WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 406521
CAS#: 1401033-86-0
Description: FLX925, also known as AMG-925, is a potent and selective type 1 inhibitor of FLT3 that retains its cellular potency against clinically relevant secondary resistance mutations in FLT3 occurring with quizartinib or sorafenib treatment (FLX925 IC50: MOLM13ITD, 15 nM; MOLM13ITD/D835, 28 nM; MV4-11ITD, 16 nM; MV4-11ITD/D835, 19 nM; MV4-11ITD/N841, 16 nM; MV4-11ITD/F691, 73 nM).
MedKoo Cat#: 406521
Name: FLX925 (AMG-925)
CAS#: 1401033-86-0
Chemical Formula: C26H29N7O2
Exact Mass: 471.23827
Molecular Weight: 471.55
Elemental Analysis: C, 66.22; H, 6.20; N, 20.79; O, 6.79
Synonym: AMG925; AMG-925; AMG 925; FLX925; FLX-925; FLX 925.
IUPAC/Chemical Name: 2-hydroxy-1-(2-((9-((1r,4r)-4-methylcyclohexyl)-9H-pyrido[4',3':4,5]pyrrolo[2,3-d]pyrimidin-2-yl)amino)-7,8-dihydro-1,6-naphthyridin-6(5H)-yl)ethanone
InChi Key: BBUVDDPUURMFOX-SAABIXHNSA-N
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)/t16-,18-
SMILES Code: C[C@H]1CC[C@H](N2C3=CN=CC=C3C4=CN=C(NC5=NC6=C(CN(C(CO)=O)CC6)C=C5)N=C42)CC1
Appearance: white solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
| Biological target: | AMG 925 is a potent, selective, and orally available FLT3/CDK4 dual inhibitor with IC50s of 2±1 nM and 3±1 nM, respectively. |
| In vitro activity: | 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). |
| In vivo activity: | 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). Reference: Mol Cancer Ther. 2014 Apr;13(4):880-9. http://mct.aacrjournals.org/cgi/pmidlookup?view=long&pmid=24526162 |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 0.01 | 0.02 |
The following data is based on the product molecular weight 471.55 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| In vitro protocol: | 1. Li C, Liu L, Liang L, Xia Z, Li Z, Wang X, McGee LR, Newhall K, Sinclair A, Kamb A, Wickramasinghe D, Dai K. AMG 925 is a dual FLT3/CDK4 inhibitor with the potential to overcome FLT3 inhibitor resistance in acute myeloid leukemia. Mol Cancer Ther. 2015 Feb;14(2):375-83. doi: 10.1158/1535-7163.MCT-14-0388. Epub 2014 Dec 8. PMID: 25487917. 2. 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. doi: 10.1158/1535-7163.MCT-13-0858. Epub 2014 Feb 13. PMID: 24526162. |
| In vivo protocol: | 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. doi: 10.1158/1535-7163.MCT-13-0858. Epub 2014 Feb 13. PMID: 24526162. |
1: Li Z, Wang X, Eksterowicz J, Gribble MW Jr, Alba GQ, Ayres M, Carlson TJ, Chen A, Chen X, Cho R, Connors RV, Degraffenreid M, Deignan JT, Duquette J, Fan P, Fisher B, Fu J, Huard JN, Kaizerman J, Keegan KS, Li C, Li K, Li Y, Liang L, Liu W, Lively SE, Lo MC, Ma J, McMinn DL, Mihalic JT, Modi K, Ngo R, Pattabiraman K, Piper DE, Queva C, Ragains ML, Suchomel J, Thibault S, Walker N, Wang X, Wang Z, Wanska M, Wehn PM, Weidner MF, Zhang AJ, Zhao X, Kamb A, Wickramasinghe D, Dai K, McGee LR, Medina JC. Discovery of AMG 925, a FLT3 and CDK4 Dual Kinase Inhibitor with Preferential Affinity for the Activated State of FLT3. J Med Chem. 2014 Apr 24;57(8):3430-49. doi: 10.1021/jm500118j. Epub 2014 Apr 2. PubMed PMID: 24641103.
2: 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. doi: 10.1158/1535-7163.MCT-13-0858. Epub 2014 Feb 13. PubMed PMID: 24526162.
