Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C19H20F3N5O5S2 |
Molecular Weight | 519.518 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 4 / 4 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
NS(=O)(=O)OC[C@H]1C[C@@H](NC2=CC=NC3=CC(=NN23)C4=CC(SC(F)(F)F)=CC=C4)[C@H](O)[C@@H]1O
InChI
InChIKey=KJDAGXLMHXUAGV-DGWLBADLSA-N
InChI=1S/C19H20F3N5O5S2/c20-19(21,22)33-12-3-1-2-10(6-12)13-8-16-24-5-4-15(27(16)26-13)25-14-7-11(17(28)18(14)29)9-32-34(23,30)31/h1-6,8,11,14,17-18,25,28-29H,7,9H2,(H2,23,30,31)/t11-,14-,17-,18+/m1/s1
TAK-243 (MLN7243) is a small molecule inhibitor of ubiquitin-activating enzyme (UAE), with potential antineoplastic activity, which was developed by Takeda Oncology, Millennium. MLN7243 binds to and inhibits UAE, which prevents both protein ubiquitination and subsequent protein degradation by the proteasome. This inhibits tumor cell proliferation and survival. UAE, also called ubiquitin E1 enzyme (UBA1; E1), is more active in cancer cells than in normal, healthy cells. Currently, TAK-243 is in phase I clinical trial evaluating safety, tolerability, pharmacokinetics, pharmacodynamics against advanced malignant solid tumors phase.
Originator
Sources: http://www.clinicalleader.com/doc/millennium-carries-on-with-the-takeda-oncology-expansion-0001
Curator's Comment: # Takeda Oncology, Millennium
Approval Year
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
179.726 ng × h/mL |
4 mg 2 times / week multiple, intravenous dose: 4 mg route of administration: Intravenous experiment type: MULTIPLE co-administered: |
TAK-243 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
509.785 ng × h/mL |
8 mg 2 times / week multiple, intravenous dose: 8 mg route of administration: Intravenous experiment type: MULTIPLE co-administered: |
TAK-243 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
752.152 ng × h/mL |
12 mg 2 times / week multiple, intravenous dose: 12 mg route of administration: Intravenous experiment type: MULTIPLE co-administered: |
TAK-243 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
864.533 ng × h/mL |
18 mg 2 times / week multiple, intravenous dose: 18 mg route of administration: Intravenous experiment type: MULTIPLE co-administered: |
TAK-243 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
5.572 h |
4 mg 2 times / week multiple, intravenous dose: 4 mg route of administration: Intravenous experiment type: MULTIPLE co-administered: |
TAK-243 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
15.212 h |
8 mg 2 times / week multiple, intravenous dose: 8 mg route of administration: Intravenous experiment type: MULTIPLE co-administered: |
TAK-243 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
27.446 h |
12 mg 2 times / week multiple, intravenous dose: 12 mg route of administration: Intravenous experiment type: MULTIPLE co-administered: |
TAK-243 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
9.873 h |
18 mg 2 times / week multiple, intravenous dose: 18 mg route of administration: Intravenous experiment type: MULTIPLE co-administered: |
TAK-243 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
18 mg 2 times / week multiple, intravenous Highest studied dose Dose: 18 mg, 2 times / week Route: intravenous Route: multiple Dose: 18 mg, 2 times / week Sources: |
unhealthy n = 8 Health Status: unhealthy Condition: Advanced Solid Tumors Sex: M+F Food Status: UNKNOWN Population Size: 8 Sources: |
Other AEs: Pyrexia, Hypertension... Other AEs: Pyrexia (1 pt) Sources: Hypertension (1 pt) Dyspnoea (2 patients) Dyspnoea exertional (1 pt) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Dyspnoea exertional | 1 pt | 18 mg 2 times / week multiple, intravenous Highest studied dose Dose: 18 mg, 2 times / week Route: intravenous Route: multiple Dose: 18 mg, 2 times / week Sources: |
unhealthy n = 8 Health Status: unhealthy Condition: Advanced Solid Tumors Sex: M+F Food Status: UNKNOWN Population Size: 8 Sources: |
Hypertension | 1 pt | 18 mg 2 times / week multiple, intravenous Highest studied dose Dose: 18 mg, 2 times / week Route: intravenous Route: multiple Dose: 18 mg, 2 times / week Sources: |
unhealthy n = 8 Health Status: unhealthy Condition: Advanced Solid Tumors Sex: M+F Food Status: UNKNOWN Population Size: 8 Sources: |
Pyrexia | 1 pt | 18 mg 2 times / week multiple, intravenous Highest studied dose Dose: 18 mg, 2 times / week Route: intravenous Route: multiple Dose: 18 mg, 2 times / week Sources: |
unhealthy n = 8 Health Status: unhealthy Condition: Advanced Solid Tumors Sex: M+F Food Status: UNKNOWN Population Size: 8 Sources: |
Dyspnoea | 2 patients | 18 mg 2 times / week multiple, intravenous Highest studied dose Dose: 18 mg, 2 times / week Route: intravenous Route: multiple Dose: 18 mg, 2 times / week Sources: |
unhealthy n = 8 Health Status: unhealthy Condition: Advanced Solid Tumors Sex: M+F Food Status: UNKNOWN Population Size: 8 Sources: |
Sample Use Guides
In Vivo Use Guide
Sources: https://clinicaltrials.gov/ct2/show/NCT02045095
Dose escalation stage:
Schedule A: IV infusion on days 1, 4, 8, 11 for a 21-day treatment cycle
Schedule B: IV infusion on days 1, 8, 15 for a 28-day treatment cycle
Dose expansion stage: MLN7243 will be administered following schedule A (twice-weekly, 21-day dosing) and/or B (once-weekly, 28-day dosing)
Route of Administration:
Intravenous
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1450833-55-2
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C113788
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V9GGV0YCDI
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71715374
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DB15013
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