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MedKoo Cat#: 202170 | Name: Abexinostat
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

Abexinostat, also known as PCI-24781 or CRA-024781, is novel, broad-spectrum hydroxamic acid-based inhibitor of histone deacetylase (HDAC) with potential antineoplastic activity. Abexinostat inhibits several isoforms of HDAC, resulting in an accumulation of highly acetylated histones, followed by the induction of chromatin remodeling; the selective transcription of tumor suppressor genes; and the tumor suppressor protein-mediated inhibition of tumor cell division and induction of tumor cell apoptosis.

Chemical Structure

Abexinostat
Abexinostat
CAS#783355-60-2 (free base)

Theoretical Analysis

MedKoo Cat#: 202170

Name: Abexinostat

CAS#: 783355-60-2 (free base)

Chemical Formula: C21H23N3O5

Exact Mass: 397.1638

Molecular Weight: 397.42

Elemental Analysis: C, 63.46; H, 5.83; N, 10.57; O, 20.13

Price and Availability

Size Price Availability Quantity
10mg USD 150.00 Ready to ship
25mg USD 250.00 Ready to ship
50mg USD 400.00 Ready to ship
100mg USD 700.00 Ready to ship
200mg USD 1,250.00 Ready to ship
500mg USD 2,450.00 Ready to ship
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Related CAS #
783356-67-2 (HCl) 783355-60-2 (free base)
Synonym
CRA-024781; CRA 024781; CRA024781; PCI24781; PCI-24781; PCI 24781; Abexinostat.
IUPAC/Chemical Name
3-(dimethylaminomethyl)-N-[2-[4-(hydroxycarbamoyl)phenoxy]ethyl]-1-benzofuran-2-carboxamide
InChi Key
MAUCONCHVWBMHK-UHFFFAOYSA-N
InChi Code
InChI=1S/C21H23N3O5/c1-24(2)13-17-16-5-3-4-6-18(16)29-19(17)21(26)22-11-12-28-15-9-7-14(8-10-15)20(25)23-27/h3-10,27H,11-13H2,1-2H3,(H,22,26)(H,23,25)
SMILES Code
O=C(C(O1)=C(CN(C)C)C2=C1C=CC=C2)NCCOC3=CC=C(C(NO)=O)C=C3
Appearance
white to off-white solid powder
Purity
>96% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, not in water
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
   
Biological target:
Abexinostat (CRA 024781) is a pan-HDAC inhibitor mostly targeting HDAC1 with Ki of 7 nM.
In vitro activity:
Abexinostat enhanced both osteoblast and adipocyte differentiation, and thus it is plausible that it targets the initial phase of commitment of hMSCs to both adipocytic and osteoblastic lineages. The previously mentioned and discussed data from DNA microarrays and ChIP-seq corroborate this hypothesis because they clearly demonstrate the induction of multiple gene and genetic pathways associated with hMSC lineage commitment. This hypothesis and its potential molecular mechanism are illustrated in the current working model (Fig. 6). Interestingly, despite marked global increase in H3K9Ac, this study observed overall fewer enriched genes in the abexinostat-treated cells compared with the control (Fig. 4D). Therefore, it seems as if abexinostat is targeting specific genomic regions, which normally have low H3K9Ac, including those related to hMSC differentiation. On the other hand, genes with high basal H3K9ac signal are not benefiting much from abexinostat. Thus, acetylation marks appear to be being diverged from genes with high basal H3K9Ac signal (such as GAPDH) to those with low basal H3K9Ac signal (such as CEBPA, PPARγ, SP7, and ALPL). Nonetheless, a plausible role for abexinostat in targeting non-H3K9 residues for acetylation or the increase in hMSC commitment could also contribute to the observed phenotype. Reference: Stem Cells Transl Med. 2016 Aug; 5(8): 1036–1047. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4954455/
In vivo activity:
An in vivo therapeutic study in BK5.erbB2 mice showed that GBCas sensitive to PCI-24781 treatment (diagnosed as PR (Partial Response)) had greatly reduced levels of p-erbB2 and total erbB2 compared to GBCas refractory to treatment (diagnosed as PG (Progressive Disease)). These results indicate that the inhibitory effect of PCI-24781 was not potent enough to reduce the levels of p-erbB2 and total erbB2 in the PG cases. This hypothesis is supported by results showing that the level of erbB2 mRNA was significantly decreased in gallbladders diagnosed as PR, but not in those diagnosed as PG (Fig. 2). Reference: J Hepatol. 2012 Jul; 57(1): 84–91. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3378818/
Solvent mg/mL mM
Solubility
DMSO 16.7 41.95
DMF 50.0 125.81
DMF:PBS (pH 7.2) (1:3) 0.1 0.25
Ethanol 3.0 7.55
5% TFA 3.0 7.55
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 397.42 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
1. Ali D, Hamam R, Alfayez M, Kassem M, Aldahmash A, Alajez NM. Epigenetic Library Screen Identifies Abexinostat as Novel Regulator of Adipocytic and Osteoblastic Differentiation of Human Skeletal (Mesenchymal) Stem Cells. Stem Cells Transl Med. 2016 Aug;5(8):1036-47. doi: 10.5966/sctm.2015-0331. Epub 2016 May 18. PMID: 27194745; PMCID: PMC4954455. 2. Bhalla S, Evens AM, Prachand S, Schumacker PT, Gordon LI. Paradoxical regulation of hypoxia inducible factor-1α (HIF-1α) by histone deacetylase inhibitor in diffuse large B-cell lymphoma. PLoS One. 2013 Nov 27;8(11):e81333. doi: 10.1371/journal.pone.0081333. PMID: 24312289; PMCID: PMC3842257. 3. Salvador MA, Wicinski J, Cabaud O, Toiron Y, Finetti P, Josselin E, Lelièvre H, Kraus-Berthier L, Depil S, Bertucci F, Collette Y, Birnbaum D, Charafe-Jauffret E, Ginestier C. The histone deacetylase inhibitor abexinostat induces cancer stem cells differentiation in breast cancer with low Xist expression. Clin Cancer Res. 2013 Dec 1;19(23):6520-31. doi: 10.1158/1078-0432.CCR-13-0877. Epub 2013 Oct 18. PMID: 24141629. 4. Kitamura T, Connolly K, Ruffino L, Ajiki T, Lueckgen A, DiGiovanni J, Kiguchi K. The therapeutic effect of histone deacetylase inhibitor PCI-24781 on gallbladder carcinoma in BK5.erbB2 mice. J Hepatol. 2012 Jul;57(1):84-91. doi: 10.1016/j.jhep.2012.01.018. Epub 2012 Feb 9. PMID: 22326466; PMCID: PMC3378818.
In vitro protocol:
1. Ali D, Hamam R, Alfayez M, Kassem M, Aldahmash A, Alajez NM. Epigenetic Library Screen Identifies Abexinostat as Novel Regulator of Adipocytic and Osteoblastic Differentiation of Human Skeletal (Mesenchymal) Stem Cells. Stem Cells Transl Med. 2016 Aug;5(8):1036-47. doi: 10.5966/sctm.2015-0331. Epub 2016 May 18. PMID: 27194745; PMCID: PMC4954455. 2. Bhalla S, Evens AM, Prachand S, Schumacker PT, Gordon LI. Paradoxical regulation of hypoxia inducible factor-1α (HIF-1α) by histone deacetylase inhibitor in diffuse large B-cell lymphoma. PLoS One. 2013 Nov 27;8(11):e81333. doi: 10.1371/journal.pone.0081333. PMID: 24312289; PMCID: PMC3842257.
In vivo protocol:
1. Salvador MA, Wicinski J, Cabaud O, Toiron Y, Finetti P, Josselin E, Lelièvre H, Kraus-Berthier L, Depil S, Bertucci F, Collette Y, Birnbaum D, Charafe-Jauffret E, Ginestier C. The histone deacetylase inhibitor abexinostat induces cancer stem cells differentiation in breast cancer with low Xist expression. Clin Cancer Res. 2013 Dec 1;19(23):6520-31. doi: 10.1158/1078-0432.CCR-13-0877. Epub 2013 Oct 18. PMID: 24141629. 2. Kitamura T, Connolly K, Ruffino L, Ajiki T, Lueckgen A, DiGiovanni J, Kiguchi K. The therapeutic effect of histone deacetylase inhibitor PCI-24781 on gallbladder carcinoma in BK5.erbB2 mice. J Hepatol. 2012 Jul;57(1):84-91. doi: 10.1016/j.jhep.2012.01.018. Epub 2012 Feb 9. PMID: 22326466; PMCID: PMC3378818.
1: De Souza C, Chatterji BP. HDAC Inhibitors as Novel Anti-Cancer Therapeutics. Recent Pat Anticancer Drug Discov. 2015;10(2):145-62. doi: 10.2174/1574892810666150317144511. PMID: 25782916. 2: Rivera S, Leteur C, Mégnin F, Law F, Martins I, Kloos I, Depil S, Modjtahedi N, Perfettini JL, Hennequin C, Deutsch E. Time dependent modulation of tumor radiosensitivity by a pan HDAC inhibitor: abexinostat. Oncotarget. 2017 Jan 25;8(34):56210-56227. doi: 10.18632/oncotarget.14813. PMID: 28915585; PMCID: PMC5593556. 3: Ali D, Hamam R, Alfayez M, Kassem M, Aldahmash A, Alajez NM. Epigenetic Library Screen Identifies Abexinostat as Novel Regulator of Adipocytic and Osteoblastic Differentiation of Human Skeletal (Mesenchymal) Stem Cells. Stem Cells Transl Med. 2016 Aug;5(8):1036-47. doi: 10.5966/sctm.2015-0331. Epub 2016 May 18. PMID: 27194745; PMCID: PMC4954455. 4: Choy E, Flamand Y, Balasubramanian S, Butrynski JE, Harmon DC, George S, Cote GM, Wagner AJ, Morgan JA, Sirisawad M, Mani C, Hornicek FJ, Duan Z, Demetri GD. Phase 1 study of oral abexinostat, a histone deacetylase inhibitor, in combination with doxorubicin in patients with metastatic sarcoma. Cancer. 2015 Apr 15;121(8):1223-30. doi: 10.1002/cncr.29175. Epub 2014 Dec 23. PMID: 25536954; PMCID: PMC4393337. 5: Salvador MA, Wicinski J, Cabaud O, Toiron Y, Finetti P, Josselin E, Lelièvre H, Kraus-Berthier L, Depil S, Bertucci F, Collette Y, Birnbaum D, Charafe- Jauffret E, Ginestier C. The histone deacetylase inhibitor abexinostat induces cancer stem cells differentiation in breast cancer with low Xist expression. Clin Cancer Res. 2013 Dec 1;19(23):6520-31. doi: 10.1158/1078-0432.CCR-13-0877. Epub 2013 Oct 18. PMID: 24141629. 6: Markozashvili D, Pichugin A, Barat A, Camara-Clayette V, Vasilyeva NV, Lelièvre H, Kraus-Berthier L, Depil S, Ribrag V, Vassetzky Y. Histone deacetylase inhibitor abexinostat affects chromatin organization and gene transcription in normal B cells and in mantle cell lymphoma. Gene. 2016 Apr 15;580(2):134-143. doi: 10.1016/j.gene.2016.01.017. Epub 2016 Jan 13. PMID: 26774800. 7: Vey N, Prebet T, Thalamas C, Charbonnier A, Rey J, Kloos I, Liu E, Luan Y, Vezan R, Graef T, Recher C. Phase 1 dose-escalation study of oral abexinostat for the treatment of patients with relapsed/refractory higher-risk myelodysplastic syndromes, acute myeloid leukemia, or acute lymphoblastic leukemia. Leuk Lymphoma. 2017 Aug;58(8):1880-1886. doi: 10.1080/10428194.2016.1263843. Epub 2016 Dec 2. PMID: 27911138. 8: Gressette M, Vérillaud B, Jimenez-Pailhès AS, Lelièvre H, Lo KW, Ferrand FR, Gattolliat CH, Jacquet-Bescond A, Kraus-Berthier L, Depil S, Busson P. Treatment of nasopharyngeal carcinoma cells with the histone-deacetylase inhibitor abexinostat: cooperative effects with cis-platin and radiotherapy on patient- derived xenografts. PLoS One. 2014 Mar 11;9(3):e91325. doi: 10.1371/journal.pone.0091325. PMID: 24618637; PMCID: PMC3949989. 9: Evens AM, Balasubramanian S, Vose JM, Harb W, Gordon LI, Langdon R, Sprague J, Sirisawad M, Mani C, Yue J, Luan Y, Horton S, Graef T, Bartlett NL. A Phase I/II Multicenter, Open-Label Study of the Oral Histone Deacetylase Inhibitor Abexinostat in Relapsed/Refractory Lymphoma. Clin Cancer Res. 2016 Mar 1;22(5):1059-66. doi: 10.1158/1078-0432.CCR-15-0624. Epub 2015 Oct 19. PMID: 26482040. 10: Gergely L. A limfómák gyógyszeres terápiája [Drug therapy of lymphomas]. Magy Onkol. 2017 Mar 8;61(1):89-96. Hungarian. Epub 2016 Jun 15. PMID: 28273193. 11: Ribrag V, Kim WS, Bouabdallah R, Lim ST, Coiffier B, Illes A, Lemieux B, Dyer MJS, Offner F, Felloussi Z, Kloos I, Luan Y, Vezan R, Graef T, Morschhauser F. Safety and efficacy of abexinostat, a pan-histone deacetylase inhibitor, in non-Hodgkin lymphoma and chronic lymphocytic leukemia: results of a phase II study. Haematologica. 2017 May;102(5):903-909. doi: 10.3324/haematol.2016.154377. Epub 2017 Jan 25. PMID: 28126962; PMCID: PMC5477609. 12: Ali A, Bluteau O, Messaoudi K, Palazzo A, Boukour S, Lordier L, Lecluse Y, Rameau P, Kraus-Berthier L, Jacquet-Bescond A, Lelièvre H, Depil S, Dessen P, Solary E, Raslova H, Vainchenker W, Plo I, Debili N. Thrombocytopenia induced by the histone deacetylase inhibitor abexinostat involves p53-dependent and -independent mechanisms. Cell Death Dis. 2013 Jul 25;4(7):e738. doi: 10.1038/cddis.2013.260. PMID: 23887629; PMCID: PMC3730430. 13: Chalret du Rieu Q, Fouliard S, White-Koning M, Kloos I, Chatelut E, Chenel M. Pharmacokinetic/Pharmacodynamic modeling of abexinostat-induced thrombocytopenia across different patient populations: application for the determination of the maximum tolerated doses in both lymphoma and solid tumour patients. Invest New Drugs. 2014 Oct;32(5):985-94. doi: 10.1007/s10637-014-0118-1. Epub 2014 May 31. PMID: 24875134. 14: Aggarwal R, Thomas S, Pawlowska N, Bartelink I, Grabowsky J, Jahan T, Cripps A, Harb A, Leng J, Reinert A, Mastroserio I, Truong TG, Ryan CJ, Munster PN. Inhibiting Histone Deacetylase as a Means to Reverse Resistance to Angiogenesis Inhibitors: Phase I Study of Abexinostat Plus Pazopanib in Advanced Solid Tumor Malignancies. J Clin Oncol. 2017 Apr 10;35(11):1231-1239. doi: 10.1200/JCO.2016.70.5350. Epub 2017 Feb 21. PMID: 28221861; PMCID: PMC5791833. 15: Morschhauser F, Terriou L, Coiffier B, Bachy E, Varga A, Kloos I, Lelièvre H, Sarry AL, Depil S, Ribrag V. Phase 1 study of the oral histone deacetylase inhibitor abexinostat in patients with Hodgkin lymphoma, non-Hodgkin lymphoma, or chronic lymphocytic leukaemia. Invest New Drugs. 2015 Apr;33(2):423-31. doi: 10.1007/s10637-015-0206-x. Epub 2015 Jan 21. PMID: 25600050. 16: Deutsch E, Moyal EC, Gregorc V, Zucali PA, Menard J, Soria JC, Kloos I, Hsu J, Luan Y, Liu E, Vezan R, Graef T, Rivera S. A phase 1 dose-escalation study of the oral histone deacetylase inhibitor abexinostat in combination with standard hypofractionated radiotherapy in advanced solid tumors. Oncotarget. 2016 Dec 24;8(34):56199-56209. doi: 10.18632/oncotarget.14147. PMID: 28915584; PMCID: PMC5593555. 17: Sholler GS, Currier EA, Dutta A, Slavik MA, Illenye SA, Mendonca MC, Dragon J, Roberts SS, Bond JP. PCI-24781 (abexinostat), a novel histone deacetylase inhibitor, induces reactive oxygen species-dependent apoptosis and is synergistic with bortezomib in neuroblastoma. J Cancer Ther Res. 2013 Dec 28;2:21. doi: 10.7243/2049-7962-2-21. PMID: 25520806; PMCID: PMC4266584. 18: Chalret du Rieu Q, Fouliard S, Jacquet-Bescond A, Robert R, Kloos I, Depil S, Chatelut E, Chenel M. Application of hematological toxicity modeling in clinical development of abexinostat (S-78454, PCI-24781), a new histone deacetylase inhibitor. Pharm Res. 2013 Oct;30(10):2640-53. doi: 10.1007/s11095-013-1089-1. Epub 2013 Jun 5. PMID: 23737346. 19: Fouliard S, Robert R, Jacquet-Bescond A, du Rieu QC, Balasubramanian S, Loury D, Loriot Y, Hollebecque A, Kloos I, Soria JC, Chenel M, Depil S. Pharmacokinetic/pharmacodynamic modelling-based optimisation of administration schedule for the histone deacetylase inhibitor abexinostat (S78454/PCI-24781) in phase I. Eur J Cancer. 2013 Sep;49(13):2791-7. doi: 10.1016/j.ejca.2013.05.009. Epub 2013 Jun 18. PMID: 23790467. 20: Saillard C, El Cheikh J, Granata A, Coso D, Schiano JM, Bouabdallah R, Blaise D, Charrier N, Broussais F. Histone deacetylase inhibitor abexinostat (S78454/PCI-24781) as a successful approach in a case of refractory peripheral angio-immunoblastic T-cell lymphoma, as a bridge to reduced intensity conditioning haplo-identical allogenic stem cell transplant. Leuk Lymphoma. 2016;57(3):714-6. doi: 10.3109/10428194.2015.1061190. Epub 2016 Jan 11. PMID: 26750740.