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Fimepinostat (CUDC-907) PI3K/HDAC Inhibitor

Name: Fimepinostat (CUDC-907)
Brand: Selleck Chemicals
SKU: S2759
Rating: 5 (37 reviews)

Kat.-Nr.S2759

Fimepinostat (CUDC-907) ist ein dualer PI3K- und HDAC-Inhibitor, der auf PI3Kα und HDAC1/2/3/10 abzielt, mit IC50-Werten von 19 nM bzw. 1,7 nM/5 nM/1,8 nM/2,8 nM. Diese Verbindung induziert Zellzyklusarrest und Apoptose in Brustkrebszellen. Phase 1.

Fimepinostat (CUDC-907) HDAC Inhibitor Chemical Structure

Chemische Struktur

Molekulargewicht: 508.55

Springe zu

Qualitätskontrolle

Charge: Reinheit: 99.98%

99.98

Verwandte Ziele	Akt Wnt/beta-catenin PKC HSP ROCK Microtubule Associated Integrin Bcr-Abl Actin FAK
Weitere HDAC Inhibitoren	ITF-2357 (Givinostat) Hydrochloride Monohydrate Trichostatin A (TSA) Entinostat (MS-275) RGFP966 Quisinostat (JNJ-26481585) Dihydrochloride Tubastatin A HCl Tubastatin A Mocetinostat (MGCD0103) Ricolinostat (ACY-1215) PCI-34051

