METHOXYAMINE HYDROCHLORIDE

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	CH5NO.ClH
Molecular Weight	83.517
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Cl.CON

InChI

InChIKey=XNXVOSBNFZWHBV-UHFFFAOYSA-N

InChI=1S/CH5NO.ClH/c1-3-2;/h2H2,1H3;1H

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/23054206
Curator's Comment: The description was created based on several sources, including https://clinicaltrials.gov/ct2/show/NCT01851369 | https://www.ncbi.nlm.nih.gov/pubmed/29108368 | https://clinicaltrials.gov/ct2/show/NCT02395692 | https://www.ncbi.nlm.nih.gov/pubmed/28670521

Methoxyamine (TRC102) is an orally bioavailable small molecule with potential adjuvant activity, that may potentiate the antitumor activity of alkylating agents. Methoxyamine covalently binds to apurinic/apyrimidinic (AP) DNA damage sites and inhibits base excision repair (BER) that causes topoisomerase II-dependent irreversible strand breaks and apoptosis. Methoxyamine is currently being studied in multiple Phase 1 and Phase 2 clinical trials sponsored by the National Cancer Institute or Case Comprehensive Cancer Center.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
DNA topoisomerase II 66 Target ID: CHEMBL2094255 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23054206	Inhibitor 8297
DNA topoisomerase II 66 Target ID: CHEMBL2094255 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23054206	Inhibitor 8297

Conditions

Condition	Modality	Highest Phase	Product
Respiratory tract infections 85 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7031458	Curative	Not Provided 504	Unknown Approved Use Unknown
Advanced peritoneal malignant mesothelioma 2 Sources: https://clinicaltrials.gov/ct2/show/NCT02535312	Primary	Phase II 1132	Unknown Approved Use Unknown
Advanced pleural malignant mesothelioma 2 Sources: https://clinicaltrials.gov/ct2/show/NCT02535312	Primary	Phase II 1132	Unknown Approved Use Unknown
Non-small cell lung cancer 206 Sources: https://clinicaltrials.gov/ct2/show/NCT02535312	Primary	Phase II 1132	Unknown Approved Use Unknown
Ovarian cancer 157 Sources: https://clinicaltrials.gov/ct2/show/NCT02535312	Primary	Phase II 1132	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
119 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23054206	60 mg/m² single, oral dose: 60 mg/m² route of administration: Oral experiment type: SINGLE co-administered:	METHOXYAMINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
152 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23054206	100 mg/m² single, oral dose: 100 mg/m² route of administration: Oral experiment type: SINGLE co-administered:	METHOXYAMINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
247 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23054206	100 mg/m² 1 times / day multiple, oral dose: 100 mg/m² route of administration: Oral experiment type: MULTIPLE co-administered:	METHOXYAMINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
327 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23054206	60 mg/m² 1 times / day multiple, oral dose: 60 mg/m² route of administration: Oral experiment type: MULTIPLE co-administered:	METHOXYAMINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
1991 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23054206	60 mg/m² single, oral dose: 60 mg/m² route of administration: Oral experiment type: SINGLE co-administered:	METHOXYAMINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2312 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23054206	100 mg/m² single, oral dose: 100 mg/m² route of administration: Oral experiment type: SINGLE co-administered:	METHOXYAMINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
3105 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23054206	100 mg/m² 1 times / day multiple, oral dose: 100 mg/m² route of administration: Oral experiment type: MULTIPLE co-administered:	METHOXYAMINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
5812 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23054206	60 mg/m² 1 times / day multiple, oral dose: 60 mg/m² route of administration: Oral experiment type: MULTIPLE co-administered:	METHOXYAMINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
21.9 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23054206	60 mg/m² single, oral dose: 60 mg/m² route of administration: Oral experiment type: SINGLE co-administered:	METHOXYAMINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
26.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23054206	100 mg/m² single, oral dose: 100 mg/m² route of administration: Oral experiment type: SINGLE co-administered:	METHOXYAMINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
25 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23054206	100 mg/m² 1 times / day multiple, oral dose: 100 mg/m² route of administration: Oral experiment type: MULTIPLE co-administered:	METHOXYAMINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
26.9 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23054206	60 mg/m² 1 times / day multiple, oral dose: 60 mg/m² route of administration: Oral experiment type: MULTIPLE co-administered:	METHOXYAMINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
100 mg/m2 1 times / day multiple, oral Highest studied dose Dose: 100 mg/m2, 1 times / day Route: oral Route: multiple Dose: 100 mg/m2, 1 times / day Co-administed with:: pemetrexed(Patients received oral TRC102 daily for 4 days. Two weeks later, patients began standard-dose pemetrexed (500 mg/m2) on day 1 in combination with oral TRC102 on days 1 to 4. The pemetrexed-TRC102 combination was repeated every 3 weeks until disease progression.) Sources: https://pubmed.ncbi.nlm.nih.gov/23054206 Page: p.7, 16	unhealthy, ADULT n = 6 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/23054206 Page: p.7, 16	DLT: Anemia... Disc. AE: Anemia... Dose limiting toxicities: Anemia (grade 3, 50%) AEs leading to discontinuation/dose reduction: Anemia (grade 2-3, 66.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/23054206 Page: p.7, 16
60 mg/m2 1 times / day multiple, oral MTD Dose: 60 mg/m2, 1 times / day Route: oral Route: multiple Dose: 60 mg/m2, 1 times / day Co-administed with:: pemetrexed(Patients received oral TRC102 daily for 4 days. Two weeks later, patients began standard-dose pemetrexed (500 mg/m2) on day 1 in combination with oral TRC102 on days 1 to 4. The pemetrexed-TRC102 combination was repeated every 3 weeks until disease progression.) Sources: https://pubmed.ncbi.nlm.nih.gov/23054206 Page: p.7	unhealthy, ADULT n = 11 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 11 Sources: https://pubmed.ncbi.nlm.nih.gov/23054206 Page: p.7	DLT: Anemia... Dose limiting toxicities: Anemia (grade 4, 9%) Sources: https://pubmed.ncbi.nlm.nih.gov/23054206 Page: p.7

