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Panobinostat (LBH589) HDAC Remmer

Cat.Nr.S1030

Panobinostat (LBH589, NVP-LBH589) is een nieuwe breedspectrum HDAC-remmer met een IC50 van 5 nM in een celvrije test. Het induceert autophagy en apoptosis en verstoort effectief de HIV-latentie in vivo. Fase 3.
Panobinostat (LBH589) HDAC Remmer Chemical Structure

Chemische structuur

Moleculair gewicht: 349.43

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Kwaliteitscontrole (Quality Control)

Batch: Zuiverheid: 99.96%
99.96

Celkweek, behandeling & werkconcentratie
(Cell Culture, Treatment & Working Concentration)

Cellijnen Assaytype Concentratie Incubatietijd Formulering Activiteitsbeschrijving PMID
HT29 Growth Inhibition Assay 0-10 μM 0-4 d inhibits cell growth in both time- and dose-dependent manner 26702784
HepG2 Growth Inhibition Assay 0-10 μM 0-4 d inhibits cell growth in both time- and dose-dependent manner 26702784
HT29 Function Assay 50 nM 24-72 h induced activation of caspase 3 after 48 h  26702784
HepG2 Function Assay 50 nM 24-72 h induced activation of caspase 3 after 24 h  26702784
HCC827 Growth Inhibition Assay 5/7.5/10 nM 72 h DMSO enhances the antiproliferative effect of erlotinib 26675484
A549  Growth Inhibition Assay 10/15/20 nM 72 h DMSO enhances the antiproliferative effect of erlotinib 26675484
NCI-H460  Growth Inhibition Assay 10/20/30 nM 72 h DMSO enhances the antiproliferative effect of erlotinib 26675484
J89GFP Growth Inhibition Assay DMSO  EC50=49.85 ± 12.65 nM 26563568
THP89GFP Growth Inhibition Assay DMSO  EC50=19.34 ± 6.43 nM 26563568
SK-NEP-1 Growth Inhibition Assay 0.01–10.0 μM 24 h DMSO  IC50=76.34 nM 26176219
G401 Growth Inhibition Assay 0.01–10.0 μM 24 h DMSO  IC50=143.02 nM 26176219
SK-NEP-1 Cell Viability Assay 50 nM 1–4 d DMSO  reduces cell survival in a time dependent manner 26176219
G401 Cell Viability Assay 50 nM 1–4 d DMSO  reduces cell survival in a time dependent manner 26176219
SK-NEP-1 Apoptosis Assay 50/100 nM 24 h DMSO  induces cell apoptosis in a dose-dependent manner 26176219
G401 Apoptosis Assay 50/100 nM 24 h DMSO  induces cell apoptosis in a dose-dependent manner 26176219
SK-NEP-1 Function Assay 50/100 nM 24 h DMSO  shows the induction of DNA fragmentation 26176219
G401 Function Assay 50/100 nM 24 h DMSO  shows the induction of DNA fragmentation 26176219
SK-NEP-1 Function Assay 50/100 nM 24 h DMSO  induces cell cycle disorder  26176219
G401 Function Assay 50/100 nM 24 h DMSO  induces cell cycle disorder  26176219
RPMI 8226 Cell Survival Assay 2/4/6 nM 48 h induces a significant decrease in the cell growth 26000292
OPM2 Cell Survival Assay 2/4/6 nM 48 h induces a significant decrease in the cell growth 26000292
U266 Cell Survival Assay 2/4/6 nM 48 h induces a significant decrease in the cell growth 26000292
H929 Cell Survival Assay 2/4/6 nM 48 h induces a significant decrease in the cell growth 26000292
RPMI 8226  Apoptosis Assay 4 nM 24/48 h induces cell apoptosis in a time-dependent manner 26000292
HCC827 Growth Inhibition Assay 10 nM 48 h DMSO enhances cisplatin sensitivity  25944617
NCI-H23 Growth Inhibition Assay 10 nM 48 h DMSO enhances cisplatin sensitivity  25944617
AML3 Function Assay 0-1 μM 24 h induces DNA fragmentation in a dose-dependent manner 25612941
ML-1 Function Assay 0-1 μM 24 h induces DNA fragmentation in a dose-dependent manner 25612941
RPMI-8226vr10  Function Assay 0-1 μM 24 h induces DNA fragmentation in a dose-dependent manner 25612941
ML-1 Function Assay 1 μM 24 h increases caspase-3 activity 4-fold 25612941
RPMI-8226vr10  Function Assay 1 μM 24 h increases caspase-3 activity 2.5-fold 25612941
SK-N-BE (2) Growth Inhibition Assay 24 h IC50=104.0 ± 7.8 nM 25308916
SK-N-BE (2), PAN  MK Growth Inhibition Assay 24 h IC50=104.0 ± 7.8 nM 25308916
SK-N-BE (2), MK  PAN Growth Inhibition Assay 24 h IC50=382.0 ± 43.2 nM 25308916
SK-N-AS Growth Inhibition Assay 24 h IC50=37.1 ± 2.4 nM 25308916
SK-N-DZ Growth Inhibition Assay 24 h IC50=17.1 ± 0.4 nM 25308916
Caki-1 Growth Inhibition Assay 10/25/50 nM 48 h inhibits cell growth in a dose dependent manner synergistically with ritonavir 25279191
ACHN Growth Inhibition Assay 10/25/50 nM 48 h inhibits cell growth in a dose dependent manner synergistically with ritonavir 25279191
769-P Growth Inhibition Assay 10/25/50 nM 48 h inhibits cell growth in a dose dependent manner synergistically with ritonavir 25279191
786-O  Growth Inhibition Assay 10/25/50 nM 48 h inhibits cell growth in a dose dependent manner synergistically with ritonavir 25279191
