Naquotinib free base
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MedKoo CAT#: 206137

CAS#: 1448232-80-1 (free base)

Description: Naquotinib, also known as ASP8273, is an orally available, irreversible, third-generation, mutant-selective, epidermal growth factor receptor (EGFR) inhibitor, with potential antineoplastic activity. Upon oral administration, ASP8273 covalently binds to and inhibits the activity of mutant forms of EGFR, including the T790M EGFR mutant, thereby preventing EGFR-mediated signaling. This may both induce cell death and inhibit tumor growth in EGFR-overexpressing tumor cells. EGFR, a receptor tyrosine kinase mutated in many tumor cell types, plays a key role in tumor cell proliferation and tumor vascularization. ASP8273 preferentially inhibits mutated forms of EGFR including T790M, a secondarily acquired resistance mutation, and may have therapeutic benefits in tumors with T790M-mediated resistance when compared to other EGFR tyrosine kinase inhibitors.

Chemical Structure

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Naquotinib free base
CAS# 1448232-80-1 (free base)
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 206137
Name: Naquotinib free base
CAS#: 1448232-80-1 (free base)
Chemical Formula: C30H42N8O3
Exact Mass: 562.34
Molecular Weight: 562.719
Elemental Analysis: C, 64.03; H, 7.52; N, 19.91; O, 8.53

Price and Availability

Size Price Availability Quantity
5mg USD 350 2 Weeks
10mg USD 550 2 Weeks
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Related CAS #: 1448237-05-5 (mesylate)   1448232-80-1 (free base)    

Synonym: ASP8273; ASP-8273; ASP 8273; Naquotinib free base.

IUPAC/Chemical Name: (R)-5-((1-acryloylpyrrolidin-3-yl)oxy)-6-ethyl-3-((4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)amino)pyrazine-2-carboxamide

InChi Key: QKDCLUARMDUUKN-XMMPIXPASA-N

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

SMILES Code: O=C(C1=NC(CC)=C(O[C@H]2CN(C(C=C)=O)CC2)N=C1NC3=CC=C(N4CCC(N5CCN(C)CC5)CC4)C=C3)N

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info:   Related CAS# CAS#1448237-05-5 (Naquotinib mesylate); CAS#1448232-80-1 (Naquotinib free base).      

Product Data:
Product Data
Instruction:
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Biological target: Naquotinib (ASP8273) is an orally available, mutant-selective and irreversible EGFR inhibitor; with IC50s of 8-33 nM toward EGFR mutants and 230 nM for EGFR.
In vitro activity: The efficacy of naquotinib in cells with L858R, exon 19 deletion and exon 19 deletion+T790M was comparable with that of osimertinib. Interestingly, naquotinib was more potent than osimertinib for L858R+T790M. Additionally, naquotinib and osimertinib had comparable efficacy and a wide therapeutic window for cells with EGFR exon 20 insertions. Reference: Mol Cancer Ther. 2018 Apr;17(4):740-750. https://pubmed.ncbi.nlm.nih.gov/29467275/
In vivo activity: In in vivo murine xenograft models using cell lines and a patient-derived xenograft model, naquotinib induced tumor regression of NSCLC with EGFR-activating mutations with or without T790M resistance mutation, whereas it did not significantly inhibit WT EGFR signaling in skin. Furthermore, naquotinib suppressed tumor recurrence during the treatment period of 90 days. In addition, unlike erlotinib and osimertinib, naquotinib inhibited the phosphorylation of AXL and showed antitumor activity against PC-9 cells overexpressing AXL in vitro and in vivo. Reference: Mol Cancer Ther. 2019 Aug;18(8):1366-1373. https://pubmed.ncbi.nlm.nih.gov/31092564/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMF 30.0 53.31
DMSO 2.0 3.55
Ethanol 30.0 55.31

Preparing Stock Solutions

The following data is based on the product molecular weight 562.72 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Tanaka H, Kaneko N, Sakagami H, Matsuya T, Hiramoto M, Yamanaka Y, Mori M, Koshio H, Hirano M, Takeuchi M. Naquotinib exerts antitumor activity in activated B-cell-like diffuse large B-cell lymphoma. Leuk Res. 2020 Jan;88:106286. doi: 10.1016/j.leukres.2019.106286. Epub 2019 Dec 10. PMID: 31865062. 2. Hirano T, Yasuda H, Hamamoto J, Nukaga S, Masuzawa K, Kawada I, Naoki K, Niimi T, Mimasu S, Sakagami H, Soejima K, Betsuyaku T. Pharmacological and Structural Characterizations of Naquotinib, a Novel Third-Generation EGFR Tyrosine Kinase Inhibitor, in EGFR-Mutated Non-Small Cell Lung Cancer. Mol Cancer Ther. 2018 Apr;17(4):740-750. doi: 10.1158/1535-7163.MCT-17-1033. Epub 2018 Feb 21. PMID: 29467275. 3. Tanaka H, Sakagami H, Kaneko N, Konagai S, Yamamoto H, Matsuya T, Yuri M, Yamanaka Y, Mori M, Takeuchi M, Koshio H, Hirano M, Kuromitsu S. Mutant-Selective Irreversible EGFR Inhibitor, Naquotinib, Inhibits Tumor Growth in NSCLC Models with EGFR-Activating Mutations, T790M Mutation, and AXL Overexpression. Mol Cancer Ther. 2019 Aug;18(8):1366-1373. doi: 10.1158/1535-7163.MCT-18-0976. Epub 2019 May 15. PMID: 31092564.
In vitro protocol: 1. Tanaka H, Kaneko N, Sakagami H, Matsuya T, Hiramoto M, Yamanaka Y, Mori M, Koshio H, Hirano M, Takeuchi M. Naquotinib exerts antitumor activity in activated B-cell-like diffuse large B-cell lymphoma. Leuk Res. 2020 Jan;88:106286. doi: 10.1016/j.leukres.2019.106286. Epub 2019 Dec 10. PMID: 31865062. 2. Hirano T, Yasuda H, Hamamoto J, Nukaga S, Masuzawa K, Kawada I, Naoki K, Niimi T, Mimasu S, Sakagami H, Soejima K, Betsuyaku T. Pharmacological and Structural Characterizations of Naquotinib, a Novel Third-Generation EGFR Tyrosine Kinase Inhibitor, in EGFR-Mutated Non-Small Cell Lung Cancer. Mol Cancer Ther. 2018 Apr;17(4):740-750. doi: 10.1158/1535-7163.MCT-17-1033. Epub 2018 Feb 21. PMID: 29467275.
In vivo protocol: 1. Tanaka H, Sakagami H, Kaneko N, Konagai S, Yamamoto H, Matsuya T, Yuri M, Yamanaka Y, Mori M, Takeuchi M, Koshio H, Hirano M, Kuromitsu S. Mutant-Selective Irreversible EGFR Inhibitor, Naquotinib, Inhibits Tumor Growth in NSCLC Models with EGFR-Activating Mutations, T790M Mutation, and AXL Overexpression. Mol Cancer Ther. 2019 Aug;18(8):1366-1373. doi: 10.1158/1535-7163.MCT-18-0976. Epub 2019 May 15. PMID: 31092564.

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