Tinostamustine free base | CAS#1236199-60-2

MedKoo Cat#: 407990 | Name: Tinostamustine free base

Description:

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

Tinostamustine, also known as EDO-S101, is an alkylatlng histone-deacetylase inhibitor (HDACi) fusion molecule. EDO-S101 is a functional pan-histone-deacetylase inhibitor and is assumed to potentiate the alkylating activity of the compound and/or may help to overcome resistance to other therapeutic agents.

Chemical Structure

Tinostamustine free base

CAS#1236199-60-2 (free base)

Theoretical Analysis

MedKoo Cat#: 407990

Name: Tinostamustine free base

CAS#: 1236199-60-2 (free base)

Chemical Formula: C19H28Cl2N4O2

Exact Mass: 414.1589

Molecular Weight: 415.36

Elemental Analysis: C, 54.94; H, 6.80; Cl, 17.07; N, 13.49; O, 7.70

Price and Availability

Size	Price	Availability
5mg	USD 110.00	Ready to ship
10mg	USD 180.00	Ready to ship
25mg	USD 350.00	Ready to ship
50mg	USD 650.00	Ready to ship
100mg	USD 1,050.00	Ready to ship
250mg	USD 1,950.00	Ready to ship
500mg	USD 2,650.00	Ready to ship
1g	USD 3,650.00	Ready to ship
2g	USD 6,250.00	2 Weeks

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Related CAS #

1793059-58-1 (HCl) 1236199-60-2 (free base)

Synonym

Tinostamustine free base; EDO-S101; EDO-S 101; EDO-S-101;

IUPAC/Chemical Name

7-(5-(bis(2-chloroethyl)amino)-1-methyl-1H-benzo[d]imidazol-2-yl)-N-hydroxyheptanamide

InChi Key

GISXTRIGVCKQBX-UHFFFAOYSA-N

InChi Code

InChI=1S/C19H28Cl2N4O2/c1-24-17-9-8-15(25(12-10-20)13-11-21)14-16(17)22-18(24)6-4-2-3-5-7-19(26)23-27/h8-9,14,27H,2-7,10-13H2,1H3,(H,23,26)

SMILES Code

O=C(NO)CCCCCCC1=NC2=CC(N(CCCl)CCCl)=CC=C2N1C

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

Shelf Life

>3 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

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#C20R01B18

QC Data

View QC data: current batch, Lot#C20R01B18

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Tinostamustine(EDO-S101) is a first-in-class alkylating deacetylase inhibitor with IC50 values of 9 nM, 9 nM, 25 nM and 107 nM for HDAC1, HDAC2, HDAC3 and HDAC8 (Class 1 HDACs) respectively and 6 nM, 72 nM for HDAC6 and HDAC10 (Class II HDACs).

In vitro activity:

Tinostamustine was demonstrated to possess stronger antiproliferative and pro-apoptotic effects than those observed for vorinostat and bendamustine alone and similar to their combination and irrespective of MGMT expression. In addition, a stronger radio-sensitization of single treatment and temozolomide was used as control due to reduced expression and increased time of disappearance of γH2AX indicative of reduced signal and DNA repair. This was associated with higher caspase-3 activation and reduction of RT-mediated autophagy. Reference: J Hematol Oncol. 2018 Feb 27;11(1):32. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/29486795/

In vivo activity:

Tinostamustine increased time-to-progression (TTP) and this was additive/synergistic to RT. Tinostamustine had significant therapeutic activity with suppression of tumor growth and prolongation of DFS (disease-free survival) and OS (overall survival) in orthotopic intra-brain models that was superior to bendamustine, RT and temozolomide and showing stronger radio sensitivity. Reference: J Hematol Oncol. 2018 Feb 27;11(1):32. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/29486795/

	Solvent	mg/mL	mM
Solubility
	DMSO	14.0	33.71
	Ethanol	2.0	4.82

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 415.36 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:

In vitro protocol:

1. Festuccia C, Mancini A, Colapietro A, Gravina GL, Vitale F, Marampon F, Delle Monache S, Pompili S, Cristiano L, Vetuschi A, Tombolini V, Chen Y, Mehrling T. The first-in-class alkylating deacetylase inhibitor molecule tinostamustine shows antitumor effects and is synergistic with radiotherapy in preclinical models of glioblastoma. J Hematol Oncol. 2018 Feb 27;11(1):32. doi: 10.1186/s13045-018-0576-6. Erratum in: J Hematol Oncol. 2018 Mar 14;11(1):38. PMID: 29486795; PMCID: PMC5830080.

