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
| Molecular Formula | C19H20F3N5O5S2 |
| Molecular Weight | 519.518 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ABSOLUTE |
| Additional Stereochemistry | No |
| Defined Stereocenters | 4 / 4 |
| E/Z Centers | 0 |
| Optical Activity | UNSPECIFIED |
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
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
| Substance Class |
Chemical
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V9GGV0YCDI
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Validated (UNII)
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| Related Record | Type | Details | ||
|---|---|---|---|---|
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ACTIVE MOIETY |
Official Title: An Open-Label, Phase 1b, Multi-Arm Study to Evaluate the Safety, Tolerability, and Pharmacodynamics of Investigational Treatments in Combination With Standard of Care Immune Checkpoint Inhibitors in Patients With Advanced Melanoma
Purpose: The purpose of this study is to determine the initial safety profile of the combination treatments (immune checkpoint inhibitors (nivolumab, ipilimumab) with investigational drugs (TAK-580, TAK-202 (plozalizumab), vedolizumab)) in the 3 arms when administered to participants with advanced melanoma.
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ACTIVE MOIETY |
Originator: Biogen Idec, Sunesis Pharmaceuticals; Developer: Takeda Oncology; Class: Anti-neoplastic; Mechanism of Action: Raf kinase inhibitor; Orphan Drug Status: No; On Fast track: No; New Molecular Entity: Yes; Highest Development Phases: Phase I for Malignant melanoma, Solid tumours; Most Recent Events: 16 Jul 2016 No recent reports of development identified for phase-I development in Solid-tumours(Second-line therapy or greater) in United Kingdom (PO, Tablet),
16 Jul 2016 No recent reports of development identified for phase-I development in Solid-tumours(Second-line therapy or greater) in USA (PO, Tablet), 01 May 2016 Phase-I clinical trials in Malignant melanoma (Combination therapy, Inoperable/Unresectable, Late-stage disease) in USA (PO) (NCT02723006)
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ACTIVE MOIETY |
A UAE inhibitor potentially for the treatment of solid tumors.
TAK-243, also known as MLN7243 and AOB87172, is a small molecule inhibitor of ubiquitin-activating enzyme (UAE), with potential antineoplastic activity. UAE inhibitor MLN7243 binds to and inhibits UAE, which prevents both protein ubiquitination and subsequent protein degradation by the proteasome. This results in an excess of proteins in the cells and may lead to endoplasmic reticulum (ER) stress-mediated apoptosis. 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.
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ACTIVE MOIETY |
Drug: TAK 243(Primary); Indication: Solid tumours; Focus: Adverse reactions; Sponsor: Takeda Oncology; Most Recent Event: 16 Feb 2014 New trial record
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