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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 of Methoxyamine hydrochloride

SMILES

Cl.CON

InChI

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

HIDE SMILES / InChI
Molecular Formula CH5NO
Molecular Weight 47.0565
Charge 0
Count
MOL RATIO 1 MOL RATIO (average)
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE
Molecular Formula ClH
Molecular Weight 36.461
Charge 0
Count
MOL RATIO 1 MOL RATIO (average)
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description

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

Farbwerke Hoechst
6

Approval Year

Unknown
149,124

Targets

Primary TargetPharmacologyConditionPotency
DNA topoisomerase II
66
Inhibitor
8,504
DNA topoisomerase II
66
Inhibitor
8,504

Conditions

ConditionModalityTargetsHighest PhaseProduct
Respiratory tract infections
85
 Curative
Not Provided
511
Unknown
Advanced peritoneal malignant mesothelioma
2
 Primary
Phase II
1,147
Unknown
Advanced pleural malignant mesothelioma
2
 Primary
Phase II
1,147
Unknown
Non-small cell lung cancer
211
 Primary
Phase II
1,147
Unknown
Ovarian cancer
160
 Primary
Phase II
1,147
Unknown

Cmax

ValueDoseCo-administeredAnalytePopulation
64.3 ng/mL
30 mg/m² single, oral
 METHOXYAMINE plasma
Homo sapiens
19.7 ng/mL
15 mg/m² single, oral
 METHOXYAMINE plasma
Homo sapiens
126 ng/mL
30 mg/m² 1 times / day multiple, oral
 METHOXYAMINE plasma
Homo sapiens
68.1 ng/mL
15 mg/m² 1 times / day multiple, oral
 METHOXYAMINE plasma
Homo sapiens
327 ng/mL
60 mg/m² 1 times / day multiple, oral
 METHOXYAMINE plasma
Homo sapiens
152 ng/mL
100 mg/m² single, oral
 METHOXYAMINE plasma
Homo sapiens
119 ng/mL
60 mg/m² single, oral
 METHOXYAMINE plasma
Homo sapiens
247 ng/mL
100 mg/m² 1 times / day multiple, oral
 METHOXYAMINE plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
1041 ng × h/mL
30 mg/m² single, oral
 METHOXYAMINE plasma
Homo sapiens
287 ng × h/mL
15 mg/m² single, oral
 METHOXYAMINE plasma
Homo sapiens
1960 ng × h/mL
30 mg/m² 1 times / day multiple, oral
 METHOXYAMINE plasma
Homo sapiens
1136 ng × h/mL
15 mg/m² 1 times / day multiple, oral
 METHOXYAMINE plasma
Homo sapiens
5812 ng × h/mL
60 mg/m² 1 times / day multiple, oral
 METHOXYAMINE plasma
Homo sapiens
2312 ng × h/mL
100 mg/m² single, oral
 METHOXYAMINE plasma
Homo sapiens
1991 ng × h/mL
60 mg/m² single, oral
 METHOXYAMINE plasma
Homo sapiens
3105 ng × h/mL
100 mg/m² 1 times / day multiple, oral
 METHOXYAMINE plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
21.8 h
30 mg/m² single, oral
 METHOXYAMINE plasma
Homo sapiens
37.3 h
15 mg/m² single, oral
 METHOXYAMINE plasma
Homo sapiens
30.9 h
30 mg/m² 1 times / day multiple, oral
 METHOXYAMINE plasma
Homo sapiens
41.5 h
15 mg/m² 1 times / day multiple, oral
 METHOXYAMINE plasma
Homo sapiens
26.9 h
60 mg/m² 1 times / day multiple, oral
 METHOXYAMINE plasma
Homo sapiens
26.8 h
100 mg/m² single, oral
 METHOXYAMINE plasma
Homo sapiens
21.9 h
60 mg/m² single, oral
 METHOXYAMINE plasma
Homo sapiens
25 h
100 mg/m² 1 times / day multiple, oral
 METHOXYAMINE plasma
Homo sapiens

Doses

AEs

PubMed

Patents

03944567
3
03953506
4
03953606
3
03972895
2
03998959
4
04005140
7
04034101
4
04054650
2
04059623
4
04062856
4
04069231
3
04074056
2
04087460
3
04093445
6
04151296
2
04154740
3
04161591
5
04166115
2
04174210
2
04260410
5
04267176
2
04268509
3
04278671
2
04279818
5
04280957
6
04304770
4
04307237
7
04314082
2
04316019
5
04326077
2
04327089
2
04331664
5
04337268
2
04347364
3
04347365
5
04349475
5
04349476
7
04349477
5
04364943
4
04367336
2
04368157
7
04368158
5
04368159
5
04371468
3
04376074
4
04377523
7
04382934
2
04390471
6
04395411
3
04401597
5
04409214
2
04420477
2
04423213
2
04500345
2
04504305
2
04870084
4
05597940
2
06933319
4
07253286
10
07425547
2
07704997
2
08088760
9
08101611
32
08211921
32
08410264
2
08524911
3
08796257
2
08841459
3

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.
Substance Class Chemical
Record UNII
203546OLMF
Record Status Validated (UNII)
Record Version
NIH
NCATS
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