Fimepinostat (CUDC-907)

For research use only.

Catalog No.S2759

28 publications

Fimepinostat (CUDC-907) Chemical Structure

CAS No. 1339928-25-4

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.

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Selleck's Fimepinostat (CUDC-907) has been cited by 28 publications

Purity & Quality Control

Choose Selective HDAC Inhibitors

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)
1.7 nM 1.8 nM 2.8 nM 5.0 nM 5.4 nM
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]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
human Glioma cells (HF2885) M164cGN6fG:2b4jpZ4l1gSCjc4PhfS=> NVjyd3hHPzJiaB?= NGDTNWJEgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBIdGmxbXGgZ4VtdHNiKFjGNlg5PSliYX\0[ZIhPzJiaILzJIJ6KEOnbHz0bZRmekeubzDhd5NigSxiRVO1NF0xNjdibl2= M2\STlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4Mki4Olk6Lz5{NkK4PFY6QTxxYU6=
human Glioma cells (HF3013) MXvDfZRwfG:6aXPpeJkh[XO|YYm= M3TvRVczKGh? M3nRSGN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJGdtcW:vYTDj[YxteyBqSF[zNFE{MSCjZoTldkA4OiCqcoOgZpkhS2WubITpeIVzT2yxIHHzd4F6NCCHQ{WwQVAvPyCwTR?= NGr5U3A9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NkK4PFY6QSd-Mk[yPFg3QTl:L3G+
human Glioma cells (HF2876)  MVLDfZRwfG:6aXPpeJkh[XO|YYm= NEPMS|k4OiCq NE\0SpdEgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBIdGmxbXGgZ4VtdHNiKFjGNlg4PiliYX\0[ZIhPzJiaILzJIJ6KEOnbHz0bZRmekeubzDhd5NigSxiRVO1NF0xNjdibl2= NYXrfpdXRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[yPFg3QTlpPkK2Nlg5Pjl7PD;hQi=>
human Glioma cells (HF2790)  MoizR5l1d3SxeHnjbZR6KGG|c3H5 MmfuO|IhcA>? MXzDfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDHcIlwdWFiY3XscJMhMEiIMke5NEkh[W[2ZYKgO|IhcHK|IHL5JGNmdGy2aYTldmdtdyCjc4PhfUwhTUN3ME2wMlchdk1? MnS5QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZ{OEi2PVkoRjJ4Mki4Olk6RC:jPh?=
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human Glioma cells (HF2381) M{Xi[WN6fG:2b4jpZ4l1gSCjc4PhfS=> NXznXVQ3PzJiaB?= M{LsNmN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJGdtcW:vYTDj[YxteyBqSF[yN|gyMSCjZoTldkA4OiCqcoOgZpkhS2WubITpeIVzT2yxIHHzd4F6NCCHQ{WwQVAvPyCwTR?= NXPHZohFRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[yPFg3QTlpPkK2Nlg5Pjl7PD;hQi=>
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DU145 NVr6doQ6SW62aYDyc4xq\mW{YYTpeoUh[XO|YYm= M2LXb|k3KGi{cx?= MnfIRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6|dDDoeY1idiCGVUG0OUBk\WyuczDh[pRmeiB7NjDodpMh[nliTWTUJIF{e2G7LDC9NE42Ps7:TT6= NVvtfHliRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxM{GxNVc2OTdpPkOxNVE4PTF5PD;hQi=>
HuH7 MUHBcpRqeHKxbHnm[ZJifGm4ZTDhd5NigQ>? NF\QZ4I6PiCqcoO= M3zzOWFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iSIXIO{Bk\WyuczDh[pRmeiB7NjDodpMh[nliTWTUJIF{e2G7LDC9NE42Ps7:TT6= MYC8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8{OTFzN{WxO{c,OzFzMUe1NVc9N2F-
MV4-11 NGPNenFCdnSrcILvcIln\XKjdHn2[UBie3OjeR?= MoPvNlUhfG9iNUCgcm0> NX\odFg2PzJiaILz Mnf6RY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6|dDDoeY1idiCPVkStNVEh[2WubIOgZZN{\XO|ZXSgZZMhemWmdXP0bY9vKGmwIHPlcIwhfmmjYnnsbZR6KGG2IEK1JJRwKDVyIH7NJIFnfGW{IEeyJIhzeyCkeTD0dplxcGGwIHLseYUh[XO|YYm= M3\B[|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzN{MkGyO|MxLz5|MkKxNlc{ODxxYU6=

... Click to View More Cell Line Experimental Data

Assay
Methods Test Index PMID
Western blot
AKT / p-AKT / P-p70S6K1 / Ac-H3K9 / p-MEK / p-ERK / p-STAT3 / MCL-1 / Bcl-2 / Bcl-xl / PARP; 

PubMed: 30353642     


Western blots showing protein expression in lysates of MEC-1 cells treated with CUDC-907 at various concentrations or DMSO as a control (0) for 12 h. AKT, p-AKT (Ser473), p-p70S6K (Thr389), Ac-H3K9, ERK, p-ERK (Thr202/Tyr204), p-MEK (Ser217/221), STAT3, p-STAT3 (Tyr705), MCL-1, BCL-2, BCL-xL, and PARP were detected with specific antibodies. β-actin was used as a loading control. 

