Physicochemical Properties
| Molecular Formula | C31H31FN8O3 |
| Molecular Weight | 582.628049135208 |
| Exact Mass | 582.25 |
| CAS # | 2364326-23-6 |
| PubChem CID | 137535407 |
| Appearance | Off-white to light yellow solid powder |
| LogP | 4.8 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 10 |
| 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 |
| 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 |
| 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: (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) |
Biological Activity
| ln Vitro | Tumor cell lines are resistant to the anti-proliferative effects of SPH5030 (0–10 μM; 72 hours) [1]. |
| 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 |
[1]. Discovery of SPH5030, a Selective, Potent, and Irreversible Tyrosine Kinase Inhibitor for HER2-Amplified and HER2-Mutant Cancer Treatment. J Med Chem. 2022 Apr 14;65(7):5334-5354. |
| 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. |
Solubility Data
| Solubility (In Vitro) | DMSO : ≥ 100 mg/mL (~171.64 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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (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 |