Details
Stereochemistry | ACHIRAL |
Molecular Formula | C19H17F6N7O.CH4O3S |
Molecular Weight | 569.481 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CS(O)(=O)=O.CC(C)(O)CNC1=NC(NC2=CC=NC(=C2)C(F)(F)F)=NC(=N1)C3=CC=CC(=N3)C(F)(F)F
InChI
InChIKey=ORZHZQZYWXEDDL-UHFFFAOYSA-N
InChI=1S/C19H17F6N7O.CH4O3S/c1-17(2,33)9-27-15-30-14(11-4-3-5-12(29-11)18(20,21)22)31-16(32-15)28-10-6-7-26-13(8-10)19(23,24)25;1-5(2,3)4/h3-8,33H,9H2,1-2H3,(H2,26,27,28,30,31,32);1H3,(H,2,3,4)
Molecular Formula | C19H17F6N7O |
Molecular Weight | 473.375 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
Molecular Formula | CH4O3S |
Molecular Weight | 96.106 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
DescriptionCurator's Comment: Description was created based on several sources, including
http://www.agios.com/patients-trials.php
http://www.selleckchem.com/products/ag-221-enasidenib.html
http://adisinsight.springer.com/drugs/800038591
Curator's Comment: Description was created based on several sources, including
http://www.agios.com/patients-trials.php
http://www.selleckchem.com/products/ag-221-enasidenib.html
http://adisinsight.springer.com/drugs/800038591
Enasidenib, aslo known as AG-221 and CC-90007, is a potent and selective IDH2 inhibitor with potential anticancer activity (IDH2 = Isocitrate dehydrogenase 2). The mutations of IDH2 present in certain cancer cells result in a new ability of the enzyme to catalyze the NAPH-dependent reduction of α-ketoglutarate to R(-)-2-hydroxyglutarate (2HG). The production of 2HG is believed to contribute to the formation and progression of cancer. The inhibition of mutant IDH2 and its neoactivity is therefore a potential therapeutic treatment for cancer. Enasidenib is an orally available, selective, potent inhibitor of the mutated IDH2 protein, making it a highly targeted investigational medicine for the potential treatment of patients with cancers that harbor an IDH2 mutation. Enasidenib has received orphan drug and fast track designations from the U.S. FDA. Enasidenib mesylate is in phase II clinical trials for Solid tumours and phase III clinical trials for the treatment of acute myeloid leukaemia.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: P48735 Gene ID: 3418.0 Gene Symbol: IDH2 Target Organism: Homo sapiens (Human) |
12.0 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | IDHIFA Approved UseIDHIFA is indicated for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with an isocitrate dehydrogenase-2 (IDH2) mutation as detected by an FDA-approved test. Launch Date2017 |
|||
Primary | Unknown Approved UseUnknown |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
822 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/30386625 |
100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered: |
ENASIDENIB plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
13 μg/mL |
100 mg 1 times / day steady-state, oral dose: 100 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
ENASIDENIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
49500 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/30386625 |
100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered: |
ENASIDENIB plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
25.5 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/30386625 |
100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered: |
ENASIDENIB plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
137 h |
100 mg 1 times / day steady-state, oral dose: 100 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
ENASIDENIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
1.5% |
100 mg 1 times / day steady-state, oral dose: 100 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
ENASIDENIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
Doses
Dose | Population | Adverse events |
---|---|---|
650 mg 1 times / day multiple, oral Highest studied dose Dose: 650 mg, 1 times / day Route: oral Route: multiple Dose: 650 mg, 1 times / day Sources: |
unhealthy, adult n = 5 Health Status: unhealthy Condition: myeloid leukemia Age Group: adult Sex: unknown Population Size: 5 Sources: |
Other AEs: Abdominal distension, Diarrhea... Other AEs: Abdominal distension (1 patient) Sources: Diarrhea (1 patient) Fatigue (1 patient) Hyperbilirubinemia (3 patients) Rash (1 patient) |
100 mg 1 times / day multiple, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: Page: 5 |
unhealthy, adult n = 214 Health Status: unhealthy Condition: myeloid leukemia Age Group: adult Sex: unknown Population Size: 214 Sources: Page: 5 |