Caki-1 Apoptosis Assay 50 nM 48 h induces cell apoptosis combined ritonavir 25279191
ACHN Apoptosis Assay 50 nM 48 h induces cell apoptosis combined ritonavir 25279191
769-P Apoptosis Assay 50 nM 48 h induces cell apoptosis combined ritonavir 25279191
786-O  Apoptosis Assay 50 nM 48 h induces cell apoptosis combined ritonavir 25279191
Caki-1 Growth Inhibition Assay 25/50 nM 48 h DMSO inhibits cell growth in a dose dependent manner synergistically with bortezomib 25176354
ACHN Growth Inhibition Assay 25/50 nM 48 h DMSO inhibits cell growth in a dose dependent manner synergistically with bortezomib 25176354
769-P Growth Inhibition Assay 25/50 nM 48 h DMSO inhibits cell growth in a dose dependent manner synergistically with bortezomib 25176354
Caki-1 Colony Formation Assay 50 nM 7-14 d DMSO suppressed colony formation significantly combined with with bortezomib   25176354
ACHN Colony Formation Assay 50 nM 7-14 d DMSO suppressed colony formation significantly combined with with bortezomib   25176354
769-P Colony Formation Assay 50 nM 7-14 d DMSO suppressed colony formation significantly combined with with bortezomib   25176354
Caki-1 Apoptosis Assay 50 nM 48 h DMSO induces cell apoptosis 25176354
ACHN Apoptosis Assay 50 nM 48 h DMSO induces cell apoptosis 25176354
769-P Apoptosis Assay 50 nM 48 h DMSO induces cell apoptosis 25176354
MDA-MB-231 Morphological Crystal Violet (CV) Assay 10 nM 3 d DMSO alters cell morphology  24810497
BT-549 Morphological Crystal Violet (CV) Assay 10 nM 3 d DMSO alters cell morphology  24810497
MCF-7  Morphological Crystal Violet (CV) Assay 10 nM 3 d DMSO alters cell morphology  24810497
MCF-7 Function Assay 5-50 nM 24 h DMSO reduced the level of expression of ERα, PR and FoxA1  24366407
CTS Apoptosis Assay 0–40 nM  48 h induces apoptosis in a dose-dependent manner 24244429
OCI-AML3  Apoptosis Assay 0–40 nM  48 h induces apoptosis in a dose-dependent manner 24244429
U937 Apoptosis Assay 0–40 nM  48 h induces apoptosis in a dose-dependent manner 24244429
PC3 Apoptosis Assay 0-100 nM 24/48 h induces apoptosis in a dose-dependent manner 24163230
PC3-AR Apoptosis Assay 0-100 nM 24/48 h induces apoptosis in both time- and dose-dependent manner 24163230
PC3 Growth Inhibition Assay 0-100 nM 24/48 h induces accumulation of subG1 population 24163230
PC3-AR Growth Inhibition Assay 0-100 nM 24/48 h induces cell cycle arrest in the G2M phase 24163230
PC3 Function Assay 0-100 nM 24 h suppresses expression of activated ATM, Akt and Erk1/2 protein 24163230
PC3-AR Function Assay 0-100 nM 24 h suppresses expression of activated ATM, Akt and Erk1/2 protein 24163230
OS-RC-2 Cell Viability Assay 0-1000 nM 24/48/72 h DMSO decreases cell viability in both time- and dose-dependent manner 24144737
OS-RC-2 Growth Inhibition Assay 50 nM 48 h DMSO induces G2/M arrest 24144737
OS-RC-2 Apoptosis Assay 50 nM 48 h DMSO induces cell apoptosis 24144737
SK-N-AS Growth Inhibition Assay 0–80 nM 48 h IC50=27.4 nM 24098799
SK-N-DZ Growth Inhibition Assay 0–80 nM 48 h IC50=21.9 nM 24098799
SK-N-SH Growth Inhibition Assay 0–80 nM 48 h IC50=72.3 nM 24098799
SK-N-BE Growth Inhibition Assay 0–80 nM 48 h IC50=75.4 nM 24098799
SK-N-AS Apoptosis Assay 0–80 nM 48 h potently induced apoptosis in a dose-dependent fashion 24098799
SK-N-DZ Apoptosis Assay 0–80 nM 48 h potently induced apoptosis in a dose-dependent fashion 24098799
SK-N-SH Apoptosis Assay 0–40 nM 48 h potently induced apoptosis in a dose-dependent fashion 24098799
SK-N-BE Apoptosis Assay 0–40 nM 48 h potently induced apoptosis in a dose-dependent fashion 24098799
SK-N-AS Function Assay 0–80 nM 48 h induces a dose-dependent cleavage of caspase 3 and PARP 24098799
SK-N-DZ Function Assay 0–80 nM 48 h induces a dose-dependent cleavage of caspase 3 and PARP 24098799
SK-N-SH Function Assay 0–40 nM 48 h induces a dose-dependent cleavage of caspase 3 and PARP 24098799
SK-N-BE Function Assay 0–40 nM 48 h induces a dose-dependent cleavage of caspase 3 and PARP 24098799
HCC-LM3 Growth Inhibition Assay 1-1000 nM 24/48/72 h DMSO inhibits cell growth in both time- and dose-dependent manner 24093956
HepG2 Growth Inhibition Assay 1-1000 nM 24/48/72 h DMSO inhibits cell growth in both time- and dose-dependent manner 24093956
SMMC-7721 Growth Inhibition Assay 1-1000 nM 24/48/72 h DMSO inhibits cell growth in both time- and dose-dependent manner 24093956
