Didemnin B | CAS#77327-05-0 | Diverse depsipeptide

MedKoo Cat#: 598041 | Name: Didemnin B

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Description:

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

Didemnin B is a depsipeptide that has been found in sea squirts and has diverse biological activities. It reduces viral titers of coxsackievirus A21, equine rhinovirus, parainfluenza virus 3, herpes simplex virus 1 (HSV-1), and HSV-2 in infected Vero cells when used at a concentration of 50 µg/ml. Didemnin B is cytotoxic to murine L1210 lymphocytic leukemia cells (IC50 = 1.1 ng/ml) and increases survival time in a P388 murine leukemia model when administered at a dose of 0.06 mg/kg. It also reduces splenomegaly in a mouse model of graft versus host reaction (GVHR) when administered at doses ranging from 0.05 to 0.3 mg/kg.

Chemical Structure

Didemnin B

CAS#77327-05-0

Theoretical Analysis

MedKoo Cat#: 598041

Name: Didemnin B

CAS#: 77327-05-0

Chemical Formula: C57H89N7O15

Exact Mass: 1111.6417

Molecular Weight: 1112.37

Elemental Analysis: C, 61.55; H, 8.06; N, 8.81; O, 21.57

Price and Availability

Size	Price	Availability
5mg	USD 1,050.00	2 Weeks
10mg	USD 1,550.00	2 Weeks
25mg	USD 3,150.00	2 Weeks

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Synonym

Didemnin B; Didemnin-B; NSC 325319; NSC-325319; NSC325319; NSC 333841; NSC333841; NSC-333841;

IUPAC/Chemical Name

(S)-N-((R)-1-(((3S,6R,7S,10R,11S,15S,17S,20S,25aS)-10-((S)-sec-butyl)-11-hydroxy-20-isobutyl-15-isopropyl-3-(4-methoxybenzyl)-2,6,17-trimethyl-1,4,8,13,16,18,21-heptaoxodocosahydro-15H-pyrrolo[2,1-f][1,15]dioxa[4,7,10,20]tetraazacyclotricosin-7-yl)amino)-4-methyl-1-oxopentan-2-yl)-1-((S)-2-hydroxypropanoyl)-N-methylpyrrolidine-2-carboxamide

InChi Key

KYHUYMLIVQFXRI-SJPGYWQQSA-N

InChi Code

InChI=1S/C57H89N7O15/c1-15-33(8)46-44(66)29-45(67)79-49(32(6)7)48(68)34(9)50(69)58-39(26-30(2)3)54(73)64-25-17-19-41(64)56(75)62(13)43(28-37-20-22-38(77-14)23-21-37)57(76)78-36(11)47(52(71)59-46)60-51(70)42(27-31(4)5)61(12)55(74)40-18-16-24-63(40)53(72)35(10)65/h20-23,30-36,39-44,46-47,49,65-66H,15-19,24-29H2,1-14H3,(H,58,69)(H,59,71)(H,60,70)/t33-,34-,35-,36+,39-,40-,41-,42+,43-,44-,46+,47-,49-/m0/s1

SMILES Code

O=C([C@H]1N(C([C@@H](O)C)=O)CCC1)N([C@H](CC(C)C)C(N[C@@H]2C(N[C@H]([C@@H](C)CC)[C@@H](O)CC(O[C@@H](C(C)C)C([C@H](C)C(N[C@@H](CC(C)C)C(N3[C@](CCC3)([H])C(N(C)[C@@H](CC4=CC=C(OC)C=C4)C(O[C@@H]2C)=O)=O)=O)=O)=O)=O)=O)=O)C

Appearance

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

2934.99.03.00

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Product Data

Product Data

Instruction

View handling instruction

Biological target:

A depsipeptide with diverse biological activities.

In vitro activity:

Didemnin B can induce apoptosis in a wide range of transformed cell lines. Resting normal lymphocytes, however, are apparently unaffected by exposure to the drug. Didemnin B induced apoptosis in normal lymphocytes only after mitogenic stimulation and therefore warrants further examination for its potential as a chemotherapeutic agent, especially for treatment of leukemia. Reference: Apoptosis. 2002 Oct;7(5):407-12. https://pubmed.ncbi.nlm.nih.gov/12207173/

In vivo activity:

As expected, several other ER stress‐ and inflammation‐related transcripts were significantly induced in obese mice, but most were decreased to similar extents by didemnin B and caloric restriction (Table 2). Taken together, these data suggest that although didemnin B treatment did not inhibit the initiation of ER stress and induction of the UPR as indicated by eIF2α phosphorylation, it did diminish the later phases of the ER stress response (GRP78 and Xbp1s expression), and limited the activation of some inflammatory pathways (Mcp1 and Tnfa expression) – both to a greater extent than caloric restriction alone. Reference: Physiol Rep. 2016 Sep; 4(17): e12963. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5027364/

