BS-194 is a novel, potent, and orally bioavailable inhibitor of cyclin-dependent protein kinases (CDKs) 1, 2, 7 and 9 with anticancer activities.
Physicochemical Properties
| Molecular Formula | C20H27N5O3 |
| Molecular Weight | 385.47 |
| Exact Mass | 385.211 |
| CAS # | 1092443-55-4 |
| Related CAS # | 1092443-55-4; |
| PubChem CID | 25125014 |
| Appearance | Typically exists as solid at room temperature |
| Density | 1.3±0.1 g/cm3 |
| Index of Refraction | 1.651 |
| LogP | 1.37 |
| Hydrogen Bond Donor Count | 5 |
| Hydrogen Bond Acceptor Count | 7 |
| Rotatable Bond Count | 9 |
| Heavy Atom Count | 28 |
| Complexity | 463 |
| Defined Atom Stereocenter Count | 2 |
| SMILES | CC(C)C1=C2N=C(C=C(NCC3=CC=CC=C3)N2N=C1)N[C@@H](CO)[C@@H](CO)O |
| InChi Key | KRIWIRSMQRQYJG-DLBZAZTESA-N |
| InChi Code | InChI=1S/C20H27N5O3/c1-13(2)15-10-22-25-19(21-9-14-6-4-3-5-7-14)8-18(24-20(15)25)23-16(11-26)17(28)12-27/h3-8,10,13,16-17,21,26-28H,9,11-12H2,1-2H3,(H,23,24)/t16-,17+/m0/s1 SMILES |
| Chemical Name | (2S,3S)-3-[[7-(benzylamino)-3-propan-2-ylpyrazolo[1,5-a]pyrimidin-5-yl]amino]butane-1,2,4-triol |
| Synonyms | BS-194 BS194 BS194. |
| 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 | Compound 4k, also known as BS-194, has a 72-hour half-life of 100 nM to 1 μM and can suppress the growth of multiple cancer cells, including MCF-7, MDA-MB-231, MCF-10A, CPLO-205, HCT-116, A549, SaOS2, PC3, HepG2, and SK-Ov-3[1]. In the S phase and G2/M phase of HCT116 cells, BS-194 (10 μM, 24 hours) stimulates cell cycle arrest [1]. In HCT116 cells, BS-194 (10 μM, 24 hours) reduces CDK substrate phosphorylation and encourages cyclin loss [1]. |
| ln Vivo | In MCF-7 tumor xenografts, BS-194 (Compound 4K, intraperitoneally administered, 5 or 10 mg/kg twice daily for 14 days) reduces tumor growth without appearing to be harmful [1]. With elimination half-lives of 147 minutes (ip), 210 minutes (iv), and 178 minutes (po), BS-194 (ip, iv, po, 10 mg/kg) is orally accessible [1]. In nu/nu-BALB/c athymic nude mice, BS-194 (oral gavage, 25 mg/mL) decreases the fast phosphorylation of RB and PolII (RNA polymerase II) but restores it in less than a day [1]. In HCT116 tumor xenografts, BS-194 (oral gavage, 25 mg/kg daily for 14 days) suppresses tumor growth without significantly lowering the animal's body weight [1]. |
| Cell Assay |
Cell cycle analysis [1] Cell Types: HCT116 Tested Concentrations: 0, 0.01, 0.1, 1, 10 μM Incubation Duration: 24 h Experimental Results: G1 phase was Dramatically diminished, S phase and G2/M phase were increased. Western Blot Analysis[1] Cell Types: HCT116 Tested Concentrations: 0, 0.1, 10, 20 μM Incubation Duration: 0, 0.1, 10, 20 μM Experimental Results: Inhibition of CDK2 Substrate RB (Retinoblastoma) Ser-780, Ser Phospho-795, Ser-801, Ser-807/Ser-811 and Thr-821. Levels of cyclin A, cyclin B, and cyclin D1 were inhibited. Inhibits the phosphorylation of CDK2 Thr-170. |
| Animal Protocol |
Animal/Disease Models: Nude mice carrying MCF-7 cells [1] Doses: 5 or 10 mg/kg twice (two times) daily for 14 days. Mode of Route of Administration: intraperitoneal (ip) injection Experimental Results: Inhibition of tumor growth in a dose-dependent manner (30% and 40% reduction at 5 mg/kg dose and 10 mg/kg dose, respectively). Animal/Disease Models: HCT116 tumor xenografts [1] Doses: 25 mg/kg daily for 14 days. Mode of Route of Administration: po (oral gavage). Experimental Results: At 25 mg/kg, the tumor growth inhibition rate was diminished by 50%. Rb phosphorylation levels at Ser807/811 and Thr821 were diminished (in resected tumors). Animal/Disease Models: Mice (pharmacokinetic/PK/PK determination) [1] Doses: 10 mg/kg Route of Administration: intraperitoneal (ip) injection, intravenous (iv) (iv)injection, oral administration Experimental Results: pharmacokinetic/PK/PK characteristics of BS-194 (compound 4k). Route of administration dose (mg/kg) Bioavailability (%) Cmax (min) T1/2 (min) ip 10 73 30 147 po 10 88 15 178 Route of administration dose (mg/kg) T1/2 (min) Cl (mL/min/kg) Vz intravenous (iv) (iv)injection 10 210 5 1391 |
| References |
[1]. A novel pyrazolo[1,5-a]pyrimidine is a potent inhibitor of cyclin-dependent protein kinases 1, 2, and 9, which demonstrates antitumor effects in human tumor xenografts following oral administration. J Med Chem. 2010 Dec 23;53(24):. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~100 mg/mL (~259.43 mM) |
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5942 mL | 12.9712 mL | 25.9424 mL | |
| 5 mM | 0.5188 mL | 2.5942 mL | 5.1885 mL | |
| 10 mM | 0.2594 mL | 1.2971 mL | 2.5942 mL |