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

Chemical and Physical Properties

• Solubility: Solubility (25°C) In vitro DMSO: 63 mg/mL warmed with 50ºC Water: bath (199.74 mM); Water: Insoluble; Ethanol: Insoluble