| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
EGFR (IC50 = 230 nM); EGFRT790M; EGFRL858R/T790M; EGFRL858R; EGFRExon 19 deletion/T790M
Naquotinib targets the epidermal growth factor receptor (EGFR), specifically mutant forms of EGFR including EGFRT790M, EGFRL858R/T790M, EGFRL858R, and EGFRExon 19 deletion/T790M. It is an irreversible/covalent inhibitor that binds to the ATP-binding site of the kinase domain. Naquotinib selectively inhibits mutant EGFR over wild-type EGFR, as demonstrated by its lack of inhibitory effects at 1000 nM in A431 cells (which express wild-type EGFR) while potently inhibiting phosphorylation of EGFR and downstream signaling pathways in EGFR-mutant cell lines. |
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| ln Vitro |
Naquotinib inhibits the growth of PC-9(del ex19), HCC827(del ex19), NCI-H1975(del ex19/T790M), and PC-9ER(del ex19/T790M) with IC50s ranging from 8 to 33 nM in assays utilizing endogenously EGFR-dependent cells[1]. Naquotinib only exhibits inhibitory effects at 1000 nM in A431, but it selectively inhibits the phosphorylation of EGFR and its downstream signal pathway, ERK and Akt, starting at 10 nM in HCC827 and NCI-H1975. While other EGFR-TKIs are only partially effective, Naquotinib inhibits cell growth in NCI-H1650 (del ex19) with an IC50 value of 70nM[2].
In vitro, Naquotinib inhibits the growth of EGFR-mutant NSCLC cell lines with IC50 values ranging from 8 to 33 nM in assays utilizing endogenously EGFR-dependent cells, including PC-9 (del ex19), HCC827 (del ex19), NCI-H1975 (L858R/T790M), and PC-9ER (del ex19/T790M). It selectively inhibits the phosphorylation of EGFR and its downstream signaling pathways, ERK and Akt, starting at 10 nM in HCC827 and NCI-H1975 cells. Naquotinib inhibits cell growth in NCI-H1650 (del ex19) cells with an IC50 value of 70 nM. While other EGFR-TKIs are only partially effective against resistant mutants, Naquotinib demonstrates potent activity. |
| ln Vivo |
NCI-H1975 (L858R/T790M), HCC827 (del ex19), and PC-9 (del ex19) xenograft models show dose-dependent tumor regression upon oral Naquotinib treatment. Naquotinib is effective regardless of dosage schedules. Two weeks of treatment with Naquotinib results in complete tumor regression in an NCI-H1975 xenograft model. Over 85 days following the end of Naquotinib treatment, 50% of mice continue to exhibit complete regression[2].
In vivo, oral administration of Naquotinib produces dose-dependent tumor regression in xenograft models of NCI-H1975 (L858R/T790M), HCC827 (del ex19), and PC-9 (del ex19). Efficacy is observed regardless of dosage schedules. Treatment with Naquotinib for two weeks results in complete tumor regression in the NCI-H1975 xenograft model. Over 85 days following the end of treatment, 50% of mice continue to exhibit complete regression. These findings demonstrate the potent in vivo antitumor activity of Naquotinib against EGFR-mutant tumors, including those with the T790M resistance mutation. |
| Enzyme Assay |
The in vitro enzymatic activity of Naquotinib is assessed using cell-free kinase assays with recombinant EGFR proteins, including wild-type EGFR and mutant variants such as EGFRT790M and EGFRL858R/T790M. The kinase is incubated with a peptide substrate and ATP in the presence of varying concentrations of the inhibitor. The extent of phosphorylation is measured using techniques such as radioactive labeling, fluorescence-based detection, or immunoassay. The IC50 value of 70 nM for EGFR inhibition is determined from dose-response curves.
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| Cell Assay |
To evaluate the cellular effects of Naquotinib, EGFR-mutant NSCLC cell lines such as PC-9, HCC827, NCI-H1975, and NCI-H1650 are treated with the compound. Cell proliferation and viability are assessed using standard assays such as CellTiter-Glo or MTT. The inhibition of EGFR phosphorylation and downstream signaling through ERK and Akt is confirmed by Western blotting using phospho-specific antibodies. IC50 values for cell growth inhibition are determined from dose-response curves.
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| Animal Protocol |
In vivo studies with Naquotinib typically involve oral administration to tumor-bearing mice in xenograft models. Tumor size is measured regularly using calipers, and tumor growth inhibition is calculated. Treatment schedules may include daily dosing for several weeks. Efficacy endpoints include tumor regression, complete response rates, and duration of response. Pharmacodynamic markers such as EGFR phosphorylation in tumor tissue are assessed by immunohistochemistry or Western blotting.
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| ADME/Pharmacokinetics |
Naquotinib free base has a molecular formula of C30H42N8O3 and a molecular weight of 562.72 g/mol. Its CAS number is 1448232-80-1. The compound is a solid powder with a purity of ≥98%. It is soluble in DMSO and should be stored at -20°C for up to 3 years in powder form. The related mesylate salt has a CAS number of 1448237-05-5.
