Tucatinib,937263-43-9, IC-01211003
Product Introduction
Tucatinib is a potent, selective, and orally bioavailable small-molecule tyrosine kinase inhibitor (TKI) that specifically targets human epidermal growth factor receptor 2 (HER2/ErbB2) with high selectivity over the closely related epidermal growth factor receptor (EGFR). Tucatinib binds reversibly to the kinase domain of HER2, inhibiting its phosphorylation and downstream signaling through the PI3K/Akt and MAPK pathways, thereby suppressing the proliferation and survival of HER2-amplified or HER2-overexpressing cancer cells. Tucatinib was specifically designed to spare EGFR inhibition, which significantly reduces the dose-limiting toxicities (rash, diarrhea) commonly associated with dual HER2/EGFR inhibitors. It has demonstrated potent antitumor activity in preclinical models of HER2-positive breast cancer, gastric cancer, and colorectal cancer, including brain metastasis models, and is clinically approved for the treatment of HER2-positive metastatic breast cancer. Tucatinib serves as a valuable pharmacological tool for investigating HER2-dependent signaling, drug resistance mechanisms, and combination therapy strategies.
Product Features
1. Potent and Highly Selective HER2 Inhibitor: Inhibits HER2 with an IC50 of 8 nM while displaying greater than 1,000-fold selectivity over EGFR, minimizing EGFR-related toxicities.
2. Brain-Penetrant: Demonstrates significant penetration of the blood-brain barrier and antitumor activity in preclinical models of HER2-positive brain metastases.
3. Synergistic Activity: Exhibits enhanced antitumor efficacy when combined with trastuzumab, capecitabine, and other anti-HER2 agents.
4. Orally Bioavailable: Suitable for oral administration in in vivo efficacy studies.
5. High Purity: Supplied at 98% purity for reproducible pharmacological studies.
Specifications
Size: Available in 1 mg, 5 mg, 10 mg, 1 mL (10 mM in DMSO), 25 mg, 50 mg, 100 mg, and 1 g
CAS Number: 937263-43-9
Purity: 98%
Molecular Weight: 480.52
Molecular Formula: C26H24N8O2
Solubility: DMSO: ¡Ý20 mg/mL; limited solubility in aqueous buffers
Storage and Stability
Storage Conditions: Store at 2-8¡æ under inert atmosphere, sealed in dry conditions, and keep in a dark place. Protect from light and moisture. For the 10 mM DMSO solution, store at -20¡æ under inert atmosphere protected from light.
Shelf Life: The product is stable for 24 months from the date of manufacture when stored as directed. For reconstituted solutions in DMSO, aliquot into single-use vials, purge with inert gas, and store at -20¡æ or -80¡æ. Avoid repeated freeze-thaw cycles.
Protocol (For Reference Only)
Important: Tucatinib is light-sensitive and oxygen-sensitive. Protect from light and moisture during handling and storage. Prepare stock solutions in anhydrous DMSO under inert atmosphere.
1. Stock Solution Preparation (Solid): Dissolve Tucatinib in anhydrous DMSO under inert gas (nitrogen or argon) to prepare a concentrated stock solution (e.g., 10-50 mM). Aliquot into single-use airtight vials and store at -20¡æ protected from light. The 10 mM ready-to-use DMSO solution may be used directly for dilution into culture medium.
2. In Vitro Working Solution Preparation: Dilute DMSO stock solution into pre-warmed complete culture medium to achieve working concentrations typically ranging from 10-500 nM for HER2-dependent cell lines. Limit final DMSO concentration in culture medium to ¡Ü0.1% to avoid solvent-related cytotoxicity.
3. HER2 Signaling Inhibition: For complete inhibition of HER2 signaling, treat HER2-positive cells with Tucatinib at 50-200 nM for 1-4 hours. Assess pathway inhibition by Western blot for phospho-HER2 (Tyr1248), phospho-Akt (Ser473), and phospho-ERK (Thr202/Tyr204).
4. Cell Proliferation and Viability Assays: Treat HER2-positive and HER2-negative control cells with Tucatinib at concentrations ranging from 1 nM to 10 µM for 72-96 hours and assess cell viability by MTT or CellTiter-Glo assay. Calculate IC50 values to determine sensitivity. Note that HER2-negative cell lines should be largely insensitive to Tucatinib at concentrations below 1 µM.
