Tarloxotinib bromide

This product is for research use only, not for human use. We do not sell to patients.

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Size	Price	Stock
100mg	$2250	Check With Us
200mg	$3375	Check With Us
500mg	$5695	Check With Us

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Cat #: V15759 CAS #: 1636180-98-7 Purity ≥ 98%

Description: Tarloxotinib bromide (formerly TH-4000; PR-610) is a novel quarternary amine-based and irreversible EGFR/HER2 inhibitor designed as a prodrug to selectively release a covalent (irreversible (covalent)) EGFR tyrosine kinase inhibitor under severe hypoxia, a feature of many solid tumors.

References: 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-

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Physicochemical and Storage Information
Protocol
Related Biological Data
Stock Solution Preparation
Quality Control Documentation

Molecular Weight (MW)	681.77
Molecular Formula	C24H24Br2ClN9O3
CAS No.	1636180-98-7
SMILES Code	O=C(NC1=CC2=C(NC3=CC=C(Cl)C(Br)=C3)N=CN=C2C=N1)/C=C/C[N+](C)(C)CC4=C([N+]([O-])=O)N=CN4C.[Br-]
Synonyms	PR-610, PR 610, PR610, TH-4000, TH 4000, TH4000, Hypoxin, Tarloxotinib bromide, Tarloxotinib

Protocol	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.
Protocol	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.

These protocols are for reference only. InvivoChem does not independently validate these methods.

Preparing Stock Solutions

Solvent volume to be added	Mass (the weight of a compound)
Mother liquor concentration	1mg	5mg	10mg	20mg
1mM	1.4668 mL	7.3339 mL	14.6677 mL	29.3354 mL
5mM	0.2934 mL	1.4668 mL	2.9335 mL	5.8671 mL
10mM	0.1467 mL	0.7334 mL	1.4668 mL	2.9335 mL
20mM	0.0733 mL	0.3667 mL	0.7334 mL	1.4668 mL

Quality Control Documentation	Select Batch Purity ≥ 98% COA MSDS NMR HPLC

The molarity calculator equation

Mass(g) = Concentration(mol/L) × Volume(L) × Molecular Weight(g/mol)

Mass

Concentration

Volume

Molecular Weight*

The dilution calculator equation

Concentration_(start) × Volume_(start) = Concentration_(final) × Volume_(final)

This equation is commonly abbreviated as: C₁ V₁ = C₂ V₂

Concentration_(start)

Volume_(start)

Concentration_(final)

Volume_(final)

Step One: Enter information below

Dosage mg/kg Average weight of animals g Dosing volume per animal µL Number of animals

Step Two: Enter the in vivo formulation

%DMSO + % + %Tween 80 + %ddH₂O

Calculation Results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in µL DMSO(Master liquid 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 master liquid, next add µL PEG300, mix and clarify, next add µL Tween 80,mix and clarify, next add µL ddH₂O,mix and clarify.

Note:

(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.