BML-277 (Chk2 Inhibitor II)

Catalog No.S8632 Batch:S863201

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Technical Data

Formula

C20H14ClN3O2
Molecular Weight 363.80 CAS No. 516480-79-8
Solubility (25°C)* In vitro DMSO 72 mg/mL (197.91 mM)
Ethanol 21 mg/mL (57.72 mM)
Water Insoluble
In vivo (Add solvents to the product individually and in order)
Clear solution
5%DMSO 40%PEG300 5%Tween80 50%ddH2O
3.6mg/ml Taking the 1 mL working solution as an example, add 50 μL of 72 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 
Clear solution
5% DMSO 95% Corn oil
3.6mg/ml Taking the 1 mL working solution as an example, add 50 μL of 72 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results. 
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description BML-277 (Chk2 Inhibitor II) is an ATP-competitive inhibitor of Chk2 with IC50 of 15 nM. It is 1000-fold more selective toward Chk2 serine/threonine kinase than for Chk1 and Cdk1/B kinases. Chk2 Inhibitor II (BML-277) dose dependently protects human CD4(+) and CD8(+) T-cells from apoptosis due to ionizing radiation.
Targets
Chk2 [1]
(Cell-free assay)
15 nM
In vitro The CHK2 Inhibitor II shows 1,000-fold greater selectivity for the CHK2 serine/threonine kinase than for the Cdk1/B and CK1 kinases and was first discovered to be a potent, selective small molecule showing radioprotection towards human T cells. Different doses of CHK2 inhibitor II specifically inhibit CHK2 phosphorylation at Thr68 at different time course, but not CHK1 phosphorylation. Treatment with combination of CHK2 inhibitor II and ERK inhibitor results in substantially more apoptosis compared with treatment of either drug alone[2].
In vivo SUDHL6 DLBCL xenografts mice treated every other day intraperitoneally with either vehicle, ERK inhibitor (5 mg kg−1), CHK2 inhibitor II (1 mg kg−1), or both ERK inhibitor and CHK2 inhibitor II for 20 days show no lethal toxicity, significant weight loss or any gross abnormalities. Both 5 mg/kg ERK inhibitor and 1 mg/kg CHK2 inhibitor II modestly inhibit tumour growth but combined treatment with ERK inhibitor and CHK2 inhibitor II results in a statistically significant suppression of tumour growth[2].

Protocol (from reference)

Cell Assay:

[2]
  • Cell lines

    human DLBCLs cells

  • Concentrations

    5 μM

  • Incubation Time

    48 h

  • Method

    Single-cell suspensions are obtained from lymph node biopsies of patients diagnosed with DLBCL and are treated with DMSO, ERK inhibitor and CHK2 inhibitor II alone or in combination for 48 h after which the percentage of apoptotic cells is determined by Annexin V analysis.
Animal Study:

[2]
  • Animal Models

    SUDHL6 DLBCL xenografts (SCID mice)

  • Dosages

    1 mg/kg

  • Administration

    i.p.

Selleck's BML-277 (Chk2 Inhibitor II) has been cited by 13 publications

Mild replication stress causes premature centriole disengagement via a sub-critical Plk1 activity under the control of ATR-Chk1 [ Nat Commun, 2023, 14(1):6088] PubMed: 37773176
Suppression of TREX1 deficiency-induced cellular senescence and interferonopathies by inhibition of DNA damage response [ iScience, 2023, 26(7):107090] PubMed: 37416470
Cannabidiol Enhances Cabozantinib-Induced Apoptotic Cell Death via Phosphorylation of p53 Regulated by ER Stress in Hepatocellular Carcinoma [ Cancers (Basel), 2023, 15(15)3987] PubMed: 37568803
Precision Combination Therapies Based on Recurrent Oncogenic Coalterations [ Cancer Discov, 2022, 12(6):1542-1559] PubMed: 35412613
ATM Regulates Differentiation of Myofibroblastic Cancer-Associated Fibroblasts and Can Be Targeted to Overcome Immunotherapy Resistance [ Cancer Res, 2022, 82(24):4571-4585.] PubMed: 36353752
Wwox Binding to the Murine Brca1-BRCT Domain Regulates Timing of Brip1 and CtIP Phospho-Protein Interactions with This Domain at DNA Double-Strand Breaks, and Repair Pathway Choice [ Int J Mol Sci, 2022, 23(7)3729] PubMed: 35409089
Chronically Radiation-Exposed Survivor Glioblastoma Cells Display Poor Response to Chk1 Inhibition under Hypoxia [ Int J Mol Sci, 2022, 23(13)7051] PubMed: 35806055
CHK2 Inhibition Provides a Strategy to Suppress Hematologic Toxicity from PARP Inhibitors [ Mol Cancer Res, 2021, 10.1158/1541-7786.MCR-20-0791] PubMed: 33863812
Interaction of Wwox with Brca1 and associated complex proteins prevents premature resection at double-strand breaks and aberrant homologous recombination [ DNA Repair (Amst), 2021, 110:103264] PubMed: 34998176
Pharmacologically targetable vulnerability in prostate cancer carrying RB1-SUCLA2 deletion [ Oncogene, 2020, 10.1038/s41388-020-1381-6] PubMed: 32694611

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.