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Purity: ≥98%
AMG 925 (also called FLX-925; AMG-925) is a novel, potent, selective and orally bioavailable FLT3/CDK4 dual inhibitor with potential antitumor activity. Its IC50 values for FLT3/CDK4 inhibition are 1 nM and 3 nM, respectively. By inhibiting P-FLT3 and P-STAT5 and causing apoptosis, AMG 925 inhibits cell growth with IC50 values of 19 nM and 18 nM, respectively, and demonstrates excellent anti-proliferative activity in vitro. AMG 925 treatment inhibits P-STAT5 and P-RB as well as cell growth in both the systemic MOLM13-Luc xenograft tumor model and the subcutaneous MOLM13 xenograft tumor model, demonstrating its high in vivo antitumor efficacy in mice bearing AML tumors.
| Targets |
FLT3 (IC50 = 2 nM); CDK4 (IC50 = 3 nM); CDK6 (IC50 = 8 nM); CDK2 (IC50 = 375 nM); CDK1 (IC50 = 1.9 μM)
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| Enzyme Assay |
AMG 925 also has IC50s of 8±2 nM, 375±150 nM, and 1.90±0.51 μM for CDK6, CDK2, and CDK1 inhibition in kinase tests, respectively. Based on KinomScan's analysis of 442 different kinases, AMG 925 has a fair overall kinase selectivity.
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| Cell Assay |
MOLM13 and Mv4-11 are employed. By transfecting MOLM13 cells with the pLV218G luciferin/lentivector, which expresses luciferase under the murine EF1α promoter, MOLM13-Luc cells are created. By passing the cells through growth media containing increasing concentrations of sorafenib (1–1 nM), sorafenib-resistant MOLM13 (MOLM13sr) and Mv4-11 (Mv4-11sr) can be isolated. A DNA synthesis assay is used to quantify cell growth. In a 96-well Cytostar T plate, 5×103 cells/well are seeded with a total volume of 160 μL. Test compounds (such as AMG 925; 0.03 and 0.3μM) are added to each well of the plate in increments of 20 μL/0.1 μCi after being serially diluted into each well (20 μL/well). After an additional 72 hours of incubation, isotope incorporation is measured with a β plate counter. The Vybrant Apoptosis Assay Kit is used to test for apoptosis. In summary, 5×105 cells per well of a 6-well plate are seeded, and compounds (such as AMG 925; 0.003, 0.01, 0.03, 0.1, 0.3, and 1 μM) are applied for a full day. After staining the cells using the kit's included reagents, the cells are examined using flow cytometry. The resolution of living, apoptotic, and dead cells—which are quantified using the Flowjo software—is displayed in the Sytox Green fluorescence versus allophycocyanin fluorescence dot plot. After subjecting the cells to AMG 925 treatment for a full day, the CycleTest Kit is used to analyze the cell cycle. The cells are treated with AMG 925 for 24 hours, and then the CycleTest Kit is used to analyze the cell cycle. Using the ModFit software, 10,000 events are collected, and the percentages of cells in each cycle phase are computed[1].
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| Animal Protocol |
Mice: NCR-Foxn1nu (CrTac:NCR) nude mice are employed. On the flank of NCR nude mice, 2×106 cells are inoculated, and they are left to grow for 13 days. AMG 925 is then given orally to mice twice a day, six hours apart, at doses of 12.5, 25, 37.5, and 50 mg/kg for ten days in a row[1].
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| References | ||
| Additional Infomation |
AMG-925 is an organic heterotricyclic compound that is 9H-pyrido[4',3':4,5]pyrrolo[2,3-d]pyrimidine which is substituted by a [6-(hydroxyacetyl)-5,6,7,8-tetrahydro-1,6-naphthyridin-2-yl]nitrilo group at position 2 and by a trans-4-methylcyclohexyl group at position 9. It is a FLT3 and CDK4 dual kinase inhibitor that has antineoplastic activity. Currently under clinical investigation in patients with relapsed or refractory acute myeloid leukemia (AML). It has a role as an antineoplastic agent, an apoptosis inducer, an EC 2.7.11.22 (cyclin-dependent kinase) inhibitor and an EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor. It is a secondary amino compound, a tertiary amino compound, a naphthyridine derivative, a primary alpha-hydroxy ketone and an organic heterotricyclic compound.
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| Molecular Formula |
C26H29N7O2
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| Molecular Weight |
471.55
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| Exact Mass |
471.238
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| Elemental Analysis |
C, 66.22; H, 6.20; N, 20.79; O, 6.79
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| CAS # |
1401033-86-0
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| Related CAS # |
AMG 925 HCl;1401034-19-2
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| PubChem CID |
60202647
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| Appearance |
white solid powder
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| Density |
1.5±0.1 g/cm3
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| Boiling Point |
712.3±70.0 °C at 760 mmHg
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| Flash Point |
384.6±35.7 °C
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| Vapour Pressure |
0.0±2.4 mmHg at 25°C
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| Index of Refraction |
1.766
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| LogP |
1.67
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
35
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| Complexity |
747
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1(NC2C=CC3CN(C(CO)=O)CCC=3N=2)N=CC2C3C=CN=CC=3N([C@H]3CC[C@H](C)CC3)C=2N=1
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| InChi Key |
BBUVDDPUURMFOX-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C26H29N7O2/c1-16-2-5-18(6-3-16)33-22-13-27-10-8-19(22)20-12-28-26(31-25(20)33)30-23-7-4-17-14-32(24(35)15-34)11-9-21(17)29-23/h4,7-8,10,12-13,16,18,34H,2-3,5-6,9,11,14-15H2,1H3,(H,28,29,30,31)
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| Chemical Name |
2-hydroxy-1-[2-[[8-(4-methylcyclohexyl)-4,6,8,11-tetrazatricyclo[7.4.0.02,7]trideca-1(9),2,4,6,10,12-hexaen-5-yl]amino]-7,8-dihydro-5H-1,6-naphthyridin-6-yl]ethanone
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| Synonyms |
FLX 925; AMG925; FLX925; FLX-925; AMG-925; AMG 925
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1207 mL | 10.6033 mL | 21.2067 mL | |
| 5 mM | 0.4241 mL | 2.1207 mL | 4.2413 mL | |
| 10 mM | 0.2121 mL | 1.0603 mL | 2.1207 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Activity of AMG 925 in subcutaneous MOLM13 xenograft tumor model.Mol Cancer Ther. 2014 Apr;13(4):880-9. |
Activity of AMG 925 in systemic MOLM13-Luc xenograft tumor model. Mol Cancer Ther. 2014 Apr;13(4):880-9. |
Activity of AMG 925 in Colo205 xenograft tumor model. Mol Cancer Ther. 2014 Apr;13(4):880-9. |
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