CRT 0066101 is a novel, potent and selective inhibitor of protein kinase D (PKD) with IC50 values of 1, 2.5 and 2 nM for PKD1, 2, and 3 respectively. CRT 0066101 demonstrates selectivity for PKD against more than 90 protein kinases, such as PKCα, MEK, ERK, c-Raf, and c-Src.
Physicochemical Properties
| Molecular Formula | C18H24CL2N6O |
| Molecular Weight | 411.3288 |
| Exact Mass | 410.14 |
| Elemental Analysis | C, 52.56; H, 5.88; Cl, 17.24; N, 20.43; O, 3.89 |
| CAS # | 1883545-60-5 |
| Related CAS # | 1883545-60-5 |
| PubChem CID | 136664697 |
| Appearance | Off-white to light yellow solid powder |
| Hydrogen Bond Donor Count | 5 |
| Hydrogen Bond Acceptor Count | 6 |
| Rotatable Bond Count | 6 |
| Heavy Atom Count | 27 |
| Complexity | 411 |
| Defined Atom Stereocenter Count | 1 |
| SMILES | CC[C@H](CNC1=NC(=NC=C1)C2=C(C=CC(=C2)C3=CN(N=C3)C)O)N.Cl.Cl |
| InChi Key | CXYCRYGNFKDPRH-FMOMHUKBSA-N |
| InChi Code | InChI=1S/C18H22N6O.2ClH/c1-3-14(19)10-21-17-6-7-20-18(23-17)15-8-12(4-5-16(15)25)13-9-22-24(2)11-13;;/h4-9,11,14,25H,3,10,19H2,1-2H3,(H,20,21,23);2*1H/t14-;;/m1../s1 |
| Chemical Name | 2-[4-[[(2R)-2-aminobutyl]amino]pyrimidin-2-yl]-4-(1-methylpyrazol-4-yl)phenol;dihydrochloride |
| Synonyms | CRT 0066101; CRT-0066101; CRT0066101 |
| 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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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 | CRT0066101 Multiple phosphotype hubs including A549 (lung) and MiaPaCa-2 (pancreas) enhance PKD1/2 activity without inhibiting PKCα/PKCβ/PKCε activity. CRT0066101 significantly inhibits Panc-1 cell tumors with an IC50 value of 1 μM. Treatment with CRT0066101 resulted in 6-10-fold cellular inflammation of Panc-1 cells. CRT0066101 significantly reduces cell swelling of Colo357, Panc-1, MiaPaCa-2 and AsPC-1, but not Capan-2 CRT0066101 (5 μM) burns basal and NT induced in Panc-1 and Panc-28 cells pS916-PKD1/2 (activated PKD1/2). CRT0066101 reduces PKD signaling NF-κB activation and NF-κB-dependent gene expression in Panc-1 [1]. |
| ln Vivo | The optimal treatment concentration of CRT0066101 (8 μM) was detectable 6 hours after oral administration of the drug. Oral CRT0066101 (80 mg/kg/day) for 28 days significantly eliminated PaCa growth in the Panc-1 subcutaneous xenograft model. Activated PKD1/2 expression was significantly inhibited in treated tumor explants, reaching tumor concentrations of CRT0066101 (12 μM) within 2 hours after substratification. In addition, administration of CRT0066101 (80 mg/kg/day) in the Panc-1 orthotopic model resulted in effective tumor expansion and growth in vivo for 21 days. CRT0066101 significantly reduced the Ki-67+ proliferation index, increased TUNEL+ pancreatic cells (p<0.05), and eliminated the expression of NF-κB proteins, including cyclin D1, histulin, and cIAP-1[1]. |
| References |
[1]. Mol Cancer Ther . 2010 May;9(5):1136-46. [2]. J Biol Chem . 2016 May 20;291(21):11285-99. |
Solubility Data
| Solubility (In Vitro) |
H2O : ~50 mg/mL (~121.56 mM) DMSO : ~11.36 mg/mL (~27.62 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.14 mg/mL (2.77 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 11.4 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of 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: ≥ 1.14 mg/mL (2.77 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 11.4 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: ≥ 1.14 mg/mL (2.77 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 11.4 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 4: 25 mg/mL (60.78 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4311 mL | 12.1557 mL | 24.3114 mL | |
| 5 mM | 0.4862 mL | 2.4311 mL | 4.8623 mL | |
| 10 mM | 0.2431 mL | 1.2156 mL | 2.4311 mL |