LY2334737
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MedKoo CAT#: 201792

CAS#: 892128-60-8

Description: LY2334737 is an orally available valproic acid ester of gemcitabine, a broad-spectrum antimetabolite with antineoplastic activity. LY2334737 is hydrolyzed by carboxylesterase 2 (CES2) and releases gemcitabine systemically over a period of time consistent with formation rate-limited kinetics. In turn, gemcitabine is converted into the active metabolites difluorodeoxycytidine diphosphate and triphosphate (dFdCDP and dFdCTP) by deoxycytidine kinase. dFdCDP inhibits ribonucleotide reductase, thereby decreasing the deoxynucleotide pool available for DNA replication; dFdCTP is incorporated into DNA, resulting in premature termination of DNA replication and eventually the induction of apoptosis. Compared to gemcitabine, this prodrug is able to avoid hydrolysis in enterocytes and the portal circulation thus avoiding first pass metabolism and increasing systemic gemcitabine availability.


Chemical Structure

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LY2334737
CAS# 892128-60-8

Theoretical Analysis

MedKoo Cat#: 201792
Name: LY2334737
CAS#: 892128-60-8
Chemical Formula: C17H25F2N3O5
Exact Mass: 389.17623
Molecular Weight: 389.39
Elemental Analysis: C, 52.44; H, 6.47; F, 9.76; N, 10.79; O, 20.54

Price and Availability

Size Price Availability Quantity
25.0mg USD 190.0 2 Weeks
50.0mg USD 350.0 2 Weeks
100.0mg USD 550.0 2 Weeks
200.0mg USD 1050.0 2 Weeks
500.0mg USD 1950.0 2 Weeks
1.0g USD 2950.0 2 Weeks
2.0g USD 4950.0 2 Weeks
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Synonym: LY2334737; LY 2334737; LY-2334737; gemcitabine prodrug

IUPAC/Chemical Name: N-(1-((2S,4R,5R)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-2-oxo-1,2-dihydropyrimidin-4-yl)-2-propylpentanamide

InChi Key: MEOYFIHNRBNEPI-KYOSRNDESA-N

InChi Code: InChI=1S/C17H25F2N3O5/c1-3-5-10(6-4-2)14(25)20-12-7-8-22(16(26)21-12)15-17(18,19)13(24)11(9-23)27-15/h7-8,10-11,13,15,23-24H,3-6,9H2,1-2H3,(H,20,21,25,26)/t11-,13-,15+/m1/s1

SMILES Code: CCCC(CCC)C(NC(C=CN1[C@H]2O[C@H](CO)[C@@H](O)C2(F)F)=NC1=O)=O

Appearance: Solid powder

Purity: >98%

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: >5 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

Preparing Stock Solutions

The following data is based on the product molecular weight 389.39 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.

Recalculate based on batch purity %
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

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1: Bildstein L, Dubernet C, Marsaud V, Chacun H, Nicolas V, Gueutin C, Sarasin A, Bénech H, Lepêtre-Mouelhi S, Desmaële D, Couvreur P. Transmembrane diffusion of gemcitabine by a nanoparticulate squalenoyl prodrug: An original drug delivery pathway. J Control Release. 2010 Aug 5. [Epub ahead of print] PubMed PMID: 20691740.

2: Adema AD, Losekoot N, Smid K, Kathmann I, Myhren F, Sandvold ML, Peters GJ. Induction of resistance to the lipophilic cytarabine prodrug elacytarabine (CP-4055) in CEM leukemic cells. Nucleosides Nucleotides Nucleic Acids. 2010 Jun;29(4-6):394-9. PubMed PMID: 20544525.

3: Beumer JH, Eiseman JL, Gilbert JA, Holleran JL, Yellow-Duke AE, Clausen DM, D'Argenio DZ, Ames MM, Hershberger PA, Parise RA, Bai L, Covey JM, Egorin MJ. Plasma pharmacokinetics and oral bioavailability of the 3,4,5,6-tetrahydrouridine (THU) prodrug, triacetyl-THU (taTHU), in mice. Cancer Chemother Pharmacol. 2010 May 5. [Epub ahead of print] PubMed PMID: 20443002.

