[CAS NO. 41931-13-9] LCS-1
PRODUCTS SPECIFICATIONS [41931-13-9]
DESCRIPTION [41931-13-9]
Overview
| MDL | MFCD00814448 |
|---|---|
| Molecular Weight | 255.10 |
| Molecular Formula | C11H8Cl2N2O |
| SMILES | O=C1C(Cl)=C(Cl)C=NN1C2=CC=CC(C)=C2 |
Summary
IC50 & Target
|
SOD1 1.07 μM (IC 50 ) |
In Vitro
LCS-1 (1-10000 nM; 24 hours) has selective cytotoxicity towards bloom syndrome gene product (BLM) -proficient and BLM-deficient HCT116 cells
[1]
.
LCS-1 shows growth inhibitory effect on 10/27 adenocarcinoma cell lines (median IC
50
=0.20 μM; such as H23, H2347, HCC827 cell lines) and normal human bronchial epithelial (NHBE) cells (IC
50
=2.66 μM)
[2]
.
LCS-1 (0, 1.25, 2 μM; 4 h) in a concentration-dependent manner triggers significant inhibition of SOD1 enzymatic activity in multiple myeloma (MM) cells
[3]
.
LCS-1 (0, 1.25, 2.5, 5 μM; 48 h) in a dose-dependent manner reduces the viability of various MM cell lines, including MM.1R (Dexamethasone-resistant), Dox40 (Doxorubicin-resistant), or LR5 (Melphalan-resistant) cell lines
[3]
.
LCS-1 (48 h) has IC
50
values of 2.5 and 4.6 μM for cell viability of ANBL6-WT (Bortezomib-sensitive) and ANBL6-BR (Bortezomib- resistant) cells, respectively
[3]
.
LCS-1 (1.25 μM; 16 h) induces a significant increase in ROS levels and O
2
−
levels in MM.1S cells
[3]
.
LCS-1 (1.25 μM; 16 h) shows a significant decrease in GSH/GSSG ratio in MM.1S cells
[3]
.
LCS-1 (1.25 μM; 24h) induces the release of mitochondrial cytochrome-c into the cytosol, and enriches the proteins (HSP60/CLPP) mediating mtUPR signaling in MM.1S cells
[3]
.
LCS-1-induced O
2
−
(1.25 μM; 5 h) triggers a marked decrease in both RP
2
CP and RP
1
CP forms of 26S proteasomes
[3]
.
LCS-1 (2 μM; 16 h) induces the early- and late-stage apoptosis of MM.1S cells
[3]
.
LCS-1 (0, 0.5, 1, 1.5, 2 μM) upregulates p53/p21 signaling, as well as downregulates survival pathway proteins MCL-1, BclxL, or c-Myc in MM.1S cells
[3]
.
LCS-1 (0, 4, 8, 16, 24 h; 2 μM) shows a rapid and robust induction of mitochondrial unfolded protein response (UPR) proteins (BIP, PERK, phosphorylated eIF2α, or a lectin protein calnexin) in MM.1S and ANBL6-BR cells
[3]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Viability Assay [1]
| Cell Line: | BLM-proficient and BLM-deficient HCT116 cells |
| Concentration: | 1-10000 nM |
| Incubation Time: | 24 hours |
| Result: | Had IC 50 values of 1462 nM and 24.92 nM for the viability of BLM-proficient and BLM-deficient HCT116 cells, respectively. |
Western Blot Analysis [3]
| Cell Line: | MM.1S and ANBL6-BR cells |
| Concentration: | 2 μM |
| Incubation Time: | 16 hours |
| Result: | Decreased the expression of cell-cycle regulatory proteins (cyclin-B1, CDC25C, and CDC2). |
Western Blot Analysis [3]
| Cell Line: | MM.1S cells |
| Concentration: | 0, 0.5, 1, 1.5, 2 μM |
| Incubation Time: | |
| Result: | Upregulated p53/p21 signaling, as well as downregulated survival pathway proteins MCL-1, BclxL, or c-Myc. |
Western Blot Analysis [3]
| Cell Line: | MM.1S cells |
| Concentration: | 2 μM |
| Incubation Time: | 0, 4, 8, 16, 24 hours |
| Result: | Showed a rapid and robust induction of UPR proteins (BIP, PERK, phosphorylated eIF2α, or a lectin protein calnexin). |
In Vivo
LCS-1 (20 mg/kg; i.p. every other day for 14 days) inhibits MM growth and prolongs host survival in MM.1S-bearing mice [3] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
| Animal Model: | 5-week-old female CB17 SCID mice (MM.1S tumors volume=100 mm 3 ) [3] |
| Dosage: | 20 mg/kg (diluted in saline) |
| Administration: | Intraperitoneal injections; treated on an every other day schedule for 14 days |
| Result: | Inhibited MM growth and prolongs host survival. |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Powder | -20°C | 3 years |
|---|---|---|
| 4°C | 2 years | |
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
DMSO : 50 mg/mL ( 196.00 mM ; Need ultrasonic)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 3.9200 mL | 19.6002 mL | 39.2003 mL |
| 5 mM | 0.7840 mL | 3.9200 mL | 7.8401 mL |
| 10 mM | 0.3920 mL | 1.9600 mL | 3.9200 mL |
-
1.
Add each solvent one by one: 10% DMSO >> 90% corn oil
Solubility: ≥ 2.5 mg/mL (9.80 mM); Clear solution
References
- [1] Gupta A, et al. Nanocarrier Composed of Magnetite Core Coated with Three Polymeric Shells Mediates LCS-1 Delivery for Synthetic Lethal Therapy of BLM-Defective Colorectal Cancer Cells. Biomacromolecules. 2018 Mar 12;19(3):803-815.
- [2] Somwar R, et al. Superoxide dismutase 1 (SOD1) is a target for a small molecule identified in a screen for inhibitors of the growth of lung adenocarcinoma cell lines. Proc Natl Acad Sci U S A. 2011;108(39):16375-16380.
- [3] Du T, et al. Proteomic analysis identifies mechanism(s) of overcoming bortezomib resistance via targeting ubiquitin receptor Rpn13. Leukemia. 2021 Feb;35(2):550-561.