| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg | |||
| Other Sizes |
| Targets |
Mavelertinib targets the epidermal growth factor receptor (EGFR). It is an irreversible inhibitor, meaning it forms a covalent bond with a cysteine residue (Cys797) in the ATP-binding pocket of the EGFR kinase domain. This covalent binding provides prolonged inhibition. It is designed to be potent against both activating EGFR mutations and the T790M resistance mutation, while showing less activity against wild-type EGFR.
|
|---|---|
| ln Vitro |
Selectivity against wild-type EGFR is demonstrated by mavelertinib (IC50=307 nM)[1]. Less than 50% of non-kinase targets are affected or inhibited by mavelertinib (10 μM) [1]. With an IC50 > 100 μM, mavelertinib suppresses hERG26 current[1].
In vitro, Mavelertinib is a potent inhibitor of mutant EGFR kinases. It shows activity against EGFR with the T790M mutation and other activating mutations. Its activity is characterized by its IC50 values against these mutant kinases in biochemical assays. In cellular assays, it inhibits the proliferation of NSCLC cell lines harboring these mutations, including those resistant to first- and second-generation EGFR inhibitors. |
| ln Vivo |
Following oral dosing (1 in mice, 30 in rats, and 3 mg/kg in dogs), mavelertinib has low to moderate oral bioavailability (60% in mice, 11% in rats, and 66% in dogs) [1]. Intravenous injection (1 mg/kg) in small rats, rats, and dogs [1].
In vivo, Mavelertinib has demonstrated efficacy in preclinical models of NSCLC. In xenograft models bearing tumors with the T790M mutation, it induces tumor regression. Its in vivo activity is a result of its potent and irreversible inhibition of the mutant EGFR. It has also been evaluated in clinical trials for patients with EGFR-mutant NSCLC. |
| Enzyme Assay |
In vitro enzyme/receptor binding studies for Mavelertinib are performed using kinase activity assays. In these assays, the recombinant EGFR kinase domain (wild-type or mutant) is incubated with ATP and a substrate in the presence of varying concentrations of the inhibitor. The inhibition of kinase activity is measured, and the IC50 value is calculated.
|
| Cell Assay |
In vitro cellular assays for Mavelertinib are used to study its effects on cancer cells. Cells harboring EGFR mutations are treated with the compound. Key readouts include cell viability (MTT or CellTiter-Glo assays), apoptosis (Annexin V/PI staining), and the inhibition of EGFR phosphorylation and downstream signaling (Western blotting).
|
| Animal Protocol |
Animal/Disease Models: Female Nu/nu (nude) mice [1]
Doses: 1 mg/kg (pharmacokinetic/PK/PK analysis) Route of Administration: Po and iv Administration Experimental Results: Oral bioavailability (60%), T1/2 (1.48 h). In vivo animal studies for Mavelertinib are conducted in xenograft models. Tumor-bearing mice are treated with the compound, and tumor growth inhibition is measured. These studies confirm its in vivo efficacy against EGFR-mutant tumors. |
| ADME/Pharmacokinetics |
Pharmacokinetic properties of Mavelertinib include good oral bioavailability. It has a molecular weight of 588.74 g/mol and a formula of C30H28ClF2N7O3. It is metabolized in the liver. Its half-life supports once-daily dosing.
|
| Toxicity/Toxicokinetics |
Mavelertinib is a research compound and is not an approved drug. As an EGFR inhibitor, its side effects are likely similar to other drugs in its class, including skin rash, diarrhea, and interstitial lung disease. Its safety and efficacy have been evaluated in clinical trials.
|
| References |
|
| Additional Infomation |
Mavelertinib is being investigated in the clinical trial NCT02349633 (a study in patients with non-small cell lung cancer carrying EGFR mutations (Del 19 or L858R +/- T790M)). Mavelertinib is an oral epidermal growth factor receptor (EGFR) T790M mutant inhibitor with potential antitumor activity. Mavelertinib specifically binds to and inhibits EGFR T790M (a secondary acquired resistance mutation), thereby blocking EGFR-mediated signaling and leading to the death of tumor cells expressing EGFR/T790M. Compared to some other EGFR inhibitors, PF-06747775 may have a therapeutic advantage against tumors with T790M-mediated resistance. This drug has very low activity against wild-type EGFR (WT EGFR) and does not cause the dose-limiting toxicities associated with the use of non-selective EGFR inhibitors (which inhibit WT EGFR). EGFR is a receptor tyrosine kinase that can be mutated in various tumor cell types and plays a key role in tumor cell proliferation and tumor angiogenesis.
Mavelertinib is a third-generation EGFR inhibitor developed for the treatment of NSCLC. Its CAS number is 1776112-90-3. It is also known as PF06747775. It represents a strategy to overcome resistance to earlier EGFR inhibitors by targeting the T790M mutation. |
| Molecular Formula |
C18H22FN9O2
|
|---|---|
| Molecular Weight |
415.424785137177
|
| Exact Mass |
415.188
|
| CAS # |
1776112-90-3
|
| PubChem CID |
91668194
|
| Appearance |
White to off-white solid powder
|
| Density |
1.5±0.1 g/cm3
|
| Index of Refraction |
1.715
|
| LogP |
-1.82
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
9
|
| Rotatable Bond Count |
6
|
| Heavy Atom Count |
30
|
| Complexity |
643
|
| Defined Atom Stereocenter Count |
2
|
| SMILES |
CN1C=C(C(=N1)OC)NC2=C3C(=NC(=N2)N4C[C@H]([C@@H](C4)F)NC(=O)C=C)N(C=N3)C
|
| InChi Key |
JYIUNVOCEFIUIU-GHMZBOCLSA-N
|
| InChi Code |
InChI=1S/C18H22FN9O2/c1-5-13(29)21-11-8-28(6-10(11)19)18-23-15(14-16(24-18)26(2)9-20-14)22-12-7-27(3)25-17(12)30-4/h5,7,9-11H,1,6,8H2,2-4H3,(H,21,29)(H,22,23,24)/t10-,11-/m1/s1
|
| Chemical Name |
N-((3R,4R)-4-fluoro-1-(6-((3-methoxy-1-methyl-1H-pyrazol-4-yl)amino)-9-methyl-9H-purin-2-yl)pyrrolidin-3-yl)acrylamide
|
| Synonyms |
PF-06747775 PF6747775PF06747775 PF 6747775PF 06747775 PF-6747775
|
| 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 : ~47.5 mg/mL (~114.34 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 | 2.4072 mL | 12.0360 mL | 24.0720 mL | |
| 5 mM | 0.4814 mL | 2.4072 mL | 4.8144 mL | |
| 10 mM | 0.2407 mL | 1.2036 mL | 2.4072 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