Zellkultur, Behandlung & Arbeitskonzentration

Zelllinien	Assay-Typ	Konzentration	Inkubationszeit	Aktivitätsbeschreibung	PMID
human Glioma cells (HF2885)	Cytotoxicity assay		72 h	Cytotoxicity against human Glioma cells (HF2885) after 72 hrs by CelltiterGlo assay, EC50=0.7 nM	26288699
human Glioma cells (HF3013)	Cytotoxicity assay		72 h	Cytotoxicity against human Glioma cells (HF3013) after 72 hrs by CelltiterGlo assay, EC50=0.7 nM	26288699
human Glioma cells (HF2876)	Cytotoxicity assay		72 h	Cytotoxicity against human Glioma cells (HF2876) after 72 hrs by CelltiterGlo assay, EC50=0.7 nM	26288699
human Glioma cells (HF2790)	Cytotoxicity assay		72 h	Cytotoxicity against human Glioma cells (HF2790) after 72 hrs by CelltiterGlo assay, EC50=0.7 nM	26288699
human Glioma cells (HF2476)	Cytotoxicity assay		72 h	Cytotoxicity against human Glioma cells (HF2476) after 72 hrs by CelltiterGlo assay, EC50=0.7 nM	26288699
human Glioma cells (HF2381)	Cytotoxicity assay		72 h	Cytotoxicity against human Glioma cells (HF2381) after 72 hrs by CelltiterGlo assay, EC50=0.7 nM	26288699
human Glioma cells (HF2303)	Cytotoxicity assay		72 h	Cytotoxicity against human Glioma cells (HF2303) after 72 hrs by CelltiterGlo assay, EC50=0.7 nM	26288699
MV4-11	Cytotoxicity assay		24 hrs	Cytotoxicity against human MV4-11 cells assessed as growth inhibition after 24 hrs by MTT assay, =0.00043μM.	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, =0.0018μM.	27186676
Sf9	Function assay		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, =0.0028μM.	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, =0.005μM.	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 , =0.0054μM.	27186676
A2780S	Cytotoxicity assay		24 hrs	Cytotoxicity against human A2780S cells assessed as growth inhibition after 24 hrs by MTT assay, =0.00615μM.	27186676
HCT116	Cytotoxicity assay		24 hrs	Cytotoxicity against human HCT116 cells assessed as growth inhibition after 24 hrs by MTT assay, =0.00734μM.	27186676
Sf9	Function assay		60 mins	Inhibition of full length recombinant human N-terminal GST-tagged p110 alpha/untagged p85 alpha expressed in baculovirus infected insect Sf9 cells using PI:3PS as substrate incubated for 60 mins by ADP-Glo luminescence assay, =0.019μM.	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, =0.027μM.	27186676
Sf9	Function assay		2 hrs	Inhibition of N-terminal His6-tagged recombinant full-length human p110delta/untagged recombinant full length human p85alpha expressed in baculovirus infected insect Sf9 cells incubated for 2 hrs by kinase-glo assay, =0.039μM.	27186676
Sf9	Function assay		1 hr	Inhibition of recombinant human p110beta expressed in baculovirus infected insect Sf9 cells incubated for 1 hr by ADP-gloreagen assay, =0.054μM.	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, =0.12625μM.	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 , =0.191μM.	27186676
A2780S	Function assay		6 hrs	Inhibition of HDAC6 in human A2780S cells assessed as tubulin acetylation incubated for 6 hrs by cytoblot assay, =0.22175μM.	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, =0.409μM.	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, =0.426μM.	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, =0.554μM.	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, =0.674μM.	27186676
Sf9	Function assay			Inhibition of recombinant full length human N-terminal GST-tagged PI3K p110alpha/untagged p85alpha expressed in baculovirus infected insect Sf9 cells by ADP-Glo luminescent assay, =0.019μM.	28494256
Sf9	Function assay			Inhibition of recombinant full length human N-terminal GST-tagged PI3K p110delta/untagged p85alpha expressed in baculovirus infected insect Sf9 cells by ADP-Glo luminescent assay, =0.039μM.	28494256
Sf9	Function assay			Inhibition of recombinant full length human N-terminal GST-tagged PI3K p110beta/untagged p85alpha expressed in baculovirus infected insect Sf9 cells by ADP-Glo luminescent assay, =0.054μM.	28494256
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
Rh30	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh30 cells	29435139
Rh41	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells	29435139
NB1643	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for NB1643 cells	29435139
A673	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for A673 cells)	29435139
BT-12	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for BT-12 cells	29435139
LAN-5	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for LAN-5 cells	29435139
DAOY	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for DAOY cells	29435139
MG 63 (6-TG R)	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for MG 63 (6-TG R) 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
Rh41	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh41 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
