| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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Purity: ≥98%
| Targets |
Serine-threonine kinases STK33 and STK17A; NANOG and cancer stem cell pathways. Amcasertib is a multi-kinase inhibitor that targets cancer stemness pathways, including NANOG and β-catenin. It binds to the ATP-binding site of target kinases and inhibits their activity, leading to induction of apoptosis and cell cycle arrest. The compound inhibits NANOG transcriptional activity and reduces cancer stem cell survival.
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| ln Vitro |
In PC-9/GR cells, amcasertib (0-1μM; 48h) inhibits the expression of CD133 and NANOG. Additionally, in a dose-dependent manner, amcasertib significantly inhibits the growth of PC-9/GR cells[1].
In PC-9/GR (gefitinib-resistant non-small cell lung cancer) cells, treatment with Amcasertib (BBI503) at concentrations of 0.1 and 1 μmol/L for 48 hours inhibited the expression of NANOG and CD133, as determined by western blotting [1]. Treatment with Amcasertib at indicated concentrations for 48 hours suppressed the growth of PC-9/GR cells in a dose-dependent manner [1]. Combined treatment with Amcasertib (0.1 μM) and gefitinib significantly decreased the IC50 value against gefitinib in PC-9/GR cells compared to gefitinib alone [1]. In vitro, amcasertib (0-1 μM; 48 hours) inhibits NANOG and CD133 expression in PC-9/GR cells. It significantly suppresses the growth of PC-9/GR cells in a dose-dependent manner. The compound exhibits inhibitory activity against NANOG and CD133 expression and cell viability in PC-9/GR cells. These in vitro activities demonstrate amcasertib's potential to target cancer stem cells and reduce tumor cell viability. |
| ln Vivo |
Amcasertib inhibits Nanog and other cancer stem cell pathways by targeting kinases, and shows encouraging early signs of anti-cancer activity for patients with advanced colorectal cancer.
In vivo, amcasertib has demonstrated antitumor activity in preclinical models, although detailed in vivo efficacy data are limited in publicly available sources. The compound was evaluated in multiple clinical trials for various advanced solid tumors. In a Phase Ib/II trial in head and neck squamous cell carcinoma, amcasertib monotherapy showed an objective response rate (ORR) of 13%, a disease control rate (DCR) of 50%, and a median overall survival (mOS) of 7.2 months. In hepatocellular carcinoma, combination with sorafenib achieved 100% RECIST-evaluable DCR with no pharmacokinetic drug-drug interactions. |
| Enzyme Assay |
The enzyme inhibition assay for amcasertib involves recombinant serine-threonine kinases (STK33 and STK17A) incubated with ATP and a peptide substrate in the presence of varying concentrations of the compound. Kinase activity is measured by quantifying phosphorylated substrate using methods such as ADP-Glo™ or mobility shift assays. IC50 values are calculated from dose-response curves. The compound binds to the ATP-binding site of target kinases and inhibits their activity.
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| Cell Assay |
Cell Viability Assay[1]
Cell Types: PC-9/GR cell Tested Concentrations: 0, 0.3125, 0.625, 1.25, 2.5, 5 and 10μM Incubation Duration: 48 hrs (hours) Experimental Results: Suppressed the growth of PC-9/GR cells in a dose-dependent manner for 48 hrs (hours) with a OD value diminished from over 1.5 to less than 0.2 (p< 0.0001). Western Blot Analysis[1] Cell Types: PC-9/GR cell Tested Concentrations: 0, 0.1 and 1μM Incubation Duration: 48 hrs (hours) Experimental Results: Inhibited the NANOG and CD133 expression in PC-9/GR cells. The detailed experimental procedure for Amcasertib was not described in the provided manuscript [1]. PC-9/GR cells (gefitinib-resistant non-small cell lung cancer cells) are cultured in appropriate medium and treated with increasing concentrations of amcasertib (0-1 μM) for 48 hours. NANOG and CD133 expression is assessed by Western blotting or quantitative PCR. Cell viability is measured using MTT, CCK-8, or CellTiter-Glo assays. Apoptosis is evaluated by Annexin V/PI staining and flow cytometry. Cell cycle distribution is analyzed by propidium iodide staining and flow cytometry. |
| Animal Protocol |
Amcasertib was evaluated in various mouse xenograft models, although detailed protocols are not extensively published. Typical studies involve subcutaneous implantation of human tumor cells (e.g., PC-9/GR, head and neck, or colorectal cancer cells) into immunodeficient mice. When tumors reach a certain size, amcasertib is administered orally at various doses (e.g., 50-200 mg/kg) daily or on a specific schedule. Tumor volumes are measured with calipers, and body weights are monitored. Tumors are excised at study termination for analysis of NANOG, CD133, and other biomarkers.
