N6-(4,5-Dihydro-4,4-dimethyl-2-oxazolyl)-N4-[3-methyl-4-([1,2,4]triazolo[1,5-a]pyridin-7-yloxy)phenyl]-4,6-quinazolinediamine
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![N6-(4,5-Dihydro-4,4-dimethyl-2-oxazolyl)-N4-[3-methyl-4-([1,2,4]triazolo[1,5-a]pyridin-7-yloxy)phenyl]-4,6-quinazolinediamine structure](https://file.echemi.com/fileManage/upload/canonicalSmiles/20220812/bbb95cfd58954da381165da8dbbdce13.png "N6-(4,5-Dihydro-4,4-dimethyl-2-oxazolyl)-N4-[3-methyl-4-([1,2,4]triazolo[1,5-a]pyridin-7-yloxy)phenyl]-4,6-quinazolinediamine")
N6-(4,5-Dihydro-4,4-dimethyl-2-oxazolyl)-N4-[3-methyl-4-([1,2,4]triazolo[1,5-a]pyridin-7-yloxy)phenyl]-4,6-quinazolinediamine
structure -
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CAS No:
937263-43-9
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Formula:
C26H24N8O2
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Chemical Name:
N6-(4,5-Dihydro-4,4-dimethyl-2-oxazolyl)-N4-[3-methyl-4-([1,2,4]triazolo[1,5-a]pyridin-7-yloxy)phenyl]-4,6-quinazolinediamine
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Synonyms:
4,6-Quinazolinediamine,N6-(4,5-dihydro-4,4-dimethyl-2-oxazolyl)-N4-[3-methyl-4-([1,2,4]triazolo[1,5-a]pyridin-7-yloxy)phenyl]-;N6-(4,5-Dihydro-4,4-dimethyl-2-oxazolyl)-N4-[3-methyl-4-([1,2,4]triazolo[1,5-a]pyridin-7-yloxy)phenyl]-4,6-quinazolinediamine;ARRY 380;ONT 380;Tucatinib;Tukysa
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CAS No:
Description
Tucatinib (Irbinitinib; ARRY-380; ONT-380) is a potent and selective HER2 inhibitor with an IC50 of 8 nM.
Tucatinbib is a kinase inhibitor drug used with [trastuzumab] and [capecitabine] in the treatment of unresectable or metastatic HER-2 positive breast cancer. It was developed by Seattle Genetics and approved by the FDA on April 17, 2020. Tucatinib is a promising new treatment for patients with metastatic breast cancer who have not responded adequately to other chemotherapy regimens.|Tucatinib is a Kinase Inhibitor. The mechanism of action of tucatinib is as a Tyrosine Kinase Inhibitor, and Cytochrome P450 3A Inhibitor, and P-Glycoprotein Inhibitor, and Cytochrome P450 2C8 Inhibitor.|Tucatinib is an orally bioavailable inhibitor of the human epidermal growth factor receptor tyrosine kinase ErbB-2 (also called HER2) with potential antineoplastic activity. Tucatinib selectively binds to and inhibits the phosphorylation of ErbB-2, which may prevent the activation of ErbB-2 signal transduction pathways, resulting in growth inhibition and death of ErbB-2-expressing tumor cells. ErbB-2 is overexpressed in a variety of cancers and plays an important role in cellular proliferation and differentiation.
N6-(4,5-Dihydro-4,4-dimethyl-2-oxazolyl)-N4-[3-methyl-4-([1,2,4]triazolo[1,5-a]pyridin-7-yloxy)phenyl]-4,6-quinazolinediamine Basic Attributes
480.52116
480.52
234248D0HH
C77896
L01|L - Antineoplastic and immunomodulating agents
Toxicity
LD50 information and overdose information for tucatinib are not readily available in the literature. In the case of an overdose with this drug, increased adverse effects, such as diarrhea, nausea, abdominal pain, vomiting fatigue, hepatotoxicity, vomiting, decreased appetite, anemia, headache, and rash are expected.
