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532372 Cdk7 Inhibitor VIII, THZ1 - Calbiochem

Cdk7 Inhibitor; THZ1

Cdk7 Inhibitor VIII, THZ1 - Calbiochem MSDS (material safety data sheet) or SDS, CoA and CoQ, dossiers, brochures and other available documents.

Synonyms: (E)-N-(3-(5-Chloro-4-(1H-indol-3-yl)pyrimidin-2-ylamino)phenyl)-4-(4-(dimethylamino)but-2-enamido)benzamide, 4HCl, THZ1, HCl

Primary Target: Cdk7
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Overview

Replacement Information

Key Specifications Table

Empirical Formula
C₃₁H₂₈ClN₇O₂ •4HCl

Products

Catalog NumberPackaging Qty/Pack
5.32372.0001 Glass bottle 10 mg
Description
OverviewA cell-permeable, non-toxic, phenylaminopyrimidinyl-acrylamide compound that acts as a highly potent, selective, ATP-site directed, and irreversible inhibitor of Cdk7 (IC50 = 3.2 nM). Acts by allosterically and covalently modifying Cys312 located outside the canonical kinase domain. Shown to block the phosphorylation of Ser5 and Ser7 in RNAPII CTD, the intracellular substrate of Cdk7 (< 250 nM, 4 h in Jurkat cells). Does not affect the activity of C312S mutated Cdk7. Exhibits comparatively week activity towards Cdk12 (IC50 = 250 nM), Cdk1, and Cdk2. Suppresses the proliferation and cell viability of T-ALL and CLL cell lines and induces apoptosis with significant reduction in the levels of MCL-1 and XIAP. Also induces a significant reduction in the transcript and protein levels of RUNX1, TAL, and GATA3 (~ 50 nM). Suppresses the growth of KOPTK1 cells xenografts in murine model (10 mg/kg, b.i.d).

Please note that the molecular weight for this compound is batch-specific due to variable water content.
Catalogue Number532372
Brand Family Calbiochem®
Synonyms(E)-N-(3-(5-Chloro-4-(1H-indol-3-yl)pyrimidin-2-ylamino)phenyl)-4-(4-(dimethylamino)but-2-enamido)benzamide, 4HCl, THZ1, HCl
References
ReferencesKwiatkowski, N., et al. 2014. Nature 511, 616.
Chipumuro, E., et al. Cell 159, 1126.
Product Information
FormYellow solid
Hill FormulaC₃₁H₂₈ClN₇O₂ •4HCl
Chemical formulaC₃₁H₂₈ClN₇O₂ •4HCl
Hygroscopic Hygroscopic
ReversibleN
Quality LevelMQ100
Applications
Biological Information
Primary TargetCdk7
Secondary targetCdk12
Purity≥96% by HPLC
Physicochemical Information
Cell permeableY
Dimensions
Materials Information
Toxicological Information
Safety Information according to GHS
Safety Information
Product Usage Statements
Storage and Shipping Information
Ship Code Ambient Temperature Only
Toxicity Standard Handling
Storage -20°C
Protect from Light Protect from light
Hygroscopic Hygroscopic
Do not freeze Ok to freeze
Special InstructionsFollowing reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.
Packaging Information
Packaged under inert gas Packaged under inert gas
Transport Information
Supplemental Information
Specifications
Global Trade Item Number
Catalog Number GTIN
5.32372.0001 04055977260083

Documentation

Cdk7 Inhibitor VIII, THZ1 - Calbiochem SDS

Title

Safety Data Sheet (SDS) 

Cdk7 Inhibitor VIII, THZ1 - Calbiochem Certificates of Analysis

TitleLot Number
532372

References

Reference overview
Kwiatkowski, N., et al. 2014. Nature 511, 616.
Chipumuro, E., et al. Cell 159, 1126.

Brochure

Title
NPI Flyer- Epigenetics and Nuclear Function Feature
New Products - Antibodies, Small Molecule, Inhibitors

Technical Info

Title
White Paper: Further considerations of antibody validation and usage.
Data Sheet

Note that this data sheet is not lot-specific and is representative of the current specifications for this product. Please consult the vial label and the certificate of analysis for information on specific lots. Also note that shipping conditions may differ from storage conditions.

Revision19-December-2014 JSW
Synonyms(E)-N-(3-(5-Chloro-4-(1H-indol-3-yl)pyrimidin-2-ylamino)phenyl)-4-(4-(dimethylamino)but-2-enamido)benzamide, 4HCl, THZ1, HCl
DescriptionA cell-permeable, acrylamide-bearing phenylaminopyrimidine that, despite its ATP-competitive affinities toward multiple kinases (IC50 ≤1 µM against ATP probe binding to 22 kinases in a KiNativ panel screening), only effectively acts as an irreversible inhibitor against Cdk7 & Cdk12, and likely also Ckd13 & Cdk19, due to conformational positioning of a C-terminal Cys outside the kinase domain (C312 of human & murine Cdk7; C1539, C1517, C349 of human Cdk12, Cdk13, Cdk19, respectively) adjacent to the drug′s acrylamide moiety in the ATP cleft, allowing covalent bond formation. Due to the irreversible mode of action, 3 to 5 h incubation is shown to most effectively inhibit intracellular Ckd7 & Cdk12 (Effective conc. 100 to 500 nM in 293A, HeLa S3, Jurkat, and Loucy cultures). Likewise, drug washout following THZ1 incubation is demonstrated not to affect its potency against cellular Cdk7 substrates phosphorylatio(RNAPII S2/5/7, Cdk1 T161, Cdk2 T160, Cdk9 T186) or cell proliferation. A strong enrichment of factors involved in Cdk7 substrate RNAPII/RPB1-driven transcriptional regulation is found among THZ1-sensitive cell lines with T cell acute lymphoblastic leukemia (T-ALL; IC50 in nM = 0.49/KOPTK1, 0.54/Loucy, 0.61/DND-41, 50 nM/Jurkat by cellular ATP measurement post 72 incubation) that depend on RUNX1 transcription for proliferation being particularly sensitive to THZ1-induced apoptotic death. Intravenous injection is efficacious in suppression KOPTK1 proliferation in mice (by 91%;10 mg/3.3 mL/Kg/12 h, BID, for 29 d one week following cancer cells injection) in vivo without affecting animal body weight.
FormYellow solid
Intert gas (Yes/No) Packaged under inert gas
Chemical formulaC₃₁H₂₈ClN₇O₂ •4HCl
Purity≥96% by HPLC
SolubilityDMSO (50 mg/ml). Use only fresh DMSO for reconstitution.
Storage Protect from light
-20°C
Hygroscopic
Do Not Freeze Ok to freeze
Special InstructionsFollowing reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.
Toxicity Standard Handling
ReferencesKwiatkowski, N., et al. 2014. Nature 511, 616.
Chipumuro, E., et al. Cell 159, 1126.