AEs

AE	Significance	Dose	Population
Anemia	grade 2-3, 66.7% Disc. AE	100 mg/m2 1 times / day multiple, oral Highest studied dose Dose: 100 mg/m2, 1 times / day Route: oral Route: multiple Dose: 100 mg/m2, 1 times / day Co-administed with:: pemetrexed(Patients received oral TRC102 daily for 4 days. Two weeks later, patients began standard-dose pemetrexed (500 mg/m2) on day 1 in combination with oral TRC102 on days 1 to 4. The pemetrexed-TRC102 combination was repeated every 3 weeks until disease progression.) Sources: https://pubmed.ncbi.nlm.nih.gov/23054206 Page: p.7, 16	unhealthy, ADULT n = 6 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/23054206 Page: p.7, 16
Anemia	grade 3, 50% DLT	100 mg/m2 1 times / day multiple, oral Highest studied dose Dose: 100 mg/m2, 1 times / day Route: oral Route: multiple Dose: 100 mg/m2, 1 times / day Co-administed with:: pemetrexed(Patients received oral TRC102 daily for 4 days. Two weeks later, patients began standard-dose pemetrexed (500 mg/m2) on day 1 in combination with oral TRC102 on days 1 to 4. The pemetrexed-TRC102 combination was repeated every 3 weeks until disease progression.) Sources: https://pubmed.ncbi.nlm.nih.gov/23054206 Page: p.7, 16	unhealthy, ADULT n = 6 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/23054206 Page: p.7, 16
Anemia	grade 4, 9% DLT, Disc. AE	60 mg/m2 1 times / day multiple, oral MTD Dose: 60 mg/m2, 1 times / day Route: oral Route: multiple Dose: 60 mg/m2, 1 times / day Co-administed with:: pemetrexed(Patients received oral TRC102 daily for 4 days. Two weeks later, patients began standard-dose pemetrexed (500 mg/m2) on day 1 in combination with oral TRC102 on days 1 to 4. The pemetrexed-TRC102 combination was repeated every 3 weeks until disease progression.) Sources: https://pubmed.ncbi.nlm.nih.gov/23054206 Page: p.7	unhealthy, ADULT n = 11 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 11 Sources: https://pubmed.ncbi.nlm.nih.gov/23054206 Page: p.7

