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
SMILES
Cl.CON
InChI
InChIKey=XNXVOSBNFZWHBV-UHFFFAOYSA-N
InChI=1S/CH5NO.ClH/c1-3-2;/h2H2,1H3;1H
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/23054206Curator'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
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.
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL2094255 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23054206 |
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Target ID: CHEMBL2094255 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23054206 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Curative | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
Cmax
Value | Dose | Co-administered | 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 | Co-administered | 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 |
T1/2
Value | Dose | Co-administered | 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: 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: Page: p.7, 16 |
DLT: Anemia... Disc. AE: Anemia... Dose limiting toxicities: Anemia (grade 3, 50%) AEs leading todiscontinuation/dose reduction: Anemia (grade 2-3, 66.7%) Sources: 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: 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: Page: p.7 |
DLT: Anemia... Dose limiting toxicities: Anemia (grade 4, 9%) Sources: 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: 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: 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: 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: 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: 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: Page: p.7 |
PubMed
Title | Date | PubMed |
---|---|---|
A new sensitive HPLC assay for methoxyamine and its analogs. | 2002 Oct 15 |
|
Inhibition of base excision repair potentiates iododeoxyuridine-induced cytotoxicity and radiosensitization. | 2003 Feb 15 |
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Synthesis and insecticidal activity of novel N-oxydihydropyrrole derivatives with a substituted spirocyclohexyl group. | 2003 Jun |
|
Blockage of abasic site repair enhances antitumor efficacy of 1,3-bis-(2-chloroethyl)-1-nitrosourea in colon tumor xenografts. | 2003 Oct |
|
The kinetics and mechanism of the ferrate(VI) oxidation of hydroxylamines. | 2003 Oct 20 |
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Measurement of anti-cancer agent methoxyamine in plasma by tandem mass spectrometry with on-line sample extraction. | 2003 Oct 5 |
|
Role of MutSalpha in the recognition of iododeoxyuridine in DNA. | 2003 Sep 1 |
|
Crystal structure of extended-spectrum beta-lactamase Toho-1: insights into the molecular mechanism for catalytic reaction and substrate specificity expansion. | 2003 Sep 16 |
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Synthesis and conformational analysis of novel N(OCH3)-linked disaccharide analogues. | 2004 Mar 19 |
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A new approach towards ikimine A analogues. | 2004 Oct |
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Effects of gemcitabine on APE/ref-1 endonuclease activity in pancreatic cancer cells, and the therapeutic potential of antisense oligonucleotides. | 2004 Sep 13 |
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Enhancement of manumycin A-induced apoptosis by methoxyamine in myeloid leukemia cells. | 2005 Apr |
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Improved measurement of dibenzo[a,l]pyrene-induced abasic sites by the aldehyde-reactive probe assay. | 2005 Dec 30 |
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GC-MS quantitation of codeine, morphine, 6-acetylmorphine, hydrocodone, hydromorphone, oxycodone, and oxymorphone in blood. | 2005 Jul-Aug |
|
Biomarker metabolites capturing the metabolite variance present in a rice plant developmental period. | 2005 May 31 |
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DNA repair inhibition: a selective tumour targeting strategy. | 2005 Nov |
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Development and validation of an HPLC-UV method for the analysis of methoxyamine using 4-(diethylamino)benzaldehyde as a derivatizing agent. | 2005 Sep 15 |
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Methoxyamine potentiates iododeoxyuridine-induced radiosensitization by altering cell cycle kinetics and enhancing senescence. | 2006 Apr |
|
On systems and control approaches to therapeutic gain. | 2006 Apr 25 |
|
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 |
|
Enantioselective oxidation of O-methyl-N-hydroxylamines using monoamine oxidase N as catalyst. | 2007 Apr 21 |
|
GC-MS analysis of multiply derivatized opioids in urine. | 2007 Aug |
|
Role for DNA polymerase beta in response to ionizing radiation. | 2007 Feb 4 |
|
Manipulation of base excision repair to sensitize ovarian cancer cells to alkylating agent temozolomide. | 2007 Jan 1 |
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The mismatch repair-mediated cell cycle checkpoint response to fluorodeoxyuridine. | 2008 Sep 1 |
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Flame acceleration and the development of detonation in fuel-oxygen mixtures at elevated temperatures and pressures. | 2009 Apr 30 |
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Influence of high dietary sodium intake on the functional subtypes of alpha-adrenoceptors in the renal cortical vasculature of Wistar-Kyoto rats. | 2009 Jan |
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Metabolite profiling studies in Saccharomyces cerevisiae: an assisting tool to prioritize host targets for antiviral drug screening. | 2009 Jan 30 |
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Novel metabolites of amodiaquine formed by CYP1A1 and CYP1B1: structure elucidation using electrochemistry, mass spectrometry, and NMR. | 2009 Mar |
|
Water deficit alters differentially metabolic pathways affecting important flavor and quality traits in grape berries of Cabernet Sauvignon and Chardonnay. | 2009 May 8 |
Patents
Sample Use Guides
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/23054206
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/28670521
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.
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NCI_THESAURUS |
C274
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FDA ORPHAN DRUG |
777120
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3801
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C78085
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DTXSID9025615
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m7330
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ACTIVE MOIETY
SUBSTANCE RECORD