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CUDC-907 Potent PI3K/HDAC inhibitor

Catalog No.A4097
Size Price Stock Qty
10mM (in 1mL DMSO)
$190.00
In stock
5mg
$170.00
In stock
10mg
$230.00
In stock
50mg
$650.00
In stock
200mg
$1,490.00
In stock

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Email: [email protected]

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Sample solution is provided at 25 µL, 10mM.

Quality Control

Chemical structure

CUDC-907

Biological Activity

Description CUDC-907 is a dual inhibitor of PI3K and HDAC with IC50 values of 19 nM, 1.7 nM, 5 nM, 1.8 nM and 2.8 nM for PI3Kα, HDAC1, 2, 3 and 10, respectively.
Targets PI3Kα HDAC1 HDAC2 HDAC3 HDAC10  
IC50 19 nM 1.7 nM 5 nM 1.8 nM 2.8 nM  

Protocol

Cell experiment [1]:

Cell lines

H460 cells

Preparation method

The solubility of this compound in DMSO is > 25.5 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C for several months.

Reacting condition

1 μM; 16 hrs

Applications

In H460 cells, CUDC-907 increased the levels of activated caspase-7, p21 and c-PARP. Meanwhile, CUDC-907 decreased the levels of BCL-2, BCL-xL and survivin.

Animal experiment [1]:

Animal models

Daudi NHL xenograft mouse model

Dosage form

25, 50 or 100 mg/kg; p.o.

Applications

In the Daudi NHL xenograft mouse model, CUDC-907 inhibited tumor growth in a dose-dependent manner. At the dose of 100 mg/kg, CUDC-907 resulted in tumor stasis without causing obvious toxicity.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

References:

[1]. Qian C, Lai CJ, Bao R, Wang DG, Wang J, Xu GX, Atoyan R, Qu H, Yin L, Samson M et al: Cancer network disruption by a single molecule inhibitor targeting both histone deacetylase activity and phosphatidylinositol 3-kinase signaling. Clin Cancer Res 2012, 18(15):4104-4113.

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Chemical Properties

Cas No. 1339928-25-4 SDF Download SDF
Chemical Name N-hydroxy-2-[[2-(6-methoxypyridin-3-yl)-4-morpholin-4-ylthieno[3,2-d]pyrimidin-6-yl]methyl-methylamino]pyrimidine-5-carboxamide
Canonical SMILES CN(CC1=CC2=C(S1)C(=NC(=N2)C3=CN=C(C=C3)OC)N4CCOCC4)C5=NC=C(C=N5)C(=O)NO
Formula C23H24N8O4S M.Wt 508.55
Solubility >25.5mg/mL in DMSO Storage Store at -20°C
Shipping Condition Evaluation sample solution : ship with blue ice.All other available size: ship with RT , or blue ice upon request
General tips For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.

Background

CUDC-907 is a dual-acting inhibitor of HDAC and PI3K with IC50 values of 1.7/5.0/1.8/2.8 nM (HDAC1/2/3/10) and 19/54/39 nM (PI3K).[1]

The phosphoinositide 3-kinases (PI3Ks) contain three classes of PI3K each with its own distinct lipid products and specific substrate. They are a family of lipid kinases that regulates a wide range of pathway by propagating intracellular signaling cascades. PI3K phosphorylates the 3’-OH group of phosphatidylinositols. This activated AKT, the protein Ser/Thr-kinase, by recruiting them to the cell membrane. The PI3K/AKT signaling pathway is critical in cancer, because it promotes cell growth and survival. The studies have proved that PI3K pathway plays an important role in cancer progression and treatment for lung cancers, breast cancer.[2, 3] Histone deacetylases (HDACs) and histone acetyltransferases (HATs) mediates the balance between histone deacetylation and acetylation. HDACs also regulate the acetylation status of signaling molecules, chaperones, and transcription factors that are non-histone proteins.[4]

CUDC-907 is a potent inhibitor of class I PI3K kinases and HDAC classes I and II enzymes. CUDC-907 resulted in increase of acetylated histones and non-histone proteins such as tubulin and p53. CUDC-907 also induced p21 protein in H460 cell lines. CUDC-907 dose-dependently decreases phosphorylation of AKT and its downstream targets, p70S6 and 4EBP-1 by inhibiting the PI3K pathway,, in H460 cells. CUDC-907 were able to inhibit the activation of MEK in cancer cell lines including NSCLC H460 cells, breast cancer BT-474 cells and NSCLC H1975 cells. CUDC-907 suppresses the RAF- MEK-MAPK signaling pathway through HDAC inhibition. CUDC-907 can also cause the decrease of both p-SRC) and p-SRC in RPMI-8226 multiple myeloma cells. CUDC-907 induced cell-cycle arrest at G2–M phase at the dose of 1 μM for 24h.[1]

CUDC-907 inhibited growth of the tumor in Daudi cancer cell xenografts dose-dependently. In a xenograft tumor model of DLBCL (SU-DHL4 diffuselarge B-cell lymphoma) CUDC-907 induced tumor regression after oral administration (100 mg/kg) or intravenous (50 mg/kg). CUDC-907 also caused tumor stasis in NSCLC cell xenografts [1].

References:
[1].  Qian C, Lai CJ, Bao R, Wang DG, Wang J, Xu GX, Atoyan R, Qu H, Yin L, Samson M et al: Cancer network disruption by a single molecule inhibitor targeting both histone deacetylase activity and phosphatidylinositol 3-kinase signaling. Clin Cancer Res 2012, 18(15):4104-4113.
[2].  Wong KK, Engelman JA, Cantley LC: Targeting the PI3K signaling pathway in cancer. Curr Opin Genet Dev 2010, 20(1):87-90.
[3].  Engelman JA: Targeting PI3K signalling in cancer: opportunities, challenges and limitations. Nat Rev Cancer 2009, 9(8):550-562.
[4].  Kim HJ, Bae SC: Histone deacetylase inhibitors: molecular mechanisms of action and clinical trials as anti-cancer drugs. Am J Transl Res 2011, 3(2):166-179.