HCC-LM3 Apoptosis Assay 50 nM 48 h DMSO induces cell apoptosis significantly in a caspase-dependent manner by cleavage of caspases 3, 8 and 9 24093956
HepG2 Apoptosis Assay 50 nM 48 h DMSO induces cell apoptosis significantly in a caspase-dependent manner by cleavage of caspases 3, 8 and 9 24093956
SMMC-7721 Apoptosis Assay 50 nM 48 h DMSO induces cell apoptosis significantly in a caspase-dependent manner by cleavage of caspases 3, 8 and 9 24093956
HCC-LM3 Function Assay 50/100 nM 24 h DMSO decreases the levels of p-STAT3 and p-Akt  24093956
HepG2 Function Assay 50/100 nM 24 h DMSO decreases the levels of p-STAT3 and p-Akt  24093956
SMMC-7721 Function Assay 50/100 nM 24 h DMSO decreases the levels of p-STAT3 and p-Akt  24093956
HCC-LM3 Function Assay 50/100 nM 24 h DMSO downregulates Bcl-xL expression 24093956
HepG2 Function Assay 50/100 nM 24 h DMSO downregulates Bcl-xL expression 24093956
SMMC-7721 Function Assay 50/100 nM 24 h DMSO downregulates Bcl-xL expression 24093956
FaDu Growth Inhibition Assay 100 nM 8/10/12 h displayed a significant and prolonged G2/M arrest at 8 and 12 h post release 24026482
FaDu Function Assay 100 nM 2/4/8/12 h induced p21Waf1/Cip1 expression 24026482
PC-3  Growth Inhibition Assay 0-10 μM 24/48/72 h inhibits cell growth in both time- and dose-dependent manner 23991216
LNCaP Growth Inhibition Assay 0-5 μM 24/48/72 h inhibits cell growth in both time- and dose-dependent manner 23991216
RWPE-1  Growth Inhibition Assay 0-20 μM 24/48/72 h inhibits cell growth in both time- and dose-dependent manner 23991216
Capan-1 Function Assay 25/50/100 nM 8/24/48 h DMSO downregulated Ron mRNA and protein expression and downstream signaling 23922886
L3.6pl Function Assay 25/50/100 nM 8/24/48 h DMSO downregulated Ron mRNA and protein expression and downstream signaling 23922886
CFPAC-1  Function Assay 25/50/100 nM 8/24/48 h DMSO downregulated Ron mRNA and protein expression and downstream signaling 23922886
Capan-1 Growth Inhibition Assay 25/50/100 nM 48 h DMSO reduces cell growth in a dose-dependent manner 23922886
L3.6pl Growth Inhibition Assay 25/50/100 nM 48 h DMSO reduces cell growth in a dose-dependent manner 23922886
CFPAC-1  Growth Inhibition Assay 25/50/100 nM 48 h DMSO reduces cell growth in a dose-dependent manner 23922886
Capan-1 Apoptosis Assay 25/50/100 nM 48 h DMSO induces cell growth in a dose-dependent manner 23922886
L3.6pl Apoptosis Assay 25/50/100 nM 48 h DMSO induces cell growth in a dose-dependent manner 23922886
CFPAC-1  Apoptosis Assay 25/50/100 nM 48 h DMSO induces cell growth in a dose-dependent manner 23922886
HN22 Growth Inhibition Assay 0-20 nM 24/48 h DMSO inhibits cell viability in both time- and dose- dependent manner 23877235
HSC4  Growth Inhibition Assay 0-20 nM 24/48 h DMSO inhibits cell viability in both time- and dose- dependent manner 23877235
HN22 Apoptosis Assay 0-20 nM 48 h DMSO induces cell apoptosis 23877235
HSC4  Apoptosis Assay 0-20 nM 48 h DMSO induces cell apoptosis 23877235
HN22 Growth Inhibition Assay 0-20 nM 48 h DMSO induces G1 phase cell cycle arrest  23877235
HSC4  Growth Inhibition Assay 0-20 nM 48 h DMSO induces G1 phase cell cycle arrest  23877235
HN22 Function Assay 0-20 nM 48 h DMSO suppresses Sp1 expression  23877235
HSC4  Function Assay 0-20 nM 48 h DMSO suppresses Sp1 expression  23877235
Cal62 Growth Inhibition Assay IC50=33 ± 4 nM 23824064
Hth7 Growth Inhibition Assay IC50=15 ± 2 nM 23824064
Hth83 Growth Inhibition Assay IC50=34 ± 5 nM 23824064
C643 Growth Inhibition Assay IC50=71 ± 10 nM 23824064
SW1736 Growth Inhibition Assay IC50=35 ± 8 nM 23824064
T241 Growth Inhibition Assay IC50=65 ± 7 nM 23824064
T351 Growth Inhibition Assay IC50=50 ± 10 nM 23824064
BHP2-7 Growth Inhibition Assay IC50=37 ± 6 nM 23824064
T238 Growth Inhibition Assay IC50=1,500 ± 200 nM 23824064
HCT8 Growth Inhibition Assay 72 h DMSO IC50=12.9 ± 1.9 nM 23299388
H630 Growth Inhibition Assay 72 h DMSO IC50=12.4 ± 3.1 nM 23299388
cH630 5-FU-res Growth Inhibition Assay 72 h DMSO IC50=15.5 ± 1.2 nM 23299388
HCT116 Growth Inhibition Assay 72 h DMSO IC50=10.7 ± 2.2 nM 23299388
HCT116 p53−/− Growth Inhibition Assay 72 h DMSO IC50=8.6 ± 1.7 nM 23299388
dHCT116 p21−/− Growth Inhibition Assay 72 h DMSO IC50=5.9 ± 1.3 nM 23299388
HT29 Growth Inhibition Assay 72 h DMSO IC50=16.3 ± 2.3 nM 23299388
LoVo Growth Inhibition Assay 72 h DMSO IC50=5.1 ± 0.6 nM 23299388
RKO Growth Inhibition Assay 72 h DMSO IC50=7.9 ± 2.2 nM 23299388
SW480 Growth Inhibition Assay 72 h DMSO IC50=17.5 ± 0.8 nM 23299388
eSW620 Growth Inhibition Assay 72 h DMSO IC50=9.1 ± 2.1 nM 23299388
