[CAS NO. 2704316-82-3] AbemaciclibmetaboliteM18hydrochloride
PRODUCTS SPECIFICATIONS [2704316-82-3]
DESCRIPTION [2704316-82-3]
Overview
| MDL | - |
|---|---|
| Molecular Weight | 531.00 |
| Molecular Formula | C25H29ClF2N8O |
| SMILES | FC(C=N1)=C(C2=CC(N(C(C)C)C(CO)=N3)=C3C(F)=C2)N=C1NC4=NC=C(C=C4)CN5CCNCC5.[H]Cl |
1 Publications Citing Use of MCE
Summary
Abemaciclib metabolite M18 (LSN3106729) hydrochloride, the metabolite of Abemaciclib (HY-16297A), is a CDK inhibitor with antitumor activity. Abemaciclib metabolite M18 hydrochloride and a CRBN ligand have been used to design PROTAC CDK4/6 degrader [1] [2] .
IC50 & Target
|
CDK4 |
CDK6 |
In Vitro
Abemaciclib metabolite M18 hydrochloride exhibits T
1/2
of 43.1 hr in plasma in healthy subjects
[3]
.
CDK4/6 inhibitors’ chief mechanism of action is inhibition of retinoblastoma (RB) protein phosphorylation and thus the induction of cell cycle arrest, CDK4/6 inhibitors alter cancer cell biology in other ways
[4]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
CDK4/6 inhibitors results T-cell persistence and immunologic memory increasing in mice receiving tumor-specific CD8
+
T cells
[5]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
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 : 125 mg/mL ( 235.40 mM ; Need ultrasonic)
H 2 O : 100 mg/mL ( 188.32 mM ; Need ultrasonic)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 1.8832 mL | 9.4162 mL | 18.8324 mL |
| 5 mM | 0.3766 mL | 1.8832 mL | 3.7665 mL |
| 10 mM | 0.1883 mL | 0.9416 mL | 1.8832 mL |
-
1.
Add each solvent one by one: PBS
Solubility: 50 mg/mL (94.16 mM); Clear solution; Need ultrasonic
References
- [1] Edward S. Kim, et al. Abemaciclib in Combination with Single-Agent Options in Patients with Stage IV Non–Small Cell Lung Cancer: A Phase Ib Study.
- [2] Nathanael Gray, et al. Degradation of cyclin-dependent kinase 4/6 (cdk4/6) by conjugation of cdk4/6 inhibitors with e3 ligase ligand and methods of use. WO2017185031A1.
- [3] Palaniappan, et al. Abstract CT153: Pharmacokinetic drug interactions between abemaciclib and CYP3A inducers and inhibitors. Cancer Res. 2016-7-15; 76 (14_Supplement): CT153.
- [4] Goel S, et al. CDK4/6 Inhibition in Cancer: Beyond Cell Cycle Arrest. Trends Cell Biol. 2018 Nov;28(11):911-925.
