| Size | Price | Stock | Qty |
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| 50mg |
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| 100mg |
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| 500mg | |||
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| Targets |
AMP-945 targets focal adhesion kinase (FAK), a non-receptor tyrosine kinase that plays a key role in cell adhesion, migration, proliferation, and survival. FAK is involved in the formation of scar tissue (fibrosis) in diseases such as cancer and IPF. AMP-945 acts primarily through competitive inhibition of FAK by binding to its active site, preventing the phosphorylation of specific tyrosine residues crucial for FAK's activation and downstream signaling. It is highly selective for FAK across 468 kinases in screening assays.
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| ln Vitro |
AMP-945 binds to FAK with a KD of 0.21 nM. It inhibits autophosphorylation of 397Y-FAK in MDA-MB-231 cells with an IC50 of 7 nM. The compound exhibits low general cellular toxicity with an IC50 of 2.7 μM in MDA-MB-231 cells. Its high selectivity for FAK across 468 kinases indicates a favorable kinase selectivity profile. AMP-945 suppresses downstream signaling pathways associated with cancer cell proliferation and survival.
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| ln Vivo |
In vivo, AMP-945 has emerged as a promising therapeutic candidate for the treatment of pancreatic cancer and fibrosis. It shows potential in combination with standard-of-care agents such as gemcitabine and nab-paclitaxel for pancreatic cancer treatment. The compound possesses pharmacokinetic properties suitable for further development. In vivo efficacy studies have demonstrated its ability to inhibit tumor growth and reduce fibrosis in relevant disease models.
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| Enzyme Assay |
FAK kinase activity is measured using in vitro kinase assays with recombinant FAK enzyme. The assay is performed in kinase buffer containing ATP and a peptide substrate. AMP-945 is incubated at varying concentrations, and phosphorylation is measured using HTRF or radiometric methods. IC50 values are calculated from dose-response curves. Binding affinity (KD) is determined using surface plasmon resonance (SPR) or isothermal titration calorimetry (ITC).
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| Cell Assay |
Cellular activity of AMP-945 is evaluated in FAK-dependent cancer cell lines such as MDA-MB-231 breast cancer cells. Cells are treated with escalating concentrations of AMP-945 for 48-72 hours. FAK autophosphorylation at Tyr397 is assessed by Western blot using phospho-specific antibodies. Cell viability is measured using CellTiter-Glo or MTT assays to determine cytotoxicity. The IC50 for FAK phosphorylation inhibition is 7 nM, while general cytotoxicity is observed at 2.7 μM.
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| Animal Protocol |
In vivo efficacy of AMP-945 is evaluated in xenograft mouse models or fibrosis models. Tumor-bearing or fibrosis-induced mice are administered AMP-945 orally at various doses. Tumor volume is measured bi-weekly, and tissue samples are collected for pharmacodynamic analysis. FAK phosphorylation in tumor or fibrotic tissues is assessed by immunohistochemistry or Western blot. Efficacy is evaluated by measuring tumor growth inhibition or reduction in fibrosis markers.
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| ADME/Pharmacokinetics |
AMP-945 has favorable pharmacokinetic properties suitable for further development. It has a molecular formula of C28H32F3N5O2 and a molecular weight of 527.58. The compound is soluble in DMSO at ≥60 mg/mL. It is stable when stored at 4°C, protected from light, in a dry, sealed container. AMP-945 is orally active. Its selectivity for FAK across 468 kinases contributes to its favorable pharmacokinetic and safety profile.
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| Toxicity/Toxicokinetics |
AMP-945 exhibits low general cellular toxicity with an IC50 of 2.7 μM in MDA-MB-231 cells. It is highly selective for FAK across 468 kinases, minimizing off-target effects. In preclinical studies, the compound is well-tolerated at efficacious doses. As a research compound, comprehensive toxicology profiling would be required for clinical development. The compound is for research use only and not for human therapeutic use.
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| References | |
| Additional Infomation |
AMP-945 is also known as Narmafotinib. It is a proprietary FAK inhibitor being developed for the treatment of fibrotic diseases and pancreatic cancer. The compound shows potential in combination with gemcitabine and nab-paclitaxel. Its high selectivity for FAK across 468 kinases makes it a valuable tool for studying FAK biology and validating FAK as a therapeutic target. AMP-945 supports research in oncology, fibrosis, and cell adhesion signaling pathways.
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| Molecular Formula |
C28H32F3N5O2
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|---|---|
| Molecular Weight |
527.5812
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| Exact Mass |
527.25
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| Elemental Analysis |
C, 63.74; H, 6.11; F, 10.80; N, 13.27; O, 6.06
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| CAS # |
1393653-34-3
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| Related CAS # |
1393653-34-3;
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| PubChem CID |
60162119
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| Appearance |
White to light yellow solid powder
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| LogP |
4.6
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
38
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| Complexity |
749
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| Defined Atom Stereocenter Count |
0
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| SMILES |
FC(C1=C([H])N=C(N=C1C([H])([H])C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1C([H])([H])C(N([H])[H])=O)N([H])C1C([H])=C([H])C(=C([H])C=1OC([H])([H])[H])C1([H])C([H])([H])C([H])([H])N(C([H])([H])[H])C([H])([H])C1([H])[H])(F)F
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| InChi Key |
AWJVIOYPZZZYAX-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C28H32F3N5O2/c1-36-13-11-19(12-14-36)21-8-10-24(25(15-21)38-2)35-27-33-17-22(28(29,30)31)23(34-27)9-7-18-5-3-4-6-20(18)16-26(32)37/h3-6,8,10,15,17,19H,7,9,11-14,16H2,1-2H3,(H2,32,37)(H,33,34,35)
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| Chemical Name |
2-[2-[2-[2-[2-Methoxy-4-(1-methylpiperidin-4-yl)anilino]-5-(trifluoromethyl)pyrimidin-4-yl]ethyl]phenyl]acetamide
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| Synonyms |
AMP945, amp945, Narmafotinib
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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 Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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) |
DMSO : ~100 mg/mL (~189.54 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.74 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (4.74 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (4.74 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8954 mL | 9.4772 mL | 18.9545 mL | |
| 5 mM | 0.3791 mL | 1.8954 mL | 3.7909 mL | |
| 10 mM | 0.1895 mL | 0.9477 mL | 1.8954 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.
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