| Size | Price | Stock | Qty |
|---|---|---|---|
| 10mg |
|
||
| 100mg | |||
| 250mg | |||
| Other Sizes |
| Targets |
EGFRT790M (IC50 = 0.37 nM); EGFRL858R/T790M (IC50 = 0.29 nM); EGFRdel19 T790M (IC50 = 0.21 nM)
Almonertinib mesylate targets the epidermal growth factor receptor (EGFR), a receptor tyrosine kinase that is frequently mutated in non-small cell lung cancer. The compound is a third-generation EGFR TKI with high selectivity for EGFR-sensitizing mutations (such as exon 19 deletions and L858R) and the T790M resistance mutation. It is less effective against wild-type EGFR (3.39 nM). By irreversibly binding to the EGFR kinase domain, the compound inhibits EGFR signaling and suppresses tumor growth. |
|---|---|
| ln Vitro |
NSCLC patients may benefit from the usage of HS-10296 mesylate, an oral epidermal growth factor receptor (EGFR) mutant T790M inhibitor with possible anti-tumor action [2]. Moreover, G719X, del19, L858R, and L861Q are among the various EGFR-sensitive mutations that HS-10296 mesylate can suppress [3].
In vitro, Almonertinib mesylate inhibits EGFR tyrosine kinase activity with high selectivity for mutant EGFR over wild-type EGFR. It shows potent anti-proliferative activity against NSCLC cell lines harboring EGFR-sensitizing and T790M mutations. The compound irreversibly binds to the EGFR kinase domain, providing sustained inhibition. However, specific IC50 values and detailed in vitro activity data are not extensively reported in the available literature. |
| ln Vivo |
The experimental results of nude mice showed that compared with the control group and the positive control ositinib (AZD9291) group, the tumor growth was significantly inhibited, the weight of nude mice, the tumor volume and the tumor mass were significantly reduced in the almonertinib treatment group (all P<0.05)[4].
In vivo, Almonertinib mesylate has been studied in animal models of NSCLC. As an orally active EGFR TKI, it shows efficacy in xenograft models of EGFR-mutant NSCLC. The compound's high selectivity for mutant EGFR over wild-type EGFR may result in a better safety profile compared to earlier-generation EGFR TKIs. However, specific in vivo efficacy data and dosing regimens are not extensively detailed. |
| Enzyme Assay |
In vitro enzyme/receptor binding assays for Almonertinib mesylate typically involve kinase activity assays using purified recombinant EGFR enzymes (wild-type, L858R, T790M, and double mutant). The assay is performed in 96-well plates with kinase buffer containing ATP and a peptide substrate. The compound (0.001-100 μM) is incubated with the enzyme and substrate at 30°C for 60 minutes. Phosphorylated substrate is detected using a specific antibody in an ELISA or TR-FRET format. IC50 values are determined from dose-response curves.
|
| Cell Assay |
NSCLC cells H1975 and PC-9 were cultured in vitro. The effects of almonertinib on the proliferation, apoptosis, invasion, and migration of H1975 and PC-9 cells were detected by CCK-8 assay, apoptotic assay and Transwell assay. The expression of invasion and migration related proteins was detected by Western blotting[4].
In vitro cellular assays for Almonertinib mesylate use NSCLC cell lines such as HCC827 (exon 19 deletion), H1975 (L858R/T790M), and A549 (wild-type EGFR). Cells are cultured in RPMI-1640 with 10% FBS and treated with various concentrations of the compound (0.001-10 μM) for 48-72 hours. Cell viability is assessed using MTT or CellTiter-Glo assays. EGFR phosphorylation and downstream signaling (AKT, ERK) are assessed by Western blotting. Apoptosis is assessed by caspase-3/7 activity. |
| Animal Protocol |
Centrifuge H1975 cells, wash with PBS, and suspend in serum-free RPMI 1640 medium. Then inject 3 × 106 cells per mouse subcutaneously into the right shoulder of 4-6 week old nude mice. After the tumor grows to 100 mm3, it will be randomly divided into three groups, with 5 mice in each group. Each group will be given 0.2 mL of dimethyl sulfoxide, 5 mg/kg AZD9291, and 5 mg/kg of amitinib by gavage, once every two days. Monitor the weight and tumor size of nude mice before each injection. The tumor volume is 2/2 of its length and width, and the entire process lasts for 21 days[4].