Disc. AE: Leukocytosis... Other AEs: Nausea, Diarrhea... AEs leading to discontinuation/dose reduction: Leukocytosis (1%) Other AEs:Nausea (all grades, 50%) Sources: Page: 5Diarrhea (all grades, 43%) Vomiting (all grades, 34%) Decreased appetite (all grades, 34%) Tumor lysis syndrome (all grades, 6%) Differentiation syndrome (all grades, 14%) Leukocytosis (all grades, 12%) Dysgeusia (all grades, 12%) Nausea (grade 3-4, 5%) Diarrhea (grade 3-4, 8%) Vomiting (grade 3-4, 2%) Decreased appetite (grade 3-4, 4%) Tumor lysis syndrome (grade 3-4, 6%) Differentiation syndrome (grade 3-4, 7%) Leukocytosis (grade 3-4, 6%) Bilirubin total increased (all grades, 81%) Calcium decreased (all grades, 74%) Potassium decreased (all grades, 41%) Blood phosphorus decreased (all grades, 27%) Differentiation syndrome (4%) Leukocytosis (3%) |
100 mg 1 times / day multiple, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: Page: 6 |
unhealthy, adult n = 214 Health Status: unhealthy Condition: myeloid leukemia Age Group: adult Sex: unknown Population Size: 214 Sources: Page: 6 |
Other AEs: Bilirubin total increased, Calcium decreased... Other AEs: Bilirubin total increased (grade 3-4, 15%) Sources: Page: 6Calcium decreased (grade 3-4, 8%) Potassium decreased (grade 3-4, 15%) Blood phosphorus decreased (grade 3-4, 8%) Hyperbilirubinemia (3.7%) Hyperbilirubinemia (1.4%) |
100 mg 1 times / day multiple, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: Page: 45 |
unhealthy, adult n = 214 Health Status: unhealthy Condition: myeloid leukemia Age Group: adult Sex: unknown Population Size: 214 Sources: Page: 45 |
Disc. AE: Death... AEs leading to discontinuation/dose reduction: Death (grade 5, 4.2%) Sources: Page: 45 |
100 mg 1 times / day multiple, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: Page: 45 |
unhealthy, adult n = 214 Health Status: unhealthy Condition: myeloid leukemia Age Group: adult Sex: unknown Population Size: 214 Sources: Page: 45 |
Disc. AE: Death... AEs leading to discontinuation/dose reduction: Death (grade 5, 11.7%) Sources: Page: 45 |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Abdominal distension | 1 patient | 650 mg 1 times / day multiple, oral Highest studied dose Dose: 650 mg, 1 times / day Route: oral Route: multiple Dose: 650 mg, 1 times / day Sources: |
unhealthy, adult n = 5 Health Status: unhealthy Condition: myeloid leukemia Age Group: adult Sex: unknown Population Size: 5 Sources: |
Diarrhea | 1 patient | 650 mg 1 times / day multiple, oral Highest studied dose Dose: 650 mg, 1 times / day Route: oral Route: multiple Dose: 650 mg, 1 times / day Sources: |
unhealthy, adult n = 5 Health Status: unhealthy Condition: myeloid leukemia Age Group: adult Sex: unknown Population Size: 5 Sources: |
Fatigue | 1 patient | 650 mg 1 times / day multiple, oral Highest studied dose Dose: 650 mg, 1 times / day Route: oral Route: multiple Dose: 650 mg, 1 times / day Sources: |
unhealthy, adult n = 5 Health Status: unhealthy Condition: myeloid leukemia Age Group: adult Sex: unknown Population Size: 5 Sources: |
Rash | 1 patient | 650 mg 1 times / day multiple, oral Highest studied dose Dose: 650 mg, 1 times / day Route: oral Route: multiple Dose: 650 mg, 1 times / day Sources: |
unhealthy, adult n = 5 Health Status: unhealthy Condition: myeloid leukemia Age Group: adult Sex: unknown Population Size: 5 Sources: |
Hyperbilirubinemia | 3 patients | 650 mg 1 times / day multiple, oral Highest studied dose Dose: 650 mg, 1 times / day Route: oral Route: multiple Dose: 650 mg, 1 times / day Sources: |
unhealthy, adult n = 5 Health Status: unhealthy Condition: myeloid leukemia Age Group: adult Sex: unknown Population Size: 5 Sources: |
Leukocytosis | 1% Disc. AE |
100 mg 1 times / day multiple, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: Page: 5 |
unhealthy, adult n = 214 Health Status: unhealthy Condition: myeloid leukemia Age Group: adult Sex: unknown Population Size: 214 Sources: Page: 5 |
Leukocytosis | 3% | 100 mg 1 times / day multiple, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: Page: 5 |
unhealthy, adult n = 214 Health Status: unhealthy Condition: myeloid leukemia Age Group: adult Sex: unknown Population Size: 214 Sources: Page: 5 |
Differentiation syndrome | 4% | 100 mg 1 times / day multiple, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: Page: 5 |
unhealthy, adult n = 214 Health Status: unhealthy Condition: myeloid leukemia Age Group: adult Sex: unknown Population Size: 214 Sources: Page: 5 |
Dysgeusia | all grades, 12% | 100 mg 1 times / day multiple, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: Page: 5 |