	Solvent	mg/mL	mM	comments
Solubility
	Acetonitrile	1.0	0.90

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 1,112.37 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. Wilson RB, Chen YJ, Sutherland BG, Sawyez CG, Zhang R, Woolnough T, Hetherington AM, Peters KM, Patel K, Kennelly JP, Leonard KA, Schuurman M, Jacobs RL, Wang R, Borradaile NM. The marine compound and elongation factor 1A1 inhibitor, didemnin B, provides benefit in western diet-induced non-alcoholic fatty liver disease. Pharmacol Res. 2020 Nov;161:105208. doi: 10.1016/j.phrs.2020.105208. Epub 2020 Sep 22. PMID: 32977024. 2. Baker MA, Grubb DR, Lawen A. Didemnin B induces apoptosis in proliferating but not resting peripheral blood mononuclear cells. Apoptosis. 2002 Oct;7(5):407-12. doi: 10.1023/a:1020078907108. PMID: 12207173. 3. Hetherington AM, Sawyez CG, Sutherland BG, Robson DL, Arya R, Kelly K, Jacobs RL, Borradaile NM. Treatment with didemnin B, an elongation factor 1A inhibitor, improves hepatic lipotoxicity in obese mice. Physiol Rep. 2016 Sep;4(17):e12963. doi: 10.14814/phy2.12963. PMID: 27613825; PMCID: PMC5027364.

In vitro protocol:

In vivo protocol:

1. Wilson RB, Chen YJ, Sutherland BG, Sawyez CG, Zhang R, Woolnough T, Hetherington AM, Peters KM, Patel K, Kennelly JP, Leonard KA, Schuurman M, Jacobs RL, Wang R, Borradaile NM. The marine compound and elongation factor 1A1 inhibitor, didemnin B, provides benefit in western diet-induced non-alcoholic fatty liver disease. Pharmacol Res. 2020 Nov;161:105208. doi: 10.1016/j.phrs.2020.105208. Epub 2020 Sep 22. PMID: 32977024. 2. Hetherington AM, Sawyez CG, Sutherland BG, Robson DL, Arya R, Kelly K, Jacobs RL, Borradaile NM. Treatment with didemnin B, an elongation factor 1A inhibitor, improves hepatic lipotoxicity in obese mice. Physiol Rep. 2016 Sep;4(17):e12963. doi: 10.14814/phy2.12963. PMID: 27613825; PMCID: PMC5027364.