Tucatinib is about 97% bound to plasma proteins.
Drug Information
Tucatinib is indicated with trastuzumab and capecitabine for treatment of adults diagnosed with advanced unresectable or metastatic HER2-positive breast cancer. This includes patients with brain metastases and those who have received one or more prior anti-HER2-based regimens in the metastatic setting.|Treatment of breast malignant neoplasms|Tukysa is indicated in combination with trastuzumab and capecitabine for the treatment of adult patients with HER2‑positive locally advanced or metastatic breast cancer who have received at least 2 prior anti‑HER2 treatment regimens.|Drug: Tucatinib
By inhibiting tyrosine kinase, tucatinib exerts anti-tumor activity, reducing the size of HER-2 positive breast cancer tumors. In clinical trials, the regimen of tucatinib and [trastuzumab] showed enhanced activity both in vitro and in vivo when compared to either drug administered by itself.
Substances that inhibit or prevent the proliferation of NEOPLASMS. (See all compounds classified as Antineoplastic Agents.)|Agents that inhibit PROTEIN KINASES. (See all compounds classified as Protein Kinase Inhibitors.)
The Tmax for tucatinib ranges from 1 to 4 hours. One pharmacokinetic study revealed a Cmax of 1120 ng/mL after a dose of 350 mg twice daily with a Tmax ranging from 1 to 3 hours. The AUCtau was reported to be about 7120 hours×ng/mL.|In a study of radiolabled tucatinib, about 86% of the total dose was excreted in the feces and 4.1% was found in the urine. About 16% of the tucatinib dose recovered in the feces was identified as unchanged tucatinib.|The volume of distribution of tucatinib is about 1670 L. This drug penetrates the blood-brain barrier.|The apparent clearance is 148 L/h.
Tucatinib is metabolized by CYP2C8 with some contributions from CYP3A.
A pharmacokinetic study revealed a half-life of approximately 5.38 hours. Prescribing information mentions a geometric mean half-life of about 8.21 hours.
Mutations in the HER-2 gene are observed in some types of breast carcinoma. Tucatinib inhibits the tyrosine kinase enzyme of the HER-2 gene. Mutations of tyrosine kinase in the HER-2 gene lead to cascade effects of increased cell signaling and proliferation, resulting in malignancy. Results of in vitro studies show that tucatinib inhibits the phosphorylation of both HER-2 and HER-3, leading to downstream changes in MAPK and AKT signaling and cell proliferation. Anti-tumor activity occured in the cells that expressed HER-2. In vivo, tucatinib has been shown to inhibit HER-2 expressing tumors, likely by the same mechanism.
irbinitinib
N6-(4,5-Dihydro-4,4-dimethyl-2-oxazolyl)-N4-[3-methyl-4-([1,2,4]triazolo[1,5-a]pyridin-7-yloxy)phenyl]-4,6-quinazolinediamine Use and Manufacturing
N6-(4,5-Dihydro-4,4-dimethyl-2-oxazolyl)-N4-[3-methyl-4-([1,2,4]triazolo[1,5-a]pyridin-7-yloxy )phenyl]-4,6-quinazolinediamine is a novel listening diarylamine ErbB inhibitor.
Human Drugs -> EU pediatric investigation plans|Human drugs -> Tukysa -> EMA Drug Category|Antineoplastic agents -> Human pharmacotherapeutic group|Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients
Computed Properties
Molecular Weight:480.5
XLogP3:4
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:8
Rotatable Bond Count:6
Exact Mass:480.20222204
Monoisotopic Mass:480.20222204
Topological Polar Surface Area:111
Heavy Atom Count:36
Complexity:796
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes
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N6-(4,5-Dihydro-4,4-dimethyl-2-oxazolyl)-N4-[3-methyl-4-([1,2,4]triazolo[1,5-a]pyridin-7-yloxy)phenyl]-4,6-quinazolinediamine
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