unhealthy, adult n = 214 Health Status: unhealthy Condition: myeloid leukemia Age Group: adult Sex: unknown Population Size: 214 Sources: Page: 5 |
Leukocytosis | all grades, 12% | 100 mg 1 times / day multiple, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: Page: 5 |
unhealthy, adult n = 214 Health Status: unhealthy Condition: myeloid leukemia Age Group: adult Sex: unknown Population Size: 214 Sources: Page: 5 |
Differentiation syndrome | all grades, 14% | 100 mg 1 times / day multiple, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: Page: 5 |
unhealthy, adult n = 214 Health Status: unhealthy Condition: myeloid leukemia Age Group: adult Sex: unknown Population Size: 214 Sources: Page: 5 |
Blood phosphorus decreased | all grades, 27% | 100 mg 1 times / day multiple, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: Page: 5 |
unhealthy, adult n = 214 Health Status: unhealthy Condition: myeloid leukemia Age Group: adult Sex: unknown Population Size: 214 Sources: Page: 5 |
Decreased appetite | all grades, 34% | 100 mg 1 times / day multiple, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: Page: 5 |
unhealthy, adult n = 214 Health Status: unhealthy Condition: myeloid leukemia Age Group: adult Sex: unknown Population Size: 214 Sources: Page: 5 |
Vomiting | all grades, 34% | 100 mg 1 times / day multiple, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: Page: 5 |
unhealthy, adult n = 214 Health Status: unhealthy Condition: myeloid leukemia Age Group: adult Sex: unknown Population Size: 214 Sources: Page: 5 |
Potassium decreased | all grades, 41% | 100 mg 1 times / day multiple, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: Page: 5 |
unhealthy, adult n = 214 Health Status: unhealthy Condition: myeloid leukemia Age Group: adult Sex: unknown Population Size: 214 Sources: Page: 5 |
Diarrhea | all grades, 43% | 100 mg 1 times / day multiple, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: Page: 5 |
unhealthy, adult n = 214 Health Status: unhealthy Condition: myeloid leukemia Age Group: adult Sex: unknown Population Size: 214 Sources: Page: 5 |
Nausea | all grades, 50% | 100 mg 1 times / day multiple, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: Page: 5 |
unhealthy, adult n = 214 Health Status: unhealthy Condition: myeloid leukemia Age Group: adult Sex: unknown Population Size: 214 Sources: Page: 5 |
Tumor lysis syndrome | all grades, 6% | 100 mg 1 times / day multiple, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: Page: 5 |
unhealthy, adult n = 214 Health Status: unhealthy Condition: myeloid leukemia Age Group: adult Sex: unknown Population Size: 214 Sources: Page: 5 |
Calcium decreased | all grades, 74% | 100 mg 1 times / day multiple, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: Page: 5 |
unhealthy, adult n = 214 Health Status: unhealthy Condition: myeloid leukemia Age Group: adult Sex: unknown Population Size: 214 Sources: Page: 5 |
Bilirubin total increased | all grades, 81% | 100 mg 1 times / day multiple, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: Page: 5 |
unhealthy, adult n = 214 Health Status: unhealthy Condition: myeloid leukemia Age Group: adult Sex: unknown Population Size: 214 Sources: Page: 5 |
Vomiting | grade 3-4, 2% | 100 mg 1 times / day multiple, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: Page: 5 |
unhealthy, adult n = 214 Health Status: unhealthy Condition: myeloid leukemia Age Group: adult Sex: unknown Population Size: 214 Sources: Page: 5 |
Decreased appetite | grade 3-4, 4% | 100 mg 1 times / day multiple, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: Page: 5 |
unhealthy, adult n = 214 Health Status: unhealthy Condition: myeloid leukemia Age Group: adult Sex: unknown Population Size: 214 Sources: Page: 5 |
Nausea | grade 3-4, 5% | 100 mg 1 times / day multiple, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: Page: 5 |
unhealthy, adult n = 214 Health Status: unhealthy Condition: myeloid leukemia Age Group: adult Sex: unknown Population Size: 214 Sources: Page: 5 |
Leukocytosis | grade 3-4, 6% | 100 mg 1 times / day multiple, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: Page: 5 |
unhealthy, adult n = 214 Health Status: unhealthy Condition: myeloid leukemia Age Group: adult Sex: unknown Population Size: 214 Sources: Page: 5 |
Tumor lysis syndrome | grade 3-4, 6% | 100 mg 1 times / day multiple, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: Page: 5 |
unhealthy, adult n = 214 Health Status: unhealthy Condition: myeloid leukemia Age Group: adult Sex: unknown Population Size: 214 Sources: Page: 5 |
Differentiation syndrome | grade 3-4, 7% | 100 mg 1 times / day multiple, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: Page: 5 |
