LY2334737 | CAS#892128-60-8 | antimetabolite | gemcitabine prodrug

MedKoo Cat#: 201792 | Name: LY2334737

Description:

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

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

LY2334737

CAS#892128-60-8

Theoretical Analysis

MedKoo Cat#: 201792

Name: LY2334737

CAS#: 892128-60-8

Chemical Formula: C17H25F2N3O5

Exact Mass: 389.1762

Molecular Weight: 389.40

Elemental Analysis: C, 52.44; H, 6.47; F, 9.76; N, 10.79; O, 20.54

Price and Availability

Size	Price	Availability
50mg	USD 750.00	2 Weeks
100mg	USD 1,350.00	2 Weeks
200mg	USD 2,450.00	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

More Info

Product Data

Product Data

Instruction

View handling instruction

Biological target:

LY2334737 exhibits inhibitory activity against enterovirus A71 (EV-A71) infection.

In vitro activity:

Human recombinant CES isozymes were assayed for LY2334737 hydrolysis. Stable CES-overexpressing HCT-116 transfectants and a SK-OV-3 knockdown were prepared. Five cell lines that express CES2 responded to LY2334737 treatment. LY2334737 was less cytotoxic to a SK-OV-3 CES2 knockdown than parental cells. Bystander studies showed statistically greater PC-3-GFP growth inhibition by LY2334737 when cells were cocultured with CES2 and not mock transfectants. Reference: Clin Cancer Res. 2013 Mar 1;19(5):1159-68. https://pubmed.ncbi.nlm.nih.gov/23325581/

In vivo activity:

This study reports results evaluating the properties of metronomic administration of an oral prodrug of gemcitabine LY2334737 in nontumor-bearing mice and in preclinical models of human ovarian (SKOV3-13) and breast cancer (LM2-4) xenografts. Unexpectedly, metronomic LY2334737 administration caused increased blood flow in luciferase-tagged LM2-4 tumor xenografts, and this effect, readily measured using contrast micro-ultrasound, coincided with a relative increase in tumor bioluminescence. Reference: Mol Cancer Ther. 2012 Mar;11(3):680-9. https://pubmed.ncbi.nlm.nih.gov/22188817/

	Solvent	mg/mL	mM
Solubility
	DMSO	100.0	256.81

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 389.40 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. Pratt SE, Durland-Busbice S, Shepard RL, Heinz-Taheny K, Iversen PW, Dantzig AH. Human carboxylesterase-2 hydrolyzes the prodrug of gemcitabine (LY2334737) and confers prodrug sensitivity to cancer cells. Clin Cancer Res. 2013 Mar 1;19(5):1159-68. doi: 10.1158/1078-0432.CCR-12-1184. Epub 2013 Jan 16. PMID: 23325581. 2. Pratt SE, Durland-Busbice S, Shepard RL, Donoho GP, Starling JJ, Wickremsinhe ER, Perkins EJ, Dantzig AH. Efficacy of low-dose oral metronomic dosing of the prodrug of gemcitabine, LY2334737, in human tumor xenografts. Mol Cancer Ther. 2013 Apr;12(4):481-90. doi: 10.1158/1535-7163.MCT-12-0654. Epub 2013 Jan 31. PMID: 23371859. 3. Francia G, Shaked Y, Hashimoto K, Sun J, Yin M, Cesta C, Xu P, Man S, Hackl C, Stewart J, Uhlik M, Dantzig AH, Foster FS, Kerbel RS. Low-dose metronomic oral dosing of a prodrug of gemcitabine (LY2334737) causes antitumor effects in the absence of inhibition of systemic vasculogenesis. Mol Cancer Ther. 2012 Mar;11(3):680-9. doi: 10.1158/1535-7163.MCT-11-0659. Epub 2011 Dec 21. PMID: 22188817; PMCID: PMC3409688.

In vitro protocol:

In vivo protocol:

1. Pratt SE, Durland-Busbice S, Shepard RL, Donoho GP, Starling JJ, Wickremsinhe ER, Perkins EJ, Dantzig AH. Efficacy of low-dose oral metronomic dosing of the prodrug of gemcitabine, LY2334737, in human tumor xenografts. Mol Cancer Ther. 2013 Apr;12(4):481-90. doi: 10.1158/1535-7163.MCT-12-0654. Epub 2013 Jan 31. PMID: 23371859. 2. Francia G, Shaked Y, Hashimoto K, Sun J, Yin M, Cesta C, Xu P, Man S, Hackl C, Stewart J, Uhlik M, Dantzig AH, Foster FS, Kerbel RS. Low-dose metronomic oral dosing of a prodrug of gemcitabine (LY2334737) causes antitumor effects in the absence of inhibition of systemic vasculogenesis. Mol Cancer Ther. 2012 Mar;11(3):680-9. doi: 10.1158/1535-7163.MCT-11-0659. Epub 2011 Dec 21. PMID: 22188817; PMCID: PMC3409688.

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