| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 50mg |
|
||
| Other Sizes |
| Targets |
EGFR
Rezivertinib targets the epidermal growth factor receptor (EGFR), specifically selective EGFR mutations. It is a third-generation EGFR TKI with high potency against common EGFR activating and resistant T790M mutations. By covalently binding to and inhibiting these mutants, it prevents EGFR mutant-mediated signaling and leads to cell death in EGFR mutant-expressing tumor cells. Its selectivity for the T790M mutation is a key feature. |
|---|---|
| ln Vitro |
In cell lines with GI50 values of 13.3 nM (PC9, del19), 6.8 nM (HCC827, L858R), 22 nM (NCI-H1975, del19/T790M), and > 1000 nM (A431, EGFR WT), rezivertinib (BPI-7711) specifically inhibits the cellular proliferation of EGFR mutations[1].
In vitro, Rezivertinib has been shown to be a potent inhibitor of EGFR kinase activity. Its activity is assessed using kinase assays and cell-based proliferation assays in NSCLC cell lines harboring EGFR mutations. These studies confirm its potential as a therapeutic agent for EGFR-mutant NSCLC. |
| ln Vivo |
Significant tumor regression is observed when rezivertinib (BPI-7711; 6.25–25 mg/kg/day; oral; 14 days) is used[2]. The H1975-luc human NSCLC mouse model had an average survival time of 112% longer when rezivertinib (12.5 mg/kg/day; oral; 14 days) is administered[2]. The anti-tumor activity of rezivertinib (50 mg/kg/day; oral) has been linked to an increase in the animals' average overall survival of 115% (28 days vs. 13 days)[2].
In vivo, Rezivertinib has demonstrated antitumor activity in preclinical models. Its oral bioavailability and potent activity against EGFR mutations support its evaluation in clinical settings for the treatment of NSCLC. It may have therapeutic benefits in patients with T790M-mediated drug resistance. |
| Enzyme Assay |
Cell-free assays for Rezivertinib typically involve measuring its inhibitory activity against wild-type and mutant EGFR kinases using biochemical kinase assays. The compound's IC50 values are determined by measuring the phosphorylation of a substrate in the presence of varying concentrations of the inhibitor. These assays are used to characterize the compound's potency and selectivity.
|
| Cell Assay |
In vitro cellular assays are conducted to evaluate the functional activity of Rezivertinib. NSCLC cell lines harboring EGFR mutations, including the T790M mutation, are treated with the compound. Cell viability and proliferation are measured to assess the compound's anti-proliferative effects. EGFR phosphorylation is also measured to confirm inhibition of the target kinase.
|
| Animal Protocol |
In vivo animal experiments typically involve xenograft models of NSCLC with EGFR mutations. Mice bearing these tumors are administered Rezivertinib orally. Tumor growth is monitored over time to assess the compound's efficacy. These studies are essential for demonstrating the in vivo antitumor activity of the compound.
|
| ADME/Pharmacokinetics |
The pharmacokinetic properties of Rezivertinib are characteristic of an orally bioavailable small molecule inhibitor. Its molecular formula is C27H30N6O3, and it has a CAS number of 1835667-12-3. The compound is designed to have favorable drug-like properties, including good oral bioavailability and metabolic stability, to support once-daily dosing.
|
| Toxicity/Toxicokinetics |
The toxicity profile of Rezivertinib is likely consistent with other third-generation EGFR TKIs. Common adverse effects may include diarrhea, skin rash, and fatigue. Its selectivity for mutant EGFR over wild-type EGFR may lead to a more favorable safety profile with reduced skin and gastrointestinal toxicities.
|
| References |
|
| Additional Infomation |
Rezivertinib is an oral, third-generation selective epidermal growth factor receptor (EGFR) inhibitor that inhibits certain EGFR activating mutations, including resistance mutations T790M and L858R, as well as exon 19 deletions, and possesses potential antitumor activity. After administration, rezivertinib specifically covalently binds to and inhibits specific EGFR mutations, exhibiting particularly high selectivity for the T790M mutation, thereby blocking EGFR mutation-mediated signaling and leading to the death of EGFR-mutant tumor cells. Compared to some other EGFR inhibitors, rezivertinib may offer a therapeutic advantage against T790M-mediated resistant tumors. The drug has very low activity against wild-type EGFR (wt EGFR) and does not cause the dose-limiting toxicities observed with non-selective EGFR inhibitors (which also inhibit wt EGFR). EGFR is a receptor tyrosine kinase that is mutated in many tumor cell types and plays a crucial role in tumor cell proliferation and tumor angiogenesis.
Rezivertinib is a third-generation EGFR TKI developed to overcome T790M-mediated resistance in NSCLC. Its mechanism of action involves covalent binding to mutant EGFR. The compound is in clinical development for the treatment of EGFR-mutant NSCLC. It represents a promising therapeutic option for patients who have developed resistance to earlier-generation EGFR inhibitors. |
| Molecular Formula |
C27H30N6O3
|
|---|---|
| Molecular Weight |
486.57
|
| Exact Mass |
486.237
|
| CAS # |
1835667-12-3
|
| PubChem CID |
118912975
|
| Appearance |
White to yellow solid powder
|
| Density |
1.2±0.1 g/cm3
|
| Index of Refraction |
1.617
|
| LogP |
3.53
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
7
|
| Rotatable Bond Count |
10
|
| Heavy Atom Count |
36
|
| Complexity |
724
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
CN1C=C(C2=CC=CC=C21)C3=NC(=NC=C3)NC4=CC(=C(C=C4OC)OCCN(C)C)NC(=O)C=C
|
| InChi Key |
BPMZUKYFIDPLEA-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C27H30N6O3/c1-6-26(34)29-22-15-21(24(35-5)16-25(22)36-14-13-32(2)3)31-27-28-12-11-20(30-27)19-17-33(4)23-10-8-7-9-18(19)23/h6-12,15-17H,1,13-14H2,2-5H3,(H,29,34)(H,28,30,31)
|
| Chemical Name |
N-[2-[2-(dimethylamino)ethoxy]-4-methoxy-5-[[4-(1-methylindol-3-yl)pyrimidin-2-yl]amino]phenyl]prop-2-enamide
|
| 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 |
| 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: 125 mg/mL (256.90 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.27 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 20.8 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: ≥ 2.08 mg/mL (4.27 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0552 mL | 10.2760 mL | 20.5520 mL | |
| 5 mM | 0.4110 mL | 2.0552 mL | 4.1104 mL | |
| 10 mM | 0.2055 mL | 1.0276 mL | 2.0552 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.
Link: https://clinicaltrials.gov/ct2/show/NCT06955325
Conditions:Non-Small Cell Lung CancerLink: https://clinicaltrials.gov/ct2/show/NCT03866499
Conditions:NSCLCLink: https://clinicaltrials.gov/ct2/show/NCT03812809
Conditions:NSCLC
Title:BPI-7711 Capsule in Patients With EGFR Mutation T790M Positive Non-small Cell Lung Cancer
Status:Completed
updateDate:2022-05-16
Ctid:NCT03386955
Link: https://clinicaltrials.gov/ct2/show/NCT03386955
Conditions:Non-small Cell Lung CancerLink: https://clinicaltrials.gov/ct2/show/NCT04135833
Conditions:NSCLCLink: https://clinicaltrials.gov/ct2/show/NCT04135820
Conditions:NSCLCProducts are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