In vivo protocol:

1: M'kacher R, Frenzel M, Al Jawhari M, Junker S, Cuceu C, Morat L, Bauchet AL, Stimmer L, Lenain A, Dechamps N, Hempel WM, Pottier G, Heidingsfelder L, Laplagne E, Borie C, Oudrhiri N, Jouni D, Bennaceur-Griscelli A, Colicchio B, Dieterlen A, Girinsky T, Boisgard R, Bourhis J, Bosq J, Mehrling T, Jeandidier E, Carde P. Establishment and Characterization of a Reliable Xenograft Model of Hodgkin Lymphoma Suitable for the Study of Tumor Origin and the Design of New Therapies. Cancers (Basel). 2018 Oct 31;10(11). pii: E414. doi: 10.3390/cancers10110414. PubMed PMID: 30384446; PubMed Central PMCID: PMC6265845. 2: Dooley D, van Timmeren MM, O'Reilly VP, Brady G, O'Brien EC, Fazekas B, Hickey FB, Leacy E, Pusey CD, Tam FWK, Mehrling T, Heeringa P, Little MA. Alkylating histone deacetylase inhibitors may have therapeutic value in experimental myeloperoxidase-ANCA vasculitis. Kidney Int. 2018 Nov;94(5):926-936. doi: 10.1016/j.kint.2018.05.028. Epub 2018 Aug 26. PubMed PMID: 30158055. 3: Qiu Y, Li Z, Copland JA, Mehrling T, Tun HW. Combined alkylation and histone deacetylase inhibition with EDO-S101 has significant therapeutic activity against brain tumors in preclinical models. Oncotarget. 2018 Jun 15;9(46):28155-28164. doi: 10.18632/oncotarget.25588. eCollection 2018 Jun 15. PubMed PMID: 29963268; PubMed Central PMCID: PMC6021334. 4: Festuccia C, Mancini A, Colapietro A, Gravina GL, Vitale F, Marampon F, Delle Monache S, Pompili S, Cristiano L, Vetuschi A, Tombolini V, Chen Y, Mehrling T. The first-in-class alkylating deacetylase inhibitor molecule tinostamustine shows antitumor effects and is synergistic with radiotherapy in preclinical models of glioblastoma. J Hematol Oncol. 2018 Feb 27;11(1):32. doi: 10.1186/s13045-018-0576-6. Erratum in: J Hematol Oncol. 2018 Mar 14;11(1):38. PubMed PMID: 29486795; PubMed Central PMCID: PMC5830080. 5: Besse L, Kraus M, Besse A, Bader J, Silzle T, Mehrling T, Driessen C. The first-in-class alkylating HDAC inhibitor EDO-S101 is highly synergistic with proteasome inhibition against multiple myeloma through activation of multiple pathways. Blood Cancer J. 2017 Jul 28;7(7):e589. doi: 10.1038/bcj.2017.69. PubMed PMID: 28753594; PubMed Central PMCID: PMC5549260. 6: López-Iglesias AA, Herrero AB, Chesi M, San-Segundo L, González-Méndez L, Hernández-García S, Misiewicz-Krzeminska I, Quwaider D, Martín-Sánchez M, Primo D, Paíno T, Bergsagel PL, Mehrling T, González-Díaz M, San-Miguel JF, Mateos MV, Gutiérrez NC, Garayoa M, Ocio EM. Preclinical anti-myeloma activity of EDO-S101, a new bendamustine-derived molecule with added HDACi activity, through potent DNA damage induction and impairment of DNA repair. J Hematol Oncol. 2017 Jun 20;10(1):127. doi: 10.1186/s13045-017-0495-y. PubMed PMID: 28633670; PubMed Central PMCID: PMC5477689. 7: Mehrling T, Chen Y. The Alkylating-HDAC Inhibition Fusion Principle: Taking Chemotherapy to the Next Level with the First in Class Molecule EDO-S101. Anticancer Agents Med Chem. 2016;16(1):20-8. PubMed PMID: 25980817.