In vivo animal studies with Almonertinib mesylate use mouse xenograft models of NSCLC. Immunodeficient mice are implanted subcutaneously with H1975 or HCC827 cells. When tumors reach approximately 100-200 mm3, mice are treated with the compound orally at doses of 1-30 mg/kg daily for 2-4 weeks. Tumor volume is measured every 2-3 days. At study termination, tumors are harvested for analysis of EGFR phosphorylation, proliferation (Ki67), and apoptosis (cleaved caspase-3). |
| ADME/Pharmacokinetics |
Pharmacokinetic properties of Almonertinib mesylate: The compound is orally active, indicating good oral bioavailability. It is soluble in DMSO at 31.25 mg/mL (50.26 mM). Specific PK parameters such as Cmax, Tmax, AUC, half-life, and tissue distribution are not extensively reported. The compound is expected to be metabolized by hepatic CYP450 enzymes. As a third-generation TKI, it is designed to have improved pharmacokinetic properties compared to earlier-generation TKIs.
|
| Toxicity/Toxicokinetics |
The toxicity profile of Almonertinib mesylate is not extensively reported. As an EGFR TKI, potential toxicities may include rash, diarrhea, and hepatotoxicity, which are common to this class of drugs. The high selectivity for mutant EGFR may result in a better safety profile. The compound is for research use only and not for human therapeutic use. Standard toxicity studies would include acute and subchronic toxicity in rodents.
|
| References |
[1]. Safety, Efficacy, and Pharmacokinetics of Almonertinib (HS-10296) in Pretreated Patients With EGFR-Mutated Advanced NSCLC: A Multicenter, Open-label, Phase 1 Trial [published online ahead of print, 2020 Sep 9]. J Thorac Oncol. 2020;S1556-0.
[2]. Next-Generation EGFR Tyrosine Kinase Inhibitors for Treating EGFR-Mutant Lung Cancer beyond First Line. Front Med (Lausanne). 2017 Jan 18;3:76. [3]. Management of acquired resistance to EGFR TKI-targeted therapy in advanced non-small cell lung cancer. Mol Cancer. 2018 Feb 19;17(1):38. [4]. Effect of almonertinib on the proliferation, invasion, and migration in non-small cell lung cancer cells. Zhong Nan Da Xue Xue Bao Yi Xue Ban . 2021 Oct 28;46(10):1045-1053. |
| Additional Infomation |
Almonertinib mesylate (CAS 2134096-06-1, HS-10296 mesylate) is an oral, irreversible, third-generation EGFR tyrosine kinase inhibitor with high selectivity for EGFR-sensitizing and T790M resistance mutations. It has a molecular formula of C30H35N7O2 · CH4O3S and a molecular weight of 621.75. The compound is used in non-small cell lung cancer research and is available for research purposes only.
|
| Molecular Formula |
C31H39N7O5S
|
|---|---|
| Molecular Weight |
621.75
|
| Exact Mass |
621.273
|
| Elemental Analysis |
C, 59.89; H, 6.32; N, 15.77; O, 12.87; S, 5.16
|
| CAS # |
2134096-06-1
|
| Related CAS # |
Almonertinib;1899921-05-1;Almonertinib hydrochloride;2134096-03-8; Almonertinib mesylate;2134096-06-1;Almonertinib hydrochloride;2134096-03-8; 1899921-05-1; 2134096-04-9 (sulfate); 2134096-07-2 (fumarate); 2134096-08-3
|
| PubChem CID |
162368359
|
| Appearance |
Typically exists as light yellow to yellow solids at room temperature
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
10
|
| Rotatable Bond Count |
11
|
| Heavy Atom Count |
44
|
| Complexity |
916
|
| Defined Atom Stereocenter Count |
0
|
| InChi Key |
WTEXJDGTVUQRQY-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C30H35N7O2.CH4O3S/c1-6-29(38)32-24-17-25(28(39-5)18-27(24)36(4)16-15-35(2)3)34-30-31-14-13-23(33-30)22-19-37(20-11-12-20)26-10-8-7-9-21(22)26;1-5(2,3)4/h6-10,13-14,17-20H,1,11-12,15-16H2,2-5H3,(H,32,38)(H,31,33,34);1H3,(H,2,3,4)
|
| Chemical Name |
N-[5-[[4-(1-cyclopropylindol-3-yl)pyrimidin-2-yl]amino]-2-[2-(dimethylamino)ethyl-methylamino]-4-methoxyphenyl]prop-2-enamide;methanesulfonic acid
|
| Synonyms |
HS-10296 Mesylate; Aumolertinib mesylate; Almonertinib (mesylate); RZ6I9WX68U; Aumolertinib mesylate [USAN]; N-(5-((4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide mesylate;
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO : ~31.25 mg/mL (~50.26 mM)
|
|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6084 mL | 8.0418 mL | 16.0836 mL | |
| 5 mM | 0.3217 mL | 1.6084 mL | 3.2167 mL | |
| 10 mM | 0.1608 mL | 0.8042 mL | 1.6084 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