5. In Vivo Efficacy Studies: For mouse xenograft models, administer Tucatinib via oral gavage at doses of 50-150 mg/kg twice daily. Formulate in an appropriate vehicle such as 0.5% methylcellulose or 1% Tween 80 in water. Monitor tumor volume, body weight, and potential adverse effects throughout the study.
Precautions
1. Tucatinib is light-sensitive and oxygen-sensitive; always store under inert atmosphere at 2-8¡æ and protect from light.
2. Verify HER2 expression and amplification status of experimental cell lines before use; Tucatinib is highly selective for HER2 and exhibits minimal activity against HER2-negative cells at concentrations below 1 µM.
3. Use appropriate vehicle controls in all experiments; DMSO concentration in culture medium should not exceed 0.1% to avoid solvent-related cytotoxicity.
4. Tucatinib is a reversible inhibitor; washout experiments will restore HER2 signaling. Plan time-course experiments accordingly.
5. For research use only. Not for use in diagnostic or therapeutic procedures.
FAQ (Simplified)
Q1: What is the difference between Tucatinib and other HER2 inhibitors like lapatinib or neratinib?
A1: Tucatinib is highly selective for HER2 over EGFR (>1,000-fold selectivity), whereas lapatinib is a dual HER2/EGFR inhibitor and neratinib is an irreversible pan-ErbB inhibitor. This EGFR-sparing property of Tucatinib significantly reduces EGFR-related toxicities while maintaining potent anti-HER2 activity.
Q2: What cell lines are suitable for studying Tucatinib?
A2: HER2-amplified or HER2-overexpressing cell lines such as BT-474, SK-BR-3, NCI-N87, and OE19 are highly sensitive to Tucatinib. MDA-MB-231 (HER2-negative) or MCF-7 (HER2-low) cells serve as appropriate negative controls. Verify HER2 status before experimentation.
Q3: Can Tucatinib cross the blood-brain barrier?
A3: Yes. Tucatinib has been demonstrated to effectively penetrate the blood-brain barrier and exhibits antitumor activity in preclinical models of HER2-positive brain metastases, making it a valuable tool for studying HER2-driven central nervous system tumors.
Q4: What combination strategies have been studied with Tucatinib?
A4: Tucatinib has demonstrated synergistic antitumor activity in combination with trastuzumab, capecitabine, ado-trastuzumab emtansine (T-DM1), and immune checkpoint inhibitors in preclinical models. The combination of Tucatinib, trastuzumab, and capecitabine is clinically approved for HER2-positive metastatic breast cancer.
Disclaimer
1. For Research Use Only. Not for use in diagnostic or therapeutic procedures.
2. Due to the variable nature of biological research, optimization of conditions using a small-scale pilot experiment is strongly recommended before processing valuable samples.
3. This warranty is limited to the replacement of the product. The manufacturer assumes no liability for incidental or consequential damages, including loss of samples or data.
4. Wear appropriate protective clothing and gloves when handling this product.
Ordering Information
Catalog Number: IC-01211003
Product Name: Tucatinib
Size: 1 mL (10 mM in DMSO) / 1 mg / 5 mg / 10 mg / 25 mg / 50 mg / 100 mg / 1 g
Price:
1 mL (10 mM in DMSO): CNY ¥1300.00 / USD $130.00 / EUR €156.00 / JPY ¥23400.00
1 mg: CNY ¥400.00 / USD $40.00 / EUR €48.00 / JPY ¥7200.00
5 mg: CNY ¥890.00 / USD $89.00 / EUR €106.80 / JPY ¥16020.00
10 mg: CNY ¥1300.00 / USD $130.00 / EUR €156.00 / JPY ¥23400.00
25 mg: CNY ¥2250.00 / USD $225.00 / EUR €270.00 / JPY ¥40500.00
50 mg: CNY ¥2700.00 / USD $270.00 / EUR €324.00 / JPY ¥48600.00
100 mg: CNY ¥4860.00 / USD $486.00 / EUR €583.20 / JPY ¥87480.00
1 g: CNY ¥19500.00 / USD $1950.00 / EUR €2340.00 / JPY ¥351000.00
2023 Version