SK-N-SH	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-SH cells	29435139
SK-N-SH	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Orthogonal 3D viability screen for SK-N-SH cells	29435139
SJ-GBM2	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Orthogonal 3D viability screen for SJ-GBM2 cells	29435139
Daoy	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Orthogonal 3D viability screen for Daoy cells	29435139
Sf9	Function assay			Inhibition of recombinant human full-length N-terminal GST-tagged p110alpha/untagged full-length p85alpha expressed in baculovirus infected Sf9 cells using PIP2 as substrate by ADP-glo luminescence assay, =0.019μM.	30418766
Sf9	Function assay			Inhibition of recombinant human full-length N-terminal GST-tagged p110delta/untagged full-length p85alpha expressed in baculovirus infected Sf9 cells using PIP2 as substrate by ADP-glo luminescence assay, =0.039μM.	30418766
Sf9	Function assay			Inhibition of recombinant human full-length N-terminal GST-tagged p110beta/untagged full-length p85alpha expressed in baculovirus infected Sf9 cells using PIP2 as substrate by ADP-glo luminescence assay, =0.054μM.	30418766
Sf9	Function assay		15 mins	Inhibition of recombinant C-terminal His/FLAG-tagged HDAC1 (unknown origin) expressed in baculovirus infected Sf9 insect cells using Ac-peptide as substrate preincubated for 15 mins followed by substrate addition and measured after 1 hr, =0.00036μM.	31117517
Sf9	Function assay		15 mins	Inhibition of recombinant human full length C-terminal His-tagged HDAC8 expressed in baculovirus infected Sf9 insect cells using Ac-peptide as substrate preincubated for 15 mins followed by substrate addition and measured after 1 hr, =0.0014μM.	31117517
Sf9	Function assay		15 mins	Inhibition of recombinant human full length HDAC2 expressed in baculovirus infected Sf9 insect cells using Ac-peptide as substrate preincubated for 15 mins followed by substrate addition and measured after 1 hr, =0.0016μM.	31117517
HCT116	Antiproliferative assay		96 hrs	Antiproliferative activity against human HCT116 cells after 96 hrs by MTT assay, =0.005μM.	31117517
HCT8	Antiproliferative assay		96 hrs	Antiproliferative activity against human HCT8 cells after 96 hrs by MTT assay, =0.005μM.	31117517
U87	Antiproliferative assay		96 hrs	Antiproliferative activity against human U87 cells after 96 hrs by MTT assay, =0.007μM.	31117517
Capan2	Antiproliferative assay		96 hrs	Antiproliferative activity against human Capan2 cells after 96 hrs by MTT assay, =0.007μM.	31117517
MDA-MB-453	Antiproliferative assay		96 hrs	Antiproliferative activity against human MDA-MB-453 cells after 96 hrs by MTT assay, =0.009μM.	31117517
Bel7402	Antiproliferative assay		96 hrs	Antiproliferative activity against human Bel7402 cells after 96 hrs by MTT assay, =0.013μM.	31117517
HepG2	Antiproliferative assay		96 hrs	Antiproliferative activity against human HepG2 cells after 96 hrs by MTT assay, =0.015μM.	31117517
NCI-H1299	Antiproliferative assay		96 hrs	Antiproliferative activity against human NCI-H1299 cells after 96 hrs by MTT assay, =0.025μM.	31117517
MCF7	Antiproliferative assay		96 hrs	Antiproliferative activity against human MCF7 cells after 96 hrs by MTT assay, =0.041μM.	31117517
HGC27	Antiproliferative assay		96 hrs	Antiproliferative activity against human HGC27 cells after 96 hrs by MTT assay, =0.041μM.	31117517
Sf9	Function assay		15 mins	Inhibition of recombinant human full length HDAC11 expressed in baculovirus infected Sf9 insect cells using Ac-peptide as substrate preincubated for 15 mins followed by substrate addition and measured after 1 hr, =0.132μM.	31117517
NCI-H460	Antiproliferative assay		96 hrs	Antiproliferative activity against human NCI-H460 cells after 96 hrs by MTT assay, =0.15μM.	31117517
SW1990	Antiproliferative assay		96 hrs	Antiproliferative activity against human SW1990 cells after 96 hrs by MTT assay, =0.18μM.	31117517
K562	Antiproliferative assay		96 hrs	Antiproliferative activity against human K562 cells after 96 hrs by MTT assay, =0.28μM.	31117517
Sf9	Function assay		15 mins	Inhibition of recombinant human full length HDAC4 expressed in baculovirus infected Sf9 insect cells using Ac-peptide as substrate preincubated for 15 mins followed by substrate addition and measured after 1 hr, =0.445μM.	31117517
DU145	Antiproliferative assay		96 hrs	Antiproliferative activity against human DU145 cells after 96 hrs by MTT assay, =0.56μM.	31117517
HuH7	Antiproliferative assay		96 hrs	Antiproliferative activity against human HuH7 cells after 96 hrs by MTT assay, =0.56μM.	31117517
MV4-11	Antiproliferative assay	25 to 50 nM	72 hrs	Antiproliferative activity against human MV4-11 cells assessed as reduction in cell viability at 25 to 50 nM after 72 hrs by tryphan blue assay	32212730
Klicken Sie hier, um weitere experimentelle Daten zu Zelllinien anzuzeigen