unhealthy, adult n = 214 Health Status: unhealthy Condition: myeloid leukemia Age Group: adult Sex: unknown Population Size: 214 Sources: Page: 5 |
Diarrhea | grade 3-4, 8% | 100 mg 1 times / day multiple, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: Page: 5 |
unhealthy, adult n = 214 Health Status: unhealthy Condition: myeloid leukemia Age Group: adult Sex: unknown Population Size: 214 Sources: Page: 5 |
Hyperbilirubinemia | 1.4% | 100 mg 1 times / day multiple, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: Page: 6 |
unhealthy, adult n = 214 Health Status: unhealthy Condition: myeloid leukemia Age Group: adult Sex: unknown Population Size: 214 Sources: Page: 6 |
Hyperbilirubinemia | 3.7% | 100 mg 1 times / day multiple, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: Page: 6 |
unhealthy, adult n = 214 Health Status: unhealthy Condition: myeloid leukemia Age Group: adult Sex: unknown Population Size: 214 Sources: Page: 6 |
Bilirubin total increased | grade 3-4, 15% | 100 mg 1 times / day multiple, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: Page: 6 |
unhealthy, adult n = 214 Health Status: unhealthy Condition: myeloid leukemia Age Group: adult Sex: unknown Population Size: 214 Sources: Page: 6 |
Potassium decreased | grade 3-4, 15% | 100 mg 1 times / day multiple, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: Page: 6 |
unhealthy, adult n = 214 Health Status: unhealthy Condition: myeloid leukemia Age Group: adult Sex: unknown Population Size: 214 Sources: Page: 6 |
Blood phosphorus decreased | grade 3-4, 8% | 100 mg 1 times / day multiple, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: Page: 6 |
unhealthy, adult n = 214 Health Status: unhealthy Condition: myeloid leukemia Age Group: adult Sex: unknown Population Size: 214 Sources: Page: 6 |
Calcium decreased | grade 3-4, 8% | 100 mg 1 times / day multiple, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: Page: 6 |
unhealthy, adult n = 214 Health Status: unhealthy Condition: myeloid leukemia Age Group: adult Sex: unknown Population Size: 214 Sources: Page: 6 |
Death | grade 5, 4.2% Disc. AE |
100 mg 1 times / day multiple, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: Page: 45 |
unhealthy, adult n = 214 Health Status: unhealthy Condition: myeloid leukemia Age Group: adult Sex: unknown Population Size: 214 Sources: Page: 45 |
Death | grade 5, 11.7% Disc. AE |
100 mg 1 times / day multiple, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: Page: 45 |
unhealthy, adult n = 214 Health Status: unhealthy Condition: myeloid leukemia Age Group: adult Sex: unknown Population Size: 214 Sources: Page: 45 |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Drug as victim
Sample Use Guides
In Vivo Use Guide
Sources: https://clinicaltrials.gov/ct2/show/NCT02577406
Continuous 28-day cycles of Enasidenib (AG 221) 100 mg orally (PO) once a day (QD) for 28 days, plus BSC.
Route of Administration:
Oral
Substance Class |
Chemical
Created
by
admin
on
Edited
Sat Dec 16 11:07:29 GMT 2023
by
admin
on
Sat Dec 16 11:07:29 GMT 2023
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Record UNII |
UF6PC17XAV
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Record Status |
Validated (UNII)
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Record Version |
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NCI_THESAURUS |
C137826
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EU-Orphan Drug |
EU/3/16/1640
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DBSALT002582
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UF6PC17XAV
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DTXSID501027943
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m12047
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100000175240
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145374
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1940331
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DE-122
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C137825
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PARENT -> SALT/SOLVATE |
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ACTIVE MOIETY |
Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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SOLUBILITY | CHEMICAL |
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SOLVENT CHEMICAL CHEMICAL |
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SOLUBILITY | CHEMICAL |
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SOLVENT CHEMICAL CHEMICAL |
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