Sourcing

Vendor/Aggregator	ID	URL
Acadechem	ACDS-028758	http://www.acadechemical.com/product/103457
Alichem	490022510	http://www.alichem.com/en/products/67-62-9.html
Ambinter	Amb13777310	http://www.ambinter.com/reference/13777310
Aurora Fine Chemicals LLC	A00.658.173	http://online.aurorafinechemicals.com/info?ID=A00.658.173
Aurora Fine Chemicals LLC	K02.871.539	http://online.aurorafinechemicals.com/info?ID=K02.871.539
BOC Sciences	67-62-9	https://www.bocsci.com/o-methylhydroxylamine-cas-67-62-9-item-31121.html
ChemMol	99122228	http://www.chemmol.com/chemmol/99122228.html
Chemspace	CSSB00000234925	https://chem-space.com/CSSB00000234925
Hairui	HR101304	http://www.hairuichem.com/en/product/67-62-9.html
Lab Network	LN03244274	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN03244274
MolPort	MolPort-001-786-611	https://www.molport.com/shop/molecule-link/MolPort-001-786-611
Sinfoo Biotech	S013101	http://www.sinfoobiotech.com/product/1016499
Smolecule	S564660	https://www.smolecule.com/products/s564660
THE BioTek	bt-363875	https://www.thebiotek.com/product/others/bt-363875
Vitas-M Laboratory	BBL028003	http://www.request.vitasmlab.biz/index.php?option=com_search_stk&Itemid=22&stk=BBL028003&?utm_source=pubchem&utm_medium=p_search_link&utm_campaign=pubchem_search&utm_content=pubchem_slink
Vitas-M Laboratory	STL373472	http://www.request.vitasmlab.biz/index.php?option=com_search_stk&Itemid=22&stk=STL373472&?utm_source=pubchem&utm_medium=p_search_link&utm_campaign=pubchem_search&utm_content=pubchem_slink
abcr GmbH	AB482181	http://www.abcr.de/shop/en/AB482181
eNovation Chemicals	D618697	http://www.enovationchem.com/productDetails.asp?productID=D618697
iChemical	EBD2321783	http://www.ichemical.com/products/67-62-9.html?utm_source=PubChem&utm_medium=website&utm_campaign=product%20catalogs
mcule	MCULE-1068458971	https://mcule.com/MCULE-1068458971/