S2 Function assay Inhibition of Plasmodium falciparum HDAC1 expressed in Drosophila melanogaster S2 cells, IC50 = 0.0018 μM. 19317450
COLO205 Antiproliferative assay 96 hrs Antiproliferative activity against human COLO205 cells after 96 hrs by celltiter 96 assay, IC50 = 0.018 μM. 21634430
PC3 Antiproliferative assay 96 hrs Antiproliferative activity against human PC3 cells after 96 hrs by celltiter 96 assay, IC50 = 0.024 μM. 21634430
A2780 Antiproliferative assay 96 hrs Antiproliferative activity against human A2780 cells after 96 hrs by celltiter 96 assay, IC50 = 0.035 μM. 21634430
HCT116 Antiproliferative assay 96 hrs Antiproliferative activity against human HCT116 cells after 96 hrs by celltiter 96 assay, IC50 = 0.048 μM. 21634430
HEK293 Function assay Inhibition of HDAC3 (unknown origin) expressed in HEK293 cells using [3H]acetylated human histone H4 peptide as substrate by scintillation counting, IC50 = 0.0021 μM. 22344701
HEK293 Function assay Inhibition of HDAC1 (unknown origin) expressed in HEK293 cells using [3H]acetylated human histone H4 peptide as substrate by scintillation counting, IC50 = 0.0025 μM. 22344701
HEK293 Function assay Inhibition of HDAC6 (unknown origin) expressed in HEK293 cells using [3H]acetylated human histone H4 peptide as substrate by scintillation counting, IC50 = 0.011 μM. 22344701
SF21 Function assay Inhibition of flag-tagged HDAC2 (unknown origin) expressed in SF21 cells using [3H]acetylated human histone H4 peptide as substrate by scintillation counting, IC50 = 0.013 μM. 22344701
HEK293 Function assay Inhibition of HDAC4 (unknown origin) expressed in HEK293 cells using [3H]acetylated human histone H4 peptide as substrate by scintillation counting, IC50 = 0.2 μM. 22344701
SF9 Function assay Inhibition of his-strep-tagged HDAC8 (unknown origin) expressed in SF9 cells using [3H]acetylated human histone H4 peptide as substrate by scintillation counting, IC50 = 0.28 μM. 22344701
B16 Growth inhibition assay 48 hrs Growth inhibition of mouse B16 cells incubated for 48 hrs by MTT assay, GI50 = 0.15 μM. 23009203
HeLa Function assay Inhibition of HDAC in human HeLa cells using Fluor de Lys as substrate by fluorescence assay, IC50 = 0.03 μM. 23639537
HuH7 Cytotoxicity assay 3 days Cytotoxicity against human HuH7 cells assessed as inhibition of cell viability after 3 days by CellTiter 96 assay, CC50 = 0.0035 μM. 25490700
Sf9 Function assay 15 mins Inhibition of full length C-terminal His/FLAG-tagged human recombinant HDAC1 expressed in baculovirus infected insect Sf9 cells using Ac-peptide-AMC as substrate assessed as release of AMC preincubated for 15 mins followed by substrate addition measured a, IC50 = 0.00126 μM. 27186676
Sf9 Function assay 15 mins Inhibition of full length C-terminal His-tagged human recombinant HDAC3/NCOR2 (395 to 489 residues) expressed in baculovirus infected insect Sf9 cells using Ac-peptide-AMC as substrate assessed as release of AMC preincubated for 15 mins followed by substr, IC50 = 0.00227 μM. 27186676
MV4-11 Cytotoxicity assay 24 hrs Cytotoxicity against human MV4-11 cells assessed as growth inhibition after 24 hrs by MTT assay, IC50 = 0.00297 μM. 27186676
Sf9 Function assay 15 mins Inhibition of full length human recombinant HDAC2 expressed in baculovirus infected insect Sf9 cells using Ac-peptide-AMC as substrate assessed as release of AMC preincubated for 15 mins followed by substrate addition measured after 1 hr by fluorescence a, IC50 = 0.00328 μM. 27186676
HCT116 Cytotoxicity assay 24 hrs Cytotoxicity against human HCT116 cells assessed as growth inhibition after 24 hrs by MTT assay, IC50 = 0.00336 μM. 27186676
Sf9 Function assay 15 mins Inhibition of full length human recombinant HDAC6 expressed in baculovirus infected insect Sf9 cells using Ac-peptide-AMC as substrate assessed as release of AMC preincubated for 15 mins followed by substrate addition measured after 1 hr by fluorescence a, IC50 = 0.00416 μM. 27186676
Sf9 Inhibition of human 15 mins Inhibition of human recombinant HDAC10 expressed in baculovirus infected insect Sf9 cells using Ac-peptide-AMC as substrate assessed as release of AMC preincubated for 15 mins followed by substrate addition measured after 1 hr by fluorescence assay, IC50 = 0.00445 μM. 27186676
Sf9 Function assay 15 mins Inhibition of full length C-terminal His-tagged human recombinant HDAC8 expressed in baculovirus infected insect Sf9 cells using Ac-peptide-AMC as substrate assessed as release of AMC preincubated for 15 mins followed by substrate addition measured after , IC50 = 0.00486 μM. 27186676
