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

AMG 925 HCl 

Cat. No.: HY-15889A Purity: 98.01%
Handling Instructions

AMG 925 HCl 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 HCl Chemical Structure

AMG 925 HCl Chemical Structure

CAS No. : 1401034-19-2

Size Price Stock Quantity
5 mg USD 100 In-stock
Estimated Time of Arrival: December 31
10 mg USD 150 In-stock
Estimated Time of Arrival: December 31
50 mg USD 350 In-stock
Estimated Time of Arrival: December 31
100 mg USD 550 In-stock
Estimated Time of Arrival: December 31
200 mg   Get quote  
500 mg   Get quote  

* Please select Quantity before adding items.

Customer Review

Based on 1 publication(s) in Google Scholar

Other Forms of AMG 925 HCl:

Top Publications Citing Use of Products
  • Biological Activity

  • Protocol

  • Purity & Documentation

  • References

  • Customer Review

Description

AMG 925 HCl 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)

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].

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].

Molecular Weight

508.02

Formula

C₂₆H₃₀ClN₇O₂

CAS No.

1401034-19-2

SMILES

OCC(N1CC2=C(N=C(NC3=NC=C4C(N([[email protected]]5CC[[email protected]](C)CC5)C6=CN=CC=C64)=N3)C=C2)CC1)=O.Cl

Shipping

Room temperature in continental US; may vary elsewhere.

Storage
Powder -20°C 3 years
  4°C 2 years
In solvent -80°C 6 months
  -20°C 1 month
Solvent & Solubility
In Vitro: 

DMSO : 1 mg/mL (1.97 mM; Need ultrasonic)

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 1.9684 mL 9.8421 mL 19.6843 mL
5 mM --- --- ---
10 mM --- --- ---
*Please refer to the solubility information to select the appropriate solvent.
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
  • No file chosen (Maximum size is: 1024 Kb)
  • If you have published this work, please enter the PubMed ID.
  • Your name will appear on the site.
  • Molarity Calculator

  • Dilution Calculator

The molarity calculator equation

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass   Concentration   Volume   Molecular Weight *
= × ×

The dilution calculator equation

Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2

Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
× = ×
C1   V1   C2   V2

KeyWords:

AMG 925 HCl | FLT3 | CDK | Cluster of differentiation antigen 135 | CD135 | Fms like tyrosine kinase 3 | Cyclin dependent kinase | Inhibitor | inhibitor | inhibit

Your Recently Viewed Products:

Inquiry Online

Your information is safe with us. * Required Fields.

Product name

 

Salutation

Applicant name *

 

Email address *

Phone number *

 

Organization name *

Country or Region *

 

Requested quantity *

Remarks

Bulk Inquiry

Inquiry Information

Product name:
AMG 925 HCl
Cat. No.:
HY-15889A
Quantity:
MCE Japan Authorized Agent: