2. Protein Tyrosine Kinase/RTK Cell Cycle/DNA Damage
  3. FLT3 CDK
  4. AMG 925

AMG 925 is a potent, selective, and orally available FLT3/CDK4 dual inhibitor with IC50s of 2±1 nM and 3±1 nM, respectively.

For research use only. We do not sell to patients.

AMG 925 Chemical Structure

AMG 925 Chemical Structure

CAS No. : 1401033-86-0

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Customer Review

Based on 2 publication(s) in Google Scholar

Other Forms of AMG 925:

AMG 925 Related Antibodies

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CDK1 CDK2 CDK3 CDK4 CDK5 CDK6 CDK7 CDK8 CDK9 CDK11 CDK12 CDK13 CDK14 CDK16 CDK19 CDC CLK Pho85

  • Biological Activity

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  • Purity & Documentation

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  • Customer Review

Description

AMG 925 is a potent, selective, and orally available FLT3/CDK4 dual inhibitor with IC50s of 2±1 nM and 3±1 nM, respectively.

IC50 & Target[1]

FLT3

2 nM (IC50)

CDK4

3 nM (IC50)

CDK6

8 nM (IC50)

CDK2

375 nM (IC50)

CDK1

1.9 μM (IC50)

Cellular Effect
Cell Line Type Value Description References
COLO 205 IC50
0.055 μM
Compound: 28, AMG 925
Antiproliferative activity against Rb-positive human COLO205 cells assessed as incorporation of [3H]thymidine into DNA after 72 hrs by beta-plate counting analysis
Antiproliferative activity against Rb-positive human COLO205 cells assessed as incorporation of [3H]thymidine into DNA after 72 hrs by beta-plate counting analysis
[PMID: 24641103]
MDA-MB-436 IC50
3.83 μM
Compound: 28, AMG 925
Antiproliferative activity against Rb-negative human MDA-MB-436 cells assessed as incorporation of [3H]thymidine into DNA after 72 hrs by beta-plate counting analysis
Antiproliferative activity against Rb-negative human MDA-MB-436 cells assessed as incorporation of [3H]thymidine into DNA after 72 hrs by beta-plate counting analysis
[PMID: 24641103]
MOLM-13 IC50
0.005 μM
Compound: 28, AMG 925
Inhibition of FLT3 ITD mutant in human MOLM13 cells assessed as inhibition of STAT5 phosphorylation at Tyr694 after 24 hrs
Inhibition of FLT3 ITD mutant in human MOLM13 cells assessed as inhibition of STAT5 phosphorylation at Tyr694 after 24 hrs
[PMID: 24641103]
MOLM-13 IC50
0.019 μM
Compound: 28, AMG 925
Antiproliferative activity against human MOLM13 cells harboring FLT3 ITD mutant assessed as incorporation of [3H]thymidine into DNA after 72 hrs by beta-plate counting analysis
Antiproliferative activity against human MOLM13 cells harboring FLT3 ITD mutant assessed as incorporation of [3H]thymidine into DNA after 72 hrs by beta-plate counting analysis
[PMID: 24641103]
MOLM-13 IC50
0.023 μM
Compound: 28, AMG 925
Inhibition of CDK4 in human MOLM13 cells assessed as inhibition of Rb phosphorylation at Ser780 after 24 hrs
Inhibition of CDK4 in human MOLM13 cells assessed as inhibition of Rb phosphorylation at Ser780 after 24 hrs
[PMID: 24641103]
MOLM-13 IC50
0.023 μM
Compound: 28, AMG 925
Antiproliferative activity against sorafenib-resistant human MOLM13 cells assessed as incorporation of [3H]thymidine into DNA after 72 hrs by beta-plate counting analysis
Antiproliferative activity against sorafenib-resistant human MOLM13 cells assessed as incorporation of [3H]thymidine into DNA after 72 hrs by beta-plate counting analysis
[PMID: 24641103]
MOLM-13 IC50
0.028 μM
Compound: 28, AMG 925
Antiproliferative activity against human MOLM13 cells harboring FLT3 ITD mutant assessed as incorporation of [3H]thymidine into DNA after 4 months by beta-plate counting analysis
Antiproliferative activity against human MOLM13 cells harboring FLT3 ITD mutant assessed as incorporation of [3H]thymidine into DNA after 4 months by beta-plate counting analysis
[PMID: 24641103]
MOLM-13 ED50
22 mg/kg
Compound: 28, AMG 925
Antitumor activity against human MOLM13 cells xenografted in po dosed CrTac:NCR-Foxn1nu (NCR) nude mouse assessed as tumor growth inhibition administered qd for 8 days
Antitumor activity against human MOLM13 cells xenografted in po dosed CrTac:NCR-Foxn1nu (NCR) nude mouse assessed as tumor growth inhibition administered qd for 8 days
[PMID: 24641103]
U-937 IC50
0.052 μM
Compound: 28, AMG 925
Antiproliferative activity against human U937 cells assessed as incorporation of [3H]thymidine into DNA after 72 hrs by beta-plate counting analysis
Antiproliferative activity against human U937 cells assessed as incorporation of [3H]thymidine into DNA after 72 hrs by beta-plate counting analysis
[PMID: 24641103]
In Vitro

