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Product Data Sheet
Product Name:Cat. No.:
CobimetinibGC10033
Chemical Properties
Cas No.ChemicalNameCanonicalSMILESFormulaSolubilityGeneraltipsShippingCondition
934660-93-2
[3,4-difluoro-2-(2-fluoro-4-iodoanilino)phenyl]-[3-hydroxy-3-[(2S)-piperidin-2-yl]azetidin-1-yl]methanone
C1CCNC(C1)C2(CN(C2)C(=O)C3=C(C(=C(C=C3)F)F)NC4=C(C=C(C=C4)I)F)OC21H21F3IN3O2
≥26.55 mg/mL in DMSO, ≥33.53mg/mL in EtOH with gentlewarming, <2.22 mg/mL in H2O
M.WtStorage
531.31Store at -20°C
For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in theultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.Evaluation sample solution : ship with blue ice All other available size: ship with RT , orblue ice upon request.
Structure
Caution: Producthasnot been fully validated for medical applications. For research use only.
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Product Data Sheet
实验参考方法
Cell experiment [1]:
KRAS G13D and B-RAF G464V mutant MDA-MB-231T breast adenocarcinoma cell
Cell lines
lines
The solubility of this compound in DMSO is >26.6 mg/mL. General tips for
obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes
Preparation method
and/or shake it in the ultrasonic bath for a while. Stock solution can be storedbelow -20℃ for several months.
Reacting condition0-10 nM
In the biochemical activity c-Raf/MEK1/ERK study, cobimetinib inhibited MEK1activity with a IC50 value of 0.9 nM. Additionally, in MDA-MB-231T breast
Applications
adenocarcinoma cells with KRAS G13D and B-RAF G464V mutant, cobimetinibwas found to be able to inhibit MEK with the IC50 value of 0.2 nM.
Animal experiment [1]:Animal modelsMDA-MB-231T mouse xenograft modelDosage form0.3-30 mg/kg, oral, qd
In an MDA-MB-231T efficacy study, cobimetinib demonstrated tumor growthinhibition values of 60 and 93% at 1 and 3 mg/kg, respectively, and statisticallysignificant tumor regression was observed at higher doses. Overall, predicted
Application
ED50 and ED90 values were 0.6 and around 3 mg/kg/day, respectively, in thelatter case corresponding to peak circulating plasma levels in the range of 130nM.
Please test the solubility of all compounds indoor, and the actual solubility may
Other notesslightly differ with the theoretical value. This is caused by an experimental
system error and it is normal.
References:
[1] Rice KD, Aay N, Anand NK, et al. Novel Carboxamide-Based Allosteric MEK Inhibitors: Discoveryand Optimization Efforts toward XL518 (GDC-0973). ACS Med Chem Lett, 2012, 3(5): 416-421.
Background
Cobimetinib is a selective inhibitor of mitogen-activated protein kinase kinase (MEK) with IC50 valueof 0.9 nM [1].
MEK is a kinase enzyme which selectively phosphorylates Ser/Thr and Tyr residues and involved in themitogen-activated protein kinase (MAPK) signaling pathways that play an important role in regulationof cell proliferation, survival, differentiation, motility and angiogenesis [2].
In a KRAS G13D and B-RAF G464V mutant MDA-MB-231T breast adenocarcinoma cells, Cobimetinibinhibited MEK with IC50 value of 0.2 nM [1]. In pharmacokinetic-pharmacodynamic (PK-PD) model,
Caution: Producthasnot been fully validated for medical applications. For research use only.
Tel: (626) 353-8530 Fax: (626) 353-8530 E-mail: tech@glpbio.com
Address: 10292 Central Ave. #205, Montclair, CA, USA
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Peptides, Inhibitors, Agonists
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Product Data Sheet
Cobimetinib showed a sustained tumor pharmacodynamic response due to longer residence in tumorthan in plasma [3].
In WM-266-4 xenograft mice, Cobimetinib decreased %pERK in tumor with IC50 values of 0.78(WM-266-4) and 0.52 mM. Also, Cobimetinib (3.89 mM) increased IC50 value in WM-266-4 mice. InA375 xenograft mice, Cobimetinib (0.3-30 mg/kg) showed antitumor efficacy in a dose-dependentway. Cobimetinib is currently in phase I clinical trials as a potential antitumor agent [3].References:
[1]. Rice KD, Aay N, Anand NK, et al. Novel Carboxamide-Based Allosteric MEK Inhibitors: Discoveryand Optimization Efforts toward XL518 (GDC-0973). ACS Med Chem Lett, 2012, 3(5): 416-421.
[2]. Akinleye A, Furqan M, Mukhi N, et al. MEK and the inhibitors: from bench to bedside. J HematolOncol, 2013, 6: 27.
[3]. Wong H, Vernillet L, Peterson A, et al. Bridging the gap between preclinical and clinical studiesusing pharmacokinetic-pharmacodynamic modeling: an analysis of GDC-0973, a MEK inhibitor. ClinCancer Res, 2012, 18(11): 3090-3099.
Caution: Producthasnot been fully validated for medical applications. For research use only.
Tel: (626) 353-8530 Fax: (626) 353-8530 E-mail: tech@glpbio.com
Address: 10292 Central Ave. #205, Montclair, CA, USA
3www.glpbio.com
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