BML-277 | Chk2 Inhibitor II | CAS#516480-79-8 | Chk2 Inhibitor

MedKoo Cat#: 407150 | Name: BML-277

Description:

WARNING: This product is for research use only, not for human or veterinary use.

BML-277, also known as Chk2 Inhibitor II, is a Chk2 (checkpoint kinase 2) inhibitor. BML-277 protects T cells from apoptosis by controlling the response of p53 to radiation-induced DNA breaks. ML-277 has IC50 = 15 nM; Ki = 37 nM. ML-277 shows 1000-fold greater selectivity for the Chk2 serine/threonine kinase than for the Cdk1/B and CK1 kinases (for which IC50 = 12 μM and 17 μM, respectively).

Chemical Structure

BML-277

CAS#516480-79-8

Theoretical Analysis

MedKoo Cat#: 407150

Name: BML-277

CAS#: 516480-79-8

Chemical Formula: C20H14ClN3O2

Exact Mass: 363.0775

Molecular Weight: 363.80

Elemental Analysis: C, 66.03; H, 3.88; Cl, 9.74; N, 11.55; O, 8.80

Price and Availability

Size	Price	Availability
10mg	USD 110.00	Ready to ship
25mg	USD 220.00	Ready to ship
50mg	USD 385.00	Ready to ship
100mg	USD 685.00	Ready to ship
200mg	USD 1,250.00	Ready to ship
500mg	USD 2,650.00	Ready to ship
1g	USD 3,750.00	Ready to ship

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Related CAS #

516480-79-8 516480-80-1 (acid)

Synonym

BML-277; BML 277; BML277; Chk2 Inhibitor II.

IUPAC/Chemical Name

2-(4-(4-Chlorophenoxy)phenyl)-1H-benzimidazole-5-carboxamide

InChi Key

UXGJAOIJSROTTN-UHFFFAOYSA-N

InChi Code

InChI=1S/C20H14ClN3O2/c21-14-4-8-16(9-5-14)26-15-6-1-12(2-7-15)20-23-17-10-3-13(19(22)25)11-18(17)24-20/h1-11H,(H2,22,25)(H,23,24)

SMILES Code

O=C(C1=CC=C2C(N=C(C3=CC=C(OC4=CC=C(Cl)C=C4)C=C3)N2)=C1)N

Appearance

White to off-white solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO, not in water

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#CRB60927

QC Data

View QC data: current batch, Lot#CRB60927

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Chk2 Inhibitor II (BML-277) is an ATP-competitive inhibitor of Chk2 with IC50 of 15 nM.

In vitro activity:

BML-277 is an ATP-competitive inhibitor of Chk2 that dose dependently protects human CD4+ and CD8+ T-cells from apoptosis due to ionizing radiation. BML-277 efficiently rescues both T-cell populations from radiation-induced apoptosis in a dose-dependent manner with an observed EC50 of 3−7.6 μM. The concentration of BML-277 required for radioprotection is consistent with the biochemical measurement of chk2 inhibition. Providing the Km of ATP for Chk2 is determined to be 99 μM and the Ki for BML-277 is 37 nM, and assuming that the intracellular ATP concentration is 10 mM, a 5 μM concentration of BML-277 would be expected to produce 42% inhibition of intracellular chk2. Reference: J Med Chem. 2005 Mar 24;48(6):1873-85. https://doi.org/10.1021/jm0495935

In vivo activity:

CHK2 inhibition was examined to determine if it cooperated with ERK inhibition in the treatment of DLBCL tumours in vivo. SUDHL6 DLBCL xenografts in 28 severe combined immunodeficient (SCID) mice (7 mice per group) were estabilished. Once the tumour reached the size of 60–163 mm3, the mice were treated every other day intraperitoneally with either vehicle, ERK inhibitor (5 mg kg−1), CHK2 inhibitor II (BML-277) (1 mg kg−1), or both ERK inhibitor and CHK2 inhibitor II for 20 days. At these doses, no lethal toxicity, significant weight loss or any gross abnormalities were observed among treated animals (data not shown). No evidence of tissue damage was detected by microscopic examination of mouse organs (Supplementary Fig. S3). Both 5 mg kg−1 ERK inhibitor and 1 mg kg−1 CHK2 inhibitor II modestly inhibited tumour growth but combined treatment with ERK inhibitor and CHK2 inhibitor II resulted in a statistically significant suppression of tumour growth (Fig. 6a,b). Moreover, western blot analysis revealed that combined treatment with the ERK inhibitor and CHK2 inhibitors caused a striking increase in H2AX phosphorylation and PARP cleavage (Fig. 6c). This further confirmed that co-administration of the CHK2 inhibitor markedly potentiates DNA damage in DLBCL cells exposed to ERK inhibitor and this event precedes induction of extensive apoptosis. Immunohistochemical analysis of tumour sections showed that co-administration of the ERK and CHK2 inhibitors markedly reduced expression of the cell proliferation marker Ki67 whereas each inhibitor alone had slight impact (Fig. 6d). In addition, TdT-mediated dUTP nick end labelling (TUNEL) assay showed that the combined treatment with ERK inhibitor and CHK2 inhibitor II resulted in greater induction of apoptosis compared with either inhibitor alone (Fig. 6d). Reference: Nat Commun. 2011 Jul 19;2:402. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21772273/

	Solvent	mg/mL	mM
Solubility
	DMSO	72.0	197.91
	Ethanol	21.0	57.72

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 363.80 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

In vitro protocol:

1. Arienti KL, Brunmark A, Axe FU, McClure K, Lee A, Blevitt J, Neff DK, Huang L, Crawford S, Pandit CR, Karlsson L, Breitenbucher JG. Checkpoint kinase inhibitors: SAR and radioprotective properties of a series of 2-arylbenzimidazoles. J Med Chem. 2005 Mar 24;48(6):1873-85. doi: 10.1021/jm0495935. PMID: 15771432.

In vivo protocol:

1. Dai B, Zhao XF, Mazan-Mamczarz K, Hagner P, Corl S, Bahassi el M, Lu S, Stambrook PJ, Shapiro P, Gartenhaus RB. Functional and molecular interactions between ERK and CHK2 in diffuse large B-cell lymphoma. Nat Commun. 2011 Jul 19;2:402. doi: 10.1038/ncomms1404. PMID: 21772273; PMCID: PMC3144586.