A2780S Cytotoxicity assay 24 hrs Cytotoxicity against human A2780S cells assessed as growth inhibition after 24 hrs by MTT assay, IC50 = 0.00832 μM. 27186676
A2780S Function assay 6 hrs Inhibition of HDAC6 in human A2780S cells assessed as tubulin acetylation incubated for 6 hrs by cytoblot assay, EC50 = 0.15071 μM. 27186676
A2780S Function assay 6 hrs Inhibition of HDAC1/2/3 in human A2780S cells assessed as histone H3 acetylation incubated for 6 hrs by cytoblot assay, EC50 = 0.1695 μM. 27186676
Sf9 Function assay 15 mins Inhibition of human recombinant HDAC5 expressed in baculovirus infected insect Sf9 cells using Ac-peptide-AMC as substrate assessed as release of AMC preincubated for 15 mins followed by substrate addition measured after 1 hr by fluorescence assay, IC50 = 0.1903 μM. 27186676
Sf9 Function assay 15 mins Inhibition of N-terminal GST/C-terminal His-tagged human recombinant HDAC4 (627 to 1084 residues) expressed in baculovirus infected insect Sf9 cells using Ac-peptide-AMC as substrate assessed as release of AMC preincubated for 15 mins followed by substrat, IC50 = 0.3378 μM. 27186676
Sf9 Function assay 15 mins Inhibition of C-terminal His-tagged human recombinant HDAC9 (604 to 1066 residues) expressed in baculovirus infected insect Sf9 cells using Ac-peptide-AMC as substrate assessed as release of AMC preincubated for 15 mins followed by substrate addition meas, IC50 = 0.8878 μM. 27186676
Sf9 Function assay 15 mins Inhibition of full length human recombinant HDAC11 expressed in baculovirus infected insect Sf9 cells using Ac-peptide-AMC as substrate assessed as release of AMC preincubated for 15 mins followed by substrate addition measured after 1 hr by fluorescence , IC50 = 4.112 μM. 27186676
Sf9 Function assay 15 mins Inhibition of N-terminal GST-tagged human recombinant HDAC7 (518 to end residues) expressed in baculovirus infected insect Sf9 cells using Ac-peptide-AMC as substrate assessed as release of AMC preincubated for 15 mins followed by substrate addition measu, IC50 = 4.354 μM. 27186676
Sf9 Function assay Inhibition of C-terminal His-tagged and C-terminal FLAG-tagged full length human recombinant HDAC1 expressed in baculovirus coexpressed in fall armyworm Sf9 cells using carboxyfluorescein (FAM)-labeled acetylated/ trifluoroacetylated peptide as substrate , IC50 = 0.001 μM. 27377864
Sf9 Function assay 60 mins Inhibition full length human recombinant HDAC2 expressed in baculovirus coexpressed in fall armyworm Sf9 cells using carboxyfluorescein (FAM)-labeled acetylated/ trifluoroacetylated peptide as substrate after 60 mins by fluorescence assay, IC50 = 0.002 μM. 27377864
Sf9 Function assay 60 mins Inhibition of human recombinant HDAC6 expressed in baculovirus coexpressed in fall armyworm Sf9 cells using carboxyfluorescein (FAM)-labeled acetylated/ trifluoroacetylated peptide as substrate after 60 mins by fluorescence assay, IC50 = 0.002 μM. 27377864
Sf9 Function assay 60 mins Inhibition of N-terminal GST-tagged full length human recombinant HDAC5 expressed in baculovirus coexpressed in fall armyworm Sf9 cells using carboxyfluorescein (FAM)-labeled acetylated/ trifluoroacetylated peptide as substrate after 60 mins by fluorescen, IC50 = 0.092 μM. 27377864
Sf9 Function assay 60 mins Inhibition of C-terminal His-tagged full length human recombinant HDAC8 expressed in baculovirus coexpressed in fall armyworm Sf9 cells using carboxyfluorescein (FAM)-labeled acetylated/ trifluoroacetylated peptide as substrate after 60 mins by fluorescen, IC50 = 0.231 μM. 27377864
Sf9 Function assay Inhibition of N-terminal GST-tagged and C-terminal His-tagged human recombinant HDAC4 (627 to 1084 residues ) expressed in baculovirus coexpressed in fall armyworm Sf9 cells using carboxyfluorescein (FAM)-labeled acetylated/ trifluoroacetylated peptide as, IC50 = 0.373 μM. 27377864
Sf9 Function assay 60 mins Inhibition of C-terminal His-tagged human recombinant HDAC9 (604 to 1066 residues) expressed in baculovirus coexpressed in fall armyworm Sf9 cells using carboxyfluorescein (FAM)-labeled acetylated/ trifluoroacetylated peptide as substrate after 60 mins by, IC50 = 2.68 μM. 27377864
Sf9 Function assay 60 mins Inhibition of N-terminal GST-tagged human recombinant HDAC7 (518 to end residues) expressed in baculovirus coexpressed in fall armyworm Sf9 cells using carboxyfluorescein (FAM)-labeled acetylated/ trifluoroacetylated peptide as substrate after 60 mins by , IC50 = 2.83 μM. 27377864
HEK293 Cytotoxicity assay 48 hrs Cytotoxicity against HEK293 cells after 48 hrs by resazurin assay, IC50 = 0.07 μM. 28241112
NFF Cytotoxicity assay 72 hrs Cytotoxicity against human NFF cells after 72 hrs by SRB assay, IC50 = 0.07 μM. 28241112
HUT78 Apoptosis assay 18 hrs Pro-apoptotic activity in human HUT78 cells after 18 hrs by caspase-Glo 3/7 assay, EC50 = 0.0043 μM. 30122227
NFF Cytotoxicity assay 72 hrs Cytotoxicity against human NFF cells after 72 hrs by sulforhodamine B assay, IC50 = 0.07 μM. 30245402
HEK293 Cytotoxicity assay 48 hrs Cytotoxicity against HEK293 cells after 48 hrs by resazurin dye based assay, IC50 = 0.07 μM. 30245402
M14 Apoptosis assay 24 to 48 hrs Induction of apoptosis human M14 cells assessed as caspase activity after 24 to 48 hrs using DEVD peptide as substrate by ApoTox-Glo triplex assay 24471466
U937 Function assay 1 uM 24 hrs Inhibition of HDAC6 in human U937 cells assessed as increase of intracellular acetylated alpha-tubulin level at 1 uM after 24 hrs by Western blot analysis 24694055
U937 Function assay 1 uM 24 hrs Inhibition of HDAC1 in human U937 cells assessed as increase of intracellular acetylated histone H3 level at 1 uM after 24 hrs by Western blot analysis 24694055
U937 Function assay 1 uM 24 hrs Inhibition of HDAC2 in human U937 cells assessed as increase of intracellular acetylated histone H3 level at 1 uM after 24 hrs by Western blot analysis 24694055
U937 Function assay 1 uM 24 hrs Inhibition of HDAC3 in human U937 cells assessed as increase of intracellular acetylated histone H4 level at 1 uM after 24 hrs by Western blot analysis 24694055
MV4-11 Function assay 10 to 1000 nM 6 hrs Inhibition of HDAC6 in human MV4-11 cells assessed as upregulation of alpha tubulin acetylation at 10 to 1000 nM after 6 hrs by Western blot analysis 26443078
HCT116 Function assay 10 to 1000 nM 6 hrs Inhibition of HDAC6 in human HCT116 cells assessed as upregulation of alpha tubulin acetylation at 10 to 1000 nM after 6 hrs by Western blot analysis 26443078
HCT116 Function assay 10 to 1000 nM 6 hrs Inhibition of HDAC1/2/3 in human HCT116 cells assessed as upregulation of histone H3 acetylation at 10 to 1000 nM after 6 hrs by Western blot analysis 26443078
MV4-11 Function assay 10 to 1000 nM 6 hrs Inhibition of HDAC1/2/3 in human MV4-11 cells assessed as upregulation of histone H3 acetylation at 10 to 1000 nM after 6 hrs by Western blot analysis 26443078
Raji Cytotoxicity assay 24 hrs Cytotoxicity against human Raji cells assessed as growth inhibition after 24 hrs by MTT assay 27186676
Ramos Cytotoxicity assay 24 hrs Cytotoxicity against human Ramos cells assessed as growth inhibition after 24 hrs by MTT assay 27186676
U266 Cytotoxicity assay 24 hrs Cytotoxicity against human U266 cells assessed as growth inhibition after 24 hrs by MTT assay 27186676
RPMI8226 Cytotoxicity assay 24 hrs Cytotoxicity against human RPMI8226 cells assessed as growth inhibition after 24 hrs by MTT assay 27186676
HBL1 Cytotoxicity assay 24 hrs Cytotoxicity against human HBL1 cells assessed as growth inhibition after 24 hrs by MTT assay 27186676
MM1S Cytotoxicity assay 24 hrs Cytotoxicity against human MM1S cells assessed as growth inhibition after 24 hrs by MTT assay 27186676
OCI-LY1 Cytotoxicity assay 24 hrs Cytotoxicity against human OCI-LY1 cells assessed as growth inhibition after 24 hrs by MTT assay 27186676
SUDHL4 Cytotoxicity assay 24 hrs Cytotoxicity against human SUDHL4 cells assessed as growth inhibition after 24 hrs by MTT assay 27186676
MV4-11 Function assay 50 nM 24 hrs Induction of HDAC6 degradation in human MV4-11 cells at 50 nM after 24 hrs by Western blot method 29589441
MV4-11 Function assay 50 nM 2 to 24 hrs Inhibition of HDAC6 in human MV4-11 cells assessed as induction of alpha-tubulin hyperacetylation at 50 nM after 2 to 24 hrs by Western blot method 29589441
MV4-11 Cell cycle arrest assay 30 to 50 nM 24 hrs Cell cycle arrest in human MV4-11 cells assessed as accumulation at sub-G1 phase at 30 to 50 nM after 24 hrs by propidium iodide staining-based flow cytometric method 29589441
MV4-11 Apoptosis assay 30 nM 24 to 48 hrs Induction of apoptosis in human MV4-11 cells at 30 nM after 24 to 48 hrs by Annexin V-PI staining based flow cytometry 29738953
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Chemische informatie, Opslag en Stabiliteit (Chemical Information, Storage & Stability)

Moleculair gewicht 349.43 Formule

C21H23N3O2

 Opslag (Vanaf de ontvangstdatum)
CAS-nr. 404950-80-7 SDF downloaden Opslag van stamoplossingen

Synoniemen NVP-LBH589 Smiles CC1=C(C2=CC=CC=C2N1)CCNCC3=CC=C(C=C3)C=CC(=O)NO

Oplosbaarheid (Solubility)

In vitro
Batch:

DMSO : 70 mg/mL (200.32 mM)
(Met vocht verontreinigde DMSO kan de oplosbaarheid verminderen. Gebruik verse, watervrije DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molariteitscalculator

Massa Concentratie Volume Moleculair gewicht
Verdunningscalculator Moleculair gewicht calculator

In vivo
Batch:

In vivo Formuleringscalculator (Heldere oplossing)

Stap 1: Voer de onderstaande informatie in (Aanbevolen: Een extra dier voor het geval van verlies tijdens het experiment)

mg/kg g μL

Stap 2: Voer de in vivo formulering in (Dit is alleen de calculator, geen formulering. Neem eerst contact met ons op als er geen in vivo formulering is in het gedeelte Oplosbaarheid.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Berekeningsresultaten:

Werkconcentratie: mg/ml;

Methode voor het bereiden van DMSO-mastervloeistof: mg geneesmiddel vooraf opgelost in μL DMSO ( Concentratie mastervloeistof mg/mL, Neem eerst contact met ons op als de concentratie de DMSO-oplosbaarheid van de partij geneesmiddel overschrijdt. )

Methode voor het bereiden van in vivo formulering: Neem μL DMSO mastervloeistof, voeg vervolgens toeμL PEG300, mengen en helder maken, voeg vervolgens toeμL Tween 80, mengen en helder maken, voeg vervolgens toe μL ddH2O, mengen en helder maken.

Methode voor het bereiden van in vivo formulering: Neem μL DMSO mastervloeistof, voeg vervolgens toe μL Maïsolie, mengen en helder maken.

Opmerking: 1. Zorg ervoor dat de vloeistof helder is voordat u het volgende oplosmiddel toevoegt.
2. Zorg ervoor dat u het/de oplosmiddel(en) in de juiste volgorde toevoegt. U moet ervoor zorgen dat de verkregen oplossing, bij de vorige toevoeging, een heldere oplossing is voordat u verdergaat met het toevoegen van het volgende oplosmiddel. Fysische methoden zoals vortexen, echografie of een warmwaterbad kunnen worden gebruikt om het oplossen te bevorderen.

