In vitro: CFI-402257 is highly selective to TTK. CFI-402257 is tested against a panel of human kinases at 1 μM and inhibits none of the 262 kinases tested. CFI-402257 is a potent inhibitor of cell growth. CFI-402257 shows strong antineoplastic activity on a broad panel of human cancer-derived cell lines, and causes effects consistent with depletion or inhibition of Mps1. CFI-402257 inhibits Mps1 with an IC50 value of 1.2 nM, and is ATP competitive with a Ki value of 0.09 nM. CFI-402257 inhibits autophosphorylation of Mps1 at threonine 12/serine 15 with an EC50 value of 6.5 nM in cells exogenously expressing human Mps1. CFI-402257 exerts potent growth inhibitory activity across the vast majority of cell lines with a median IC50 value of 15 nM. In vivo: The upper dose level for once-daily administration of CFI-402257 is between 6 and 6.5 mg/kg. CFI-402257 given orally QD shows dose-dependent activity in mice with established tumors from xenografted MDA-MB-231 human TNBC cells [5 mg/kg CFI-402257, tumor growth inhibition (TGI)=74%; 6 mg/kg, TGI=89%], from xenografted MDA-MB-468 human TNBC cells in mice (5 mg/kg, TGI=75%; 6 mg/kg, TGI=94%). CFI-402257 also demonstrates antitumor activity in a platinum-resistant PDX model of high-grade serous ovarian cancer (6.5 mg/kg, TGI=61%). CFI-402257 is found to be similarly efficacious in a platinum-sensitive PDX model of high-grade serous ovarian cancer.
Cell Experiment | |
---|---|
Cell lines | HCT116 cells |
Preparation method | Cells were pretreated with 0.5 μM MG132 for 30 min before treatment with CFI-402257 or DMSO for 4 h. For cellular histone H3 (S10) EC50 determination, HCT116 cells were treated with 200 ng/mL nocodazole for 17 h before treatment with CFI-402257 or DMSO for 4 h. |
Concentrations | 10 μM |
Incubation time | 17 h |
Animal Experiment | |
---|---|
Animal models | CD-1 nude mice |
Formulation | 10% (vol/vol) NMP/40% (vol/vol) PEG-300/50% (vol/vol) water |
Dosages | 10, 25, and 55 mg/kg |
Administration | oral |
Molecular Weight | 498.58 |
Formula | C28H30N6O3 |
CAS Number | 1610759-22-2 |
Solubility (25°C) | 10 mM in DMSO |
Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
Species | Mouse | Rat | Rabbit | Guinea pig | Hamster | Dog |
Weight (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
Body Surface Area (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
Km factor | 3 | 6 | 12 | 8 | 5 | 20 |
Animal A (mg/kg) = Animal B (mg/kg) multiplied by | Animal B Km |
Animal A Km |
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
Related Products |
---|
DiosMetin 7-O-β-D-Glucuronide
DiosMetin 7-O-β-D-Glucuronide is an antioxidant constituent in the fruits of Luffa cylindrical. |
Bendazac L-Lysine
Bendazac L-Lysine is an aldose reductase (AR) inhibitor, which can be used to inhibit the activity of AR in the eye to prevent cataracts. |
Ro5-3335
Ro5-3335 acts as an inhibitor of core binding factor (CBF) leukemia. Ro5-3335 is a RUNX1-CBFβ interaction inhibitor that represses RUNX1/CBFB-dependent transactivation. |
Bendazac
Bendazac is an oxyacetic acid with anti-inflammatory, antinecrotic, choleretic and antilipidaemic properties. Bendazac acts by preventing protein denaturation. |
Dexamethasone palmitate
Dexamethasone palmitate (DXP) is a proagent of Dexamethasone. Dexamethasone palmitate can be used for the research of inflammation. |
Products are for research use only. Not for human use. We do not sell to patients.
© Copyright 2010-2023 AbMole BioScience. All Rights Reserved.