1: Potts MB, McMillan EA, Rosales TI, Kim HS, Ou YH, Toombs JE, Brekken RA, Minden MD, MacMillan JB, White MA. Mode of action and pharmacogenomic biomarkers for exceptional responders to didemnin B. Nat Chem Biol. 2015 Jun;11(6):401-8. doi: 10.1038/nchembio.1797. Epub 2015 Apr 13. PubMed PMID: 25867045; PubMed Central PMCID: PMC4433765. 2: Hetherington AM, Sawyez CG, Sutherland BG, Robson DL, Arya R, Kelly K, Jacobs RL, Borradaile NM. Treatment with didemnin B, an elongation factor 1A inhibitor, improves hepatic lipotoxicity in obese mice. Physiol Rep. 2016 Sep;4(17). pii: e12963. doi: 10.14814/phy2.12963. PubMed PMID: 27613825; PubMed Central PMCID: PMC5027364. 3: Henne WA, Kularatne SA, Ayala-López W, Doorneweerd DD, Stinnette TW, Lu Y, Low PS. Synthesis and activity of folate conjugated didemnin B for potential treatment of inflammatory diseases. Bioorg Med Chem Lett. 2012 Jan 1;22(1):709-12. doi: 10.1016/j.bmcl.2011.10.042. Epub 2011 Oct 21. PubMed PMID: 22100311. 4: Xu Y, Kersten RD, Nam SJ, Lu L, Al-Suwailem AM, Zheng H, Fenical W, Dorrestein PC, Moore BS, Qian PY. Bacterial biosynthesis and maturation of the didemnin anti-cancer agents. J Am Chem Soc. 2012 May 23;134(20):8625-32. doi: 10.1021/ja301735a. Epub 2012 Apr 6. PubMed PMID: 22458477; PubMed Central PMCID: PMC3401512. 5: SirDeshpande BV, Toogood PL. Mechanism of protein synthesis inhibition by didemnin B in vitro. Biochemistry. 1995 Jul 18;34(28):9177-84. PubMed PMID: 7619818. 6: Tsukimoto M, Nagaoka M, Shishido Y, Fujimoto J, Nishisaka F, Matsumoto S, Harunari E, Imada C, Matsuzaki T. Bacterial production of the tunicate-derived antitumor cyclic depsipeptide didemnin B. J Nat Prod. 2011 Nov 28;74(11):2329-31. doi: 10.1021/np200543z. Epub 2011 Oct 28. PubMed PMID: 22035372. 7: Baker MA, Grubb DR, Lawen A. Didemnin B induces apoptosis in proliferating but not resting peripheral blood mononuclear cells. Apoptosis. 2002 Oct;7(5):407-12. PubMed PMID: 12207173. 8: Cain JM, Liu PY, Alberts DE, Gallion HH, Laufman L, O'Sullivan J, Weiss G, Bickers JN. Phase II trial of didemnin-B in advanced epithelial ovarian cancer. A Southwest Oncology Group study. Invest New Drugs. 1992 Apr;10(1):23-4. PubMed PMID: 1607250. 9: Beasley VR, Bruno SJ, Burner JS, Choi BW, Rinehart KL, Koritz GD, Levengood JM. Fate of tritiated didemnin B in mice: excretion and tissue concentrations after an intraperitoneal dose. Biopharm Drug Dispos. 2005 Nov;26(8):341-51. PubMed PMID: 16082719. 10: Johnson KL, Lawen A. Rapamycin inhibits didemnin B-induced apoptosis in human HL-60 cells: evidence for the possible involvement of FK506-binding protein 25. Immunol Cell Biol. 1999 Jun;77(3):242-8. PubMed PMID: 10361256. 11: Benvenuto JA, Newman RA, Bignami GS, Raybould TJ, Raber MN, Esparza L, Walters RS. Phase II clinical and pharmacological study of didemnin B in patients with metastatic breast cancer. Invest New Drugs. 1992 Jul;10(2):113-7. PubMed PMID: 1500265. 12: Meng L, Sin N, Crews CM. The antiproliferative agent didemnin B uncompetitively inhibits palmitoyl protein thioesterase. Biochemistry. 1998 Jul 21;37(29):10488-92. PubMed PMID: 9671519. 13: Crampton SL, Adams EG, Kuentzel SL, Li LH, Badiner G, Bhuyan BK. Biochemical and cellular effects of didemnins A and B. Cancer Res. 1984 May;44(5):1796-801. PubMed PMID: 6713383. 14: Li LH, Timmins LG, Wallace TL, Krueger WC, Prairie MD, Im WB. Mechanism of action of didemnin B, a depsipeptide from the sea. Cancer Lett. 1984 Jul;23(3):279-88. PubMed PMID: 6744252. 15: Chun HG, Davies B, Hoth D, Suffness M, Plowman J, Flora K, Grieshaber C, Leyland-Jones B. Didemnin B. The first marine compound entering clinical trials as an antineoplastic agent. Invest New Drugs. 1986;4(3):279-84. Review. PubMed PMID: 3546184. 16: Yuh DD, Zurcher RP, Carmichael PG, Morris RE. Efficacy of didemnin B in suppressing allograft rejection in mice and rats. Transplant Proc. 1989 Feb;21(1 Pt 1):1141-3. PubMed PMID: 2650081. 17: Tarver JE Jr, Pfizenmayer AJ, Joullié MM. Total syntheses of conformationally constrained didemnin B analogues. replacements of N,O-dimethyltyrosine with L-1,2,3,4-tetrahydroisoquinoline and L-1,2,3,4-tetrahydro-7-methoxyisoquinoline. J Org Chem. 2001 Nov 16;66(23):7575-87. PubMed PMID: 11701008. 18: Grubb DR, Ly JD, Vaillant F, Johnson KL, Lawen A. Mitochondrial cytochrome c release is caspase-dependent and does not involve mitochondrial permeability transition in didemnin B-induced apoptosis. Oncogene. 2001 Jul 5;20(30):4085-94. PubMed PMID: 11494136. 19: Hossain MB, van der Helm D, Antel J, Sheldrick GM, Sanduja SK, Weinheimer AJ. Crystal and molecular structure of didemnin B, an antiviral and cytotoxic depsipeptide. Proc Natl Acad Sci U S A. 1988 Jun;85(12):4118-22. PubMed PMID: 3380783; PubMed Central PMCID: PMC280377. 20: Raybould TJ, Grothaus PG, Simpson SB, Bignami GS, Lazo CB, Newman RA. An enzyme immunoassay for determining plasma concentrations of didemnin B. J Clin Lab Anal. 1992;6(3):136-42. PubMed PMID: 1506980.