CGP60474 (CGP-60474) is a novel and potent CDK1/2 (cyclin-dependent kinases) with IC50 value of ~17 nM. Also acts as a Protein Kinase C (PKC) inhibitor. It inhibits CDK1/B, CDK2/E, CDK2/A, CDK4/D, CDK5/p25, CDK7/H and CDK9/T with IC50s of 26, 3, 4, 216, 10, 200 and 13 nM, respectively.
Physicochemical Properties
| Molecular Formula | C18H18CLN5O |
| Molecular Weight | 355.83 |
| Exact Mass | 355.12 |
| CAS # | 164658-13-3 |
| PubChem CID | 644215 |
| Appearance | Light yellow to yellow solid powder |
| Density | 1.356g/cm3 |
| Boiling Point | 630.6ºC at 760mmHg |
| Flash Point | 335.2ºC |
| Vapour Pressure | 9.02E-17mmHg at 25°C |
| Index of Refraction | 1.685 |
| LogP | 3.224 |
| Hydrogen Bond Donor Count | 3 |
| Hydrogen Bond Acceptor Count | 6 |
| Rotatable Bond Count | 7 |
| Heavy Atom Count | 25 |
| Complexity | 389 |
| Defined Atom Stereocenter Count | 0 |
| InChi Key | IYNDTACKOAXKBJ-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C18H18ClN5O/c19-14-3-1-4-15(12-14)23-18-22-9-6-16(24-18)13-5-8-21-17(11-13)20-7-2-10-25/h1,3-6,8-9,11-12,25H,2,7,10H2,(H,20,21)(H,22,23,24) |
| Chemical Name | 3-[[4-[2-(3-chloroanilino)pyrimidin-4-yl]pyridin-2-yl]amino]propan-1-ol |
| Synonyms | CGP 60474 CGP-60474 CGP60474 |
| 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 | CGP60474 (Compound A) has an IC50 of 84 nM, making it a strong inhibitor of VEGFR-2 [1]. Another PKC inhibitor with competitive kinetics against ATP is CGP60474 [2]. |
| ln Vivo | In the LPS endotoxemia paradigm, CGP-60474 (10?mg/kg; ip) reduces IL-6 levels and increases survival [2]. |
| Animal Protocol |
Animal/Disease Models: C57Bl/6 mice (LPS endotoxemia model) [2] Doses: 10 mg/kg Route of Administration: intraperitoneal (ip) injection Experimental Results:higher survival rate. |
| References |
[1]. How Selective Are Pharmacological Inhibitors of Cell-Cycle-Regulating Cyclin-Dependent Kinases?. J Med Chem. 2018;61(20):9105-9120. [2]. LINCS L1000 dataset-based repositioning of CGP-60474 as a highly potent anti-endotoxemic agent. Sci Rep. 2018;8(1):14969. Published 2018 Oct 8. [3]. Novel and efficient access to phenylamino-pyrimidine type protein kinase C inhibitors utilizing a Negishi cross-coupling strategy. J Org Chem. 2005;70(13):5215-5220. |
| Additional Infomation | 3-[[4-[2-(3-chloroanilino)-4-pyrimidinyl]-2-pyridinyl]amino]-1-propanol is a substituted aniline. |
Solubility Data
| Solubility (In Vitro) | DMSO : ≥ 50 mg/mL (~140.52 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.03 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 25.0 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: ≥ 2.5 mg/mL (7.03 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 25.0 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 | 2.8103 mL | 14.0517 mL | 28.1033 mL | |
| 5 mM | 0.5621 mL | 2.8103 mL | 5.6207 mL | |
| 10 mM | 0.2810 mL | 1.4052 mL | 2.8103 mL |