Entinostat | MS-275 | SNDX-275 | CAS#209783-80-2 | HDAC inhibitor

MedKoo Cat#: 201266 | Name: Entinostat

Description:

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

Entinostat, also known as MS-275 or SNDX-275, is a potent HDAC inhibitor with potential antineoplastic activity. Entinostat binds to and inhibits histone deacetylase, an enzyme that regulates chromatin structure and gene transcription. This agent appears to exert dose-dependent effects in human leukemia cells including cyclin-dependent kinase inhibitor 1A (p21/CIP1/WAF1)-dependent growth arrest and differentiation at low drug concentrations; a marked induction of reactive oxygen species (ROS); mitochondrial damage; caspase activation; and, at higher concentrations, apoptosis.

Chemical Structure

Entinostat

CAS#209783-80-2

Theoretical Analysis

MedKoo Cat#: 201266

Name: Entinostat

CAS#: 209783-80-2

Chemical Formula: C21H20N4O3

Exact Mass: 376.1535

Molecular Weight: 376.41

Elemental Analysis: C, 67.01; H, 5.36; N, 14.88; O, 12.75

Price and Availability

Size	Price	Availability
10mg	USD 90.00	Ready to Ship
25mg	USD 150.00	Ready to ship
50mg	USD 250.00	Ready to ship
100mg	USD 450.00	Ready to ship
200mg	USD 750.00	Ready to ship
500mg	USD 1,350.00	Ready to ship
1g	USD 2,250.00	Ready to Ship
2g	USD 4,150.00	Ready to ship

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Related CAS #

No Data

Synonym

MS275; MS-275; MS 275; SNDX275; SNDX-275; SNDX 275; Entinostat

IUPAC/Chemical Name

pyridin-3-ylmethyl 4-((2-aminophenyl)carbamoyl)benzylcarbamate.

InChi Key

INVTYAOGFAGBOE-UHFFFAOYSA-N

InChi Code

InChI=1S/C21H20N4O3/c22-18-5-1-2-6-19(18)25-20(26)17-9-7-15(8-10-17)13-24-21(27)28-14-16-4-3-11-23-12-16/h1-12H,13-14,22H2,(H,24,27)(H,25,26)

SMILES Code

O=C(OCC1=CC=CN=C1)NCC2=CC=C(C(NC3=CC=CC=C3N)=O)C=C2

Appearance

white off white 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, 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

Entinostat inhibits class I HDAC1 and HDAC3 with IC50 of 0.51 μM and 1.7 μM, respectively. Entinostat preferentially inhibits cell proliferation/survival and inactivates downstream signaling in erbB2-overexpressing compared with basal breast cancer cells. Entinostat reduces the levels of both erbB2 and erbB3, as well as significantly decreases P-erbB2, P-erbB3, P-Akt, and P-MAPK in erbB2-overexpressing cells. Additionally, Entinostat promotes apoptosis and induces cell cycle arrest predominantly at G(1) phase in erbB2-overexpressing cells, whereas Entinostat mainly induces G(2)-M arrest in basal breast cancer cells. The cellular bias of Entinostat is shown to be related partly to the levels of erbB3 expression that directly impact the ability of Entinostat to inhibit proliferation/survival of the erbB2-overexpressing breast cancer cells. These findings show that Entinostat may be developed as a novel therapeutic agent to treat breast cancers with coexpression of both erbB2 and erbB3. see http://www.ncbi.nlm.nih.gov/pubmed/19826038. Entinostat is an orally bioavailable, selective, class I histone deacetylase (HDAC) inhibitor. Entinostat is currently being investigated in randomized, Phase 2 clinical studies in combination with the aromatase inhibitor, exemestane, for the treatment of metastatic or locally advanced ER+ breast cancer; in combination with erlotinib in advanced non-small-cell lung cancer, and in combination with azacitidine in myelodysplastic syndrome. Phase 2 single arm studies in non-small cell lung cancer and colorectal cancer, also are being conducted in combination with azacitidine; and a Phase 2 in Hodgkin's lymphoma is ongoing with single agent entinostat. Entinostat's long half-life allows for weekly or every-other-week oral dosing.

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#A21T05K25

View CoA: current batch, Lot#BBC50729

QC Data

View QC data: current batch, Lot#A21T05K25

View QC data: current batch, Lot#BBC50729

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Entinostat is a class I HDAC inhibitor, with IC50s of 243 nM, 453 nM, and 248 nM for HDAC1, HDAC2, and HDAC3, respectively.

In vitro activity:

In summary, entinostat increased surface expression of MICA/B, ULBP1, ULBP2/5/6, HLA, CD155, CD112, and PD-L1 in RD. In A-673, MICA/B surface expression was increased 73% by percent positive (p = 0.21) and 46% by MFI (p = 0.001) (Figure 2A–2D). ULBP1 was increased 216% by percent positive (p = 0.15) and 62% by MFI (p = 0.003). Expression of ULBP2/5/6, ULBP3, HLA, CD155, and CD112 was not significantly changed based on the percent of positive or MFI. However, expression of PD-L1 was increased 151% by percent positive cells (p = 0.06) and 30% by MFI (p = 0.02). In summary, entinostat increased surface expression of MICA/B, ULBP1, and PD-L1 in A-673. Collectively, entinostat significantly upregulated ligands for both activating and inhibitory NK receptors in both RD and A-673. Reference: Oncotarget. 2020 May 19; 11(20): 1799–1815. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7244011/

In vivo activity:

This study next investigated the antitumor efficacy of ENT and VCR as single agents and in combination in three biologically independent patient-derived tumorgraft xenograft mouse models of pleoRMS. PDX model characteristics are given in Additional file 6: Table S8. In all the cases, ENT had single-agent activity relative to control (Fig. 2e–g). Statistical summaries of three different PDX pleoRMS models are given in Additional file 6: Table S9-S11. Residual end-treatment tumors were examined histologically, and rhabdomyoblastic differentiation was scored for the CTG-800 PDX mouse model, which showed the best response to treatment. There was no difference seen between different treatment groups in terms of rhabdomyoblast differentiation (Additional file 6: Table S12). Representative histology of each treatment group is provided in Additional file 2: Figure S2. Reference: Skelet Muscle. 2019; 9: 12. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6528217/

	Solvent	mg/mL	mM
Solubility
	DMSO	30.0	79.70

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 376.41 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. Idso JM, Lao S, Schloemer NJ, Knipstein J, Burns R, Thakar MS, Malarkannan S. Entinostat augments NK cell functions via epigenetic upregulation of IFIT1-STING-STAT4 pathway. Oncotarget. 2020 May 19;11(20):1799-1815. doi: 10.18632/oncotarget.27546. PMID: 32499867; PMCID: PMC7244011. 2. Christmas BJ, Rafie CI, Hopkins AC, Scott BA, Ma HS, Cruz KA, Woolman S, Armstrong TD, Connolly RM, Azad NA, Jaffee EM, Roussos Torres ET. Entinostat Converts Immune-Resistant Breast and Pancreatic Cancers into Checkpoint-Responsive Tumors by Reprogramming Tumor-Infiltrating MDSCs. Cancer Immunol Res. 2018 Dec;6(12):1561-1577. doi: 10.1158/2326-6066.CIR-18-0070. Epub 2018 Oct 19. PMID: 30341213; PMCID: PMC6279584. 3. Bharathy N, Berlow NE, Wang E, Abraham J, Settelmeyer TP, Hooper JE, Svalina MN, Bajwa Z, Goros MW, Hernandez BS, Wolff JE, Pal R, Davies AM, Ashok A, Bushby D, Mancini M, Noakes C, Goodwin NC, Ordentlich P, Keck J, Hawkins DS, Rudzinski ER, Mansoor A, Perkins TJ, Vakoc CR, Michalek JE, Keller C. Preclinical rationale for entinostat in embryonal rhabdomyosarcoma. Skelet Muscle. 2019 May 21;9(1):12. doi: 10.1186/s13395-019-0198-x. PMID: 31113472; PMCID: PMC6528217. 4. Freundt JK, Frommeyer G, Spieker T, Wötzel F, Grotthoff JS, Stypmann J, Hempel G, Schäfers M, Jacobs AH, Eckardt L, Lange PS. Histone deacetylase inhibition by Entinostat for the prevention of electrical and structural remodeling in heart failure. BMC Pharmacol Toxicol. 2019 Mar 6;20(1):16. doi: 10.1186/s40360-019-0294-x. PMID: 30841920; PMCID: PMC6404297.

