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Chemical Structure| 783355-60-2 Chemical Structure| 783355-60-2

Structure of Abexinostat
CAS No.: 783355-60-2

Chemical Structure| 783355-60-2

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PCI-24781 is a pan-HDAC inhibitor mostly targeting HDAC1 with Ki of 7 nM, modest potent to HDACs 2, 3, 6, and 10 and greater than 40-fold selectivity against HDAC8.

Synonyms: Pci-24781; CRA 024781; CRA-24781

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Product Details of Abexinostat

CAS No. :783355-60-2
Formula : C21H23N3O5
M.W : 397.42
SMILES Code : O=C(C1=C(CN(C)C)C2=CC=CC=C2O1)NCCOC3=CC=C(C(NO)=O)C=C3
Synonyms :
Pci-24781; CRA 024781; CRA-24781
MDL No. :MFCD10565969
InChI Key :MAUCONCHVWBMHK-UHFFFAOYSA-N
Pubchem ID :11749858

Safety of Abexinostat

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Related Pathways of Abexinostat

epigenetics

Isoform Comparison

Biological Activity

Target
  • HDAC8

    HDAC8, IC50:280 nM

  • HDAC10

    HDAC10, IC50:24 nM

  • HDAC3

    HDAC3/SMRT, Ki:8.2 nM

  • HDAC6

    HDAC6, Ki:17 nM

In Vitro:

Cell Line
Concentration Treated Time Description References
Human CD34+ cells 10 to 100 nM 24 hours Abexinostat inhibited CFU-MK growth, megakaryocyte (MK) proliferation and differentiation. These effects required only a short incubation period. Cell Death Dis. 2013 Jul 25;4(7):e738.
Human skeletal (mesenchymal) stem cells (hMSCs) 500 nM 24 hours Abexinostat promoted adipocytic differentiation of hMSCs by inducing the expression of several proadipocytic genes and significantly increasing the enrichment of the H3K9Ac epigenetic mark on the promoter regions of AdipoQ, FABP4, PPARγ, KLF15, CEBPA, SP7, and ALPL. Stem Cells Transl Med. 2016 Aug;5(8):1036-47.
HCT116 colon cancer cells 0.2 µM, 0.5 µM, 1.0 µM 24 hours To measure the effect of PCI-24781 on RAD51 protein levels, results showed a significant decrease in RAD51 protein levels by 24 hours. Proc Natl Acad Sci U S A. 2007 Dec 4;104(49):19482-7.
MDA-MB-231 30 µM 48 hours To screen for epigenetic small molecule inhibitors with anti-tumor activity Theranostics. 2021 Jan 1;11(5):2058-2076.
Ramos cells 0.5 µM to 2.0 µM 48 hours PCI-24781 induced concentration-dependent apoptosis in Ramos cells with an IC50 of 0.5 μM Clin Cancer Res. 2009 May 15;15(10):3354-65.
SUDHL4 cells 0.5 µM to 2.0 µM 48 hours PCI-24781 induced concentration-dependent apoptosis in SUDHL4 cells with an IC50 of 0.8 μM Clin Cancer Res. 2009 May 15;15(10):3354-65.
HF1 cells 0.5 µM to 2.0 µM 48 hours PCI-24781 induced concentration-dependent apoptosis in HF1 cells with an IC50 of 0.9 μM Clin Cancer Res. 2009 May 15;15(10):3354-65.
L428 cells 0.5 µM to 2.0 µM 48 hours PCI-24781 induced concentration-dependent apoptosis in L428 cells with an IC50 of 1.4 μM Clin Cancer Res. 2009 May 15;15(10):3354-65.
U87 0.5–1.25 µM 48 hours To evaluate the inhibitory effect of PCI-24781 on GBM cell proliferation, results showed that PCI-24781 significantly inhibited the proliferation of U87 cells. J Exp Clin Cancer Res. 2021 Oct 25;40(1):335.
U251 0.5–1.25 µM 48 hours To evaluate the inhibitory effect of PCI-24781 on GBM cell proliferation, results showed that PCI-24781 significantly inhibited the proliferation of U251 cells. J Exp Clin Cancer Res. 2021 Oct 25;40(1):335.
U-118MG 0.5–1.25 µM 48 hours To evaluate the inhibitory effect of PCI-24781 on GBM cell proliferation, results showed that PCI-24781 significantly inhibited the proliferation of U-118MG cells. J Exp Clin Cancer Res. 2021 Oct 25;40(1):335.
DRAA8/CHO cells 2.0 µM, 3.0 µM 6 hours To determine the effect of PCI-24781 on homologous recombinational repair, results showed that 2.0 µM and 3.0 µM PCI-24781 reduced the recombination frequency to 0.27% and 0.16%, respectively. Proc Natl Acad Sci U S A. 2007 Dec 4;104(49):19482-7.
MDA-MB-231 3 µM 72 hours To screen for inhibitors that can kill cancer cells with high efficiency Theranostics. 2021 Jan 1;11(5):2058-2076.
MDA-MB-231 0.3 µM and 0.15 µM 72 hours To explore the most effective inhibitor at a low dose Theranostics. 2021 Jan 1;11(5):2058-2076.

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Mice GBM mouse model Oral 12.5 mg/kg BID, 5 days a week for 4 weeks To evaluate the inhibitory effect of PCI-24781 on GBM tumor growth in vivo, results showed that PCI-24781 significantly reduced tumor burden and increased survival. J Exp Clin Cancer Res. 2021 Oct 25;40(1):335.
BALB/c Nude mice HCT116 colon cancer xenograft model Oral 200 mg/kg 1×, 2×, or 3× over 4, 22, and 28 hours, respectively To examine the effect of PCI-24781 on RAD51 protein levels in tumors, results showed a 69% decrease in RAD51 protein levels after 3 doses over 28 hours. Proc Natl Acad Sci U S A. 2007 Dec 4;104(49):19482-7.
Nude mice MDA-MB-231 xenograft model Intravenous injection 50 mg/kg Every other day for four weeks To evaluate the anti-tumor effect of PCI-24781 in vivo Theranostics. 2021 Jan 1;11(5):2058-2076.
Rats Sprague-Dawley rats Oral 8.00 mg/kg Single dose To study the pharmacokinetic properties of Abexinostat in rats, the results showed that after oral administration, the absorption was rapid, the maximum plasma concentration (Cmax) was 28.20 ± 7.67 ng/mL, the time to peak (Tmax) was about 1.39 ± 1.29 h, and the half-life (t1/2) was 13.80 ± 2.50 h. BMC Chem. 2024 Feb 20;18(1):37

Clinical Trial:

NCT Number Conditions Phases Recruitment Completion Date Locations
NCT03934567 Lymphoma, Follicular PHASE2 RECRUITING 2024-09-30 Cancer Hospital Chinese Academ... More >>y of Medical Sciences, Beijing, 100021, China|China-Japan Friendship Hospital, Beijing, 100029, China|Peking University Third Hospital, Beijing, 100191, China|Jilin Cancer Hospital, Changchun, 130012, China|West China Hospital, Sichuan University, Chengdu, 610041, China|The First Affiliated Hospital of Dalian Medical University, Dalian, 116011, China|Fujian Medical University Union Hospital, Fuzhou, 350001, China|Cancer Center of Guangzhou Medical University, Guangzhou, 510030, China|Sun Yai-Sen Memorial Hospital, Sun Yai-Sen University, Guangzhou, 510120, China|Nanfang Hospital, Guangzhou, 510515, China|Hainan General Hospital, Hainan, 570311, China|The Second Affiliated Hospital Zhejiang University School of Medicine, Hangzhou, 310009, China|Sir Run Run Shaw Hospital, Zhejiang University School of Medical, Hangzhou, 310020, China|Zhejiang Cancer Hospital, Hangzhou, 310022, China|The Affiliated Tumor Hospital of Harbin Medical University, Harbin, 150081, China|The First Hospital of Lanzhou University, Lanzhou, 730000, China|Linyi Cancer Hospital, Linyi, 276000, China|Nantong Tumor Hospital, Nantong, 226361, China|Shanghai Sixth people's hospital, Shanghai, 200025, China|Fudan University Shanghai Cancer Center, Shanghai, 200032, China|The Forth Hospital of Hebei Medical University, Shijiazhuang, 050011, China|Tianjin People's Hospital, Tianjin, 300000, China|Tianjin Medical University General Hospital, Tianjin, 300052, China|The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221006, China|Henan Cancer Hospital, Zhengzhou, 450008, China|The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China Less <<
NCT04024696 Non Hodgkin Lymphoma PHASE1|PHASE2 ACTIVE_NOT_RECRUITING 2024-06-30 Cancer Hospital Chinese Academ... More >>y of Medical Sciences, Beijing, 100021, China|Zhejiang Cancer Hospital, Hangzhou, 310022, China|Tianjin Medical University General Hospital, Tianjin, 300052, China|The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221006, China Less <<
NCT03600441 Follicular Lymphoma PHASE2 ACTIVE_NOT_RECRUITING 2025-12-31 Advocate Medical Group - Park ... More >>Ridge, Luther Lane - Oncology, Park Ridge, Illinois, 60068, United States|Norton Cancer Institute - St. Matthews Campus, Louisville, Kentucky, 40207, United States|Clinical Research Alliance Inc, Lake Success, New York, 11042, United States|Manhattan Hematology Oncology Center, New York, New York, 10016, United States|Memorial Sloan Kettering Cancer Center, New York, New York, 10065, United States|Bone Marrow Transplant Hematology Oncology Associates, Pittsburgh, Pennsylvania, 15224-2156, United States|Arlington Cancer Center, Arlington, Texas, 76012, United States|Central Texas Veterans Health Care System - NAVREF, Temple, Texas, 76504, United States|Vista Oncology Inc. PS, Olympia, Washington, 98506, United States|Centre Hospitalier de Perpignan, Perpignan, Pyrénées-Orientales, 66046, France|Hospital Universitario de Donostia, Donostia-San Sebastián, Guipúzcoa, 20014, Spain|Hospital Universitario Vall d'Hebrón, Barcelona, 08035, Spain|Hospital del Mar, Barcelona, 28229, Spain|C.H. Regional Reina Sofia, Córdoba, 14004, Spain|Hospital Universitario Infanta Leonor, Madrid, 28031, Spain Less <<
NCT00473577 Hematologic Neoplasms|Neoplasm... More >>s Less << PHASE1 COMPLETED 2025-12-07 University of Chicago, Chicago... More >>, Illinois, 60643, United States Less <<

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.52mL

0.50mL

0.25mL

12.58mL

2.52mL

1.26mL

25.16mL

5.03mL

2.52mL

Dissolving Methods
The prepared working fluid is recommended to be prepared now and used up as soon as possible in a short period of time. The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1

References

 

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