Samuraciclib (ICEC0942) hydrochloride

Catalog No.S8722 Batch:S872201

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Technical Data

Formula

C22H31ClN6O
Molecular Weight 430.97 CAS No. 1805789-54-1
Solubility (25°C)* In vitro DMSO 86 mg/mL (199.54 mM)
Water 86 mg/mL (199.54 mM)
Ethanol 15 mg/mL (34.8 mM)
In vivo (Add solvents to the product individually and in order)
Clear solution
5%DMSO 40%PEG300 5%Tween80 50%ddH2O
4.3mg/ml Taking the 1 mL working solution as an example, add 50 μL of 86 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 
Clear solution
5% DMSO 95% Corn oil
0.43mg/ml Taking the 1 mL working solution as an example, add 50 μL of 8.6 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results. 
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description Samuraciclib (ICEC0942) hydrochloride is a new, orally bioavailable CDK7 inhibitor with an IC50 of 40nM. The IC50 values for CDK1, CDK2, CDK5 and CDK9 were 45-, 15-, 230- and 30-fold higher. ICEC0942 (CT7001) promotes cell cycle arrest and apoptosis.
Targets
CDK7 [1]
(Cell-free assay)		 CDK2 [1]
(Cell-free assay)		 CDK9 [1]
(Cell-free assay)		 CDK1 [1]
(Cell-free assay)
40 nM 620 nM 1.2 μM 1.8 μM
In vitro

A wide range of cancer types are sensitive to CDK7 inhibition by ICEC0942 with GI50 values ranging between 0.2-0.3 µM. ICEC0942 inhibits PolII, CDK1, CDK2 and RB (retinoblastoma) phosphorylation in the MCF7 breast cancer cell line in a time and dose-sependent manner. ICEC0942 inhibits phosphorylation of CDK7 substrates and promotes cell cycle arrest and apoptosis[1].
In vivo

In xenografts of both breast and colorectal cancers, ICEC0942 has substantial anti-tumor effects. For pharmacokinetics, CD1 male mice are treated intravenously (IV), subcutaneously (SC) or by oral gavage (PO) with 10 mg/kg ICEC0942. In plasma, ICEC0942 levels decline in a bi-phasic manner, indicating rapid distribution into tissues. Following IV administration of ICEC0942 at 10 mg/kg in male CD1 mice Cl(plasma) is calculated at 78 ml.min/kg. Blood/plasma ratio (Bl/Pl) is 1.81. ICEC0942 has a half-life of 1.9 hrs, a moderate half-life in this species. Only a small proportion (13.5%) of ICEC0942 is metabolized after 2 and 4 hour following a single PO administration (100 mg/kg). Comparing exposure (AUCt) after single PO and IV administration at 10 mg/kg, oral bioavailability (F%) is calculated at 30%. Median Tmax for PO administration is 2 hours and is unaffected by increasing dose. Over this dose range, Cmax is linearly associated with dose, as is the total exposure over time (AUCt). In tumor-bearing mice, there is appreciable accumulation of ICEC0942 in tumors 6-hours post administration. ICEC0942 levels in tumors lag behind plasma levels[1].

Protocol (from reference)

Cell Assay:

[2]
  • Cell lines

    HCT116 cells

  • Concentrations

    0.1, 1, 10 μM

  • Incubation Time

    4, 8, 16, 24 h

  • Method

    --
Animal Study:

[1]
  • Animal Models

    seven-week old female nu/nu-BALB/c athymic nude mice with tumour xenograft

  • Dosages

    100 mg/kg/day

  • Administration

    PO

Selleck's Samuraciclib (ICEC0942) hydrochloride has been cited by 2 publications

Genome-wide mapping of cancer dependency genes and genetic modifiers of chemotherapy in high-risk hepatoblastoma [ Nat Commun, 2023, 14(1):4003] PubMed: 37414763
Recurrent Mutations in Cyclin D3 Confer Clinical Resistance to FLT3 Inhibitors in Acute Myeloid Leukemia [ Clin Cancer Res, 2021, 10.1158/1078-0432.CCR-20-3458] PubMed: 34103301

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.