Shanghai Nianxing Industrial Co., Ltd
China
Product Name: Tarloxotinib bromide
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Purity: 98.0%
Stocking Period: 10 Day
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1636180-98-7

1636180-98-7 structure

1636180-98-7 structure

Name: tarloxotinib bromide
Chemical Name: tarloxotinib bromide
CAS Number: 1636180-98-7
Molecular Formula: C₂₄H₂₄Br₂ClN₉O₃
Molecular Weight: 681.767
Catalog: Research Areas Cancer
Create Date: 2019-01-20 23:20:00
Modify Date: 2024-01-08 17:26:49
Tarloxotinib bromide is an irreversible EGFR/HER2 inhibitor.

Name	tarloxotinib bromide
Synonyms	1H-Imidazole-5-methanaminium, N-[(2E)-4-[[4-[(3-bromo-4-chlorophenyl)amino]pyrido[3,4-d]pyrimidin-6-yl]amino]-4-oxo-2-buten-1-yl]-N,N,1-trimethyl-4-nitro-, bromide (1:1) tarloxotinib bromide 3Y31FJ8K50 (2E)-4-({4-[(3-Bromo-4-chlorophenyl)amino]pyrido[3,4-d]pyrimidin-6-yl}amino)-N,N-dimethyl-N-[(1-methyl-4-nitro-1H-imidazol-5-yl)methyl]-4-oxo-2-buten-1-aminium bromide

Description	Tarloxotinib bromide is an irreversible EGFR/HER2 inhibitor.
Related Catalog	Research Areas >> Cancer
Target	EGFR/HER2
In Vitro	To confirm the mechanism of action, Tarloxotinib bromide is shown to be metabolized efficiently under hypoxia using a panel of human NSCLC cell lines (rate of TKI release 0.4-2.1 nM/hr/106 cells), a process that is inhibited by oxygen (TKI release <0.002 nM/hr/106 cells). Cellular anti-proliferative and receptor phosphorylation assays demonstrate a 14-80 fold reduction of Tarloxotinib bromide activity relative to TKI. Using PC9 tumors, hyperbaric oxygen breathing suppresse release of TKI from Tarloxotinib bromide by >80% (538 vs 99 nM/kg; p<0.01) compared to air breathing controls. Collectively, these data further validate that Tarloxotinib bromide is a hypoxia-activated irreversible EGFR-TKI, and show that Tarloxotinib bromide has greater activity compared with erlotinib[2].
In Vivo	A prototypic WT EGFR driven xenograft model (A431) is used to benchmark Tarloxotinib bromide activity against each EGFR-TKI by ‘retrotranslation’ of reported plasma exposure for each agent in human subjects back to the xenograft model. Only treatment with clinically relevant doses and schedules of Tarloxotinib bromide is associated with tumor regression and durable inhibition of WT EGFR tumor phosphorylation. Consistent with these findings, Tarloxotinib bromide treatment can also regress the WT EGFR NSCLC tumor models H125 and H1648, demonstrating Tarloxotinib bromide provides the necessary therapeutic index to inhibit WT EGFR in vivo[1].
References	[1]. Shevan Silva, Abstract A67: Preclinical efficacy of tarloxotinib bromide (TH-4000), a hypoxia-activated EGFR/HER2 inhibitor: rationale for clinical evaluation in EGFR mutant, T790M-negative NSCLC following progression on EGFR-TKI therapy. Abstracts: AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; November 5-9, 2015; Boston, MA. [2]. Adam V. Patterson, Abstract 5358: The hypoxia-activated EGFR-TKI TH-4000 overcomes erlotinib-resistance in preclinical NSCLC models at plasma levels achieved in a Phase 1 clinical trial. AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA.

Molecular Formula	C₂₄H₂₄Br₂ClN₉O₃
Molecular Weight	681.767
Exact Mass	679.005737
Storage condition	2-8℃