KRCA-0008

SKU: orb1226209

Description

KRCA-0008 is a potent, selective ALK inhibitor with IC50 of 12 nM (wt ALK), also is potent against various ALK mutants, including L1196M, F1174L, R1275Q, and C1156Y (IC50=5-75 nM); weakly inhibits IR (IC50=210 nM), inhibits H3122 and BaF3 EML4-ALK L1196M cell proliferation with IC50 of 80 and 68 nM, respectively; demonstrates in vivo efficacy comparable to Crizotinib in xenograft mice model, has drug-like properties without hERG concerns.

Key Properties

• CAS Number: 1472795-20-2
• MW: 609.119
• Purity: >98% (HPLC)
• 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
• Target: ALK
• Solubility: 10 mM in DMSO

Bioactivity

• In Vivo:
  Animal model: NOD/SCID mice with Karpas-299 xenografts. 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.
• In Vitro:
  Cell Proliferation Assay Cell line: H3122 and H1993 cell lines. Concentration: 200 nM. Incubation time: 6 hours. Result: Inhibited cell proliferation of H3122 and H1993 cells with IC50s of 0.08 and 3.6 nM, respectively. Cell Proliferation Assay 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 GI50s of 12 nM, 3 nM and 3.5 μM, respectively. Western blot analysis. 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 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 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.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

KRCA 0008 | KRCA0008

Quick Database Links

Gene Symbol

ALK