Elisidepsin (PM02734) TFA salt is a novel and potent antineoplastic agent based on cyclic peptides.

Physicochemical Properties

Molecular Formula	C77H125F3N14O18
Molecular Weight	1591.89
Exact Mass	1590.924
Elemental Analysis	C, 58.10; H, 7.91; F, 3.58; N, 12.32; O, 18.09
CAS #	915713-02-9
Related CAS #	681272-30-0;915713-02-9 (TFA);
PubChem CID	46926348
Appearance	Typically exists as solid at room temperature
Hydrogen Bond Donor Count	15
Hydrogen Bond Acceptor Count	22
Rotatable Bond Count	33
Heavy Atom Count	112
Complexity	3070
Defined Atom Stereocenter Count	17
SMILES	FC(C(=O)O)(F)F.O=C([C@@H](C(C)C)NC([C@H](C(C)C)NC([C@H]([C@@H](C)O)NC([C@@H](C(C)C)NC(CC[C@@H](C)CC)=O)=O)=O)=O)N1CCC[C@@H]1C(N[C@H](C(N[C@@H](C(N[C@H]1C(N[C@@]([H])(C(N[C@@H](C(N[C@H](C(N/C(=C\C)/C(N[C@@H](C(C)C)C(=O)O[C@@H]1C)=O)=O)CC1C=CC=CC=1)=O)C(C)C)=O)[C@@H](C)CC)=O)=O)[C@@H](C)CC)=O)CCCN)=O
InChi Key	FUDHRLIJYPGBOX-MWGCIELCSA-N
InChi Code	InChI=1S/C75H124N14O16.C2HF3O2/c1-20-43(15)33-34-53(91)80-54(38(5)6)68(97)87-61(46(18)90)72(101)82-56(40(9)10)69(98)83-57(41(11)12)74(103)89-36-28-32-52(89)66(95)78-50(31-27-35-76)64(93)85-59(44(16)21-2)71(100)88-62-47(19)105-75(104)58(42(13)14)84-63(92)49(23-4)77-65(94)51(37-48-29-25-24-26-30-48)79-67(96)55(39(7)8)81-70(99)60(45(17)22-3)86-73(62)102;3-2(4,5)1(6)7/h23-26,29-30,38-47,50-52,54-62,90H,20-22,27-28,31-37,76H2,1-19H3,(H,77,94)(H,78,95)(H,79,96)(H,80,91)(H,81,99)(H,82,101)(H,83,98)(H,84,92)(H,85,93)(H,86,102)(H,87,97)(H,88,100);(H,6,7)/b49-23-;/t43-,44-,45-,46+,47+,50-,51-,52+,54+,55+,56-,57+,58-,59+,60+,61-,62+;/m0./s1
Chemical Name	(2R)-N-[(2S)-5-amino-1-[[(2R,3S)-1-[[(3S,6Z,9S,12R,15R,18R,19R)-9-benzyl-15-[(2S)-butan-2-yl]-6-ethylidene-19-methyl-2,5,8,11,14,17-hexaoxo-3,12-di(propan-2-yl)-1-oxa-4,7,10,13,16-pentazacyclononadec-18-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-1-oxopentan-2-yl]-1-[(2R)-2-[[(2S)-2-[[(2S,3R)-3-hydroxy-2-[[(2R)-3-methyl-2-[[(4S)-4-methylhexanoyl]amino]butanoyl]amino]butanoyl]amino]-3-methylbutanoyl]amino]-3-methylbutanoyl]pyrrolidine-2-carboxamide;2,2,2-trifluoroacetic acid
Synonyms	PM02734; PM-02734; Irvalec; 915713-02-9; Elisidepsin trifluoroacetate; UNII-3I37B5DY4Q; 3I37B5DY4Q; PM 02734
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	Anticancer cycilic peptide
ln Vitro	Elisidepsin (72 h) suppresses the growth of several cancer cells with IC50s ranging from 8.8 μM (MiaPaCa2) to 0.4 μM (ZR-75-1)[1]. Sub-G1 phase SKBR3 cells are arrested by 1 μM elidipasin after 48 hours[1]. In DU145 cells, elipsin (0–5 μM, 30 min) causes a loss of cell membrane integrity rather than apoptosis[1]. Glycosylated ceramides in the plasma cell membrane of HCT-116 cells are interacting with lipisidepsin[2]. In H322, A549, and H3255 cells, ErbB3 degradation and dephosphorylation can be effectively induced by (0.1 μM, 2 h)[4]. In H322 and A549 cells, elipsin (0.5 and 1 μM, 2 h) suppresses the phosphorylation of ErbB3 and AKT[4].
ln Vivo	Lung cancer xenografts exhibit anticancer activity when treated with elipsidepsin (100 µg/kg, IV)].
Cell Assay	Cell Viability Assay[1] Cell Types: SKBR3 cell Tested Concentrations: 0.125, 0.25, 0.5, 1 μM Incubation Duration: 48 h Experimental Results: Increased amount of dying cells represented by sub-G1 phase.
Animal Protocol	Animal/Disease Models: NSCLC xenograft models (A549 cell, iv) in nude mice[3] Doses: 100 µg/kg Route of Administration: intravenous (iv) injection (iv ) Experimental Results: Prolonged the life-span of animals bearing experimental lung metastases.
References	[1]. Serova M, et al. Predictive factors of sensitivity to elisidepsin, a novel Kahalalide F-derived marine compound. Mar Drugs. 2013 Mar 20;11(3):944-59. [2]. Molina-Guijarro JM, et al. Elisidepsin Interacts Directly with Glycosylceramides in the Plasma Membrane of Tumor Cells to Induce Necrotic Cell Death. PLoS One. 2015 Oct 16;10(10):e0140782. [3]. Yiyu Zou, et al. Antitumor activity of Irvalec (PM02734) against lung cancer xenografts. Cancer Res 1 May 2009; 69 (9_Supplement): 5466. [4]. Ling YH, et al. Molecular pharmacodynamics of PM02734 (elisidepsin) as single agent and in combination with erlotinib; synergistic activity in human non-small cell lung cancer cell lines and xenograft models. Eur J Cancer. 2009 Jul;45(10):1855-64.
Additional Infomation	See also: Elisidepsin (annotation moved to).

Solubility Data

Solubility (In Vitro)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	0.6282 mL	3.1409 mL	6.2818 mL
	5 mM	0.1256 mL	0.6282 mL	1.2564 mL
	10 mM	0.0628 mL	0.3141 mL	0.6282 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.