Resminostat | 4SC-201 | RAS2410 | CAS#864814-88-0 | HDAC inhibitor

MedKoo Cat#: 205787 | Name: Resminostat

Description:

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

Resminostat, also known as 4S-201 and RAS2410, is an orally bioavailable inhibitor of histone deacetylases (HDACs) with potential antineoplastic activity. Resminostat binds to and inhibits HDACs leading to an accumulation of highly acetylated histones. This may result in an induction of chromatin remodeling, inhibition of the transcription of tumor suppressor genes, inhibition of tumor cell division and the induction of tumor cell apoptosis.

Chemical Structure

Resminostat

CAS#864814-88-0 (free base)

Theoretical Analysis

MedKoo Cat#: 205787

Name: Resminostat

CAS#: 864814-88-0 (free base)

Chemical Formula: C16H19N3O4S

Exact Mass: 349.1096

Molecular Weight: 349.41

Elemental Analysis: C, 55.00; H, 5.48; N, 12.03; O, 18.32; S, 9.18

Price and Availability

Size	Price	Availability
50mg	USD 450.00	2 Weeks
100mg	USD 750.00	2 Weeks
200mg	USD 1,350.00	2 Weeks
500mg	USD 2,650.00	2 Weeks

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Related CAS #

1187075-34-8 (HCl) 864814-88-0 (free base)

Synonym

4SC201; 4SC-201; 4SC 201; RAS-2410; RAS2410; RAS 2410; Resminostat.

IUPAC/Chemical Name

(E)-3-(1-((4-((dimethylamino)methyl)phenyl)sulfonyl)-1H-pyrrol-3-yl)-N-hydroxyacrylamide.

InChi Key

FECGNJPYVFEKOD-VMPITWQZSA-N

InChi Code

InChI=1S/C16H19N3O4S/c1-18(2)11-13-3-6-15(7-4-13)24(22,23)19-10-9-14(12-19)5-8-16(20)17-21/h3-10,12,21H,11H2,1-2H3,(H,17,20)/b8-5+

SMILES Code

O=C(NO)/C=C/C1=CN(S(=O)(C2=CC=C(CN(C)C)C=C2)=O)C=C1

Appearance

Solid powder

Purity

>98% (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 and ethanol

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO and ethanol

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

Product Data

Product Data

Instruction

View handling instruction

Biological target:

Resminostat dose-dependently and selectively inhibits HDAC1/3/6 with IC50 of 42.5 nM/50.1 nM/71.8 nM. It is less potent to HDAC8 with IC50 of 877 nM.

In vitro activity:

The combined use of resminostat and gefitinib increased BIMEL protein level in the non-small cell lung cancer cell line PC-9 and induced apoptosis, which led to remarkable shrinkage of tumor. These findings suggest the potential of resminostat to circumvent tolerance to EGFR-TKIs associated with BIM deletion polymorphism. Reference: J Med Invest. 2020;67(3.4):343-350. https://pubmed.ncbi.nlm.nih.gov/33148913/

In vivo activity:

Resminostat plus S-1 therapy did not improve progression-free survival nor overall survival for patients with pre-treated biliary tract cancers. Addition of resminostat to S-1 was associated with higher incidence of treatment-related adverse events. Reference: Cancer Med. 2021 Mar;10(6):2088-2099. https://pubmed.ncbi.nlm.nih.gov/33635605/

	Solvent	mg/mL	mM
Solubility
	DMSO	70.0	200.34
	Ethanol	70.0	200.34

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 349.41 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.

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. Arai S, Takeuchi S, Fukuda K, Tanimoto A, Nishiyama A, Konishi H, Takagi A, Takahashi H, Ong ST, Yano S. Resminostat, a histone deacetylase inhibitor, circumvents tolerance to EGFR inhibitors in EGFR-mutated lung cancer cells with BIM deletion polymorphism. J Med Invest. 2020;67(3.4):343-350. doi: 10.2152/jmi.67.343. PMID: 33148913. 2. Palermo E, Acchioni C, Di Carlo D, Zevini A, Muscolini M, Ferrari M, Castiello L, Virtuoso S, Borsetti A, Antonelli G, Turriziani O, Sgarbanti M, Hiscott J. Activation of Latent HIV-1 T Cell Reservoirs with a Combination of Innate Immune and Epigenetic Regulators. J Virol. 2019 Oct 15;93(21):e01194-19. doi: 10.1128/JVI.01194-19. PMID: 31413127; PMCID: PMC6803272. 3. Ueno M, Morizane C, Furukawa M, Sakai D, Komatsu Y, Nakai Y, Tsuda M, Ozaka M, Mizuno N, Muto M, Fukutomi A, Ikeda M, Tsuji A, Katanuma A, Moriwaki T, Kajiwara T, Ishii H, Negoro Y, Shimizu S, Nemoto N, Kobayashi S, Makino K, Furuse J. A randomized, double-blind, phase II study of oral histone deacetylase inhibitor resminostat plus S-1 versus placebo plus S-1 in biliary tract cancers previously treated with gemcitabine plus platinum-based chemotherapy. Cancer Med. 2021 Mar;10(6):2088-2099. doi: 10.1002/cam4.3813. Epub 2021 Feb 26. PMID: 33635605; PMCID: PMC7957161. 4. Walewski J, Paszkiewicz-Kozik E, Borsaru G, Hellmann A, Janikova A, Warszewska A, Mais A, Ammendola A, Herz T, Krauss B, Henning SW. Resminostat in patients with relapsed or refractory Hodgkin lymphoma: results of the phase II SAPHIRE study. Leuk Lymphoma. 2019 Mar;60(3):675-684. doi: 10.1080/10428194.2018.1492122. Epub 2018 Aug 30. PMID: 30160566.

In vitro protocol:

In vivo protocol:

1. Ueno M, Morizane C, Furukawa M, Sakai D, Komatsu Y, Nakai Y, Tsuda M, Ozaka M, Mizuno N, Muto M, Fukutomi A, Ikeda M, Tsuji A, Katanuma A, Moriwaki T, Kajiwara T, Ishii H, Negoro Y, Shimizu S, Nemoto N, Kobayashi S, Makino K, Furuse J. A randomized, double-blind, phase II study of oral histone deacetylase inhibitor resminostat plus S-1 versus placebo plus S-1 in biliary tract cancers previously treated with gemcitabine plus platinum-based chemotherapy. Cancer Med. 2021 Mar;10(6):2088-2099. doi: 10.1002/cam4.3813. Epub 2021 Feb 26. PMID: 33635605; PMCID: PMC7957161. 2. Walewski J, Paszkiewicz-Kozik E, Borsaru G, Hellmann A, Janikova A, Warszewska A, Mais A, Ammendola A, Herz T, Krauss B, Henning SW. Resminostat in patients with relapsed or refractory Hodgkin lymphoma: results of the phase II SAPHIRE study. Leuk Lymphoma. 2019 Mar;60(3):675-684. doi: 10.1080/10428194.2018.1492122. Epub 2018 Aug 30. PMID: 30160566.

1: Bitzer M, Horger M, Giannini EG, Ganten TM, Wörns MA, Siveke JT, Dollinger MM, Gerken G, Scheulen ME, Wege H, Zagonel V, Cillo U, Trevisani F, Santoro A, Montesarchio V, Malek NP, Holzapfel J, Herz T, Ammendola AS, Pegoraro S, Hauns B, Mais A, Lauer UM, Henning SW, Hentsch B. Resminostat plus sorafenib as second-line therapy of advanced hepatocellular carcinoma - The SHELTER study. J Hepatol. 2016 Aug;65(2):280-8. doi: 10.1016/j.jhep.2016.02.043. Epub 2016 Mar 4. PMID: 26952006. 2: Zhao J, Gray SG, Wabitsch M, Greene CM, Lawless MW. The therapeutic properties of resminostat for hepatocellular carcinoma. Oncoscience. 2018 Jun 23;5(5-6):196-208. doi: 10.18632/oncoscience.420. PMID: 30035186; PMCID: PMC6049311. 3: Walewski J, Paszkiewicz-Kozik E, Borsaru G, Hellmann A, Janikova A, Warszewska A, Mais A, Ammendola A, Herz T, Krauss B, Henning SW. Resminostat in patients with relapsed or refractory Hodgkin lymphoma: results of the phase II SAPHIRE study. Leuk Lymphoma. 2019 Mar;60(3):675-684. doi: 10.1080/10428194.2018.1492122. Epub 2018 Aug 30. PMID: 30160566. 4: Ueno M, Morizane C, Furukawa M, Sakai D, Komatsu Y, Nakai Y, Tsuda M, Ozaka M, Mizuno N, Muto M, Fukutomi A, Ikeda M, Tsuji A, Katanuma A, Moriwaki T, Kajiwara T, Ishii H, Negoro Y, Shimizu S, Nemoto N, Kobayashi S, Makino K, Furuse J. A randomized, double-blind, phase II study of oral histone deacetylase inhibitor resminostat plus S-1 versus placebo plus S-1 in biliary tract cancers previously treated with gemcitabine plus platinum-based chemotherapy. Cancer Med. 2021 Mar;10(6):2088-2099. doi: 10.1002/cam4.3813. Epub 2021 Feb 26. PMID: 33635605; PMCID: PMC7957161. 5: Soukupova J, Bertran E, Peñuelas-Haro I, Urdiroz-Urricelqui U, Borgman M, Kohlhof H, Fabregat I. Resminostat induces changes in epithelial plasticity of hepatocellular carcinoma cells and sensitizes them to sorafenib-induced apoptosis. Oncotarget. 2017 Nov 30;8(66):110367-110379. doi: 10.18632/oncotarget.22775. PMID: 29299154; PMCID: PMC5746389. 6: Streubel G, Schrepfer S, Kallus H, Parnitzke U, Wulff T, Hermann F, Borgmann M, Hamm S. Histone deacetylase inhibitor resminostat in combination with sorafenib counteracts platelet-mediated pro-tumoral effects in hepatocellular carcinoma. Sci Rep. 2021 May 5;11(1):9587. doi: 10.1038/s41598-021-88983-1. PMID: 33953226; PMCID: PMC8100298. 7: Peng X, Zhang D, Li Z, Fu M, Liu H. mTOR inhibition sensitizes human hepatocellular carcinoma cells to resminostat. Biochem Biophys Res Commun. 2016 Sep 2;477(4):556-562. doi: 10.1016/j.bbrc.2016.06.060. Epub 2016 Jun 14. PMID: 27311860. 8: Kitazono S, Fujiwara Y, Nakamichi S, Mizugaki H, Nokihara H, Yamamoto N, Yamada Y, Inukai E, Nakamura O, Tamura T. A phase I study of resminostat in Japanese patients with advanced solid tumors. Cancer Chemother Pharmacol. 2015 Jun;75(6):1155-61. doi: 10.1007/s00280-015-2741-8. Epub 2015 Apr 7. PMID: 25847480. 9: Ikeda M, Ohno I, Ueno H, Mitsunaga S, Hashimoto Y, Okusaka T, Kondo S, Sasaki M, Sakamoto Y, Takahashi H, Hara R, Kobayashi S, Nakamura O, Morizane C. Phase I study of resminostat, an HDAC inhibitor, combined with S-1 in patients with pre- treated biliary tract or pancreatic cancer. Invest New Drugs. 2019 Feb;37(1):109-117. doi: 10.1007/s10637-018-0634-5. Epub 2018 Jul 11. PMID: 29995287. 10: Karagianni F, Piperi C, Casar B, de la Fuente-Vivas D, García-Gómez R, Lampadaki K, Pappa V, Papadavid E. Combination of Resminostat with Ruxolitinib Exerts Antitumor Effects in the Chick Embryo Chorioallantoic Membrane Model for Cutaneous T Cell Lymphoma. Cancers (Basel). 2022 Feb 20;14(4):1070. doi: 10.3390/cancers14041070. PMID: 35205818; PMCID: PMC8870185. 11: Arai S, Takeuchi S, Fukuda K, Tanimoto A, Nishiyama A, Konishi H, Takagi A, Takahashi H, Ong ST, Yano S. Resminostat, a histone deacetylase inhibitor, circumvents tolerance to EGFR inhibitors in EGFR-mutated lung cancer cells with BIM deletion polymorphism. J Med Invest. 2020;67(3.4):343-350. doi: 10.2152/jmi.67.343. PMID: 33148913. 12: Tak WY, Ryoo BY, Lim HY, Kim DY, Okusaka T, Ikeda M, Hidaka H, Yeon JE, Mizukoshi E, Morimoto M, Lee MA, Yasui K, Kawaguchi Y, Heo J, Morita S, Kim TY, Furuse J, Katayama K, Aramaki T, Hara R, Kimura T, Nakamura O, Kudo M. Phase I/II study of first-line combination therapy with sorafenib plus resminostat, an oral HDAC inhibitor, versus sorafenib monotherapy for advanced hepatocellular carcinoma in east Asian patients. Invest New Drugs. 2018 Dec;36(6):1072-1084. doi: 10.1007/s10637-018-0658-x. Epub 2018 Sep 10. PMID: 30198057. 13: Enzenhofer E, Kadletz L, Stanisz I, Kotowski U, Seemann R, Schmid R, Thurnher D, Heiduschka G. Effect of the histone deacetylase inhibitor resminostat on head and neck squamous cell carcinoma cell lines. Head Neck. 2017 May;39(5):900-907. doi: 10.1002/hed.24699. Epub 2017 Feb 7. PMID: 28170128. 14: Fu M, Shi W, Li Z, Liu H. Activation of mPTP-dependent mitochondrial apoptosis pathway by a novel pan HDAC inhibitor resminostat in hepatocellular carcinoma cells. Biochem Biophys Res Commun. 2016 Sep 2;477(4):527-533. doi: 10.1016/j.bbrc.2016.04.147. Epub 2016 May 1. PMID: 27144317. 15: Mandl-Weber S, Meinel FG, Jankowsky R, Oduncu F, Schmidmaier R, Baumann P. The novel inhibitor of histone deacetylase resminostat (RAS2410) inhibits proliferation and induces apoptosis in multiple myeloma (MM) cells. Br J Haematol. 2010 May;149(4):518-28. doi: 10.1111/j.1365-2141.2010.08124.x. Epub 2010 Mar 1. PMID: 20201941. 16: Karagianni F, Piperi C, Mpakou V, Spathis A, Foukas PG, Dalamaga M, Pappa V, Papadavid E. Ruxolitinib with resminostat exert synergistic antitumor effects in Cutaneous T-cell Lymphoma. PLoS One. 2021 Mar 11;16(3):e0248298. doi: 10.1371/journal.pone.0248298. PMID: 33705488; PMCID: PMC7951910. 17: Tambo Y, Hosomi Y, Sakai H, Nogami N, Atagi S, Sasaki Y, Kato T, Takahashi T, Seto T, Maemondo M, Nokihara H, Koyama R, Nakagawa K, Kawaguchi T, Okamura Y, Nakamura O, Nishio M, Tamura T. Phase I/II study of docetaxel combined with resminostat, an oral hydroxamic acid HDAC inhibitor, for advanced non-small cell lung cancer in patients previously treated with platinum-based chemotherapy. Invest New Drugs. 2017 Apr;35(2):217-226. doi: 10.1007/s10637-017-0435-2. Epub 2017 Jan 30. PMID: 28138828. 18: Brunetto AT, Ang JE, Lal R, Olmos D, Molife LR, Kristeleit R, Parker A, Casamayor I, Olaleye M, Mais A, Hauns B, Strobel V, Hentsch B, de Bono JS. First-in-human, pharmacokinetic and pharmacodynamic phase I study of Resminostat, an oral histone deacetylase inhibitor, in patients with advanced solid tumors. Clin Cancer Res. 2013 Oct 1;19(19):5494-504. doi: 10.1158/1078-0432.CCR-13-0735. Epub 2013 Sep 24. PMID: 24065624; PMCID: PMC3790647. 19: Zhao J, Lawless MW. Resminostat: Opening the door to epigenetic treatments for liver cancer. Hepatology. 2016 Feb;63(2):668-9. doi: 10.1002/hep.27853. Epub 2015 May 29. PMID: 25891162. 20: Ellerhoff TP, Berchtold S, Venturelli S, Burkard M, Smirnow I, Wulff T, Lauer UM. Novel epi-virotherapeutic treatment of pancreatic cancer combining the oral histone deacetylase inhibitor resminostat with oncolytic measles vaccine virus. Int J Oncol. 2016 Nov;49(5):1931-1944. doi: 10.3892/ijo.2016.3675. Epub 2016 Aug 31. PMID: 27601235.