Panobinostat
Panobinostat Basic information
- Product Name:
- Panobinostat
- Synonyms:
-
- (E)-N-HYDROXY-3-(4-{[2-(2-METHYL-1H-INDOL-3-YL)-ETHYLAMINO]-METHYL}-PHENYL)-ACRYLAMIDE
- N-Hydroxy-3-[4-[2-(2-methyl-1H-indol-3-yl)ethylaminomethyl]phenyl]-2(E)-propenamide
- LBH-589/Panobinostat
- LBH-589
- PANOBINOSTAT
- 2-Propenamide, N-hydroxy-3-(4-(((2-(2-methyl-1H-indol-3-yl)ethyl)amino)methyl)phenyl)-, (2E)-
- NVP-LBH589
- Panobinostat (LBH589)
- CAS:
- 404950-80-7
- MF:
- C21H23N3O2
- MW:
- 349.43
- EINECS:
- 803-814-1
- Product Categories:
-
- API
- Inhibitor
- Intracellular Signaling
- Aromatics
- Heterocycles
- Inhibitors
- Intermediates & Fine Chemicals
- Pharmaceuticals
- Isotope Labelled Compounds
- Mol File:
- 404950-80-7.mol
Panobinostat Chemical Properties
- Melting point:
- 114-117?C
- Density
- 1.241±0.06 g/cm3(Predicted)
- storage temp.
- -20°C Freezer, Under Inert Atmosphere
- solubility
- Soluble in DMSO (up to 100 mg/ml) or in Ethanol (up to 5 mg/ml with warming).
- form
- solid
- pka
- 8.71±0.23(Predicted)
- color
- Off-white
- Stability:
- Stable for 1 year from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20° for up to 1 month.
Safety Information
- Risk Statements
- 22-36/37/38-20
- Safety Statements
- 24/25
- HS Code
- 29339900
Panobinostat Usage And Synthesis
Description
Panobinostat is a potent inhibitor of all histone deacetylases (HDACs), with Ki values ranging from 0.6 to 31 nM for HDAC1-
Chemical Properties
Yellow Solid
Uses
The novel labelled histone deacetylase inhibitor, LBH589, induces expression of DNA damage response genes and apoptosis in Ph- acute lymphoblastic leukemia cells.
Uses
The novel histone deacetylase inhibitor, LBH589, induces expression of DNA damage response genes and apoptosis in Ph- acute lymphoblastic leukemia cells.
Definition
ChEBI: A hydroxamic acid obtained by formal condensation of the carboxy group of (2E)-3-[4-({[2-(2-methylindol-3-yl)ethyl]amino}methyl)phenyl]prop-2-enoic acid with the amino group of hydroxylamine. A histone deacetylase inhibitor used (as its la tate salt) in combination with bortezomib and dexamethasone for the treatment of multiple myeloma.
Clinical Use
Histone deacetylase (HDAC) inhibitor:
Treatment of relapsed and/or refractory multiple
myeloma
target
HDAC (MOLT-4 cells)
Drug interactions
Potentially hazardous interactions with other drugs
Analgesics: avoid with dextromethorphan possibly
increased risk of ventricular arrhythmias with
methadone - avoid.
Anti-arrhythmics: increased risk of ventricular
arrhythmias with amiodarone and possibly
disopyramide - avoid.
Antibacterials: increased risk of ventricular
arrhythmias with clarithromycin and moxifloxacin -
avoid; avoid with rifampicin.
Antidepressants: avoid with St John’s wort.
Antiepileptics: avoid with carbamazepine,
fosphenytoin, phenobarbital, phenytoin and
primidone.
Antifungals: concentration increased by ketoconazole
and possibly posaconazole and voriconazole - reduce
panobinostat dose; concentration possibly increased
by itraconazole - avoid.
Antimalarials: possibly increased risk of ventricular
arrhythmias with chloroquine - avoid.
Antipsychotics: avoid with pimozide.
Antivirals: concentration possibly increased
by ritonavir and saquinavir - reduce dose of
panobinostat.
Beta-blockers: possibly increased risk of ventricular
arrhythmias with sotalol - avoid.
Grapefruit juice: avoid concomitant use.
5HT3
antagonists: possibly increased risk of
ventricular arrhythmias with granisetron and
ondansetron - avoid with granisetron.
Metabolism
Panobinostat is extensively metabolised, and a large
fraction of the dose is metabolised before reaching
the systemic circulation by reduction, hydrolysis,
oxidation and glucuronidation. Oxidative metabolism
of panobinostat played a less prominent role, with
approximately 40% of the dose eliminated by this
pathway. Cytochrome P450 3A4 (CYP3A4) is the main
oxidation enzyme, with potential minor involvement of
CYP2D6 and 2C19.
Panobinostat represented 6-9% of the drug-related
exposure in plasma. The parent substance is deemed to
be responsible for the overall pharmacological activity of
panobinostat.
After a single oral dose of [14C]-panobinostat in patients,
29-51% of administered radioactivity is excreted in the
urine and 44-77% in the faeces. Unchanged panobinostat
accounted for <2.5% of the dose in urine and <3.5% of
the dose in faeces.
storage
Store at -20°C
References
1) Geng et al. (2006), Histone deacetylase (HDAC) inhibitor LBH589 increases duration of gamma H2AX foci and confines HDAC4 to the cytoplasm in irradiated non-small cell lung cancer; Cancer Res., 66 11298 2) George et al. (2005), Combination of the histone deacetylase inhibitor LBH589 and the hsp90 inhibitor 17-AAG is highly active against human CML-BC cells and AML cells with activating mutation of FLT-3; Blood, 105 1768 3) Maiso et al. (2006), The histone deacetylase inhibitor LBH589 is a potent antimyeloma agent that overcomes drug resistance; Cancer Res., 66 5781
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