p-PRAS40 / p-4EBP1 / p-S6 / c-Myc / Cleaved PARP / Caspase-3 / Celaved caspase-3 ; 

PubMed: 28147336     


Western blot analysis demonstrating the effect of increasing concentration of CUDC-907 (from 0.01 to 1 μM) on PI3K downstream targets (p4EBP1, pPRAS40 and pS6) and histone H3 acetylation (Ac Histone H3). The actual inhibition of PI3K and HDAC resulted in a decrease in c-Myc protein levels. Activation of caspase 3 and PARP was present as well. 

SYK / BTK / Bcl-10 / MyD88 / IRAK4 ; 

PubMed: 28147336     


Western blot confirming the effect of CUDC-907 (0.1 μM for 24 hours) on BCR and TLR signaling proteins in B-cell lymphoma cell lines (GCB n = 3 and ABC n = 3).

30353642 28147336
Immunofluorescence
γ-H2AX / 53BP1; 

PubMed: 29760046     


Representative images and quantification of immunofluorescence staining for γH2AX and 53BP1 in SF188 cells treated with radiotherapy (4 Gy), CUDC-907 (100 nmol/L), or combination treatment in which radiotherapy was combined with KU70 siRNA, RAD51 siRNA (48 hours after siRNA transfection), or CUDC-907 (16 hours prior to 4 Gy).

RAD51; 

PubMed: 29760046     


Representative images and quantification of immunofluorescence staining for γH2AX and RAD51 in SF188 cells treated with radiotherapy (4 Gy), CUDC-907 (100 nmol/L), or combination treatment in which radiotherapy was combined with KU70 siRNA, RAD51 siRNA (48 hours after siRNA transfection), or CUDC-907 (16 hours prior to 4 Gy).

29760046
Growth inhibition assay
Cell viability; 

PubMed: 28147336     


MTS assay of 8 representative DLBCL and 2 Hodgkin lymphoma cell lines treated with increasing dose of CUDC-907 from 0.01 to 10 μM for 24, 48, 72 hours. Error bars represent standard error of the mean (S.E.M) of triplicate experiments. 

28147336
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]

Protocol

Animal Research:

[1]

- Collapse
  • Animal Models: NHL and MM models in mice
  • Dosages: 100 mg/kg
  • Administration: Administered via p.o.
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 102 mg/mL (200.57 mM)
Water Insoluble
Ethanol Insoluble

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 508.55
Formula

C23H24N8O4S

CAS No. 1339928-25-4
Storage powder
in solvent
Synonyms 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

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
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Step 2: Enter the in vivo formulation ()
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Bio Calculators

Molarity Calculator

Molarity Calculator

Calculate the mass, volume or concentration required for a solution. The Selleck molarity calculator is based on the following equation:

Mass (mg) = Concentration (mM) × Volume (mL) × Molecular Weight (g/mol)

  • Mass
    Concentration
    Volume
    Molecular Weight

*When preparing stock solutions, please always use the batch-specific molecular weight of the product found on the via label and MSDS / COA (available on product pages).

Dilution Calculator

Dilution Calculator

Calculate the dilution required to prepare a stock solution. The Selleck dilution calculator is based on the following equation:

Concentration (start) x Volume (start) = Concentration (final) x Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2 ( Input Output )

  • C1
    V1
    C2
    V2

* When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and MSDS / COA (available online).

The Serial Dilution Calculator Equation

  • Serial Dilutions

  • Computed Result

  • 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):
Molecular Weight Calculator

Molecular Weight Calculator

Enter the chemical formula of a compound to calculate its molar mass and elemental composition:

Total Molecular Weight: g/mol

Tip: Chemical formula is case sensitive. C10H16N2O2 c10h16n2o2

Instructions to calculate molar mass (molecular weight) of a chemical compound:

To calculate molar mass of a chemical compound, please enter its chemical formula and click 'Calculate'.

Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molecular mass (molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

Molarity Calculator

Mass Concentration Volume Molecular Weight

Clinical Trial Information

NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT02909777 Recruiting Drug: CUDC-907 Lymphoma|Neuroblastoma|Brain Tumor|Solid Tumor Dana-Farber Cancer Institute|Curis Inc. October 2016 Phase 1
NCT02674750 Completed Drug: CUDC-907 Relapsed and/or Refractory Diffuse Large B-cell Lymphoma Including With Myc Alterations Curis Inc. January 2016 Phase 2
NCT02307240 Completed Drug: CUDC-907 Triple-Negative Breast Cancer|High-grade Serous Ovarian Cancer|Solid Tumors|NUT Midline Carcinoma Curis Inc. November 2014 Phase 1
NCT01742988 Completed Drug: fimepinostat|Drug: Rituximab|Drug: venetoclax 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

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

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

If you have any other enquiries, please leave a message.

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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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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID