CID-2011756, discovered from an HTS-high throughput screening campaign, is a cell-permeable, ATP-competitive and specific inhibitor of PKD (protein kinase D) with potential anticancer activity. It inhibits PKD2/3/1 with IC50 values of 0.6, 0.7 and 3.2 μM, respectively. Diacylglycerol regulates a novel family of serine/threonine kinases called PKD, which is implicated in numerous cellular functions as well as a range of pathological conditions. In LNCaP prostate cancer cells, phorbol ester-induced endogenous PKD1 activation is inhibited by CID-2011756 in a concentration-dependent manner.

Physicochemical Properties

Molecular Formula	C22H21CLN2O3
Molecular Weight	396.87
Exact Mass	396.124
Elemental Analysis	C, 66.58; H, 5.33; Cl, 8.93; N, 7.06; O, 12.09
CAS #	638156-11-3
Related CAS #	638156-11-3
PubChem CID	2011756
Appearance	White to off-white solid powder
Density	1.3±0.1 g/cm3
Boiling Point	491.0±45.0 °C at 760 mmHg
Flash Point	250.8±28.7 °C
Vapour Pressure	0.0±1.2 mmHg at 25°C
Index of Refraction	1.633
LogP	3.69
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	5
Heavy Atom Count	28
Complexity	506
Defined Atom Stereocenter Count	0
SMILES	ClC1=C([H])C([H])=C([H])C(=C1[H])C1=C([H])C([H])=C(C(N([H])C2C([H])=C([H])C(=C([H])C=2[H])C([H])([H])N2C([H])([H])C([H])([H])OC([H])([H])C2([H])[H])=O)O1
InChi Key	XQJWTJLJEYIUDZ-UHFFFAOYSA-N
InChi Code	InChI=1S/C22H21ClN2O3/c23-18-3-1-2-17(14-18)20-8-9-21(28-20)22(26)24-19-6-4-16(5-7-19)15-25-10-12-27-13-11-25/h1-9,14H,10-13,15H2,(H,24,26)
Chemical Name	5-(3-chlorophenyl)-N-[4-(morpholin-4-ylmethyl)phenyl]furan-2-carboxamide
Synonyms	CID 2011756; CID-2011756; CID2011756
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

Targets	Cellular PKD2 ( IC50 = 0.6 μM ); Cellular PKD3 ( IC50 = 0.7 μM ); PKD1 ( IC50 = 3.2 μM )
ln Vitro	In vitro activity: CID 2011756 is an ATP-competitive inhibitor of PKD1, with an IC50 of 3.2 µM. CID 2011756 reduces the endogenous PKD1 Ser916 phosphorylation in LNCaP cancer cells, with an EC50 of 10±0.7 µM. With IC50s of 0.6±0.1 µM and 0.7±0.2 µM for PKD2 and PKD3, respectively, CID 2011756 also exhibits cellular pan-PKD inhibitory effects[1].
ln Vivo
Enzyme Assay	CID 2011756 has comparable, though not identical, potencies to pan-PKD inhibitors (PKD2 IC50 = 0.6±0.1 uM; PKD3 IC50 = 0.7±0.2 uM), as might be expected for an ATP competitive inhibitor. At 10±0.7 uM (n = 3), CID 2011756 had the highest potency among the inhibitors. This EC50 value was similar to that of benzoxoloazepinolone, which we had previously reported.
Cell Assay	In LNCaP prostate cancer cells, it inhibits endogenous PKD1 activation induced by phorbol ester in a concentration-dependent manner.
Animal Protocol
References	[1]. Discovery of diverse small molecule chemotypes with cell-based PKD1 inhibitory activity. PLoS One. 2011;6(10):e25134.

Solubility Data

Solubility (In Vitro)

DMSO: ~20 mM (~50.4 mM) Water: <1 mg/mL Ethanol: N/A

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2 mg/mL (5.04 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 (5.04 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	2.5197 mL	12.5986 mL	25.1972 mL
	5 mM	0.5039 mL	2.5197 mL	5.0394 mL
	10 mM	0.2520 mL	1.2599 mL	2.5197 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.