| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| 25mg | |||
| 50mg | |||
| Other Sizes |
| Targets |
EGFR/HER2
EGFR (Epidermal Growth Factor Receptor) and HER2 (Human Epidermal Growth Factor Receptor 2). |
|---|---|
| ln Vitro |
When it comes to HER2-negative cell lines (BT474, SK-OV-3), parotinib is quite effective, while its inhibitory effects are less pronounced when it comes to MDA-MB-231. It blocks the actions of BT474 and SK-OV. -3Pyrotinib cells have respective IC50 values of 5.1 and 43 nM[1].
Pyrotinib binds to and inhibits both EGFR and HER2 tyrosine kinases in cell-free enzymatic assays. The racemate is expected to show similar inhibitory activity against both targets, though individual enantiomers may have different potencies. IC50 values for the active enantiomer are in the low nanomolar range. |
| ln Vivo |
Pyrotinib's effective bioavailability was found in 20.6%, 43.5%, and 13.5% of nude mice, sediments, and dogs, respectively. At dosages of 5 mg/kg, 10 mg/kg, and 20 mg/kg, respectively, the TGI% (growth inhibition) of pyrotinib on day 21 was 109%, 157%, and 159%. Pyrotinib demonstrated TGI% on day 21 in the ovarian xenograft model SK-OV-3 of 2%, 12%, and 83% at doses of 2.5 mg/kg, 5 mg/kg, and 10 mg/kg, respectively). This additional evidence supports Pyrotinib's strong in vivo anti-tumor effectiveness at 10 mg/kg [1].
In vivo, Pyrotinib inhibits tumor growth and angiogenesis in EGFR/HER2-expressing tumor xenograft models. Oral administration leads to tumor regression in preclinical models. The racemate is expected to show similar antitumor efficacy, though the active enantiomer is responsible for most of the therapeutic effect. |
| Enzyme Assay |
EGFR and HER2 kinase assays are performed using purified recombinant enzymes. The compound is incubated with ATP and a peptide substrate. Phosphorylation is measured using time-resolved fluorescence or radiometric methods. IC50 values are determined from concentration-response curves.
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| Cell Assay |
Cancer cell lines expressing EGFR/HER2 (e.g., BT-474, SK-BR-3, or NCI-N87) are treated with the compound. Cell proliferation (MTS assay), apoptosis (caspase-3 activation), and downstream signaling (p-EGFR, p-AKT, p-ERK) are measured.
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| Animal Protocol |
Mouse xenograft models using EGFR/HER2-positive tumor cell lines are employed. Tumor-bearing mice are treated orally with Pyrotinib Racemate. Tumor volume, body weight, and survival are monitored. Tumor tissues are collected for pharmacodynamic analysis of EGFR/HER2 signaling inhibition.
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| ADME/Pharmacokinetics |
Pyrotinib has good oral bioavailability (~50-60%) and a half-life of approximately 8-12 hours in humans. The racemate may show slightly different pharmacokinetic properties compared to the pure enantiomer due to differential metabolism of the two enantiomers.
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| Toxicity/Toxicokinetics |
Common side effects include diarrhea, rash, and hand-foot syndrome. The racemate may have a different toxicity profile compared to the pure active enantiomer due to the presence of the inactive or less active enantiomer.
|
| References | |
| Additional Infomation |
Pyrotinib (as the pure active enantiomer) is an approved anticancer drug in China for the treatment of HER2-positive breast cancer. The racemate is used for research purposes to study the pharmacological properties of both enantiomers and to develop analytical methods for quality control of Pyrotinib formulations.
|
| Molecular Formula |
C32H31CLN6O3
|
|---|---|
| Molecular Weight |
583.079945802689
|
| Exact Mass |
582.214
|
| Elemental Analysis |
C, 65.92; H, 5.36; Cl, 6.08; N, 14.41; O, 8.23
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| CAS # |
1246089-97-3
|
| Related CAS # |
Pyrotinib;1269662-73-8
|
| PubChem CID |
49847911
|
| Appearance |
Typically exists as light yellow to yellow solids at room temperature
|
| LogP |
5.4
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
8
|
| Rotatable Bond Count |
10
|
| Heavy Atom Count |
42
|
| Complexity |
960
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
CCOC1=C(C=C2C(=C1)N=CC(=C2NC3=CC(=C(C=C3)OCC4=CC=CC=N4)Cl)C#N)NC(=O)/C=C/C5CCCN5C
|
| InChi Key |
SADXACCFNXBCFY-IYNHSRRRSA-N
|
| InChi Code |
InChI=1S/C32H31ClN6O3/c1-3-41-30-17-27-25(16-28(30)38-31(40)12-10-24-8-6-14-39(24)2)32(21(18-34)19-36-27)37-22-9-11-29(26(33)15-22)42-20-23-7-4-5-13-35-23/h4-5,7,9-13,15-17,19,24H,3,6,8,14,20H2,1-2H3,(H,36,37)(H,38,40)/b12-10+/t24-/m1/s1
|
| Chemical Name |
N-(4-((3-chloro-4-(pyridin-2-ylmethoxy)phenyl)amino)-3-cyano-7-ethoxyquinolin-6-yl)-3-(1-methylpyrrolidin-2-yl)acrylamide
|
| Synonyms |
SHR-1258; SHR1258; (Rac)-Pyrotinib; Pyrotinib Racemate; 1246089-97-3; Pyrotinib (Racemate); (Rac)-SHR-1258; SCHEMBL9948627; SADXACCFNXBCFY-ZRDIBKRKSA-N; AKOS040756574; SHR 1258
|
| 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 : ~1.81 mg/mL (~3.10 mM)
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|---|---|
| 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 | 1.7150 mL | 8.5752 mL | 17.1503 mL | |
| 5 mM | 0.3430 mL | 1.7150 mL | 3.4301 mL | |
| 10 mM | 0.1715 mL | 0.8575 mL | 1.7150 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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