| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| 50mg | |||
| Other Sizes |
| Targets |
Target: EGFR (IC50 = 13.0 nM) [1]
ErbB2 (IC50 = 22.5 nM) [1] |
|---|---|
| ln Vitro |
In Vitro: A previous pharmacodynamic study confirmed that Selatinib and lapatinib exhibit the same dual EGFR/ErbB2 inhibition specificity, with IC50 values of 13.0 nM (EGFR) and 22.5 nM (ErbB2) for Selatinib [1].
Selatinib has markedly improved water solubility compared to lapatinib to meet the solubility requirements of oral drugs [1]. |
| ADME/Pharmacokinetics |
ADME/Pharmacokinetics: In healthy Chinese subjects, following single oral doses of Selatinib ditosilate tablets from 50 to 500 mg, the mean peak plasma concentration (Cmax) ranged from 69.4 ng/mL (50 mg) to 494 ng/mL (350 mg) and 486 ng/mL (500 mg). The median time to peak concentration (Tmax) ranged from 3.5 to 4.5 hours. The mean elimination half-life (t1/2) ranged from 13.8 to 15.8 hours. The area under the concentration-time curve (AUC0-t and AUC0-∞) increased with dose. The apparent volume of distribution (V/F) ranged from 853.2 L to 1650.8 L, and clearance (CL/F) ranged from 42.1 L/h to 77.3 L/h. The pharmacokinetics of Selatinib in the dose range of 50-500 mg conformed with linear characteristics. Selatinib is oxidatively metabolized in vivo to the active metabolite lapatinib [1].
In Part 2 (crossover study with 500 mg), after administration of Selatinib tablets (A) to healthy male subjects, the Cmax of Selatinib was 0.601 μg/mL, AUC0-t was 9.28 μg·h/mL, t1/2 was 15.6 h, and Tmax was 5.0 h. The Cmax of A-lapatinib (metabolite) was 0.206 μg/mL, AUC0-t was 4.88 μg·h/mL. After administration of Selatinib dry suspension (B), the Cmax of Selatinib was 0.556 μg/mL, AUC0-t was 8.78 μg·h/mL. The bioavailability of Selatinib tablets and suspension was similar (90% CI for Cmax, AUC0-t, AUC0-∞ ratios contained 1 but were not within 80-125% due to small sample size). After oral administration of Selatinib tablets (500 mg), the active drug exposure (sum of Selatinib and its metabolite lapatinib) was more than two-fold higher than that of the same dose of lapatinib tablets [1]. |
| Toxicity/Toxicokinetics |
Toxicity/Toxicokinetics: In Part 1 (single ascending dose 50-500 mg, n=52), Selatinib was well-tolerated up to 500 mg; the maximum tolerated dose (MTD) was not attained. Twenty-two adverse events (AEs) were observed in 19 (36.5%) of subjects. The most common drug-related adverse event was diarrhea (2 cases, 3.85%). Other AEs included constipation (1.92%), periodontal disease (1.92%), hematuria (3.85%), urine discoloration (5.77%), increased creatine phosphokinase (CPK) (9.62%), increased blood bilirubin (7.69%), leukocytosis (3.85%), decreased white blood cells (1.92%), and increased total serum bile acids (1.92%). All AEs were of grade 1-2 intensity, dose-independent, and self-resolving. No life-threatening AEs, QT prolongation, or liver toxicity were observed in this single-dose study. In Part 2 (n=6), 12 AEs were reported in 5 subjects, including diarrhea (3 cases with drug A, 3 with drug B, 3 with lapatinib), hematuria (1 with A), proteinuria (1 with B), and abdominal pain (1 with lapatinib); all were mild and resolved without treatment [1].
|
| References | |
| Additional Infomation |
Additional Info: Selatinib is a dual EGFR/ErbB2 tyrosine kinase inhibitor developed to overcome the poor water solubility and low oral bioavailability of lapatinib. Preclinical toxicology studies indicated lower liver toxicity and skin toxicity compared to lapatinib. This first-in-human study demonstrated acceptable safety and linear pharmacokinetics after single doses up to 500 mg in healthy Chinese subjects. The active exposure (selatinib plus its metabolite lapatinib) was more than two-fold higher than lapatinib at the same dose, supporting its further development as an adjuvant for anticancer treatment, particularly for cancers with high EGFR and ErbB2 expression such as gastric cancer, breast cancer, and non-small cell lung cancer [1].
|
| Molecular Formula |
C29H26CLFN4O3S
|
|---|---|
| Molecular Weight |
565.058147907257
|
| Exact Mass |
564.139
|
| CAS # |
1275595-86-2
|
| Related CAS # |
1452886-38-2 (ditosilate);1275595-86-2;
|
| PubChem CID |
51348455
|
| Appearance |
Yellow to orange solid powder
|
| Density |
1.4±0.1 g/cm3
|
| Boiling Point |
740.5±60.0 °C at 760 mmHg
|
| Flash Point |
401.6±32.9 °C
|
| Vapour Pressure |
0.0±2.4 mmHg at 25°C
|
| Index of Refraction |
1.676
|
| LogP |
4.81
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
9
|
| Rotatable Bond Count |
11
|
| Heavy Atom Count |
39
|
| Complexity |
787
|
| Defined Atom Stereocenter Count |
0
|
| InChi Key |
OAMVGUFHZPRXOM-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C29H26ClFN4O3S/c1-39(36)12-11-32-16-23-7-10-27(38-23)20-5-8-26-24(14-20)29(34-18-33-26)35-22-6-9-28(25(30)15-22)37-17-19-3-2-4-21(31)13-19/h2-10,13-15,18,32H,11-12,16-17H2,1H3,(H,33,34,35)
|
| Chemical Name |
N-[3-chloro-4-[(3-fluorophenyl)methoxy]phenyl]-6-[5-[(2-methylsulfinylethylamino)methyl]furan-2-yl]quinazolin-4-amine
|
| 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: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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 : ~100 mg/mL (~176.97 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 | 1.7697 mL | 8.8486 mL | 17.6972 mL | |
| 5 mM | 0.3539 mL | 1.7697 mL | 3.5394 mL | |
| 10 mM | 0.1770 mL | 0.8849 mL | 1.7697 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT01931943 | UNKNOWN STATUS | Drug: selatinib ditosilate tablets | Advanced Breast Cancer | Qilu Pharmaceutical Co., Ltd. | 2013-04 | Phase 1 |
|
|
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