4: Pili B, Bourgaux C, Amenitsch H, Keller G, Lepêtre-Mouelhi S, Desmaële D, Couvreur P, Ollivon M. Interaction of a new anticancer prodrug, gemcitabine-squalene, with a model membrane: coupled DSC and XRD study. Biochim Biophys Acta. 2010 Aug;1798(8):1522-32. Epub 2010 May 7. PubMed PMID: 20435013.

5: Kiew LV, Cheong SK, Sidik K, Chung LY. Improved plasma stability and sustained release profile of gemcitabine via polypeptide conjugation. Int J Pharm. 2010 May 31;391(1-2):212-20. Epub 2010 Mar 7. PubMed PMID: 20214970.

6: Hirai H, Arai T, Okada M, Nishibata T, Kobayashi M, Sakai N, Imagaki K, Ohtani J, Sakai T, Yoshizumi T, Mizuarai S, Iwasawa Y, Kotani H. MK-1775, a small molecule Wee1 inhibitor, enhances anti-tumor efficacy of various DNA-damaging agents, including 5-fluorouracil. Cancer Biol Ther. 2010 Apr 4;9(7). [Epub ahead of print] PubMed PMID: 20107315.

7: Saito Y, Yasunaga M, Kuroda J, Koga Y, Matsumura Y. Antitumour activity of NK012, SN-38-incorporating polymeric micelles, in hypovascular orthotopic pancreatic tumour. Eur J Cancer. 2010 Feb;46(3):650-8. Epub 2009 Dec 16. PubMed PMID: 20015633.

8: Bender DM, Bao J, Dantzig AH, Diseroad WD, Law KL, Magnus NA, Peterson JA, Perkins EJ, Pu YJ, Reutzel-Edens SM, Remick DM, Starling JJ, Stephenson GA, Vaid RK, Zhang D, McCarthy JR. Synthesis, crystallization, and biological evaluation of an orally active prodrug of gemcitabine. J Med Chem. 2009 Nov 26;52(22):6958-61. PubMed PMID: 19860433.

9: Maréchal R, Van Laethem JL. HuR modulates gemcitabine efficacy: new perspectives in pancreatic cancer treatment. Expert Rev Anticancer Ther. 2009 Oct;9(10):1439-41. PubMed PMID: 19828005.

10: Shahrokni A, Rajebi MR, Saif MW. Toxicity and efficacy of 5-fluorouracil and capecitabine in a patient with TYMS gene polymorphism: A challenge or a dilemma? Clin Colorectal Cancer. 2009 Oct;8(4):231-4. PubMed PMID: 19822515.

11: Bildstein L, Hillaireau H, Desmaële D, Lepêtre-Mouelhi S, Dubernet C, Couvreur P. Freeze-drying of squalenoylated nucleoside analogue nanoparticles. Int J Pharm. 2009 Nov 3;381(2):140-5. Epub 2009 Apr 11. PubMed PMID: 19782881.

12: Réjiba S, Bigand C, Parmentier C, Hajri A. Gemcitabine-based chemogene therapy for pancreatic cancer using Ad-dCK::UMK GDEPT and TS/RR siRNA strategies. Neoplasia. 2009 Jul;11(7):637-50. PubMed PMID: 19568409; PubMed Central PMCID: PMC2697350.

13: Laing RE, Walter MA, Campbell DO, Herschman HR, Satyamurthy N, Phelps ME, Czernin J, Witte ON, Radu CG. Noninvasive prediction of tumor responses to gemcitabine using positron emission tomography. Proc Natl Acad Sci U S A. 2009 Feb 24;106(8):2847-52. Epub 2009 Feb 5. PubMed PMID: 19196993; PubMed Central PMCID: PMC2636738. . PubMed PMID: 8703688.