CASIN is a novel, potent and selective inhibitor of Cdc42 GTPase, a small GTPase of the Rho-subfamily that plays important roles in cytoskeleton organization, cell cycle progression, signal transduction, and vesicle trafficking. The rejuvenated phenotype of hematopoietic stem cells (HSCs) was produced by CASIN, which in vivo reversed the polarity and aging-related phenotype of aged HSCs to that of young HSCs.
Physicochemical Properties
| Molecular Formula | C20H22N2O |
| Molecular Weight | 306.4015 |
| Exact Mass | 306.173 |
| Elemental Analysis | C, 78.40; H, 7.24; N, 9.14; O, 5.22 |
| CAS # | 425399-05-9 |
| Related CAS # | 425399-05-9 |
| PubChem CID | 2882155 |
| Appearance | Solid powder |
| Density | 1.2±0.1 g/cm3 |
| Boiling Point | 577.8±50.0 °C at 760 mmHg |
| Flash Point | 303.3±30.1 °C |
| Vapour Pressure | 0.0±1.7 mmHg at 25°C |
| Index of Refraction | 1.682 |
| LogP | 3.6 |
| Hydrogen Bond Donor Count | 3 |
| Hydrogen Bond Acceptor Count | 2 |
| Rotatable Bond Count | 4 |
| Heavy Atom Count | 23 |
| Complexity | 382 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | O([H])C([H])([H])C([H])([H])N([H])C1([H])C([H])([H])C([H])([H])C([H])([H])C2C3C([H])=C(C4C([H])=C([H])C([H])=C([H])C=4[H])C([H])=C([H])C=3N([H])C1=2 |
| InChi Key | RXIUMAOXORBRCY-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C20H22N2O/c23-12-11-21-19-8-4-7-16-17-13-15(14-5-2-1-3-6-14)9-10-18(17)22-20(16)19/h1-3,5-6,9-10,13,19,21-23H,4,7-8,11-12H2 |
| Chemical Name | 2-[(6-phenyl-2,3,4,9-tetrahydro-1H-carbazol-1-yl)amino]ethanol |
| Synonyms | CASIN |
| 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 | GTPase Cdc42 (IC50 = 2 μM) |
| ln Vitro |
CASIN (0-10 μM; 3 d) suppresses the growth of RPMI-8226/S, AMO-1, ARH-77, IM-9, JJN-3, L-363, and MOLP-8 cells[1]. CASIN (0-10 μM; 16 h) suppresses FANCD2 mono-ubiquitination induced by melphalan in LR5 cells but has no effect on S cells[1]. CASIN (5 μM; 2 d) promotes cell apoptosis in bortezomib-resistant MM patient cells[1]. |
| ln Vivo | CASIN (20 mg/kg; i.p. 2 times a day) extends the life of mice with busulfan injection[1]. |
| Enzyme Assay |
Cell Line: AMO-1, ARH-77, IM-9 , JJN-3, L-363, MOLP-8 and RPMI-8226/S cells Concentration: 0-10 μM Incubation Time: 3 days Result: Inhibited MM cell lines including AMO-1, ARH-77, IM-9 , JJN-3, L-363, MOLP-8 and RPMI-8226/S cells with GI50s vof 3.23, 4.31, 4.87, 2.56, 4.64, 4.67 and 3.97 μM, respectively. |
| Cell Assay | CASIN (containing 0.02-0.2% DMSO) was used at 5 μM in the culture medium for in vitro investigations. |
| Animal Protocol |
NSG mice with busulfan injection[3] 20 mg/kg Intraperitoneal injection; 20 mg/kg 2 times a day |
| References |
[1]. Cdc42 activity regulates hematopoietic stem cell aging and rejuvenation. Cell Stem Cell, 2012 May 4, 10(5):520-30. [2]. Rational Targeting of Cdc42 Overcomes Drug Resistance of Multiple Myeloma. Front Oncol. 2019 Oct 1;9:958. doi: 10.3389/fonc.2019.00958. |
Solubility Data
| Solubility (In Vitro) |
DMSO: ~61 mg/mL (~199.1 mM) Ethanol: ~61 mg/mL (~199.1 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (6.79 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 20.8 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: ≥ 2.08 mg/mL (6.79 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 20.8 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: ≥ 2.08 mg/mL (6.79 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 20.8 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 | 3.2637 mL | 16.3185 mL | 32.6371 mL | |
| 5 mM | 0.6527 mL | 3.2637 mL | 6.5274 mL | |
| 10 mM | 0.3264 mL | 1.6319 mL | 3.2637 mL |