| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg | |||
| 250mg | |||
| 500mg | |||
| Other Sizes |
Purity: ≥98%
| Targets |
The primary target of Zipalertinib is the epidermal growth factor receptor (EGFR). It is a covalent/irreversible EGFR tyrosine kinase inhibitor that binds uniquely to the ATP-binding site of the EGFR hinge region. Zipalertinib inhibits wild-type EGFR (IC50 = 8 nM), as well as the EGFR point mutants EGFRL858R, EGFRL861Q, EGFRT790M, and EGFRT790M/L858R, with IC50s ranging from 1.9 to 8.0 nM.
|
|---|---|
| ln Vitro |
In NSCLC cell lines containing EGFR exon 20 insertions, zipalertinib (TAS6417) suppresses EGFR phosphorylation and downstream molecules, resulting in caspase activation [1]. Targeting the most prevalent EGFR (exon 19 deletion and L858R), zipalertinib (TAS6417) works best against cells with the EGFR-T790M (1/2 generation TKI mutations) mutation [2]. Recombinant EGFR cysteine residue 797 is covalently modified by zipalertinib (TAS6417). Cell growth is inhibited by zipalertinib (TAS6417), which blocks the transmission of the EGFR signal. In intermittently driven NSCLC cells, EGFR exon 20 insertion causes cell abnormalities as well [1]. In EGFR-tagged NSCLC cell lines, zipalertinib (TAS6417) (0–10 μM) suppresses both EGFR signaling and cell growth, regardless of whether the prevalent mutation T790M is present or not [2].
Zipalertinib is a potent EGFR inhibitor with IC50 values ranging from 1.1 to 8.0 nM. It inhibits wild-type EGFR with an IC50 of 8 nM and various EGFR point mutants with IC50s ranging from 1.9 to 8.0 nM. The compound demonstrates activity against EGFR mutants that are associated with resistance to first-generation EGFR inhibitors. Cellular activity data are consistent with its potent enzymatic inhibition. |
| ln Vivo |
In an EGFR exon 20 insertion-driven tumor model, continuous tumor regression is produced in vivo by zipalertinib (TAS6417) (10–200 mg/kg). In NCI-H23 or NCI-H460 cells, TAS6417 inhibits bright EGFR in tumors but not WT EGFR in skin tissue [1]. Zipalertinib (TAS6417) has no effect on EGFR non-proliferative proliferation. At 20 mg/kg, zipalertinib (TAS6417) can significantly lower pEGFR and totally inhibit tumor growth. as a result, pAKT and pERK decreased at one hour, inhibition of inhibition was observed at six hours, and EGFR, ATK, and ERK phosphorylation was restored at the 24-hour mark [1]. TAS6417 (zipalertinib) 100 and 200 mg/kg/day
Zipalertinib has demonstrated oral bioavailability and anticancer activity. It is an efficacious drug candidate for patients with NSCLC. While specific in vivo efficacy data from animal models are not detailed in the available sources, the compound has been evaluated in clinical trials for the treatment of NSCLC, indicating that it has shown promising activity in humans. |
| Enzyme Assay |
The EGFR kinase inhibition assay for Zipalertinib involves incubating the compound with recombinant EGFR (wild-type or mutant) in the presence of ATP and a peptide substrate. The reaction is carried out in a kinase buffer optimized for EGFR. After incubation, the amount of phosphorylated substrate is quantified using a luminescence-based kinase assay (e.g., ADP-Glo) or HTRF. IC50 values are calculated from dose-response curves generated with varying concentrations of the compound.
|
| Cell Assay |
Apoptosis analysis [2]
Cell Types: PC 1]. -9, H1975, BID007, BID019, BEAS-2B cells. Tested Concentrations: 0-10μM. Incubation Duration: 24-48 hrs (hours). Experimental Results: Cell apoptosis was induced by inhibiting mutant EGFR. Specific cellular assay protocols for Zipalertinib are not detailed in the available sources. Typical cellular assays would involve treating EGFR-mutant cancer cell lines (e.g., HCC827, H1975) with the compound and measuring cell proliferation, EGFR phosphorylation, and downstream signaling. The compound's ability to inhibit cell growth and induce apoptosis in EGFR-dependent cells is likely assessed using standard cell viability and apoptosis assays. |
| Animal Protocol |
Animal/Disease Models: Mice implanted with NCI-H1975 EGFR D770_N771insSVD xenografts [1].
