[CAS NO. 1610964-64-1] Unesbulin
PRODUCTS SPECIFICATIONS [1610964-64-1]
DESCRIPTION [1610964-64-1]
Overview
| MDL | - |
|---|---|
| Molecular Weight | 420.34 |
| Molecular Formula | C19H13F5N6 |
| SMILES | NC1=C(F)C(NC2=CC=C(C(F)(F)F)C=C2)=NC(N3C4=CC(F)=CC=C4N=C3C)=N1 |
3 Publications Citing Use of MCE
Summary
Unesbulin (PTC596) is an orally active and selective B-cell-specific Moloney murine leukemia virus integration site 1 ( BMI-1 ) inhibitor. Unesbulin downregulates MCL-1 and induces p53-independent mitochondrial apoptosis in acute myeloid leukemia (AML) cells. Unesbulin has anti-leukemic activity [1] [2] .
IC50 & Target
BMI-1 [1]
In Vitro
Unesbulin (PTC596; 20-200 nM; for 48 hours) induces apoptosis in AML cells in a p53-independent manner. BMI-1 overexpression desensitizes AML cells to PTC596-induced apoptosis
[1]
.
Unesbulin (200 nM; for 10 hours) leads to an accumulation of cells in G2/M phase
[1]
.
Unesbulin (0.012-1 μM; for 20 hours) significantly reduces protein levels of BMI-1
[1]
.
Unesbulin inhibits APC/CCDC20 activity resulting in the persistent activation of CDK1 and CDK2 which mediate the hyperphosphorylation of BMI1
[2]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Apoptosis Analysis [1]
| Cell Line: | AML cell lines (MOLM-13, OCI-AML3, MOLM-14, MV4-11, U-937, HL-60) |
| Concentration: | 20, 50, 100, 200 nM |
| Incubation Time: | For 48 hours |
| Result: | Induced apoptosis in a dose- and time-dependent manner with the average IC 50 and ED 50 values among six cell lines were 30.7 nM and 60.3 nM, respectively. |
Cell Cycle Analysis [1]
| Cell Line: | MOLM-13 and U-937 cells |
| Concentration: | 200 nM |
| Incubation Time: | For 10 hours |
| Result: | Led to an accumulation of cells in G2/M phase, whereas the percentage of cells in G1 phase decreased. |
Western Blot Analysis [1]
| Cell Line: | MOLM-13 cell |
| Concentration: | 0.012, 0.037, 0.11, 0.33, 1 μM |
| Incubation Time: | For 20 hours |
| Result: |
Significantly reduced protein levels of BMI-1 and its downstream target ubiquitinated histone H2A.
Increased cyclin B1 and securin levels. |
In Vivo
Unesbulin (PTC596; 5 mg/kg; oral gavage; every 3 days for 13 days) significantly prolongs mouse survival
[1]
.
Unesbulin (20 mg/kg; oral gavage; once a week for 15 days) causes tumor volume significantly smaller than that of control SCID mice with K562 cells
[1]
.
Unesbulin (10 or 12.5 mg/kg; oral gavage; twice a week until death) causes the survival significantly longer than the vehicle-treated group in NOD-SCID mice with HL-60 cells
[1]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
| Animal Model: | NOD-SCID/IL2Rγ-KO (NSG) mice with MOLM-13 cells [1] |
| Dosage: | 5 mg/kg |
| Administration: | Oral gavage; every 3 days for 13 days |
| Result: | Significantly prolonged mouse survival compared with the vehicle-treated mice in a dose-dependent manner. |
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date | Phase |
|---|---|---|---|---|
| NCT02404480 | PTC Therapeutics |
Cancer
|
January 2016 | Phase 1 |
| NCT03206645 | University of Oklahoma|PTC Therapeutics |
Ovarian Cancer
|
August 28, 2017 | Phase 1 |
| NCT03605550 | Nationwide Children´s Hospital|PTC Therapeutics |
High Grade Glioma|Diffuse Intrinsic Pontine Glioma
|
August 1, 2018 | Phase 1 |
| NCT05269355 | PTC Therapeutics |
Leiomyosarcoma
|
May 23, 2022 | Phase 2|Phase 3 |
| NCT03761095 | PTC Therapeutics |
Leiomyosarcoma
|
March 13, 2019 | Phase 1 |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Powder | -20°C | 3 years |
|---|---|---|
| 4°C | 2 years | |
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
DMSO : 16.67 mg/mL ( 39.66 mM ; Need ultrasonic)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 2.3790 mL | 11.8951 mL | 23.7903 mL |
| 5 mM | 0.4758 mL | 2.3790 mL | 4.7581 mL |
| 10 mM | 0.2379 mL | 1.1895 mL | 2.3790 mL |
-
1.
-
2.
Add each solvent one by one: 10% DMSO >> 90% corn oil
Solubility: ≥ 1.67 mg/mL (3.97 mM); Clear solution
References