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AMG 925

Catalog No.GC14974

AMG 925 Chemical Structure

FLT3/CDK4 inhibitor,potent and selective

Size Price Stock Qty
5mg
$78.00
In stock
25mg
$205.00
In stock
100mg
$412.00
In stock
500mg
$1,133.00
In stock
1g
$1,957.00
In stock

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Sample solution is provided at 25 µL, 10mM.

Quality Control

Quality Control & SDS

View current batch:

Protocol

Cell experiment[1]:

Cell lines

MOLM13, MOLM13SR, and U937 cells

Preparation method

The solubility of this compound in DMSO is 10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.

Reacting condition

48 h, 1 µM

Applications

AMG 925 is an effective and orally bioavailable dual inhibitor of FLT3 and CDK4. AMG 925 inhibits the proliferation of a batch of human tumor cell lines, including Colo205 (Rb+) and U937 (FLT3WT) cells. AMG 925 also induced apoptosis in FLT3 mutant AML cells, including MOLM13 (FLT3ITD) and MOLM13 (FLT3ITD, D835Y) cells.

Animal experiment [2]:

Animal models

NCR nude mice

Dosage form

Oral administration with 12.5, 25, 37.5, and 50 mg/kg. Twice a day for 10 consecutive days.

Application

AMG 925 inhibited the growth of AML xenograft tumor in a dose-dependent manner without significant body weight loss. The concentrations of AMG 925 in plasma correlated with the inhibition of RB and STAT5 phosphorylation, which are markers for inhibition of CDK4 and FLT3, respectively.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

References:

[1]. Li Z, Wang X, Eksterowicz J, et al. Discovery of AMG 925, a FLT3 and CDK4 dual kinase inhibitor with preferential affinity for the activated state of FLT3[J]. Journal of medicinal chemistry, 2014, 57(8): 3430-3449..

[2]. Keegan K, Li C, Li Z, et al. Preclinical evaluation of AMG 925, a FLT3/CDK4 dual kinase inhibitor for treating acute myeloid leukemia[J]. Molecular cancer therapeutics, 2014, 13(4): 880-889.

Background

AMG 925 is a dual inhibitor of FLT3/CDK4 kinase with IC50 values of 2nM and 3nM, respectively [1].

AMG 925 is a potent, selective, and orally available FLT3/CDK4 dual inhibitor. It also inhibits CDK6 potently in kinase assay. In acute myeloid leukemia (AML) cell lines MOLM13 and Mv4-11, AMG 925 inhibits cell growth (IC50 values of 19nM and 18nM, respectively) through inhibiting P-FLT3 and P-STAT5 and inducing apoptosis. FLT3 mutants cause resistance to the current FLT3 inhibitors. AMG 925 is reported to inhibit cell growth in AML cells with FLT3 mutants FLT3-D835Y and FLT3-D835V. In AML tumor –bearing mice, administration of AMG 925 shows inhibition of P-STAT5 and P-RB as well as cell growth both in subcutaneous MOLM13 xenograft tumor model and systemic MOLM13-Luc xenograft tumor model. AMG 925 is also reported to have antitumor activity in a dose-dependent manner in theRB-positive Colo205 colon adenocarcinoma xenograft model [1].

References:
[1] Keegan K, Li C, Li Z, Ma J, Ragains M, Coberly S, Hollenback D, Eksterowicz J, Liang L, Weidner M, Huard J, Wang X, Alba G, Orf J, Lo MC, Zhao S, Ngo R, Chen A, Liu L, Carlson T, Quéva C, McGee LR, Medina J, Kamb A, Wickramasinghe D, Dai K. Preclinical evaluation of AMG 925, a FLT3/CDK4 dual kinase inhibitor for treating acute myeloid leukemia. Mol Cancer Ther. 2014 Apr;13(4):880-9.

Chemical Properties

Cas No. 1401033-86-0 SDF
Synonyms N/A
Chemical Name N/A
Canonical SMILES C[C@H]1CC[C@H](N2C3=CN=CC=C3C4=CN=C(NC5=NC6=C(CN(C(CO)=O)CC6)C=C5)N=C24)CC1
Formula C26H29N7O2 M.Wt 471.55
Solubility <0.94mg/mL in DMSO Storage Store at -20°C
General tips For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.
Shipping Condition Evaluation sample solution : ship with blue ice
All other available size: ship with RT , or blue ice upon request

In vivo Formulation Calculator (Clear solution)

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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.

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Average Rating: 5 ★★★★★ (Based on Reviews and 13 reference(s) in Google Scholar.)

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