AMG 925 also inhibits CDK6, CDK2, and CDK1 in kinase assays with IC50s of 8±2 nM, 375±150 nM, 1.90±0.51 μM, respectively. A fair overall kinase selectivity of AMG 925 is as determined by KinomScan against a panel of 442 various kinases. Cellular selectivity (on-target vs. off-target activity) of AMG 925 is about 50-fold as evaluated by comparison of its growth-inhibiting activity in RB-positive (RB+) and RB-negative (RB-) non- acute myeloid leukemia (AML) cancer cell lines. AMG 925 potently inhibits growth of AML cell lines MOLM13 (FLT3-ITD; IC50=19 μM) and Mv4-11 (FLT3-ITD; IC50=18 μM)[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

AMG 925 Related Antibodies
In Vivo

MOLM13 tumor-bearing mice are dosed twice daily by oral administration 6 hours apart with 12.5, 25, or 37.5 mg/kg AMG 925. Tumors are then harvested 3, 9, 12, and 24 hours after the first dose, and analyzed for levels of P-STAT5 and P-RB. Maximum inhibition of P-STAT5 and P-RB is achieved at 6 and 12 hours respectively at the 37.5 mg/kg dose of AMG 925. Interestingly, a rebound of P-STAT5 at 24 hours is observed, possibly as a result of compensational feedback. The pharmacodynamic responses of P-STAT5 and P-RB inhibition correlated with plasma concentrations of AMG 925. AMG 925 inhibits AML xenograft tumor growth by 96% to 99% without significant body weight loss. The antitumor activity of AMG 925 correlates with the inhibition of STAT5 and retinoblastoma protein (RB) phosphorylation, the pharmacodynamic markers for inhibition of FLT3 and CDK4, respectively. In addition, AMG 925 is also found to inhibit FLT3 mutants (e.g., D835Y) that are resistant to the current FLT3 inhibitors (e.g., AC220 and Sorafenib)[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Molecular Weight

471.55

Formula

C26H29N7O2
CAS No.
Appearance

Solid

Color

Off-white to light yellow

SMILES

OCC(N1CC2=C(N=C(NC3=NC=C4C(N([C@H]5CC[C@H](C)CC5)C6=CN=CC=C64)=N3)C=C2)CC1)=O
Shipping

Room temperature in continental US; may vary elsewhere.
Storage
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 2 years
-20°C 1 year
Solvent & Solubility
In Vitro: 

H2O : < 0.1 mg/mL (insoluble)

DMSO : < 1 mg/mL (insoluble or slightly soluble)

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Purity & Documentation
References
Cell Assay
[1]

MOLM13 and Mv4-11 are used. MOLM13-Luc cells are constructed by transduction of MOLM13 cells with the pLV218G luciferin/lentivector, which expresses luciferase under the murine EF1α promoter. Sorafenib-resistant MOLM13 (MOLM13sr) and Mv4-11 (Mv4-11sr) are isolated by passaging the cells in growth medium containing increasing concentrations of Sorafenib (1-1 nM). Cell growth is measured by a DNA synthesis assay. Cells are seeded in a 96-well Cytostar T plate at a density of 5×103 cells/well in a total volume of 160 μL. Test compounds (e.g., AMG 925; 0.03 and 0.3μM) are serially diluted into the plate (20 μL/well) and 20 μL/0.1 μCi of [14C]-Thymidine added to each well. Isotope incorporation is determined using a β plate counter after further 72-hour incubation. Apoptosis is assayed by using the Vybrant Apoptosis Assay Kit. Briefly, cells are seeded into a 6-well plate at 5×105 cells per well and treated with compounds (e.g., AMG 925; 0.003, 0.01, 0.03, 0.1, 0.3, and 1 μM) for 24 hours. The cells are then stained with reagents provided in the kit and analyzed by flow cytometry. The Sytox Green fluorescence versus allophycocyanin fluorescence dot plot shows resolution of live, apoptotic, and dead cells, which are quantified using the Flowjo software. The cell-cycle analysis is done by treating the cells with AMG 925 for 24 hours followed by using the CycleTest Kit. Ten thousand events are acquired and the proportions of cells in each cycle phase are calculated using the ModFit software[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration
[1]

Mice[1]
CrTac:NCR-Foxn1nu (NCR) nude mice are used. 2×106 cells are innoculated on the flank of NCR nude mice and allowed to grow for 13 days. Mice are then dosed twice a day by oral administration 6 hours apart with 12.5, 25, 37.5, and 50 mg/kg of AMG 925 for 10 consecutive days[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.
References
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AMG 925 Related Classifications

Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

AMG 9251401033-86-0AMG925AMG-925FLT3CDKCluster of differentiation antigen 135CD135Fms like tyrosine kinase 3Cyclin dependent kinaseInhibitorinhibitorinhibit

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