Chemische Informationen, Lagerung & Stabilität

Molekulargewicht	508.55	Formel	C₂₃H₂₄N₈O₄S	Lagerung (Ab dem Eingangsdatum)	3 Jahre-20°CPulver
CAS-Nr.	1339928-25-4	SDF herunterladen		Lagerung von Stammlösungen	1 Jahr-80°Cin Lösungsmittel 1 Monat-20°Cin Lösungsmittel
Synonyme	N/A			Smiles	CN(CC1=CC2=C(S1)C(=NC(=N2)C3=CN=C(C=C3)OC)N4CCOCC4)C5=NC=C(C=N5)C(=O)NO

Löslichkeit

In vitro
Charge:

DMSO : 102 mg/mL (200.57 mM)
(Feuchtigkeitskontaminiertes DMSO kann die Löslichkeit verringern. Verwenden Sie frisches, wasserfreies DMSO.)

Water : Insoluble

Ethanol : Insoluble

DMSO : 100 mg/mL (196.63 mM)
(Feuchtigkeitskontaminiertes DMSO kann die Löslichkeit verringern. Verwenden Sie frisches, wasserfreies DMSO.)

Water : Insoluble

Ethanol : Insoluble

DMSO : 102 mg/mL (200.57 mM)
(Feuchtigkeitskontaminiertes DMSO kann die Löslichkeit verringern. Verwenden Sie frisches, wasserfreies DMSO.)

Water : Insoluble

Ethanol : Insoluble

DMSO : 102 mg/mL (200.57 mM)
(Feuchtigkeitskontaminiertes DMSO kann die Löslichkeit verringern. Verwenden Sie frisches, wasserfreies DMSO.)

Water : Insoluble

Ethanol : Insoluble

DMSO : 10 mg/mL (19.66 mM)
(Feuchtigkeitskontaminiertes DMSO kann die Löslichkeit verringern. Verwenden Sie frisches, wasserfreies DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molaritätsrechner

Masse	Konzentration	Volumen	Molekulargewicht
=	×	×

Verdünnungsrechner Molekulargewichtsrechner

In vivo Charge:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Von Selleck Labs validiert. Sollten Sie Anpassungen an dieser Formulierung benötigen, kontaktieren Sie unser Verkaufsteam für kundenspezifische Tests.	5.000mg/ml (9.83mM)	Taking the 1 mL working solution as an example, add 50 μL of 100 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

In-vivo-Formulierungsrechner (Klare Lösung)

Schritt 1: Geben Sie die untenstehenden Informationen ein (Empfohlen: Ein zusätzliches Tier zur Berücksichtigung von Verlusten während des Experiments)

Dosierung: mg/kg Durchschnittsgewicht der Tiere: g Dosiervolumen pro Tier:μL Anzahl der Tiere:

Schritt 2: Geben Sie die In-vivo-Formulierung ein (Dies ist nur der Rechner, keine Formulierung. Bitte kontaktieren Sie uns zuerst, wenn es im Abschnitt "Löslichkeit" keine In-vivo-Formulierung gibt.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Berechnungsergebnisse:

Arbeitskonzentration: mg/ml;

Methode zur Herstellung der DMSO-Stammlösung: mg Wirkstoff vorgelöst in μL DMSO ( Konzentration der Stammlösung mg/mL, Bitte kontaktieren Sie uns zuerst, wenn die Konzentration die DMSO-Löslichkeit der Wirkstoffcharge überschreitet. )

Methode zur Herstellung der In-vivo-Formulierung: Nehmen Sie μL DMSO Stammlösung, dann hinzufügenμL PEG300, mischen und klären, dann hinzufügenμL Tween 80, mischen und klären, dann hinzufügen μL ddH₂O, mischen und klären.

Methode zur Herstellung der In-vivo-Formulierung: Nehmen Sie μL DMSO Stammlösung, dann hinzufügen μL Maisöl, mischen und klären.

Hinweis: 1. Bitte stellen Sie sicher, dass die Flüssigkeit klar ist, bevor Sie das nächste Lösungsmittel hinzufügen.
2. Achten Sie darauf, das/die Lösungsmittel der Reihe nach hinzuzufügen. Sie müssen sicherstellen, dass die bei der vorherigen Zugabe erhaltene Lösung eine klare Lösung ist, bevor Sie mit der Zugabe des nächsten Lösungsmittels fortfahren. Physikalische Methoden wie Vortex, Ultraschall oder ein heißes Wasserbad können zur Unterstützung des Lösens verwendet werden.

