| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
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| ln Vitro |
Tumor cell lines are resistant to the anti-proliferative effects of SPH5030 (0–10 μM; 72 hours) [1].
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|---|---|
| ln Vivo |
SPH5030 (5–40 mg/kg; given orally once daily for 13 or 21 days) showed anti-tumor activity in vivo in mice with xenograft tumor models [1]. Rats and mice's 1.19 pharmacokinetic characteristics of SPH5030 [1]. Rat IV 3 mg/kg, Rat PO 10 mg/kg, Rat PO 6 mg/kg, and CL (L/kg·h) 0.70±0.20 0.78±0.13 t1/2 (h) 3.76± 0.15 3.60±0.59 4.56±0.20 4.38±0.35 Vss (L/kg) 2.96±0.96 3.55±0.64 Cmax (μg/mL) 1.90±0.14 0.76±0.33 tmax (h) 2.67±1.15 3.33±1.15 AUC0-t (h · μg/mL) 13.07±0.48 5.47±2.82 F (%) 87.66 71.35
|
| Cell Assay |
Cytotoxicity assay[1]
Cell Types: NCI-N87, BT-474, SK-BR-3 overexpressing HER2, MDA-MB-468 overexpressing EGFR, NCI-H441, Es-2, MFE-280, NUGC -4, COLO678, KM12-luc and BaF3 cell lines Tested Concentrations: 0-10 μM Incubation Duration: 72 hrs (hours) Experimental Results: Effective inhibition of HER2 overexpression in NCI-N87, BT-474, SK-BR-3 and BaF3 cells, IC50 respectively are 1.09, 2.01, 20.09 and 6.3 nM, respectively. The inhibitory effect on EGFR overexpressing MDA-MB-468, NCI-H441, Es-2, MFE-280, NUGC-4, COLO678 and KM12-luc cells was poor, with IC50 of 2980, 4257, 2716, 3967, respectively. 1218, 6065 and 3597 nM, respectively. |
| Animal Protocol |
Animal/Disease Models: BALB/c nude mice NCI-N87 and BT474 xenografts, NPSG mice BAF3 HER2 A775_G776insYVMA xenografts [1]
Doses: 5, 10 , 20 and 40 mg/kg Dosing: po (oral gavage); 5-40 mg/kg one time/day for 13 or 21 days Experimental Results: NCI-N87, BT474 and BAF3 HER2 A775_G776 in YVMA xenograft mouse model Inhibited tumor growth in a dose-dependent manner, showing equivalent or better tumor inhibitory activity than neratinib and pyrotinib at a dose of 20 mg/kg. No mortality or significant weight loss was demonstrated in the xenograft mouse model. |
| References | |
| Additional Infomation |
HER2 Inhibitor SPH5030 is an orally bioavailable, irreversible inhibitor of the receptor tyrosine kinase human epidermal growth factor receptor 2 (HER2; ErbB2; HER-2), with potential antineoplastic activity. Upon oral administration, HER2 inhibitor SPH5030 selectively binds to and inhibits the activity of wild-type and various HER2 mutants. This prevents HER2-mediated signaling and may lead to cell death in HER2-expressing tumor cells. HER2, a receptor tyrosine kinase overexpressed on a variety of tumor cell types, plays an important role in tumor cell proliferation and tumor vascularization.
|
| Molecular Formula |
C31H31FN8O3
|
|---|---|
| Molecular Weight |
582.628049135208
|
| Exact Mass |
582.25
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| CAS # |
2364326-23-6
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| PubChem CID |
137535407
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| Appearance |
Typically exists as solid at room temperature
|
| LogP |
4.8
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
9
|
| Heavy Atom Count |
43
|
| Complexity |
975
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
CCOC1=C(C=C2C(=C1)N=CN=C2NC3=CC(=C(C=C3)OC4=CC5=NC=NN5C=C4)C)NC(=O)/C(=C/[C@H]6CCCN6C)/F
|
| InChi Key |
HTAMCULFUCGZAM-FKYOTISTSA-N
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| InChi Code |
InChI=1S/C31H31FN8O3/c1-4-42-28-16-25-23(15-26(28)38-31(41)24(32)13-21-6-5-10-39(21)3)30(35-17-33-25)37-20-7-8-27(19(2)12-20)43-22-9-11-40-29(14-22)34-18-36-40/h7-9,11-18,21H,4-6,10H2,1-3H3,(H,38,41)(H,33,35,37)/b24-13-/t21-/m1/s1
|
| Chemical Name |
(Z)-N-[7-ethoxy-4-[3-methyl-4-([1,2,4]triazolo[1,5-a]pyridin-7-yloxy)anilino]quinazolin-6-yl]-2-fluoro-3-[(2R)-1-methylpyrrolidin-2-yl]prop-2-enamide
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: (1). This product requires protection from light (avoid light exposure) during transportation and storage. (2). Please store this product in a sealed and protected environment (e.g. under nitrogen), 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 : ≥ 100 mg/mL (~171.64 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 | 1.7164 mL | 8.5818 mL | 17.1636 mL | |
| 5 mM | 0.3433 mL | 1.7164 mL | 3.4327 mL | |
| 10 mM | 0.1716 mL | 0.8582 mL | 1.7164 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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