NSC-617145 | CAS# 203115-63-3 | WRN helicase inhibitor

MedKoo Cat#: 574817 | Name: NSC-617145

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Description:

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

NSC-617145 is an inhibitor of WRN helicase that inhibits the ATPase, but not exonuclease, activity of WRN helicase in a concentration-dependent manner. NSC 617145 inhibits growth of HeLa cells via formation of DNA double strand breaks (DSBs) and induction of apoptosis in a WRN helicase-dependent manner. NSC 617145 also acts synergistically with mitomycin C to inhibit growth as well as induce DSBs and chromosomal abnormalities in Fanconia-anemia deficient (FA-D2-/-) cells.

Chemical Structure

NSC-617145

CAS#203115-63-3

Theoretical Analysis

MedKoo Cat#: 574817

Name: NSC-617145

CAS#: 203115-63-3

Chemical Formula: C13H10Cl4N2O4

Exact Mass: 397.9395

Molecular Weight: 400.03

Elemental Analysis: C, 39.03; H, 2.52; Cl, 35.45; N, 7.00; O, 16.00

Price and Availability

Size	Price	Availability
100mg	USD 750.00	2 Weeks
200mg	USD 1,250.00	2 Weeks
500mg	USD 2,650.00	2 Weeks
1g	USD 3,850.00	2 Weeks
2g	USD 6,450.00	2 Weeks

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Related CAS #

No Data

Synonym

NSC-617145; NSC617145; NSC 617145

IUPAC/Chemical Name

1,1'-(2,2-dimethylpropane-1,3-diyl)bis(3,4-dichloro-1H-pyrrole-2,5-dione)

InChi Key

PCOXPBOKDABARQ-UHFFFAOYSA-N

InChi Code

InChI=1S/C13H10Cl4N2O4/c1-13(2,3-18-9(20)5(14)6(15)10(18)21)4-19-11(22)7(16)8(17)12(19)23/h3-4H2,1-2H3

SMILES Code

CC(CN(C(C(Cl)=C1Cl)=O)C1=O)(C)CN2C(C(Cl)=C(Cl)C2=O)=O

Appearance

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

Shelf Life

>3 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#A20O11B20

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

NSC 617145 is a selective werner syndrome helicase (WRN) helicase inhibitor with an IC50 value of 230 nM that inhibits WRN ATPase and induces double-strand breaks (DSB) and chromosomal abnormalities.

In vitro activity:

It was reasoned that NSC 617145 might target cellular WRN for helicase inhibition and induce toxic DNA lesions mediated by WRN’s interaction with genomic DNA, prompting to ask if poisoned WRN became enriched in the chromatin fraction. Western blot analysis of nuclear soluble and chromatin-bound fractions prepared from HeLa cells exposed to NSC 617145 demonstrated a dose-dependent increase in WRN bound to chromatin. It was also observed that the amount of WRN from extract of HeLa cells exposed to NSC 617145 (0.75 μM) for 6 hours was reduced compared to DMSO-treated cells. Inclusion of proteasome inhibitor MG132 restored WRN level to that of DMSO-treated cells. Thus, NSC 617145 causes WRN to become degraded by a proteasome-mediated pathway. Consistent with reduction of WRN protein in NSC 617145 treated cells, helicase activity catalyzed by immunoprecipitated WRN from an equivalent amount of total extract protein from HeLa cells treated with NSC 617145 (0.75 μM, 4 h) was reduced 4-fold compared to helicase activity by immunoprecipitated WRN from DMSO-treated cells. Reference: Cancer Res. 2013 Sep 1;73(17):5497-507. https://pubmed.ncbi.nlm.nih.gov/23867477/

In vivo activity:

TBD

	Solvent	mg/mL	mM
Solubility
	DMSO	12.3	30.84

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 400.03 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:

1. Aggarwal M, Banerjee T, Sommers JA, Iannascoli C, Pichierri P, Shoemaker RH, Brosh RM Jr. Werner syndrome helicase has a critical role in DNA damage responses in the absence of a functional fanconi anemia pathway. Cancer Res. 2013 Sep 1;73(17):5497-507. doi: 10.1158/0008-5472.CAN-12-2975. Epub 2013 Jul 18. PMID: 23867477; PMCID: PMC3766423. 2. Moles R, Bai XT, Chaib-Mezrag H, Nicot C. WRN-targeted therapy using inhibitors NSC 19630 and NSC 617145 induce apoptosis in HTLV-1-transformed adult T-cell leukemia cells. J Hematol Oncol. 2016 Nov 9;9(1):121. doi: 10.1186/s13045-016-0352-4. PMID: 27829440; PMCID: PMC5103433.

In vitro protocol:

In vivo protocol:

TBD

1. Aggarwal, M., Banerjee, T., Sommers, J.A., et al. Werner syndrome helicase has a critical role in DNA damage responses in the absence of a functional fanconi anemia pathway. Cancer Res. 73(17), 5497-5507 (2013).

View History

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