KG-501 is a potent inhibitor of CREB (cAMP response element-binding protein) with an IC50 of 6.89 μM. KG-501 (2-naphthol-AS-E-phosphate), targeted a surface distal to the CREB binding groove that includes Arg-600, a residue that is required for the CREB:CBP interaction. When added to live cells, KG-501 disrupted the CREB: CBP complex and attenuated target gene induction in response to cAMP agonist. These results demonstrate the ability of small molecules to interfere with second-messenger signaling cascades by inhibiting specific protein-protein interactions in the nucleus.

Physicochemical Properties

Molecular Formula	C17H13CLNO5P
Molecular Weight	377.71
Exact Mass	377.022
CAS #	18228-17-6
Related CAS #	18228-17-6
PubChem CID	87517
Appearance	White to light yellow solid powder
Density	1.567g/cm3
Index of Refraction	1.723
LogP	4.29
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	4
Heavy Atom Count	25
Complexity	519
Defined Atom Stereocenter Count	0
InChi Key	RQAQWBFHPMSXKR-UHFFFAOYSA-N
InChi Code	InChI=1S/C17H13ClNO5P/c18-13-5-7-14(8-6-13)19-17(20)15-9-11-3-1-2-4-12(11)10-16(15)24-25(21,22)23/h1-10H,(H,19,20)(H2,21,22,23)
Chemical Name	N-(4-Chlorophenyl)-3-(phosphonooxy)naphthalene-2-carboxamide
Synonyms	KG-501; KG 501; KG501
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro	In NSCLC, KG-501 suppresses CREB-target gene expression, disrupts the CREB-CBP complex, and blocks IL-1β-mediated angiogenic activity by directly targeting the KIX domain of CBP[1]. At CREB concentrations within the binding assay's linear range, KG-501 inhibits phospho (Ser-133) CREB binding to KIX with a Ki of about 90 μM. Moreover, KG-501 treatment of HEK293T cells prevents forskolin from inducing endogenous CREB target genes (NR4A2, αCG, c-fos, and RGS2), suggesting that KG-501 probably has a broad impact on CREB activity[2]. Because NF-κB requires CBP as a cofactor to regulate gene expression, KG-501 can also suppress NF-κB transcription activity. When A549 cells are treated with IL-1β + 10 μM of KG-501, the migration of HUVECs caused by CM is much less than when A549 cells are treated with IL-1β alone. With the exception of CXCL8, all IL-1β-induced CXC chemokine genes are suppressed at 10 μM by KG-501. At the protein level, CXCL5 protein production caused by IL-1β is markedly suppressed by KG-501. KG-501 has been shown to have comparable effects in the H1734 cell line[3].
ln Vivo
Animal Protocol
References	[1]. A Novel Small-Molecule Inhibitor Targeting CREB-CBP Complex Possesses Anti-Cancer Effects along with Cell Cycle Regulation, Autophagy Suppression and Endoplasmic Reticulum Stress. PLoS One. 2015 Apr 21;10(4):e0122628. [2]. Identification of small-molecule antagonists that inhibit an activator: coactivator interaction. Proc Natl Acad Sci U S A. 2004 Dec 21;101(51):17622-7. [3]. Cyclic AMP-responsive element binding protein- and nuclear factor-kappaB-regulated CXC chemokine gene expression in lung carcinogenesis. Cancer Prev Res (Phila). 2008 Oct;1(5):316-28.

Solubility Data

Solubility (In Vitro)

DMSO:10 mM Water: Ethanol:

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2 mg/mL (5.29 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2 mg/mL (5.29 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2 mg/mL (5.29 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.6475 mL	13.2377 mL	26.4753 mL
	5 mM	0.5295 mL	2.6475 mL	5.2951 mL
	10 mM	0.2648 mL	1.3238 mL	2.6475 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.