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| Toxicity/Toxicokinetics |
Specific toxicology data for Naquotinib are not extensively detailed in the available literature. As a third-generation EGFR inhibitor, it is designed to spare wild-type EGFR, which is expected to reduce the skin rash and gastrointestinal side effects commonly associated with earlier EGFR inhibitors. However, as with all kinase inhibitors, dose-dependent toxicities may occur. Standard safety precautions should be taken when handling this compound, as it is intended for research use only.
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| References | |
| Additional Infomation |
Naquotinib has been used in clinical trials for various diseases, including solid tumors, non-small cell lung cancer (NSCLC), epidermal growth factor receptor mutations, and epidermal growth factor receptor (EGFR) mutations. Naquotinib is an orally administered, irreversible, third-generation, mutation-selective epidermal growth factor receptor (EGFR) inhibitor with potential antitumor activity. After oral administration, ASP8273 covalently binds to EGFR mutants (including the T790M EGFR mutant) and inhibits their activity, thereby blocking EGFR-mediated signaling. This may induce EGFR-overexpressing tumor cell death and inhibit tumor growth. EGFR is a receptor tyrosine kinase that is mutated in various tumor cell types and plays a crucial role in tumor cell proliferation and tumor angiogenesis. ASP8273 preferentially inhibits EGFR mutants, including the secondary resistance mutation T790M, and may offer a therapeutic advantage against T790M-mediated resistance tumors compared to other EGFR tyrosine kinase inhibitors. Because this drug is selective for EGFR mutants, it may be less toxic than non-selective EGFR inhibitors that also inhibit wild-type EGFR.
Naquotinib (ASP8273) is a third-generation EGFR inhibitor that has been investigated in clinical trials for the treatment of non-small cell lung cancer (NSCLC). It has been studied in patients with EGFR mutations, including those with the T790M resistance mutation. The compound's irreversible binding and mutant selectivity distinguish it from earlier-generation EGFR inhibitors. Naquotinib is a research compound and is not a clinically approved drug. |
| Molecular Formula |
C30H42N8O3
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|---|---|
| Molecular Weight |
562.719
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| Exact Mass |
562.338
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| Elemental Analysis |
C, 64.03; H, 7.52; N, 19.91; O, 8.53
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| CAS # |
1448232-80-1
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| Related CAS # |
Naquotinib mesylate;1448237-05-5
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| PubChem CID |
71667668
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
717.6±60.0 °C at 760 mmHg
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| Flash Point |
387.8±32.9 °C
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| Vapour Pressure |
0.0±2.3 mmHg at 25°C
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| Index of Refraction |
1.624
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| LogP |
3.74
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
41
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| Complexity |
883
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| Defined Atom Stereocenter Count |
1
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| SMILES |
O(C1=C(C([H])([H])C([H])([H])[H])N=C(C(N([H])[H])=O)C(=N1)N([H])C1C([H])=C([H])C(=C([H])C=1[H])N1C([H])([H])C([H])([H])C([H])(C([H])([H])C1([H])[H])N1C([H])([H])C([H])([H])N(C([H])([H])[H])C([H])([H])C1([H])[H])[C@@]1([H])C([H])([H])N(C(C([H])=C([H])[H])=O)C([H])([H])C1([H])[H]
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| InChi Key |
QKDCLUARMDUUKN-XMMPIXPASA-N
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| InChi Code |
InChI=1S/C30H42N8O3/c1-4-25-30(41-24-12-15-38(20-24)26(39)5-2)34-29(27(33-25)28(31)40)32-21-6-8-22(9-7-21)36-13-10-23(11-14-36)37-18-16-35(3)17-19-37/h5-9,23-24H,2,4,10-20H2,1,3H3,(H2,31,40)(H,32,34)/t24-/m1/s1
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| Chemical Name |
6-ethyl-3-[4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]anilino]-5-[(3R)-1-prop-2-enoylpyrrolidin-3-yl]oxypyrazine-2-carboxamide
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| Synonyms |
Naquotinib free base; ASP-8273; ASP8273; ASP 8273
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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 |
| 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) |
Ethanol: ~100 mg/mL (~177.7 mM)
DMSO: ~52 mg/mL (~92.4 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (4.44 mM) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), Clear solution; with ultrasonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (25.0 mg/mL) to 400 μL of PEG300 and mix well; then add 50 μL of Tween-80 and mix well; finally add 450 μL of physiological saline and adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7771 mL | 8.8854 mL | 17.7708 mL | |
| 5 mM | 0.3554 mL | 1.7771 mL | 3.5542 mL | |
| 10 mM | 0.1777 mL | 0.8885 mL | 1.7771 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 |
| NCT02588261 | Terminated | Drug: naquotinib mesilate Drug: Erlotinib |
Non-small Cell Lung Cancer (NSCLC) |
Astellas Pharma Global Development, Inc. |
February 11, 2016 | Phase 3 |
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