Wirkmechanismus

Targets/IC₅₀/Ki	HDAC1 (Cell-free assay) 1.7 nM HDAC3 (Cell-free assay) 1.8 nM HDAC10 (Cell-free assay) 2.8 nM HDAC2 (Cell-free assay) 5.0 nM HDAC11 (Cell-free assay) 5.4 nM PI3Kα (Cell-free assay) 19 nM HDAC6 (Cell-free assay) 27 nM PI3Kδ (Cell-free assay) 39 nM PI3Kβ (Cell-free assay) 54 nM
In vitro	Fimepinostat (CUDC-907) hemmt andere PI3K-Isoformen wie PI3Kβ, PI3Kγ, PI3Kδ, PI3KɑH1047R und PI3KɑE545K mit einer IC50 von 54 nM, 311 nM, 39 nM, 73 nM bzw. 62 nM. Darüber hinaus verhindert es auch HDAC-Subtypen HDAC8, HDAC6 und HDAC11 mit einer IC50 von 191 nM, 27 nM bzw. 5,4 nM. Zusätzlich unterdrückt diese Verbindung andere Arten der HDAC-enzymatischen Aktivität mit geringerer Potenz. Sie hemmt das Wachstum einer Reihe von B-Zell-Lymphomen wie Granta 519, DOHH2, RL, Pfeiffer, SuDHL4, Daudi und Raji mit einer IC50 von 7 nM, 1 nM, 2 nM, 4 nM, 3 nM, 15 nM bzw. 9 nM. Sie blockiert auch die Proliferation von Myelomen, einschließlich RPMI8226, OPM-2 und ARH77, mit einer IC50 von 2 nM, 1 nM bzw. 5 nM. Fimepinostat zeigt eine größere Antitumoraktivität bei multiplem Myelom und B-Zell-Lymphom.
In vivo	Fimepinostat (CUDC-907) hat eine lange Halbwertszeit in murinen Tumoren und induziert Apoptosis, während es die Proliferation von Krebszellen in Xenograft-Tumoren hemmt. In Wirksamkeitsstudien an NHL- und MM-Modellen ist diese Verbindung wirksamer als entweder ein Einzelwirkstoff-PI3K- oder HDAC-Inhibitor-Referenzpräparat oder eine Kombination der beiden Wirkstoffe, die in maximal tolerierten Dosen (MTD) verabreicht werden. Darüber hinaus ist sie wirksamer als der PI3Kδ-selektive Inhibitor CAL-101, wenn er in MTD-Dosen verabreicht wird.
Literatur	[1] https://pubmed.ncbi.nlm.nih.gov/22693356/

Anwendungen

Methoden	Biomarker	PMID
Western blot	AKT / p-AKT / P-p70S6K1 / Ac-H3K9 / p-MEK / p-ERK / p-STAT3 / MCL-1 / Bcl-2 / Bcl-xl / PARP p-PRAS40 / p-4EBP1 / p-S6 / c-Myc / Cleaved PARP / Caspase-3 / Celaved caspase-3 SYK / BTK / Bcl-10 / MyD88 / IRAK4	30353642
Immunofluorescence	γ-H2AX / 53BP1 RAD51	29760046
Growth inhibition assay	Cell viability	28147336

Klinische Studieninformationen

(Daten von https://clinicaltrials.gov, aktualisiert am 2024-05-22)

NCT-Nummer	Rekrutierung	Erkrankungen	Sponsor/Kooperationspartner	Startdatum	Phasen
NCT02909777	Active not recruiting	Lymphoma\|Neuroblastoma\|Brain Tumor\|Solid Tumor	Dana-Farber Cancer Institute\|Curis Inc.	October 2016	Phase 1
NCT02307240	Completed	Triple-Negative Breast Cancer\|High-grade Serous Ovarian Cancer\|Solid Tumors\|NUT Midline Carcinoma	Curis Inc.	November 2014	Phase 1
NCT01742988	Completed	Lymphoma\|Relapsed Lymphoma\|Refractory Lymphoma\|Relapsed and/or Refractory Lymphoma\|Relapsed Ddiffuse Large B-Cell Lymphoma (DLBCL)\|Refractory Diffuse Large B-Cell Lymphoma (DLBCL)\|Relapsed and/or Refractory Diffuse Large B-Cell Lymphoma (DLBCL)\|Double-hit Lymphoma (DHL)\|Triple-hit Lymphoma (THL)\|Double-expressor Lymphoma (DEL)\|High-grade B-cell Lymphoma (HGBL)	Curis Inc.\|The Leukemia and Lymphoma Society	December 2012	Phase 1

Technischer Support

Handhabungshinweise

Tel: +1-832-582-8158 Ext:3

Wenn Sie weitere Fragen haben, hinterlassen Sie bitte eine Nachricht.

Häufig gestellte Fragen

Frage 1:
How to solve it for in vivo studies (p.o.)?

Antwort:
If you decide to take P.O. as your administration route, we suggest using 1% CMC-Na to dilute it as a suspension solution for gavage.

Frage 2:
What is its half-life in vivo?

Antwort:
It is said to have a long half-life in mouse tumor model: http://cancerres.aacrjournals.org/content/72/8_Supplement/3744.short, however, its not formally published and we have no detail of how long it is.

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):