Tucatinib (Irbinitinib, ONT-380)

For research use only.

Catalog No.S8362 Synonyms: ARRY-380

7 publications

Tucatinib (Irbinitinib, ONT-380) Chemical Structure

CAS No. 937263-43-9

Tucatinib (Irbinitinib, ONT-380, ARRY-380) is an oral, potent, selective, reversible and ATP-competitive small-molecule inhibitor of ErbB-2 (also called HER2) with IC50s of 8 nM and 7 nM for ErbB-2 and p95 HER2, respectively in cell-based assays, showing ~500-fold selective for HER2 vs EGFR. It has potential antineoplastic activity.

Selleck's Tucatinib (Irbinitinib, ONT-380) has been cited by 7 publications

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Biological Activity

Description Tucatinib (Irbinitinib, ONT-380, ARRY-380) is an oral, potent, selective, reversible and ATP-competitive small-molecule inhibitor of ErbB-2 (also called HER2) with IC50s of 8 nM and 7 nM for ErbB-2 and p95 HER2, respectively in cell-based assays, showing ~500-fold selective for HER2 vs EGFR. It has potential antineoplastic activity.
Targets
p95 HER2 [2]
(Cell-based assay)
ErbB2 [2]
(Cell-based assay)
7 nM 8 nM
In vitro

The compound is a reversible, ATP-competitive inhibitor with nanomolar potency against ErbB2 in both in vitro and in cell-based assays[1]. In cell-based assays, ARRY-380 is ~500-fold selective for HER2 vs. EGFR and is equipotent against truncated p95-HER2[2].

Assay
Methods Test Index PMID
Western blot
p-HER2 / HER2 / p-AKT / AKT / p-ERK / ERK ; 

PubMed: 30370249     


Sensitivity of signaling pathways in ZR75.1, SKBR3, BT474 and NZBR3 breast cancer cell lines to ARRY-380. Cells were treated with ARRY-380 for 24 h and signaling pathway usage was measured by phosphorylation of HER2, AKT, and ERK. Immunoblots with antibodies specific for phosphorylated proteins are indicated. Actin is the loading control.

30370249
Growth inhibition assay
Cell viability; 

PubMed: 30670633     


XTT cell proliferation assays of HER2-positive breast cancer cell lines with or without PIK3CA point mutations [BT474 (K111N), SKBR3 (WT), HCC1419 (WT), MDA-MB361 (E345K), MDAMB453 (H1047R) and UACCC893 (H1047R)] treated for 4 days with the indicated concentration of HER2-targeted therapy (TZB, 6L1G, ARRY, A+T), AKT inhibitor (MK2206), or FAK inhibitor (PF562271). Data are mean ± SD of n=3 experiments.

30670633
In vivo In vivo, ARRY-380 significantly inhibits tumor growth in multiple HER2-dependent tumor xenograft models[2]. It shows excellent activity in numerous mouse tumor models including breast (BT-474, MDA-MB-453), ovarian (SKOV-3) and gastric (N87) carcinoma models. In the BT-474 model, ARRY-380 demonstrated significant dose-related tumor growth inhibition (TGI; 50% at 50 mg/kg/d and 96% at 100 mg/kg/d) with numerous partial regressions (>50% reduction from baseline size)[1].

Protocol

Solubility (25°C)

In vitro DMSO 96 mg/mL (199.78 mM)
Ethanol 15 mg/mL (31.21 mM)
Water Insoluble

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 480.52
Formula

C26H24N8O2

CAS No. 937263-43-9
Storage powder
in solvent
Synonyms ARRY-380
Smiles CC1=C(C=CC(=C1)NC2=NC=NC3=C2C=C(C=C3)NC4=NC(CO4)(C)C)OC5=CC6=NC=NN6C=C5

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Clinical Trial Information

NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT04512261 Recruiting Drug: Tucatinib|Drug: Pembrolizumab|Drug: Trastuzumab Breast Cancer|Brain Metastases|HER2-positive Breast Cancer|CNS Disease Reva Basho|Merck Sharp & Dohme Corp.|Seagen Inc.|Cedars-Sinai Medical Center October 1 2021 Phase 1|Phase 2
NCT04896320 Not yet recruiting Drug: Tucatinib Breast Cancer Stage IV Providence Health & Services|Seagen Inc. July 2021 Phase 1|Phase 2

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

Tel: +1-832-582-8158 Ext:3

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HER2 Signaling Pathway Map

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID