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Purity: ≥98%
Fimepinostat (also known as CUDC-907) is a potent, orally bioavailable, and small molecule dual inhibitor of PI3K and HDAC (PI3Kα and HDAC1/2/3/10) with potential anticancer activity. Its IC50 values for PI3Kα and HDAC1/2/3/10 are 19 nM for PI3K and 1.7 nM/5 nM/1.8 nM/2.8 nM for HDAC1/2/3/10, respectively. A Phase 2 clinical trial for the treatment of patients with relapsed, refractory diffuse large B-cell lymphoma (DLBCL) and a Phase 1 trial for patients with solid tumors are both being conducted by Curis.
| Targets |
PI3Kα (IC50 = 19 nM); PI3Kδ (IC50 = 39 nM); PI3Kβ (IC50 = 54 nM); PI3Kγ (IC50 = 311 nM); HDAC1 (IC50 = 1.7 nM); HDAC3 (IC50 = 1.8 nM); HDAC10 (IC50 = 2.8 nM); HDAC2 (IC50 = 5 nM); HDAC11 (IC50 = 5.4 nM); HDAC6 (IC50 = 27 nM); HDAC8 (IC50 = 191 nM); HDAC4 (IC50 = 409 nM); HDAC7 (IC50 = 426 nM); HDAC9 (IC50 = 554 nM); HDAC5 (IC50 = 674 nM)
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| ln 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. Additionally, CUDC-907 inhibits HDAC subtypes HDAC8, HDAC6, and HDAC11 with respective IC50 values of 191 nM, 27 nM, and 5.4 nM.[1] CUDC-907 blocks less potent forms of HDAC enzymatic activity. 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]
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| ln Vivo |
CUDC-907 has a long half-life in murine tumors. CUDC-907 induces apoptosis and inhibits cancer cell proliferation in xenograft tumors. [1]
CUDC-907 outperforms single-agent PI3K or HDAC inhibitor reference compounds as well as a combination of the two agents when given at maximally tolerated doses (MTD) in efficacy studies in NHL and MM models. Furthermore, when administered at MTD doses, CUDC-907 outperforms the PI3K-selective inhibitor CAL-101 in terms of effectiveness. [1]
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| Enzyme Assay |
The activities of classes I and II HDACs are measured using the Color-de-Lys assay system. The activity of PI3K is measured using the ADP-Glo luminescent kinase assay. In an expression system for Sf9 cells that has been infected with a baculovirus, recombinant PI3K protein is coexpressed as a complex of N-terminal GST-tagged recombinant full-length human p110 and untagged recombinant full-length human p85[1].
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| Cell Assay |
In 96-well flat-bottomed plates with the suggested culture medium, human cancer cell lines are plated at densities ranging from 5,000 to 10,000 per well. The cells are then exposed to substances (like Fimepinostat) in a culture medium that has been supplemented with 0.5% (v/v) FBS for 72 hours. The Perkin-Elmer ATPlite kit is used to measure the amount of cellular ATP to determine the degree of growth inhibition[1].
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| Animal Protocol |
Mice[1]: Right hind flank tissue of six to eight-week-old female nude nu/nu CD-1 or severe combined immunodeficient (SCID) mice obtained from Charles River Laboratories is subcutaneously injected with 3 to 20 106 cells in a medium suspension of 100 to 200 L. Depending on the indication, different dosages of Fimepinostat, common anticancer medications, or a vehicle are given orally or by injection into the tail vein.
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| References |
| Molecular Formula |
C23H24N8O4S
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|---|---|
| Molecular Weight |
508.5529
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| Exact Mass |
508.16412
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| Elemental Analysis |
C, 54.32; H, 4.76; N, 22.03; O, 12.58; S, 6.31
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| CAS # |
1339928-25-4
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| Related CAS # |
1401998-36-4 (mesylate);1339928-25-4;
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| Appearance |
Solid powder
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| SMILES |
CN(CC1=CC2=C(S1)C(=NC(=N2)C3=CN=C(C=C3)OC)N4CCOCC4)C5=NC=C(C=N5)C(=O)NO
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| InChi Key |
JOWXJLIFIIOYMS-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C23H24N8O4S/c1-30(23-25-11-15(12-26-23)22(32)29-33)13-16-9-17-19(36-16)21(31-5-7-35-8-6-31)28-20(27-17)14-3-4-18(34-2)24-10-14/h3-4,9-12,33H,5-8,13H2,1-2H3,(H,29,32)
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| 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
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| Synonyms |
Fimepinostat; CUDC907; CUDC 907; CUDC-907
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: ~102 mg/mL (~200.6 mM)
Water: <1 mg/mL Ethanol: <1 mg/mL |
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9664 mL | 9.8319 mL | 19.6637 mL | |
| 5 mM | 0.3933 mL | 1.9664 mL | 3.9327 mL | |
| 10 mM | 0.1966 mL | 0.9832 mL | 1.9664 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Status | Interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT02909777 | Active Recruiting |
Drug: CUDC-907 | Lymphoma Neuroblastoma |
Dana-Farber Cancer Institute | October 2016 | Phase 1 |
| NCT03893487 | Active Recruiting |
Drug: Fimepinostat | Recurrent Glioblastoma | Sabine Mueller, MD, PhD | August 7, 2019 | Early Phase 1 |
| NCT01742988 | Completed | Drug: Rituximab Drug: venetoclax |
Lymphoma Relapsed Lymphoma |
Curis, Inc. | December 2012 | Phase 1 |
| NCT02307240 | Completed | Drug: CUDC-907 | Solid Tumors NUT Midline Carcinoma |
Curis, Inc. | November 2014 | Phase 1 |
CUDC-907 design and its potency against PI3K and HDAC.Clin Cancer Res.2012 Aug 1;18(15):4104-13.
CUDC-907 evades drug resistance and induces apoptosis and G2–M phase cell-cycle arrest.Clin Cancer Res.2012 Aug 1;18(15):4104-13. |
CUDC-907 durably suppresses activation of AKT and modulates receptor tyrosine kinase, RAF-MEK-MAPK and SRC/STAT signaling.Clin Cancer Res.2012 Aug 1;18(15):4104-13. |
CUDC-907 suppresses tumor growth, inhibits HDAC activity, and blocks signaling of PI3K and MAPK pathways in xenograft models.Clin Cancer Res.2012 Aug 1;18(15):4104-13. |
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