[CAS NO. 1472795-20-2] KRCA-0008
PRODUCTS SPECIFICATIONS [1472795-20-2]
DESCRIPTION [1472795-20-2]
Overview
| MDL | - |
|---|---|
| Molecular Weight | 609.12 |
| Molecular Formula | C30H37ClN8O4 |
| SMILES | ClC1=CN=C(NC2=CC=C(N3CCN(C(C)=O)CC3)C=C2OC)N=C1NC4=CC=C(N5CCN(C(C)=O)CC5)C=C4OC |
1 Publications Citing Use of MCE
Summary
IC50 & Target
IC50: 12 nM (ALK), 4 nM (Ack1) [1]
In Vitro
KRCA-0008 (0-1000 μM) shows potency to ALK (wt), ALK L1196 M, ALK C1156Y, ALK F1174L, ALK R1275Q and insulin receptor with IC
50
s of 12, 75, 4, 17, 17 and 210 nM, respectively
[1]
.
KRCA-0008 (0-1000 nM; 4 h) inhibits ALK-dependent signaling pathways more potently than crizotinib
[2]
.
KRCA-0008 (0-1000 nM; 72 h) induces cell apoptosis
[2]
.
KRCA-0008 (0-100 nM; 48 h) affects cell cycle
[2]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Proliferation Assay [1]
| Cell Line: | H3122 and H1993 cell lines |
| Concentration: | 200 nM |
| Incubation Time: | 6 hours |
| Result: | Inhibited cell proliferation of H3122 and H1993 cells with IC 50 s of 0.08 and 3.6 nM, respectively. |
Cell Proliferation Assay [2]
| Cell Line: | NPM-ALK-positive ALCL cell lines (Karpas-299 and SU-DHL-1) and U937 NPM ALK-negative lymphoma cell line |
| Concentration: | 200 nM |
| Incubation Time: | 72 hours |
| Result: | Inhibited proliferation of Karpas-299, SU-DHL-1 and U937 cells with GI 50 s of 12 nM, 3 nM and 3.5 μM, respectively. |
Western Blot Analysis [2]
| Cell Line: | Karpas-299 and SU-DHL-1 cell lines |
| Concentration: | 0, 10, 100 and 1000 nM |
| Incubation Time: | 4 hours |
| Result: | Completely suppressed phosphorylation of ALK and its effectors at a dose of 100 nM in NPM-ALK-positive ALCL cells. |
Apoptosis Analysis [2]
| Cell Line: | SU-DHL-1 cell line |
| Concentration: | 0-1 μM |
| Incubation Time: | 72 hours |
| Result: | Dose-dependently increased cspase-3/7 activities and induced cell apoptosis. |
Cell Cycle Analysis [2]
| Cell Line: | Karpas-299 and SU-DHL-1 cell lines |
| Concentration: | 0-100 nM |
| Incubation Time: | 48 hours |
| Result: | Induced G0/G1 cell cycle arrest in ALCL cells expressing NPM-ALK. |
In Vivo
KRCA-0008 (25 and 50 mg/kg; p.o. twice a day for two weeks) suppresses tumor growth in an ALK-positive Karpas-299 xenograft model [2] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
| Animal Model: | NOD/SCID mice with Karpas-299 xenografts [2] |
| Dosage: | 25 and 50 mg/kg |
| Administration: | Oral gavage; 25 and 50 mg/kg twice a day; for two weeks |
| Result: | Significantly inhibited tumor growth by inhibiting NPM-ALK phosphorylation without showing overt signs of toxicity or significant compound-related body weight loss. |
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 : 230 mg/mL ( 377.59 mM ; Need ultrasonic)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 1.6417 mL | 8.2086 mL | 16.4171 mL |
| 5 mM | 0.3283 mL | 1.6417 mL | 3.2834 mL |
| 10 mM | 0.1642 mL | 0.8209 mL | 1.6417 mL |
References
- [1] Park CH, et al. Novel bis-ortho-alkoxy-para-piperazinesubstituted-2,4-dianilinopyrimidines (KRCA-0008) as potent and selective ALK inhibitors for anticancer treatment. Bioorg Med Chem Lett. 2013 Nov 15;23(22):6192-6.
- [2] Hwang J, et al. KRCA-0008 suppresses ALK-positive anaplastic large-cell lymphoma growth. Invest New Drugs. 2020 Oct;38(5):1282-1291.