CX-6258

SKU: orb1226807

Description

A potent, selective, and orally efficacious pan-Pim inhibitor with IC50 of 5/25/16 nM for Pim1/2/3, respectively; exhibits in vitro synergy with chemotherapeutics and robust in vivo efficacy in driven tumor models; also decreases steady state levels and half-life of NKX3.1 protein but not mRNA in prostate cancer cells.Blood Cancer Discontinued.

Key Properties

• CAS Number: 1202916-90-2
• MW: 461.9401
• Purity: >98% (HPLC)
• Formula: C₂₆H₂₄ClN₃O₃
• SMILES: CN1CCCN(CC1)C(=O)C2=CC=CC(=C2)C3=CC=C(O3)/C=C/4\C5=C(C=CC(=C5)Cl)NC4=O
• Target: Pim
• Solubility: 10 mM in DMSO

Bioactivity

• In Vivo:
  CX-6258 (50-100 mg/kg; p. o; daily; over a period of 21 days) exhibits robust In vivo efficacy in two Pim kinases driven tumor models. Animal model: Nude mice, MV-4-11 xenograft models. Dosage: 50 mg/kg, 100 mg/kg. Administration: Oral administration; once daily; over a period of 21 days. Result: Exhibited dose dependent efficacy, with a 50 mg/kg dose producing 45% tumor growth inhibition (TGI) and a 100 mg/kg dose producing 75% TGI.
• In Vitro:
  CX-6258 causes dose dependent inhibition of the phosphorylation of two pro-survival proteins, Bad and 4E-BP1, at the Pim kinase specific sites S112 and S65 and T37/46, respectively. CX-6258 treatment (12 mM, 3 h) treatment diminishes steady-state levels of ectopic NKX3.1 in PC3 cells. CX-6258 treatment results in a significant reduction in NKX3.1 half-life. Western blot analysis. Cell line: MV-4-11 human AML cells. Concentration: 0.1 μM, 1 μM, 10 μM Incubation time: 2 hours. Result: Caused dose dependent inhibition of the phosphorylation of two pro-survival proteins, Bad and 4E-BP1, at the Pim kinase specific sites S112 and S65 and T37/46, respectively.

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

CX6258 | CX 6258

Quick Database Links

Gene Symbol

Pim