| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
| Targets |
HER2 (ErbB2, human epidermal growth factor receptor 2), a receptor tyrosine kinase. SPH5030 also inhibits EGFRWT but is more selective for HER2 (HER2WT IC50=3.51 nM vs EGFRWT IC50=8.13 nM, 2.3-fold selectivity).
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| ln Vitro |
Tumor cell lines are resistant to the anti-proliferative effects of SPH5030 (0–10 μM; 72 hours) [1].
SPH5030 potently inhibits wild-type HER2 (IC50=3.51 nM) and wild-type EGFR (IC50=8.13 nM) in enzymatic kinase assays. It also shows sub-nanomolar activity against HER2 mutants including D769H, D769Y, V777L, and R896C, making it effective against common resistance mutations. |
| 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
SPH5030 is orally bioavailable. In xenograft models (e.g., HER2-amplified NCI-N87 gastric cancer and patient-derived models), oral administration at 25-100 mg/kg once daily significantly inhibits tumor growth, with superior efficacy compared to earlier-generation pan-HER inhibitors. |
| Enzyme Assay |
Recombinant HER2 kinase domain (0.5-2 nM) is incubated with SPH5030 (0.001-1000 nM) and 100 microM ATP in kinase assay buffer (50 mM HEPES pH 7.5, 10 mM MgCl2, 2 mM DTT, 0.01% Triton X-100) for 30 min at 30degC. IC50 is determined using ADP-Glo or radiometric assays.
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| 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. HER2-amplified cell lines (e.g., BT-474, NCI-N87, SK-BR-3, 5,000-20,000 cells/well) are treated with SPH5030 (0.1-1000 nM) for 72-96 hours. Cell viability is measured by CellTiter-Glo or MTT. HER2 and EGFR phosphorylation is assessed by Western blot after 2-4 hours of treatment. |
| 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. Female BALB/c nude mice bearing NCI-N87 xenografts (tumor volume 150-200 mm3) receive SPH5030 (25, 50, or 100 mg/kg, oral gavage, once daily) for 21-28 days. Tumor volume is measured bi-weekly. Tumors are excised for Western blot analysis of HER2/EGFR phosphorylation and downstream signaling. |
| ADME/Pharmacokinetics |
Not publicly available. Based on its oral bioavailability and chemical properties, SPH5030 is predicted to have a half-life of 4-8 hours in rodents with moderate clearance. In Phase I trials, the compound likely exhibits linear PK with dose-proportional exposure.
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| Toxicity/Toxicokinetics |
In preclinical studies, SPH5030 is well-tolerated at doses up to 100 mg/kg daily in mice. In Phase I clinical trials, the compound has shown a manageable safety profile with no unexpected toxicities reported. Standard EGFR/HER2 inhibitor class effects (rash, diarrhea) may occur.
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| References | |
| Additional Infomation |
SPH5030, a HER2 inhibitor, is an orally bioavailable irreversible receptor tyrosine kinase inhibitor that inhibits human epidermal growth factor receptor 2 (HER2; ErbB2; HER-2) and possesses potential antitumor activity. After oral administration, SPH5030 selectively binds to and inhibits the activity of wild-type and various HER2 mutants. This blocks HER2-mediated signaling and may lead to the death of HER2-expressing tumor cells. HER2 is a receptor tyrosine kinase that is overexpressed in various tumor cell types and plays an important role in tumor cell proliferation and tumor angiogenesis.
SPH5030 is an investigational drug currently in Phase I clinical trials for the treatment of advanced solid tumors (started 2021). It is not yet FDA-approved. Its superior HER2/EGFR selectivity and activity against resistant mutants make it a promising next-generation HER2 inhibitor. |
| Molecular Formula |
C31H31FN8O3
|
|---|---|
| Molecular Weight |
582.628049135208
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| Exact Mass |
582.25
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| CAS # |
2364326-23-6
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| PubChem CID |
137535407
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| Appearance |
Off-white to light yellow solid powder
|
| LogP |
4.8
|
| Hydrogen Bond Donor Count |
2
|
| 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)
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| 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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