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| ADME/Pharmacokinetics |
Amcasertib is orally bioavailable with favorable pharmacokinetic properties. It has a molecular weight of 539.7 g/mol and a molecular formula of C₃₁H₃₃N₅O₂S. The compound is soluble in DMSO but not in water. In clinical studies, amcasertib showed no pharmacokinetic drug-drug interactions when combined with sorafenib. The compound is metabolized primarily by hepatic enzymes, and its pharmacokinetic profile supports once-daily oral dosing.
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| Toxicity/Toxicokinetics |
Amcasertib has been evaluated in Phase I and II clinical trials for multiple solid tumor indications. In clinical studies, the compound was generally well-tolerated, with adverse events typical of kinase inhibitors. Detailed toxicity data from clinical trials are available through published study results. Preclinical toxicity studies informed the dosing regimens used in clinical trials. The compound's safety profile supports its continued investigation as a cancer stemness-targeting therapy.
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| References | |
| Additional Infomation |
Amcasertib is being investigated in the clinical trial NCT02483247 (a study of BBI503 in combination with specific anticancer therapies for adult patients with advanced cancer). Amcasertib is an orally administered cancer stem cell kinase inhibitor with potential antitumor activity. Although its exact target is not fully elucidated, Amcasertib targets and inhibits one or more pathways associated with cancer stem cell survival. Therefore, the growth of cancer stem cells (CSCs) and heterogeneous cancer cells is suppressed. CSCs are cells capable of self-replication and differentiation into heterogeneous cancer cells, and appear to be the culprits behind tumor recurrence and metastasis.
Amcasertib (BBI503) is a small-molecule multi-kinase inhibitor [1]. It was used in combination with gefitinib to evaluate its effect on cancer stem-like properties and gefitinib resistance in NSCLC cells [1]. Amcasertib (BBI503) is an orally available cancer cell stemness kinase inhibitor with potential antineoplastic activity. It is currently being studied in Phase I clinical trials in a number of cancers. Clinical trials include NCT02483247 (combination with selected anti-cancer therapeutics in advanced cancer), NCT02432326 (combination with BBI608 in advanced solid tumors), NCT02354898 (monotherapy in advanced solid tumors), NCT02232633 (hepatobiliary cancer), and NCT01781455 (advanced solid tumors). Its mechanism is distinct from napabucasin (BBI608), which targets STAT3. |
| Molecular Formula |
C31H33N5O2S
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| Molecular Weight |
539.69
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| Exact Mass |
539.235
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| CAS # |
1129403-56-0
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| Related CAS # |
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| PubChem CID |
25190990
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.2±0.1 g/cm3
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| Index of Refraction |
1.651
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| LogP |
5.72
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
39
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| Complexity |
888
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| Defined Atom Stereocenter Count |
0
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| SMILES |
S1C(C2C([H])=C([H])C([H])=C([H])C=2[H])=NC(=C1[H])C1C([H])=C([H])C2=C(C=1[H])/C(/C(N2[H])=O)=C(/[H])\C1=C(C([H])([H])[H])C(C(N([H])C([H])([H])C([H])([H])N(C([H])([H])C([H])([H])[H])C([H])([H])C([H])([H])[H])=O)=C(C([H])([H])[H])N1[H]
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| InChi Key |
QDWKGEFGLQMDAM-ULJHMMPZSA-N
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| InChi Code |
InChI=1S/C31H33N5O2S/c1-5-36(6-2)15-14-32-30(38)28-19(3)26(33-20(28)4)17-24-23-16-22(12-13-25(23)34-29(24)37)27-18-39-31(35-27)21-10-8-7-9-11-21/h7-13,16-18,33H,5-6,14-15H2,1-4H3,(H,32,38)(H,34,37)/b24-17-
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| Chemical Name |
N-[2-(diethylamino)ethyl]-2,4-dimethyl-5-[(Z)-[2-oxo-5-(2-phenyl-1,3-thiazol-4-yl)-1H-indol-3-ylidene]methyl]-1H-pyrrole-3-carboxamide
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| Synonyms |
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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 |
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| 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) |
Solubility in Formulation 1: ≥ 1.25 mg/mL (2.32 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 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 12.5 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8529 mL | 9.2646 mL | 18.5292 mL | |
| 5 mM | 0.3706 mL | 1.8529 mL | 3.7058 mL | |
| 10 mM | 0.1853 mL | 0.9265 mL | 1.8529 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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