Fimepinostat (CUDC-907)

CUDC-907 is a dual PI3K and HDAC inhibitor for PI3Kα and HDAC1/2/3/10 with IC50 of 19 nM and 1.7 nM/5 nM/1.8 nM/2.8 nM, respectively. CUDC-907 induces cell cycle arrest and apoptosis in breast cancer cells. Phase 1.

Fimepinostat (CUDC-907) Chemical Structure

Fimepinostat (CUDC-907) Chemical Structure

CAS No. 1339928-25-4

Purity & Quality Control

Fimepinostat (CUDC-907) Related Products

Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description 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
Click to View More Cell Line Experimental Data

Biological Activity

Description CUDC-907 is a dual PI3K and HDAC inhibitor for PI3Kα and HDAC1/2/3/10 with IC50 of 19 nM and 1.7 nM/5 nM/1.8 nM/2.8 nM, respectively. CUDC-907 induces cell cycle arrest and apoptosis in breast cancer cells. Phase 1.
Targets
HDAC1 [1]
(Cell-free assay)
HDAC3 [1]
(Cell-free assay)
HDAC10 [1]
(Cell-free assay)
HDAC2 [1]
(Cell-free assay)
HDAC11 [1]
(Cell-free assay)
Click to View More Targets
1.7 nM 1.8 nM 2.8 nM 5.0 nM 5.4 nM
In vitro
In vitro

CUDC-907 inhibits other PI3K isoforms such as PI3Kβ, PI3Kγ, PI3Kδ, PI3KɑH1047R and PI3KɑE545K with IC50 of 54 nM, 311 nM, 39 nM, 73 nM and 62 nM, respectively. Moreover, CUDC-907 also prevents HDAC subtypes HDAC8, HDAC6 and HDAC11 with IC50 of 191 nM, 27 nM and 5.4 nM, respectively. [1]

In addition, CUDC-907 suppresses other types of HDAC enzymatic activity with lower potency. CUDC-907 inhibits the growth of a series of B cell lymphoma such as Granta 519, DOHH2, RL, Pfeiffer, SuDHL4, Daudi and Raji with IC50 of 7 nM, 1 nM, 2 nM, 4 nM, 3 nM, 15 nM and 9 nM, respectively. CUDC-907 also blocks the proliferation of Myeloma including RPMI8226, OPM-2 and ARH77 with IC50 of 2 nM, 1 nM and 5 nM, respectively. CUDC-907 displays greater anti-tumor activity in multiple myeloma and B cell lymphoma. [1]

Experimental Result Images Methods Biomarkers Images 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
In Vivo
In vivo

CUDC-907 has a long half-life in murine tumors. CUDC-907 induces apoptosis and inhibits cancer cell proliferation in xenograft tumors. [1]

In efficacy studies in NHL and MM models, CUDC-907 is more efficacious than either a single-agent PI3K or HDAC inhibitor reference compound or a combination of the two agents given at maximally tolerated doses (MTD). Furthermore, CUDC-907 is more efficacious than the PI3Kδ-selective inhibitor CAL-101 when dosed at MTD doses. [1]

Animal Research Animal Models NHL and MM models in mice
Dosages 100 mg/kg
Administration Administered via p.o.
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
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

Chemical Information & Solubility

Molecular Weight 508.55 Formula

C23H24N8O4S

CAS No. 1339928-25-4 SDF Download Fimepinostat (CUDC-907) SDF
Smiles CN(CC1=CC2=C(S1)C(=NC(=N2)C3=CN=C(C=C3)OC)N4CCOCC4)C5=NC=C(C=N5)C(=O)NO
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 102 mg/mL ( (200.57 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble


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In vivo
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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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Frequently Asked Questions

Question 1:
How to solve CUDC-907 for in vivo studies (p.o.)?

Answer:
If you decided to take P.O. as your administration route, we suggest you to use 1% CMC-Na to dilute CUDC-907 as a suspension solution for gavage.

Question 2:
What is the half-life of CUDC-907 in vivo?

Answer:
GUDC-907 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.

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