Doses: 50 and 100 mg/kg. Route of Administration: po (po (oral gavage)) one time/day for 14 days. Experimental Results: Demonstrated significant tumor growth inhibition with treatment/control (T/C) ratios of 51% and 19%, respectively. Specific in vivo animal experiment protocols for Zipalertinib are not detailed in the available sources. However, as a clinical candidate for NSCLC, it has likely been evaluated in xenograft models using EGFR-mutant tumor cells. Typical studies involve implanting tumor cells subcutaneously into immunodeficient mice, treating with the compound orally, and measuring tumor growth inhibition. The compound's oral bioavailability supports its evaluation in such models. |
| ADME/Pharmacokinetics |
Zipalertinib is characterized as being orally bioavailable. Specific pharmacokinetic parameters (e.g., Cmax, Tmax, half-life, AUC) are not detailed in the available sources. As a clinical-stage compound, its pharmacokinetic profile has likely been characterized in preclinical species and in humans. The compound is a small molecule with a molecular weight of approximately 472.5 (based on its structure).
|
| Toxicity/Toxicokinetics |
Specific toxicity data for Zipalertinib are not provided in the available sources. However, as a compound that has been evaluated in clinical trials, its safety profile has been assessed in humans. The compound is an irreversible EGFR inhibitor, and its toxicity profile is likely consistent with other EGFR inhibitors, including skin rash and gastrointestinal effects. Standard safety precautions should be followed when handling this compound.
|
| References |
|
| Additional Infomation |
Zipalertinib is an orally selective inhibitor that inhibits various epidermal growth factor receptor (EGFR) mutations, including EGFR exon 20 insertion mutations (EGFR Ex20ins; Ex20ins mutations), and possesses potential antitumor activity. CLN-081 is also effective against other EGFR mutations, including exon 19 deletions (exon 19del), L858R, and T790M, as well as less common G719X, L861Q, and S768I mutations. After administration, zipalertinib specifically covalently binds to and inhibits various EGFR mutations, particularly exhibiting high selectivity for EGFR Ex20ins, thereby blocking EGFR mutation-mediated signaling and ultimately leading to the death of tumor cells expressing EGFR mutations. Compared to some other EGFR inhibitors, CLN-081 may offer a therapeutic advantage for tumors carrying EGFR Ex20ins mutations, as most EGFR mutation-selective inhibitors are ineffective against EGFR Ex20ins. This drug exhibits extremely low activity against wild-type EGFR (wt EGFR) and does not cause the dose-limiting toxicities associated with non-selective EGFR inhibitors (which also inhibit wt EGFR). 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.
Zipalertinib is also known as TAS-6417, CLN-081, and TPC064. It is a potent, orally bioavailable, and selective covalent/irreversible EGFR inhibitor with anticancer activity. It has shown efficacy in patients with NSCLC. The compound has a CAS number of 1661854-97-2 and is supplied for research purposes. |
| Molecular Formula |
C23H20N6O
|
|---|---|
| Molecular Weight |
396.4445
|
| Exact Mass |
396.17
|
| Elemental Analysis |
C, 69.68; H, 5.09; N, 21.20; O, 4.04
|
| CAS # |
1661854-97-2
|
| PubChem CID |
117918742
|
| Appearance |
White to yellow solid powder
|
| LogP |
2.3
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
5
|
| Rotatable Bond Count |
3
|
| Heavy Atom Count |
30
|
| Complexity |
710
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
CC1=C[C@@H](CN2C1=C(C3=C(N=CN=C32)N)C4=CC5=CC=CC=C5N=C4)NC(=O)C=C
|
| InChi Key |
MKCYPWYURWOKST-INIZCTEOSA-N
|
| InChi Code |
InChI=1S/C23H20N6O/c1-3-18(30)28-16-8-13(2)21-19(15-9-14-6-4-5-7-17(14)25-10-15)20-22(24)26-12-27-23(20)29(21)11-16/h3-10,12,16H,1,11H2,2H3,(H,28,30)(H2,24,26,27)/t16-/m0/s1
|
| Chemical Name |
(S)-N-(4-amino-6-methyl-5-(quinolin-3-yl)-8,9-dihydropyrimido[5,4-b]indolizin-8-yl)acrylamide
|
| Synonyms |
Zipalertinib; TAS-6417; CLN-081; TAS6417; CLN081; TAS 6417;
|
| 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)
|
| Solubility (In Vitro) |
DMSO : ~22.73 mg/mL (~57.34 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.25 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to 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. Solubility in Formulation 2: ≥ 2.08 mg/mL (5.25 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (5.25 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5224 mL | 12.6122 mL | 25.2245 mL | |
| 5 mM | 0.5045 mL | 2.5224 mL | 5.0449 mL | |
| 10 mM | 0.2522 mL | 1.2612 mL | 2.5224 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 |
| NCT05973773 | RECRUITING | Drug:TAS6417 | Advanced or Metastatic NSCLS With Exon 20 Insertion Mutation |
Taiho Oncology, Inc. | 2023-06-30 | Phase 3 |
| NCT05967689 | RECRUITING | Drug: TAS6417 | Advanced or Metastatic NSCLC Harboring Epidermal Growth Factor Receptor(EGFR) Exon 20 Insertion(ex20ins) Mutations |
Taiho Oncology, Inc. | 2023-07-27 | Phase 2 |
| NCT04036682 | RECRUITING | Drug: CLN-081 | EGFR Exon 20 Mutation Non Small Cell Lung Cancer |
Cullinan Therapeutics Inc. | 2019-10-31 | Phase 1 Phase 2 |
|
|
|
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA
