Home Epigenetics HDAC inhibitor Mocetinostat (MGCD0103)

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Mocetinostat (MGCD0103) HDAC inhibitor

Cat.No.S1122

Mocetinostat (MGCD0103, MG0103) is a potent HDAC inhibitor with most potency for HDAC1 with IC50 of 0.15 μM in a cell-free assay, 2- to 10- fold selectivity against HDAC2, 3, and 11, and no activity to HDAC4, 5, 6, 7, and 8. Mocetinostat (MGCD0103) induces apoptosis and autophagy. Phase 2.
Mocetinostat (MGCD0103) HDAC inhibitor Chemical Structure

Chemical Structure

Molecular Weight: 396.44

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Quality Control

Batch: Purity: 99.93%
99.93

Cell Culture, Treatment & Working Concentration

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
PBMC  Apoptosis Assay 0.5/2/3 μM 24/48 h induces apoptosis dose and time dependently 20406947
HeLa  Function Assay 10 μM  7 h DMSO disrupts normal spindle checkpoint function 20538840
HeLa Function Assay 10 μM  6/12/24 h DMSO induces mitotic accumulation and delayed p21 expression 20538840
HeLa Function Assay 0.3-10 μM 8 h DMSO increases caspase 3 and 7 activation dose dependently 20538840
HeLa Function Assay 0.3-10 μM 8 h DMSO increases acetylated H3 K9 (H3K9Ac) at 10 μM 20538840
DMS114 Growth Inhibition Assay IC50=640 nM 20682643
H82 Growth Inhibition Assay IC50=250 nM 20682643
H146 Growth Inhibition Assay IC50=35 nM 20682643
H526 Growth Inhibition Assay IC50=480 nM 20682643
KM-H2 Function Assay 1 μM 0.25-48 h DMSO activates NF-kB 20880107
L428 Function Assay 1 μM 0.25-48 h DMSO activates NF-kB 20880107
HD-LM2 Function Assay 1 μM 0.25-48 h DMSO activates NF-kB 20880107
KM-H2 Function Assay 0.5/1 μM 24/48 h DMSO upregulates TNF-α dose and time dependently 20880107
L428 Function Assay 0.5/1 μM 24/48 h DMSO upregulates TNF-α dose and time dependently 20880107
HD-LM2 Function Assay 0.5/1 μM 24/48 h DMSO upregulates TNF-α dose and time dependently 20880107
KM-H2 Function Assay 1 μM 24/48 h DMSO downregulates XIAP, activated caspases 9 and 3 20880107
L428 Function Assay 1 μM 24/48 h DMSO downregulates XIAP, activated caspases 9 and 3 20880107
HD-LM2 Function Assay 1 μM 24/48 h DMSO downregulates XIAP, activated caspases 9 and 3 20880107
KM-H2 Apoptosis Assay 0.1/0.5/1 μM 48 h DMSO induces apoptosis dose dependently 20880107
L428 Apoptosis Assay 0.1/0.5/1 μM 48 h DMSO induces apoptosis dose dependently 20880107
HD-LM2 Apoptosis Assay 0.1/0.5/1 μM 48 h DMSO induces apoptosis dose dependently 20880107
KM-H2 Function Assay 0.1-2 μM 24 h  DMSO shows acetylation of histone 3 and upregulation of the cell cycle regulatory protein p21 20880107
L428 Function Assay 0.1-2 μM 24 h  DMSO shows acetylation of histone 3 and upregulation of the cell cycle regulatory protein p21 20880107
HD-LM2 Function Assay 0.1-2 μM 24 h  DMSO shows acetylation of histone 3 and upregulation of the cell cycle regulatory protein p21 20880107
KM-H2 Growth Inhibition Assay 72 h DMSO IC50=2.86 μM 20880107
L428 Growth Inhibition Assay 72 h DMSO IC50=1.96 μM 20880107
HD-LM2 Growth Inhibition Assay 72 h DMSO IC50=1.88 μM 20880107
LP1 Function Assay 1 μM 24 h enhances 5-AC-induced MAGE-A3 gene expression 21171821
ANBL6  Function Assay 1 μM 24 h enhances 5-AC-induced MAGE-A3 gene expression 21171821
HMEC Growth Inhibition Assay IC50=19 μM 21317455
SW620 Growth Inhibition Assay IC50=1 μM 21317455
SW48 Growth Inhibition Assay IC50=0.8 μM 21317455
HT-29 Growth Inhibition Assay IC50=0.7 μM 21317455
HCT15 Growth Inhibition Assay IC50=0.7 μM 21317455
PAXF 1657L† Growth Inhibition Assay EC50=0.3 μM 21375679
PAXF 546L† Growth Inhibition Assay EC50=1.5 μM 21375679
Panc-1 Growth Inhibition Assay EC50=1.8 μM 21375679
MiaPaca-2 Growth Inhibition Assay EC50=0.6 μM 21375679
AsPC-1 Growth Inhibition Assay EC50=3.9 μM 21375679
BxPC-3 Growth Inhibition Assay EC50=1.1 μM 21375679
MMCs Function Assay 1 μM 6-24 h dose-dependently inhibits the trimethylation level of H3-K9 (H3-K9me3) 24451378
MMCs Function Assay 1 μM 24 h augments global acetylation levels of histone H3-K9/14 (H3-K9/14ac) and H4-K12 (H4-K12ac) 24451378
MMCs Function Assay 1 μM 24 h increases HAT activity 24451378
MMCs Function Assay 0.5/1 μM 24 h shows 45-fold stimulation in cGMP levels 24451378
MMCs Function Assay 1 μm 0-48 h increases NPRA protein expression 2.7–3.5 fold 24451378
Panc1 Cell Viability Assay 1 μM 72 h DMSO enhances gemcitabine-induces cell viability decrease 25872941
Panc1 Apoptosis Assay 1 μM 72 h DMSO sensitizes Panc1 cells for gemcitabine-induced apoptosis 25872941
Panc1 Function Assay 0.5/1/2.5 μM 48 h DMSO reduces expression of ZEB1 on both mRNA and protein level  25872941
Panc1 Function Assay 0.5/1/2.5 μM 48 h DMSO upregulates miR-203 25872941
MOLP8 Growth Inhibition Assay 48 h IC50=0.6± 0.04μM 26091518
T47D Growth Inhibition Assay 48 h IC50=1.17 μM 26378038
MCF7 Growth Inhibition Assay 48 h IC50=0.67 μM 26378038
BT549 Growth Inhibition Assay 48 h IC50=4.38 μM 26378038
MDA-MB-231 Growth Inhibition Assay 48 h IC50=3.04 μM 26378038
HEK293 Function assay Inhibition of HDAC1 in HEK293 cells, IC50=0.13μM 18308563
HEK293 Function assay Inhibition of HDAC3 in HEK293 cells, IC50=0.61μM 18308563
HCT116 Antiproliferative assay 72 hrs Antiproliferative activity against human HCT116 cells after 72 hrs by MTT assay, IC50=0.29μM 18570366
HCT116 Function assay Induction of p21cip/waf1 protein expression in human HCT116 cells relative to MS275, EC50=0.45μM 18570366
Du145 Antiproliferative assay 72 hrs Antiproliferative activity against human Du145 cells after 72 hrs by MTT assay, IC50=0.67μM 18570366
A549 Antiproliferative assay 72 hrs Antiproliferative activity against human A549 cells after 72 hrs by MTT assay, IC50=0.9μM 18570366
HCT116 Cell cycle assay Cell cycle arrest in human HCT116 cells assessed as accumulation at G2/M phase, EC50<1μM 18570366
T24 Function assay Induction of H3 histone acetylation in human T24 cells relative to MS275, EC50=1.38μM 18570366
HCT116 Apoptosis assay 1 uM Induction of apoptosis in HCT116 cells at 1 uM 18570366
HCT116 Antiproliferative assay Antiproliferative activity against human HCT116 cells by MTT assay, IC50=0.3μM 19114304
HCT116 Function assay 16 hrs Induction of p21WAF1/CIP1 expression in human HCT116 cells assessed as tubulin level after 16 hrs by luciferase assay, EC50=0.6μM 19114304
T24 Function assay 16 hrs Induction of histone H4 hyperacetylation in human T24 cells after 16 hrs by immunoblotting, EC50<1μM 19114304
HCT116 Antiproliferative assay Antiproliferative activity against human HCT116 cells assessed as growth inhibition, IC50=0.31μM 21650221
H1299 Antiproliferative assay Antiproliferative activity against human H1299 cells, IC50=1.44μM 21650221
HCT116 Antiproliferative assay Antiproliferative activity against human HCT116 cells, IC50=0.31μM 21742496
Sf9 Function assay 2 hrs Inhibition of human recombinant HDAC1 expressed in Sf9 cells incubated for 2 hrs using RHKK-Ac fluorogenic substrate, IC50=0.102μM 23009203
HCT116 Cytotoxicity assay 72 hrs Cytotoxicity against human HCT116 cells after 72 hrs by MTT assay, IC50=0.327μM 23206867
A549 Cytotoxicity assay 72 hrs Cytotoxicity against human A549 cells after 72 hrs by MTT assay, IC50=1.279μM 23206867
MCF7 Cytotoxicity assay 72 hrs Cytotoxicity against human MCF7 cells after 72 hrs by MTT assay, IC50=4.807μM 23206867
HCT116 Cytotoxicity assay 72 hrs Cytotoxicity against human HCT116 cells assessed as growth inhibition by measuring cellular ATP level after 72 hrs by cell-titer glo assay, IC50=0.7μM 23829483
MCF7 Cytotoxicity assay 72 hrs Cytotoxicity against human MCF7 cells assessed as growth inhibition by measuring cellular ATP level after 72 hrs by cell-titer glo assay, IC50=1.26μM 23829483
A549 Cytotoxicity assay 72 hrs Cytotoxicity against human A549 cells assessed as growth inhibition by measuring cellular ATP level after 72 hrs by cell-titer glo assay, IC50=1.73μM 23829483
DU145 Cytotoxicity assay 72 hrs Cytotoxicity against human DU145 cells assessed as growth inhibition by measuring cellular ATP level after 72 hrs by cell-titer glo assay, IC50=2.06μM 23829483
Jurkat Apoptosis assay 1 to 10 uM 24 hrs Induction of apoptosis in human Jurkat cells assessed as PARP cleavage at 1 to 10 uM after 24 hrs by Western blot analysis 23829483
HeLa Function assay 1 to 10 uM 24 hrs Inhibition of HDAC in human HeLa cells assessed as increase in H3K9Ac level at 1 to 10 uM after 24 hrs by Western blot analysis 23829483
Jurkat Function assay 1 to 10 uM 24 hrs Inhibition of HDAC in human Jurkat cells assessed as increase in H3K9Ac level at 1 to 10 uM after 24 hrs by Western blot analysis 23829483
High5 Function assay 3 to 24 hrs Inhibition of human recombinant HDAC1 expressed in baculovirus infected insect high5 cells using Ac-Lys-Tyr-Lys (epsilon-acetyl)-AMC as substrate after 3 to 24 hrs by fluorescence assay, IC50=0.95μM 24095018
HCT116 Antiproliferative assay 72 hrs Antiproliferative activity against human HCT116 cells assessed as cell viability after 72 hrs by MTT assay, IC50=1.57μM 24095018
A549 Antiproliferative assay 72 hrs Antiproliferative activity against human A549 cells assessed as cell viability after 72 hrs by MTT assay, IC50=1.65μM 24095018
High5 Function assay 3 to 24 hrs Inhibition of human recombinant HDAC3 expressed in baculovirus infected insect high5 cells using Ac-Lys-Tyr-Lys (epsilon-acetyl)-AMC as substrate after 3 to 24 hrs by fluorescence assay, IC50=1.67μM 24095018
SNU16 Cytotoxicity assay 72 hrs Cytotoxicity against human SNU16 cells assessed as growth inhibition after 72 hrs by MTT assay, IC50=0.142μM 25805446
High5 Function assay 24 hrs Inhibition of recombinant human HDAC2 expressed in baculovirus infected insect High5 cells using Ac-Lys-Tyr-Lys (epsilon-acetyl)-AMC as substrate after 24 hrs by fluorescence assay, IC50=0.17μM 25805446
High5 Function assay 3 hrs Inhibition of recombinant human HDAC3 expressed in baculovirus infected insect High5 cells using Ac-Lys-Tyr-Lys (epsilon-acetyl)-AMC as substrate after 3 hrs by fluorescence assay, IC50=0.36μM 25805446
High5 Function assay 24 hrs Inhibition of recombinant human HDAC1 expressed in baculovirus infected insect High5 cells using Ac-Lys-Tyr-Lys (epsilon-acetyl)-AMC as substrate after 24 hrs by fluorescence assay, IC50=0.39μM 25805446
HCT116 Cytotoxicity assay 72 hrs Cytotoxicity against human HCT116 cells assessed as growth inhibition after 72 hrs by MTT assay, IC50=0.396μM 25805446
SW620 Cytotoxicity assay 72 hrs Cytotoxicity against human SW620 cells assessed as growth inhibition after 72 hrs by MTT assay, IC50=0.419μM 25805446
MKN45 Cytotoxicity assay 72 hrs Cytotoxicity against human MKN45 cells assessed as growth inhibition after 72 hrs by MTT assay, IC50=0.61μM 25805446
Hep3B Cytotoxicity assay 72 hrs Cytotoxicity against human Hep3B cells assessed as growth inhibition after 72 hrs by MTT assay, IC50=0.823μM 25805446
HepG2 Cytotoxicity assay 72 hrs Cytotoxicity against human HepG2 cells assessed as growth inhibition after 72 hrs by MTT assay, IC50=0.876μM 25805446
SNU5 Cytotoxicity assay 72 hrs Cytotoxicity against human SNU5 cells assessed as growth inhibition after 72 hrs by MTT assay, IC50=1.009μM 25805446
A549 Cytotoxicity assay 72 hrs Cytotoxicity against human A549 cells assessed as growth inhibition after 72 hrs by MTT assay, IC50=2.08μM 25805446
SJSA1 Cytotoxicity assay 72 hrs Cytotoxicity against human SJSA1 cells assessed as growth inhibition after 72 hrs by MTT assay, IC50=3.624μM 25805446
MHCC97H Cytotoxicity assay 72 hrs Cytotoxicity against human MHCC97H cells assessed as growth inhibition after 72 hrs by MTT assay, IC50=4.563μM 25805446
PANC1 Cytotoxicity assay 72 hrs Cytotoxicity against human PANC1 cells assessed as growth inhibition after 72 hrs by MTT assay, IC50=26.774μM 25805446
U937 Function assay 10 uM 24 hrs Inhibition of HDAC3 in human U937 cells assessed as increase in histone H3 lysine-9 acetylation at 10 uM incubated for 24 hrs by Western blotting method 26287310
PC3 Function assay 10 uM 24 hrs Inhibition of HDAC3 in human PC3 cells assessed as increase in histone H3 lysine-9 acetylation at 10 uM incubated for 24 hrs by Western blotting method 26287310
U937 Function assay 10 uM 24 hrs Inhibition of HDAC in human U937 cells assessed as reduction in cyclin E expression in at 10 uM incubated for 24 hrs by Western blotting method 26287310
Sf9 Function assay 10 mins Inhibition of recombinant full length human C-terminal FLAG-tagged HDAC11 expressed in baculovirus infected Sf9 cells using Boc-Lys(epsilon-Ac)-AMC as substrate pretreated for 10 mins followed by substrate addition by fluorometric method, IC50=0.59μM 28501514
TC32 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells 29435139
DAOY qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells 29435139
SJ-GBM2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells 29435139
A673 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells 29435139
SK-N-MC qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells 29435139
BT-37 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells 29435139
NB-EBc1 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells 29435139
U-2 OS qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for U-2 OS cells 29435139
Saos-2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells 29435139
SK-N-SH qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells 29435139
NB1643 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells 29435139
LAN-5 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells 29435139
BT-12 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 cells 29435139
Rh18 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 cells 29435139
OHS-50 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells 29435139
RD qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells 29435139
MG 63 (6-TG R) qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for MG 63 (6-TG R) cells 29435139
fibroblast cells qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for control Hh wild type fibroblast cells 29435139
Rh41 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells 29435139
A673 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for A673 cells) 29435139
DAOY qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for DAOY cells 29435139
SJ-GBM2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SJ-GBM2 cells 29435139
U-2 OS qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for U-2 OS cells 29435139
RD qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for RD cells 29435139
Rh18 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh18 cells 29435139
Rh30 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh30 cells 29435139
Sf9 Function assay Inhibition Assay: HDAC inhibition assays were performed by Reaction Biology Corp. (Malvern, Pa.) using isolated human, recombinant full-length HDAC1 and -6 from a baculovirus expression system in Sf9 cells, IC50=0.102μM ChEMBL
HCT116 Antiproliferative assay 48 hrs Antiproliferative activity against human HCT116 cells assessed as reduction in cell viability after 48 hrs by MTT assay, IC50=1.24μM ChEMBL
MCF7 Antiproliferative assay 72 hrs Antiproliferative activity against human MCF7 cells assessed as reduction in cell viability after 72 hrs by MTT assay, IC50=2.49μM ChEMBL
HeLa Antiproliferative assay 48 hrs Antiproliferative activity against human HeLa cells assessed as reduction in cell viability after 48 hrs by MTT assay, IC50=3.32μM ChEMBL
HeLa Antiproliferative assay 72 hrs Antiproliferative activity against human HeLa cells assessed as reduction in cell viability after 72 hrs by MTT assay, IC50=3.42μM ChEMBL
HCT116 Antiproliferative assay 72 hrs Antiproliferative activity against human HCT116 cells assessed as reduction in cell viability after 72 hrs by MTT assay, IC50=3.51μM ChEMBL
HepG2 Antiproliferative assay 48 hrs Antiproliferative activity against human HepG2 cells assessed as reduction in cell viability after 48 hrs by MTT assay, IC50=4.05μM ChEMBL
HepG2 Antiproliferative assay 72 hrs Antiproliferative activity against human HepG2 cells assessed as reduction in cell viability after 72 hrs by MTT assay, IC50=4.25μM ChEMBL
HepG2 Antiproliferative assay 24 hrs Antiproliferative activity against human HepG2 cells assessed as reduction in cell viability after 24 hrs by MTT assay, IC50=5.79μM ChEMBL
A549 Antiproliferative assay 72 hrs Antiproliferative activity against human A549 cells assessed as reduction in cell viability after 72 hrs by MTT assay, IC50=11.87μM ChEMBL
A549 Antiproliferative assay 48 hrs Antiproliferative activity against human A549 cells assessed as reduction in cell viability after 48 hrs by MTT assay, IC50=14.57μM ChEMBL
HCT116 Antiproliferative assay 24 hrs Antiproliferative activity against human HCT116 cells assessed as reduction in cell viability after 24 hrs by MTT assay, IC50=29.69μM ChEMBL
HeLa Antiproliferative assay 24 hrs Antiproliferative activity against human HeLa cells assessed as reduction in cell viability after 24 hrs by MTT assay, IC50=43.8μM ChEMBL
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Solubility

In vitro
Batch:

DMSO : 60 mg/mL (151.34 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Water : Insoluble

Ethanol : Insoluble

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Mass Concentration Volume Molecular Weight
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In vivo
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Chemical Information, Storage & Stability

Molecular Weight 396.44 Formula

C23H20N6O

 Storage (From the date of receipt)
CAS No. 726169-73-9 Download SDF Storage of Stock Solutions

Synonyms MG0103 Smiles C1=CC=C(C(=C1)N)NC(=O)C2=CC=C(C=C2)CNC3=NC=CC(=N3)C4=CN=CC=C4

Mechanism of Action

Targets/IC50/Ki
HDAC1
(Cell-free assay)
0.15 μM
HDAC2
(Cell-free assay)
0.29 μM
HDAC11
(Cell-free assay)
0.59 μM
HDAC3
(Cell-free assay)
1.66 μM
In vitro

Mocetinostat (MGCD0103) inhibits only a subset of the nine human recombinant HDACs, including HDAC1, HDAC2, HDAC3, and HDAC11 at nanomolar or low micromolar concentrations, in a dose-dependent manner. It reveals most potent inhibitory activity against human HDAC1 and HDAC2 enzymes in vitro, and does not inhibit class II HDACs. The exocyclic amino group in this compound is necessary for enzyme inhibitory activity because HDAC-inhibitory activity against HDAC1 and HDAC2 is completely abolished with the desamino analogue. Its inhibitory activity reaches the maximum plateau at 6 μM, and the maximal inhibitable enzyme pool affected by MGCD0103 is 75% of the total enzyme activity in HCT116 cells whereas NVP-LAQ824 inhibits almost 100% of that in these cells. In A549 cells, it also exhibits dose-dependent inhibition of HDAC activity in whole cells.

Kinase Assay
HDAC enzyme assay in vitro
The deacetylase enzyme assay is based on a homogeneous fluorescence release assay. Purified recombinant HDAC enzymes are incubated with Mocetinostat (MGCD0103) diluted in various concentrations for 10 minutes in assay buffer [25 mM HEPES (pH 8.0), 137 mM NaCl, 1 mM MgCl2, 2.7 mM KCl] at room temperature. The substrate Boc-Lys(ε-Ac)-AMC is added to the reaction for further incubation at 37 °C. The concentration of the substrate and the incubation time varies for different isotypes of HDAC enzymes. A 20-min trypsin incubation at room temperature allows the release of the fluorophore from the deacetylated substrate. The fluorescent signal is detected by fluorometer at excitation of 360 nm, emission of 470 nm, and cutoff at 435 nm.
In vivo

Mocetinostat (MGCD0103) significantly inhibites growth of human tumor xenografts in nude mice and the antitumor activity correlated with induction of histone acetylation in tumors. P.O. administration of this compound (2HBr salt) significantly decreases growth of implanted advanced A549 tumors in nude mice in a dose-dependent manner after 13 days of daily administration. It (170 mg/kg for 2HBr salt, corresponding to 120 mg/kg of free base) significantly blockes growth of tumors compared with vehicle treatment alone with no change in body weight. In addition, it does not reduce WBC counts and is well tolerated. The compound is also orally active in many other human tumor xenograft models including NSCLC H1437. At 80 mg/kg (free base), it almost completely blocks the growth of H1437 tumors after 13 days of daily p.o. administration with no reduction of body weight in animals. It reduces pulmonary arterial pressure more dramatically. Moreover, this compound improves pulmonary artery acceleration time and reduced systolic notching of the pulmonary artery flow envelope, which suggests a positive impact of the HDAC inhibitor on pulmonary vascular remodeling and stiffening.

References

Applications

Methods Biomarkers Images PMID
Western blot Ac-H3 / Ac-H4 / Ac-tubulin Bad / Bid / Bak / Puma / Bax / Cleaved caspase-9 / Cleaved caspase-3 / Cleaved PARP
S1122-WB1
29186204
Immunofluorescence Nanog / MHC E-cadherin / ZEB1
S1122-IF1
26240433
Growth inhibition assay Cell viability
S1122-viability1
26378038

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT04299113 Recruiting
Rhabdomyosarcoma
Jonsson Comprehensive Cancer Center|Mirati Therapeutics Inc.|Phase One Foundation
 May 14 2020 Phase 1
NCT02993991 Withdrawn
Squamous Cell Carcinoma Head And Neck|Squamous Cell Carcinoma Mouth|Resectable Squamous Cell Carcinoma of Oral Cavity
University Health Network Toronto|Mirati Therapeutics Inc.|AstraZeneca
 October 10 2017 Phase 1
NCT02236195 Completed
Urothelial Carcinoma
Mirati Therapeutics Inc.
 October 2014 Phase 2
NCT00666497 Terminated
Acute Myeloid Leukemia (AML)|Myelodysplastic Syndrome (MDS)
Mirati Therapeutics Inc.
 June 2008 Phase 2
NCT00511576 Terminated
Breast Cancer|Lung Cancer|Pulmonary Cancer|Non-Small-Cell Lung Carcinoma|Prostate Cancer|Prostatic Cancer|Gastric Cancer|Stomach Cancer
Mirati Therapeutics Inc.
 August 2007 Phase 1

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