PubMed

Title	Date	PubMed
A new sensitive HPLC assay for methoxyamine and its analogs.	2002 Oct 15	12367666
Inhibition of base excision repair potentiates iododeoxyuridine-induced cytotoxicity and radiosensitization.	2003 Feb 15	12591735
Synthesis and insecticidal activity of novel N-oxydihydropyrrole derivatives with a substituted spirocyclohexyl group.	2003 Jun	12843647
Blockage of abasic site repair enhances antitumor efficacy of 1,3-bis-(2-chloroethyl)-1-nitrosourea in colon tumor xenografts.	2003 Oct	14578471
The kinetics and mechanism of the ferrate(VI) oxidation of hydroxylamines.	2003 Oct 20	14552644
Measurement of anti-cancer agent methoxyamine in plasma by tandem mass spectrometry with on-line sample extraction.	2003 Oct 5	14522034
Role of MutSalpha in the recognition of iododeoxyuridine in DNA.	2003 Sep 1	14500385
Crystal structure of extended-spectrum beta-lactamase Toho-1: insights into the molecular mechanism for catalytic reaction and substrate specificity expansion.	2003 Sep 16	12962487
Synthesis and conformational analysis of novel N(OCH3)-linked disaccharide analogues.	2004 Mar 19	15034887
A new approach towards ikimine A analogues.	2004 Oct	15248605
Effects of gemcitabine on APE/ref-1 endonuclease activity in pancreatic cancer cells, and the therapeutic potential of antisense oligonucleotides.	2004 Sep 13	15316562
Enhancement of manumycin A-induced apoptosis by methoxyamine in myeloid leukemia cells.	2005 Apr	15744347
Improved measurement of dibenzo[a,l]pyrene-induced abasic sites by the aldehyde-reactive probe assay.	2005 Dec 30	16298157
GC-MS quantitation of codeine, morphine, 6-acetylmorphine, hydrocodone, hydromorphone, oxycodone, and oxymorphone in blood.	2005 Jul-Aug	16105253
Biomarker metabolites capturing the metabolite variance present in a rice plant developmental period.	2005 May 31	15927065
DNA repair inhibition: a selective tumour targeting strategy.	2005 Nov	16214418
Development and validation of an HPLC-UV method for the analysis of methoxyamine using 4-(diethylamino)benzaldehyde as a derivatizing agent.	2005 Sep 15	15951147
Methoxyamine potentiates iododeoxyuridine-induced radiosensitization by altering cell cycle kinetics and enhancing senescence.	2006 Apr	16648559
On systems and control approaches to therapeutic gain.	2006 Apr 25	16638124
A re-investigation of the path of carbon in photosynthesis utilizing GC/MS methodology. Unequivocal verification of the participation of octulose phosphates in the pathway.	2006 Nov	17149533
Enantioselective oxidation of O-methyl-N-hydroxylamines using monoamine oxidase N as catalyst.	2007 Apr 21	17406697
GC-MS analysis of multiply derivatized opioids in urine.	2007 Aug	17567826
Role for DNA polymerase beta in response to ionizing radiation.	2007 Feb 4	17126614
Manipulation of base excision repair to sensitize ovarian cancer cells to alkylating agent temozolomide.	2007 Jan 1	17200364
The mismatch repair-mediated cell cycle checkpoint response to fluorodeoxyuridine.	2008 Sep 1	18543256
Flame acceleration and the development of detonation in fuel-oxygen mixtures at elevated temperatures and pressures.	2009 Apr 30	18782653
Influence of high dietary sodium intake on the functional subtypes of alpha-adrenoceptors in the renal cortical vasculature of Wistar-Kyoto rats.	2009 Jan	19302553
Metabolite profiling studies in Saccharomyces cerevisiae: an assisting tool to prioritize host targets for antiviral drug screening.	2009 Jan 30	19183481
Novel metabolites of amodiaquine formed by CYP1A1 and CYP1B1: structure elucidation using electrochemistry, mass spectrometry, and NMR.	2009 Mar	19074972
Water deficit alters differentially metabolic pathways affecting important flavor and quality traits in grape berries of Cabernet Sauvignon and Chardonnay.	2009 May 8	19426499

Patents

Sample Use Guides

In Vivo Use Guide

Twenty-eight patients were treated with TRC102 at 15, 30, 60 or 100 mg/m2/d. The MTD was exceeded at 100 mg/m2/d due to grade 3 anemia in 50 % of patients.

Route of Administration: Oral

In Vitro Use Guide

The human colorectal cancer cell line, HT29 were used for activity evaluation. HT29 cells were cultured at a density of 2×104 per well in multiwell plates (24 wells/plate, SPL). After 24 hours, we treated the cells with different concentrations of 5-FU (5-Fluorouracil) (0, 1, 5, 10, 50, 100 µM) or Mx (Methoxyamine) (0, 1, 6, 30, 60, 120 mM). After 24 hours, cell viability was determined by the trypan blue dye exclusion assay.

Name

Type

Language

METHOXYAMINE HYDROCHLORIDE

Systematic Name

English

NSC-3801

Code

English

METHOXYAMINE HCL

Common Name

English

METHOXYAMINE HYDROCHLORIDE [MI]

Common Name

English

HYDROXYLAMINE, O-METHYL- HYDROCHLORIDE

Systematic Name

English

O-METHYLHYDROXYLAMINE HYDROCHLORIDE

Systematic Name

English

Classification Tree Code System Code

NCI_THESAURUS

C274