LY2334737

Category	Enterovirus (EV)
CAS	892128-60-8
Description	LY2334737 is an orally available valproic acid ester of gemcitabine, which is a broad-spectrum antimetabolite with antineoplastic activity. It is an orally available prodrug of gemcitabine which is a nucleoside analog used as chemotherapy. It is hydrolyzed by carboxylesterase 2 (CES2) and releases gemcitabine systemically over a period of time consistent with formation rate-limited kinetics. It was less cytotoxic to a SK-OV-3 CES2 knockdown than parental cells.

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Product Information

Synonyms	LY2334737; LY 2334737; LY-2334737; gemcitabine prodrug; 2'-Deoxy-2',2'-difluoro-N-(1-oxo-2-propylpentyl)cytidine;N-[1-[(2R,4R,5R)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-2-oxopyrimidin-4-yl]-2-propylpentanamide
IUPAC Name	N-[1-[(2R,4R,5R)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-2-oxopyrimidin-4-yl]-2-propylpentanamide
Molecular Weight	389.39
Molecular Formula	C17H25F2N3O5
Canonical SMILES	CCCC(CCC)C(=O)NC1=NC(=O)N(C=C1)C2C(C(C(O2)CO)O)(F)F
InChI	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
InChIKey	MEOYFIHNRBNEPI-UXIGCNINSA-N
Purity	>98 %
Density	1.41±0.1 g/cm3 \| Condition: Temp: 20 °C Press: 760 Torr
Solubility	10 mM in DMSO
Appearance	Solid powder
Application	LY2334737 is used as chemotherapy. It has antineoplastic activity.
Shelf Life	2 month in rt, long time
Storage	-20°C Freezer
Complexity	620
Exact Mass	389.17622723
In Vitro	Five cell lines that express CES2 responded to LY2334737treatment. LY2334737 was less cytotoxic to a SK-OV-3 CES2 knockdown than parental cells. The drug response of CES2-transfected HCT-116 cells correlated with CES2 expression level. Bystander studies showed statistically greater PC-3-GFP growth inhibition by LY2334737 when cells were cocultured with CES2 and not mock transfectants.
In Vivo	Oral treatment of xenograft models with 3.2 mg/kg LY2334737 once a day for 21 days showed greater tumor growth inhibition of CES2 transfectant than the mock transfectant (P ≤ 0.001). The MTD was 40 mg LY2334737. Fatigue was the most frequent DLT for LY2334737monotherapy (4 patients) followed by elevated transaminase levels (2 patients), both observed at the 40- to 50-mg dose levels. Among the 10 patients in the combination arm, 2 had DLTs at the 40-mg dose level. These were fatigue and elevated liver enzyme levels. 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.
PSA	117.17000
Target	Nucleoside Antimetabolite/Analog; Enterovirus
XLogP3-AA	1.7