WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H407299
CAS#: 325970-71-6
Description: L67 is a DNA Ligase Inhibitor. L67 inhibited DNA ligases I and III. L67 is a simple competitive inhibitor with respect to nicked DNA. L67 inhibits DNA ligases I and III with IC₅₀ values of 10 μM and 10 μM.). L67 significantly increased the cytotoxicity of DNA-damaging.
Hodoodo Cat#: H407299
Name: L67
CAS#: 325970-71-6
Chemical Formula: C16H14Br2N4O4
Exact Mass: 483.94
Molecular Weight: 486.120
Elemental Analysis: C, 39.53; H, 2.90; Br, 32.87; N, 11.53; O, 13.16
Synonym: L67; L-67; L 67.
IUPAC/Chemical Name: E-2-((3,5-Dibromo-4-methylphenyl)amino)-N’-(2-hydroxy-5-nitrobenzylidene)acetohydrazide
InChi Key: KFEPVFJQVOMODD-IFRROFPPSA-N
InChi Code: InChI=1S/C16H14Br2N4O4/c1-9-13(17)5-11(6-14(9)18)19-8-16(24)21-20-7-10-4-12(22(25)26)2-3-15(10)23/h2-7,19,23H,8H2,1H3,(H,21,24)/b20-7+
SMILES Code: O=C(N/N=C/C1=CC([N+]([O-])=O)=CC=C1O)CNC2=CC(Br)=C(C)C(Br)=C2
Appearance: Light yellow to yellow 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:
| Biological target: | L67 is a novel, competitive human DNA ligase inhibitor, inhibits DNA ligases I and III with IC50 of 10 μM and 10 μM. |
| In vitro activity: | To determine the mechanisms underlying the cytotoxicity of the LigI/III inhibitor L67, derivatives of cell lines established from cervical (HeLa, Supplementary Figure S1A), breast (MDA-MB-231) and colon (HCT116) cancers that lack mito DNA (Rho minus) were selected by growth in the presence of ethidium bromide, pyruvate and uridine. HeLa cells with abnormal mitochondria that lack mitochondrial DNA (Supplementary Figure S1A and B) were more resistant to L67 in colony forming (Fig. 1A) and cell proliferation assays (Fig. 1B) with the absence of mitochondrial DNA increasing the IC50 from 8.2 µM to 29.7 µM (Supplementary Table 1). The differential effect of L67 on HeLa and HeLa Rho minus cells was also observed when HeLa cells were grown in the media containing pyruvate and uridine (Supplementary Figure S1C). MDA-MB-231 and HCT 116 cells lacking mitochondrial DNA were also more resistant to L67 compared with their respective parental cells (Fig. 1C and D, and Supplementary Table 1), suggesting that, at lower concentrations, L67 causes cell death by targeting mitochondrial function. Reference: Cancer Res. 2016 Sep 15; 76(18): 5431–5441. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5036517/ |
| In vivo activity: | TBD |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 21.5 | 44.23 | |
| DMF | 10.0 | 20.57 | |
| Water | 1.0 | 2.06 |
The following data is based on the product molecular weight 486.12 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. Sallmyr A, Matsumoto Y, Roginskaya V, Van Houten B, Tomkinson AE. Inhibiting Mitochondrial DNA Ligase IIIα Activates Caspase 1-Dependent Apoptosis in Cancer Cells. Cancer Res. 2016 Sep 15;76(18):5431-41. doi: 10.1158/0008-5472.CAN-15-3243. Epub 2016 Aug 8. PMID: 27503931; PMCID: PMC5036517. |
| In vitro protocol: | 1. Sallmyr A, Matsumoto Y, Roginskaya V, Van Houten B, Tomkinson AE. Inhibiting Mitochondrial DNA Ligase IIIα Activates Caspase 1-Dependent Apoptosis in Cancer Cells. Cancer Res. 2016 Sep 15;76(18):5431-41. doi: 10.1158/0008-5472.CAN-15-3243. Epub 2016 Aug 8. PMID: 27503931; PMCID: PMC5036517. |
| In vivo protocol: | TBD |
1: Chen X, Zhong S, Zhu X, Dziegielewska B, Ellenberger T, Wilson GM, MacKerell
AD Jr, Tomkinson AE. Rational design of human DNA ligase inhibitors that target
cellular DNA replication and repair. Cancer Res. 2008 May 1;68(9):3169-77. doi:
10.1158/0008-5472.CAN-07-6636. PubMed PMID: 18451142; PubMed Central PMCID:
PMC2734474.
