kb NB 142-70 (kb NB142-70; kb NB-142-70) is a novel, potent and selective PKD (protein kinase D) inhibitor with anticancer activity. With IC50 values of 28.3, 58.7, and 53.2 nM for PKD1, PKD2, and PKD3, respectively, it prevents PKD. Potential antitumor activity exists for kb NB 142-70. Numerous cellular functions and pathological conditions, including cancer, have been linked to protein kinase D (PKD). Due to the lack of a strong and focused inhibitor, it is still challenging to therapeutically target PKD and analyze PKD-mediated cellular responses. Intestinal epithelial cell migration brought on by wounds is stopped by kb NB 142-70
Physicochemical Properties
| Molecular Formula | C11H9NO2S2 |
| Molecular Weight | 251.3247 |
| Exact Mass | 251.007 |
| Elemental Analysis | C, 52.57; H, 3.61; N, 5.57; O, 12.73; S, 25.51 |
| CAS # | 1233533-04-4 |
| Related CAS # | 1233533-04-4 |
| PubChem CID | 45258277 |
| Appearance | White to gray solid powder |
| Density | 1.5±0.1 g/cm3 |
| Boiling Point | 601.9±55.0 °C at 760 mmHg |
| Flash Point | 317.8±31.5 °C |
| Vapour Pressure | 0.0±1.8 mmHg at 25°C |
| Index of Refraction | 1.746 |
| LogP | 2.39 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 4 |
| Rotatable Bond Count | 0 |
| Heavy Atom Count | 16 |
| Complexity | 300 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | S1C([H])([H])C([H])([H])N([H])C(C2=C1C1C([H])=C(C([H])=C([H])C=1S2)O[H])=O |
| InChi Key | DHUAGGSHTKPOHU-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C11H9NO2S2/c13-6-1-2-8-7(5-6)9-10(16-8)11(14)12-3-4-15-9/h1-2,5,13H,3-4H2,(H,12,14) |
| Chemical Name | 9-hydroxy-3,4-dihydro-2H-[1]benzothiolo[2,3-f][1,4]thiazepin-5-one |
| Synonyms | kb NB 142-70; kb NB 142-70; kb NB-142-70; kb NB142-70; kb NB 142 70 |
| 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 | PKD1 (IC50 = 28.3 nM); PKD3 (IC50 = 53.2 nM); PKD2 (IC50 = 58.7 nM) |
| ln Vitro |
kb NB 142-70 is a potent PKD inhibitor, with IC50s of 28.3, 58.7 and 53.2 nM for PKD1, PKD2, and PKD3, respectively. In LNCaP cells, kb NB 142-70 also inhibits PKD1 Ser916 phosphorylation (IC50, 2.2 ± 0.6 μM). Furthermore, kb NB 142-70 has an EC50 of 8.025 μM and is cytotoxic to PC3 cells[1]. In IEC-18 cells, kb NB 142-70 (0–5 μM) inhibits ANG II-induced phosphorylation of HDAC4 at Ser246 and Ser632, HDAC5 at Ser259 and Ser498, and HDAC7 at Ser155. Additionally, kb NB 142-70 (3.5 μM) inhibits the phosphorylation of HDAC4, HDAC5, and HDAC7 in IEC-18 cells stimulated with ANG II for 0-240 min or with vasopressin, lysophosphatidic acid (LPA), or phorbol 12,13-dibutyrate (PDBu)[2]. |
| Cell Assay | PC3 cells are treated with kb NB 142-70 at a concentration of 10 μM for 48 h, followed by an overnight fixation in 70% ice-cold ethanol and labeling with propidium iodide. A FACScan Benchtop Cytometer is used to analyze the labeled cells[1]. |
| References |
[1]. Novel protein kinase D inhibitors cause potent arrest in prostate cancer cell growth and motility. BMC Chem Biol. 2010 May 5;10:5. [2]. Protein kinase D1 mediates class IIa histone deacetylase phosphorylation and nuclear extrusion in intestinal epithelial cells: role in mitogenic signaling. Am J Physiol Cell Physiol. 2014 May 15; 306(10): C961-C971. |
Solubility Data
| Solubility (In Vitro) | DMSO: ~46.7 mg/mL (~185.7 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 3.5 mg/mL (13.93 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), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 35.0 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 2: ≥ 3.5 mg/mL (13.93 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 35.0 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 | 3.9790 mL | 19.8950 mL | 39.7899 mL | |
| 5 mM | 0.7958 mL | 3.9790 mL | 7.9580 mL | |
| 10 mM | 0.3979 mL | 1.9895 mL | 3.9790 mL |