KG-501

SKU: orb1225869

Description

A small-molecule antagonist of CREB-CBP interaction, inhibits the cAMP-dependent activation of cellular genes via CREB; disruptes phospho (Ser-133) CREB binding to CBP KIX domain with Ki of 90 uM, similar Ki for binding of phospho (Ser-133) CREB protein to p300; also interferes with the Myb-KIX interaction in vitro and inhibits Myb activity in vivo.

Key Properties

• CAS Number: 18228-17-6
• MW: 377.72
• Purity: >98% (HPLC)
• Formula: C₁₇H₁₃ClNO₅P
• SMILES: O=C(C1=C(OP(O)(O)=O)C=C2C=CC=CC2=C1)NC3=CC=C(Cl)C=C3
• Target: CREB/CBP
• Solubility: DMSO : 6 mg/mL 15.88 mM; H2O : < 0.1 mg/mL

Bioactivity

• In Vitro:
  KG-501, which directly targets the KIX domain of CBP, results in a disrupted CREB-CBP complex, inhibits CREB-target gene induction, and inhibits IL-1β-mediated angiogenic activity in NSCLC. KG-501 disrupts phospho (Ser-133) CREB binding to KIX with a Ki of ~90 μM, using concentrations of CREB that are within the linear range of the binding assay. Treatment of HEK293T cells with KG-501 also blocks induction of endogenous CREB target genes (NR4A2, αCG, c-fos, and RGS2) by forskolin, indicating that KG-501 likely exerts a general effect on CREB activity. KG-501 can also inhibit NF-κB transcription activity because NF-κB also uses CBP as a cofactor to regulate gene expression. The migration of HUVECs induced by CM from A549 cells treated with IL-1β plus 10 μM of KG-501 is significantly lower than that induced by CM from A549 cells treated with IL-1β alone. At 10 μM, KG-501 suppresses the expression of all of the IL-1β-induced CXC chemokine genes except CXCL8. For the protein level, KG-501 significantly suppresses IL-1β-induced CXCL5 protein secretion. Similar effects of KG-501 are also observed in the H1734 cell line.

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

Naphthol AS-E phosphate

Quick Database Links

Gene Symbol

CREB/CBP