Home Cell Cycle CDK inhibitor - Apoptosis related activator Samuraciclib (ICEC0942) hydrochloride

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Samuraciclib (ICEC0942) hydrochloride CDK inhibitor

Cat.No.S8722

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.
Samuraciclib (ICEC0942) hydrochloride CDK inhibitor Chemical Structure

Chemical Structure

Molecular Weight: 430.97

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Quality Control

Batch: S872201 DMSO]86 mg/mL]false]Water]86 mg/mL]false]Ethanol]15 mg/mL]false Purity: 99.91%
99.91

Chemical Information, Storage & Stability

Molecular Weight 430.97 Formula

C22H31ClN6O

 Storage (From the date of receipt) 3 years -20°C powder
CAS No. 1805789-54-1 -- Storage of Stock Solutions

Synonyms CT7001 hydrochloride Smiles CC(C)C1=C2N=C(C=C(N2N=C1)NCC3=CC=CC=C3)NCC4CCNCC4O.Cl

Solubility

In vitro
Batch:

DMSO : 86 mg/mL (199.54 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Water : 86 mg/mL

Ethanol : 15 mg/mL

Molarity Calculator

Mass Concentration Volume Molecular Weight

In vivo
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Mechanism of Action

Targets/IC50/Ki
CDK7 [1]
(Cell-free assay)
40 nM
CDK2 [1]
(Cell-free assay)
620 nM
CDK9 [1]
(Cell-free assay)
1.2 μM
CDK1 [1]
(Cell-free assay)
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].
References

Applications

Methods Biomarkers Images PMID
Western blot p-Ser2 PolII / p-Ser5 PolII / p-Ser7 PolII / p-CDK7 / CDK7 / p-RB S8722-WB1 29545334

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