≥99% for sensitive chromatographic and analytical workflows requiring minimal baseline interference.
Store at 2-8°C,Desiccated Ships Wet ice Check lot-specific COA for exact specifications.
SDS, COA, datasheet, and spec sheet available for download. Lot-specific COA accessible via lot number lookup.
Cited in 0 peer-reviewed publications across chromatography, organic synthesis, and cross-coupling reactions.
Tarloxotinib bromide (TH-4000) is an irreversible EGFR/HER2 inhibitor.
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/10 6 cells), a process that is inhibited by oxygen (TKI release <0.002 nM/hr/10 6 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. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
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 . MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Form:Solid
IC50& Target:EGFR/HER2
| Canonical Smiles | CN1C=NC(=C1C[N+](C)(C)CC=CC(=O)NC2=NC=C3C(=C2)C(=NC=N3)NC4=CC(=C(C=C4)Cl)Br)[N+](=O)[O-].[Br-] |
|---|---|
| IUPAC Name | [(E)-4-[[4-(3-bromo-4-chloroanilino)pyrido[3,4-d]pyrimidin-6-yl]amino]-4-oxobut-2-enyl]-dimethyl-[(3-methyl-5-nitroimidazol-4-yl)methyl]azanium;bromide |
| InChIKey | WAKIMVYUBWMMHJ-FXRZFVDSSA-N |
| INCHI | 1S/C24H23BrClN9O3.BrH/c1-33-14-30-24(34(37)38)20(33)12-35(2,3)8-4-5-22(36)32-21-10-16-19(11-27-21)28-13-29-23(16)31-15-6-7-18(26)17(25)9-15;/h4-7,9-11,13-14H,8,12H2,1-3H3,(H-,27,28,29,31,32,36);1H/b5-4+; |
| Isomeric SMILES | CN1C=NC(=C1C[N+](C)(C)C/C=C/C(=O)NC2=NC=C3C(=C2)C(=NC=N3)NC4=CC(=C(C=C4)Cl)Br)[N+](=O)[O-].[Br-] |
| Alternate CAS | 1636180-98-7 |
| PubChem CID | 51038315 |
| Molecular Weight | 681.77 |
Comprehensive hazard, handling, storage, and regulatory compliance document.
Download SDS →Lot-specific quality data. Enter your lot number to retrieve the exact COA.
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View spec sheet →Taxonomy Tree
| Kingdom | Organic compounds |
|---|---|
| Superclass | Organoheterocyclic compounds |
| Class | Pyridopyrimidines |
| Subclass | Pyrido[3,4-d]pyrimidines |
| Intermediate Tree Nodes | Not available |
| Direct Parent | Pyrido[3,4-d]pyrimidines |
| Alternative Parents | Aniline and substituted anilines N-arylamides Nitroaromatic compounds Nitroimidazoles Aminopyrimidines and derivatives Aralkylamines Bromobenzenes Chlorobenzenes Aryl bromides Aryl chlorides Pyridines and derivatives Imidolactams N-substituted imidazoles Heteroaromatic compounds Tetraalkylammonium salts Amino acids and derivatives Secondary carboxylic acid amides Secondary amines Propargyl-type 1,3-dipolar organic compounds Azacyclic compounds Organic oxoazanium compounds Organochlorides Hydrocarbon derivatives Carbonyl compounds Organobromides Organic zwitterions Organic bromide salts Organic oxides |
| Molecular Framework | Aromatic heteropolycyclic compounds |
| Substituents | Pyrido[3,4-d]pyrimidine - Nitroaromatic compound - Nitroimidazole - N-arylamide - Aniline or substituted anilines - Aminopyrimidine - Bromobenzene - Chlorobenzene - Halobenzene - Aralkylamine - Aryl bromide - Aryl chloride - Aryl halide - Monocyclic benzene moiety - N-substituted imidazole - Pyridine - Pyrimidine - Benzenoid - Imidolactam - Imidazole - Heteroaromatic compound - Tetraalkylammonium salt - Azole - Quaternary ammonium salt - Organic nitro compound - Secondary carboxylic acid amide - C-nitro compound - Carboxamide group - Amino acid or derivatives - Secondary amine - Organic oxoazanium - Allyl-type 1,3-dipolar organic compound - Propargyl-type 1,3-dipolar organic compound - Organic 1,3-dipolar compound - Carboxylic acid derivative - Azacycle - Organic bromide salt - Amine - Organic oxide - Hydrocarbon derivative - Organohalogen compound - Carbonyl group - Organic oxygen compound - Organobromide - Organochloride - Organonitrogen compound - Organooxygen compound - Organic salt - Organic nitrogen compound - Organic zwitterion - Aromatic heteropolycyclic compound |
| Description | This compound belongs to the class of organic compounds known as pyrido[3,4-d]pyrimidines. These are compounds containing the pyrido[3,4-d]pyrimidine ring system, which is a pyridopyrimidine isomer with three ring nitrogen atoms at the 1-, 3-, and 7- position. |
| External Descriptors | Not available |
| Solubility | DMSO : ≥ 33 mg/mL (48.40 mM) |
|---|---|
| Molecular Weight | 681.800 g/mol |
| XLogP3 | |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 9 |
| Rotatable Bond Count | 8 |
| Exact Mass | 681.004 Da |
| Monoisotopic Mass | 679.006 Da |
| Topological Polar Surface Area | 143.000 Ų |
| Heavy Atom Count | 39 |
| Formal Charge | 0 |
| Complexity | 862.000 |
| Isotope Atom Count | 0 |
| Defined Atom Stereocenter Count | 0 |
| Undefined Atom Stereocenter Count | 0 |
| Defined Bond Stereocenter Count | 1 |
| Undefined Bond Stereocenter Count | 0 |
| The total count of all stereochemical bonds | 1 |
| Covalently-Bonded Unit Count | 2 |