Werkingsmechanisme (Mechanism of Action)

Targets/IC50/Ki
HDAC (MOLT-4 cells)
5 nM
HDAC (Reh cells)
20 nM
In vitro
Panobinostat (LBH589) induceert apoptose in MOLT-4- en Reh-cellen op een tijd- en dosisafhankelijke manier, en is krachtiger in MOLT-4 dan in Reh-cellen. Het voorkomt de groei van beide cellijnen op een dosisafhankelijke manier na 48 uur en veroorzaakt een 2- tot 3-voudige toename van het aantal cellen in de G2/M-fase van de celcyclus vergeleken met de controlecellen. Deze verbinding is geassocieerd met inductie van histon H3K9- en histon H4K8-acetylering, evenals met afnemende niveaus van c-Myc-expressie op een dosisafhankelijke manier. Het verhoogt ook de niveaus van p21-expressie en verlaagt de niveaus van c-Myc na een initiële toename bij de laagste dosis (10 nM) in Reh-cellen. Bovendien leidt het tot substantiële toenames in mRNA-niveaus van pro-apoptotische en DNA-reparatiegenen, en induceert het verhoogde niveaus van geacetyleerd histon H3 en H4 bij de GADD45G-promotor. Daarnaast remt het de groei van niet-kleincellige longkankercellijnen (zoals menselijke H1299, L55 en A549 met IC50 van respectievelijk 5 nM, 11 nM en 30 nM), mesothelioom (zoals menselijke OK-6 en Ok-5 met IC50 van respectievelijk 5 nM en 7 nM) en kleincellige longkankercellijnen (zoals menselijke RG-1 en LD-T met IC50 van respectievelijk 4 nM en 5 nM).
In vivo
In diermodellen voor longkanker en mesothelioom vermindert Panobinostat (LBH589) de tumorgroei aanzienlijk met 62%. Het is even effectief bij immunocompetente en ernstig gecombineerde immunodeficiëntie-muizen, wat suggereert dat de remming van tumorgroei door deze verbinding niet te wijten is aan directe immunologische effecten. Dagelijkse toediening, i.p. gegeven met 20 mg/kg gedurende 5 dagen per week, leidt tot een gemiddelde afname van de groei met 70%. Vergeleken met de corresponderende controletumoren resulteert het in een afname van 53% voor H526-afgeleide tumoren, een afname van 81% voor BK-T-afgeleide tumoren, een afname van 76% voor RG-1-afgeleide tumoren en een afname van 70% voor H69-afgeleide tumoren. In tegenstelling tot het gebrek aan tumorregressie waargenomen in NSCLC- en Meso-afgeleide xenografttumoren die onder identieke omstandigheden en doses worden behandeld, leidt LBH589 tot dramatische tumorregressie in SCLC-afgeleide tumoren en RG-1-afgeleide tumoren.
Referenties
  • [4] https://pubmed.ncbi.nlm.nih.gov/16740717/
  • [5] https://pubmed.ncbi.nlm.nih.gov/19344997/

Toepassingen (Applications)

Methoden Biomarkers Afbeeldingen PMID
Western blot DNMT1 / EZH2 caspase-8 / cleaved caspase-8 / Sp1 c-Myc / IRF4 Ac-H3 / cleaved caspase-3 / CCND1 / ID1 / ID2 / ID3 / ID4 / Synaptophysin / NeuroD1 RAD51 / BRCA1 / CHK1 / RPL13a H3K9AC / H3K18AC / H3K56AC / H3 / H4K8AC / H4K16AC / H4 / p21 / p27 / cleaved PARP
S1030-WB1
19279403
Immunofluorescence Synaptophysin / NACM α-tubulin / Acetyl-α-tubulin BiP ATF4 IRE1α / S724-IRE1α
S1030-IF1
28915627
Growth inhibition assay Cell viability
S1030-viability1
27738323

Informatie klinische proef (Clinical Trial Information)

(gegevens van https://clinicaltrials.gov, bijgewerkt op 2024-05-22)

NCT-nummer Rekrutering Aandoeningen Sponsor/Medewerkers Startdatum Fasen
NCT04341311 Terminated
Diffuse Intrinsic Pontine Glioma|Pediatric Brainstem Glioma|Pediatric Brainstem Gliosarcoma Recurrent|Pediatric Cancer|Pediatric Brain Tumor|Diffuse Glioma
Dana-Farber Cancer Institute|Celgene|Secura Bio Inc.
 August 10 2020 Phase 1
NCT03632317 Withdrawn
Glioma|Diffuse Intrinsic Pontine Glioma
University of Michigan Rogel Cancer Center
 October 2019 Phase 2
NCT03982134 Withdrawn
Melanoma|Non Small Cell Lung Cancer
Muhammad Furqan|Novartis Pharmaceuticals|University of Iowa
 September 2019 Phase 1
NCT04326764 Terminated
Acute Myeloid Leukaemia (AML)|Myelodysplastic Syndromes (MDS)
Goethe University|Stichting Hemato-Oncologie voor Volwassenen Nederland|Polish Adult Leukemia Group|Schweizerische Arbeitsgemeinschaft für klinische Krebsforschung
 July 24 2018 Phase 3
NCT03515915 Unknown status
Patients With Recurrent or Refractory Multiple Myeloma
University Hospital Montpellier|Poitiers University Hospital
 April 23 2018 --

Veelgestelde vragen (Frequently Asked Questions)

Vraag 1:
How to reconstitute it for in vivo mice study?

Antwoord:
We recommend the vehicle is 2 % DMSO, 2 % Tween 80, 48%PEG300, 48% water. It is first dissolved in DMSO, then add Tween, PEG300, water in sequence.