In vitro protocol:

In vivo protocol:

1. Bharathy N, Berlow NE, Wang E, Abraham J, Settelmeyer TP, Hooper JE, Svalina MN, Bajwa Z, Goros MW, Hernandez BS, Wolff JE, Pal R, Davies AM, Ashok A, Bushby D, Mancini M, Noakes C, Goodwin NC, Ordentlich P, Keck J, Hawkins DS, Rudzinski ER, Mansoor A, Perkins TJ, Vakoc CR, Michalek JE, Keller C. Preclinical rationale for entinostat in embryonal rhabdomyosarcoma. Skelet Muscle. 2019 May 21;9(1):12. doi: 10.1186/s13395-019-0198-x. PMID: 31113472; PMCID: PMC6528217. 2. Freundt JK, Frommeyer G, Spieker T, Wötzel F, Grotthoff JS, Stypmann J, Hempel G, Schäfers M, Jacobs AH, Eckardt L, Lange PS. Histone deacetylase inhibition by Entinostat for the prevention of electrical and structural remodeling in heart failure. BMC Pharmacol Toxicol. 2019 Mar 6;20(1):16. doi: 10.1186/s40360-019-0294-x. PMID: 30841920; PMCID: PMC6404297.

1: Trapani D, Esposito A, Criscitiello C, Mazzarella L, Locatelli M, Minchella I, Minucci S, Curigliano G. Entinostat for the treatment of breast cancer. Expert Opin Investig Drugs. 2017 Aug;26(8):965-971. doi: 10.1080/13543784.2017.1353077. Epub 2017 Jul 24. PMID: 28718331. 2: Sidiropoulos DN, Rafie CI, Jang JK, Castanon S, Baugh AG, Gonzalez E, Christmas BJ, Narumi VH, Davis-Marcisak EF, Sharma G, Bigelow E, Vaghasia A, Gupta A, Skaist A, Considine M, Wheelan SJ, Ganesan SK, Yu M, Yegnasubramanian S, Stearns V, Connolly RM, Gaykalova DA, Kagohara LT, Jaffee EM, Fertig EJ, Roussos Torres ET. Entinostat Decreases Immune Suppression to Promote Antitumor Responses in a HER2+ Breast Tumor Microenvironment. Cancer Immunol Res. 2022 May 3;10(5):656-669. doi: 10.1158/2326-6066.CIR-21-0170. PMID: 35201318; PMCID: PMC9064912. 3: Gupta VG, Hirst J, Petersen S, Roby KF, Kusch M, Zhou H, Clive ML, Jewell A, Pathak HB, Godwin AK, Wilson AJ, Crispens MA, Cybulla E, Vindigni A, Fuh KC, Khabele D. Entinostat, a selective HDAC1/2 inhibitor, potentiates the effects of olaparib in homologous recombination proficient ovarian cancer. Gynecol Oncol. 2021 Jul;162(1):163-172. doi: 10.1016/j.ygyno.2021.04.015. Epub 2021 Apr 16. PMID: 33867143; PMCID: PMC8647995. 4: Kiany S, Harrison D, Gordon N. The Histone Deacetylase Inhibitor Entinostat/Syndax 275 in Osteosarcoma. Adv Exp Med Biol. 2020;1257:75-83. doi: 10.1007/978-3-030-43032-0_7. PMID: 32483732. 5: Ruiz R, Raez LE, Rolfo C. Entinostat (SNDX-275) for the treatment of non- small cell lung cancer. Expert Opin Investig Drugs. 2015;24(8):1101-9. doi: 10.1517/13543784.2015.1056779. Epub 2015 Jun 22. PMID: 26098363. 6: Knipstein J, Gore L. Entinostat for treatment of solid tumors and hematologic malignancies. Expert Opin Investig Drugs. 2011 Oct;20(10):1455-67. doi: 10.1517/13543784.2011.613822. Epub 2011 Sep 2. PMID: 21888556. 7: Ferro A, Graikioti D, Gezer E, Athanassopoulos CM, Cuendet M. Entinostat- Bortezomib Hybrids against Multiple Myeloma. Molecules. 2023 Feb 2;28(3):1456. doi: 10.3390/molecules28031456. PMID: 36771118; PMCID: PMC9920246. 8: Minnar CM, Chariou PL, Horn LA, Hicks KC, Palena C, Schlom J, Gameiro SR. Tumor-targeted interleukin-12 synergizes with entinostat to overcome PD-1/PD-L1 blockade-resistant tumors harboring MHC-I and APM deficiencies. J Immunother Cancer. 2022 Jun;10(6):e004561. doi: 10.1136/jitc-2022-004561. PMID: 35764364; PMCID: PMC9240938. 9: McCaw TR, Randall TD, Arend RC. Revisiting entinostat as an immune- potentiating adjuvant. Oncotarget. 2018 Dec 18;9(99):37278-37279. doi: 10.18632/oncotarget.26453. PMID: 30647864; PMCID: PMC6324670. 10: Ny L, Jespersen H, Karlsson J, Alsén S, Filges S, All-Eriksson C, Andersson B, Carneiro A, Helgadottir H, Levin M, Ljuslinder I, Olofsson Bagge R, Sah VR, Stierner U, Ståhlberg A, Ullenhag G, Nilsson LM, Nilsson JA. The PEMDAC phase 2 study of pembrolizumab and entinostat in patients with metastatic uveal melanoma. Nat Commun. 2021 Aug 27;12(1):5155. doi: 10.1038/s41467-021-25332-w. PMID: 34453044; PMCID: PMC8397717. 11: Connolly RM, Zhao F, Miller KD, Lee MJ, Piekarz RL, Smith KL, Brown- Glaberman UA, Winn JS, Faller BA, Onitilo AA, Burkard ME, Budd GT, Levine EG, Royce ME, Kaufman PA, Thomas A, Trepel JB, Wolff AC, Sparano JA. E2112: Randomized Phase III Trial of Endocrine Therapy Plus Entinostat or Placebo in Hormone Receptor-Positive Advanced Breast Cancer. A Trial of the ECOG-ACRIN Cancer Research Group. J Clin Oncol. 2021 Oct 1;39(28):3171-3181. doi: 10.1200/JCO.21.00944. Epub 2021 Aug 6. PMID: 34357781; PMCID: PMC8478386. 12: Bonsack F, Sukumari-Ramesh S. Entinostat improves acute neurological outcomes and attenuates hematoma volume after Intracerebral Hemorrhage. Brain Res. 2021 Feb 1;1752:147222. doi: 10.1016/j.brainres.2020.147222. Epub 2020 Dec 23. PMID: 33358731; PMCID: PMC7903810. 13: Entinostat Helps Thwart Immunotherapy Resistance. Cancer Discov. 2019 Jun;9(6):685-686. doi: 10.1158/2159-8290.CD-NB2019-048. Epub 2019 Apr 1. PMID: 30936082. 14: Idso JM, Lao S, Schloemer NJ, Knipstein J, Burns R, Thakar MS, Malarkannan S. Entinostat augments NK cell functions via epigenetic upregulation of IFIT1-STING-STAT4 pathway. Oncotarget. 2020 May 19;11(20):1799-1815. doi: 10.18632/oncotarget.27546. PMID: 32499867; PMCID: PMC7244011. 15: Truong AS, Zhou M, Krishnan B, Utsumi T, Manocha U, Stewart KG, Beck W, Rose TL, Milowsky MI, He X, Smith CC, Bixby LM, Perou CM, Wobker SE, Bailey ST, Vincent BG, Kim WY. Entinostat induces antitumor immune responses through immune editing of tumor neoantigens. J Clin Invest. 2021 Aug 16;131(16):e138560. doi: 10.1172/JCI138560. PMID: 34396985; PMCID: PMC8363284. 16: Lu Z, Zou J, Li S, Topper MJ, Tao Y, Zhang H, Jiao X, Xie W, Kong X, Vaz M, Li H, Cai Y, Xia L, Huang P, Rodgers K, Lee B, Riemer JB, Day CP, Yen RC, Cui Y, Wang Y, Wang Y, Zhang W, Easwaran H, Hulbert A, Kim K, Juergens RA, Yang SC, Battafarano RJ, Bush EL, Broderick SR, Cattaneo SM, Brahmer JR, Rudin CM, Wrangle J, Mei Y, Kim YJ, Zhang B, Wang KK, Forde PM, Margolick JB, Nelkin BD, Zahnow CA, Pardoll DM, Housseau F, Baylin SB, Shen L, Brock MV. Epigenetic therapy inhibits metastases by disrupting premetastatic niches. Nature. 2020 Mar;579(7798):284-290. doi: 10.1038/s41586-020-2054-x. Epub 2020 Feb 26. PMID: 32103175; PMCID: PMC8765085. 17: Dai C, Liu B, Peng B, Qu B, Lin J, Peng B, Li DM. Entinostat Improves Motor Function and Neuronal Damage Via Downregulating NLRP3 Inflammasome Activation After Spinal Cord Injury. Front Pharmacol. 2021 Nov 26;12:774539. doi: 10.3389/fphar.2021.774539. PMID: 34899337; PMCID: PMC8664236. 18: Cassandri M, Pomella S, Rossetti A, Petragnano F, Milazzo L, Vulcano F, Camero S, Codenotti S, Cicchetti F, Maggio R, Festuccia C, Gravina GL, Fanzani A, Megiorni F, Catanoso M, Marchese C, Tombolini V, Locatelli F, Rota R, Marampon F. MS-275 (Entinostat) Promotes Radio-Sensitivity in PAX3-FOXO1 Rhabdomyosarcoma Cells. Int J Mol Sci. 2021 Oct 1;22(19):10671. doi: 10.3390/ijms221910671. PMID: 34639012; PMCID: PMC8508838. 19: Kurmasheva RT, Bandyopadhyay A, Favours E, Del Pozo V, Ghilu S, Phelps DA, Erickson SW, Peer CJ, Figg WD, Smith MA, Houghton PJ. Evaluation of entinostat alone and in combination with standard-of-care cytotoxic agents against rhabdomyosarcoma xenograft models. Pediatr Blood Cancer. 2019 Aug;66(8):e27820. doi: 10.1002/pbc.27820. Epub 2019 May 16. Erratum in: Pediatr Blood Cancer. 2019 Oct;66(10):e27933. PMID: 31099166; PMCID: PMC6685061. 20: Marques AEM, do Nascimento Filho CHV, Marinho Bezerra TM, Guerra ENS, Castilho RM, Squarize CH. Entinostat is a novel therapeutic agent to treat oral squamous cell carcinoma. J Oral Pathol Med. 2020 Sep;49(8):771-779. doi: 10.1111/jop.13039. Epub 2020 Jun 11. PMID: 32450006.