Samuraciclib hydrochloride hydrate
PRODUCTS SPECIFICATIONS
DESCRIPTION
Overview
| MDL | - |
|---|---|
| Molecular Weight | 552.33 |
| Molecular Formula | C22H33ClN6O2 |
| SMILES | O[C@H]1CNCC[C@@H]1CNC2=NC3=C(C(C)C)C=NN3C(NCC4=CC=CC=C4)=C2.Cl.O.[2.5].[3.7] |
4 Publications Citing Use of MCE
Summary
Samuraciclib (CT7001) hydrochloride hydrate is a potent, selective, ATP-competitive and orally active CDK7 inhibitor, with an IC 50 of 41 nM. Samuraciclib hydrochloride hydrate displays 45-, 15-, 230- and 30-fold selectivity over CDK1 , CDK2 (IC 50 of 578 nM), CDK5 and CDK9 , respectively. Samuraciclib hydrochloride hydrate inhibits the growth of breast cancer cell lines with GI 50 values between 0.2-0.3 µM. Samuraciclib hydrochloride hydrate has anti-tumor effects [1] [2] .
IC50 & Target
|
CDK7/CycH/MAT1 41 nM (IC 50 ) |
CDK2/cycE1 578 nM (IC 50 ) |
CDK1 1.8 μM (IC 50 ) |
CDK4 49 μM (IC 50 ) |
CDK5 9.4 μM (IC 50 ) |
CDK6 34 μM (IC 50 ) |
CDK9 1.2 μM (IC 50 ) |
In Vitro
Samuraciclib (ICEC0942; 0-10 µM; 24 hours; HCT116 cells) hydrochloride hydrate treatment promotes cell apoptosis
[1]
.
Samuraciclib (ICEC0942; 0-10 µM; 24 hours; HCT116 cells) hydrochloride hydrate treatment induces cell cycle arrest
[1]
.
Samuraciclib (ICEC0942; 0-10 µM; 0-24 hours; HCT116 cells) hydrochloride hydrate treatment inhibits the phosphorylation of PolII CTD in a dose and time dependent manner in HCT116 colon cancer cells. Samuraciclib hydrochloride hydrate also inhibits phosphorylation of CDK1, CDK2 and retinoblastoma
[1]
.
Samuraciclib (ICEC0942) hydrochloride hydrate inhibits the growth of MCF7, T47D, MDA-MB-231, HS578T, MDA-MB-468, MCF10A and HMEC cells with GI
50
values of 0.18 µM, 0.32 µM, 0. 33 µM, 0.21 µM, 0.22 µM, 0.67 µM and 1.25 µM, respectively
[1]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Apoptosis Analysis [1]
| Cell Line: | HCT116 cells |
| Concentration: | 0 µM, 0.1 µM, 1 µM and 10 µM |
| Incubation Time: | 24 hours |
| Result: | Induced caspase 3/7 and demonstrated PARP cleavage. |
Cell Cycle Analysis [1]
| Cell Line: | HCT116 cells |
| Concentration: | 0 µM, 0.1 µM, 1 µM and 10 µM |
| Incubation Time: | 24 hours |
| Result: | Showed accumulation of cells in G2/M. |
Western Blot Analysis [1]
| Cell Line: | HCT116 cells |
| Concentration: | 0 µM, 0.1 µM, 1 µM and 10 µM |
| Incubation Time: | 0 hour, 4 hours, 8 hours, 16 hours or 24 hours |
| Result: | PolII CTD phosphorylation was inhibited in a dose and time dependent manner in HCT116 colon cancer cells. |
In Vivo
Samuraciclib (ICEC0942; 100 mg/kg; oral gavage; daily; for 14 days; female nu/nu-BALB/c athymic nude mice) hydrochloride hydrate treatment inhibits tumor growth by 60% at day 14, and is accompanied by highly significant reductions in PolII Ser2 and Ser5 phosphorylation in PBMCs and in tumors
[1]
.
The combination of Samuraciclib (ICEC0942) and ICI 47699 treatment shows complete growth arrest of estrogen receptor (ER)-positive tumor xenografts
[1]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
| Animal Model: | Female nu/nu-BALB/c athymic nude mice (7-week old) with MCF7 cells [1] . |
| Dosage: | 100 mg/kg |
| Administration: | Oral gavage; daily; for 14 days |
| Result: | At day 14, tumor growth was inhibited by 60%. |
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date | Phase |
|---|---|---|---|---|
| NCT03363893 | Carrick Therapeutics Limited |
Advanced Solid Malignancies
|
November 14, 2017 | Phase 1|Phase 2 |
| NCT04802759 | Hoffmann-La Roche |
Inoperable, Locally Advanced or Metastatic, ER-positive Breast Cancer
|
June 20, 2021 | Phase 1|Phase 2 |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
4°C, sealed storage, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
Solvent & Solubility
DMSO : 100 mg/mL ( 181.05 mM ; Need ultrasonic)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 1.8105 mL | 9.0526 mL | 18.1051 mL |
| 5 mM | 0.3621 mL | 1.8105 mL | 3.6210 mL |
| 10 mM | 0.1811 mL | 0.9053 mL | 1.8105 mL |
References
- [1] Patel H, et al. ICEC0942, an Orally Bioavailable Selective Inhibitor of CDK7 for Cancer Treatment. Mol Cancer Ther. 2018 Jun;17(6):1156-1166.
- [2] Hazel P, et al. Inhibitor Selectivity for Cyclin-Dependent Kinase 7: A Structural, Thermodynamic, and Modelling Study. ChemMedChem. 2017 Mar 7;12(5):372-380.
