LY2334737

Modify Date: 2024-01-08 17:48:54

LY2334737 structure	Common Name	LY2334737
	CAS Number	892128-60-8	Molecular Weight	389.39400
	Density	N/A	Boiling Point	N/A
	Molecular Formula	C₁₇H₂₅F₂N₃O₅	Melting Point	N/A
	MSDS	N/A	Flash Point	N/A

Use of LY2334737

LY2334737 is an orally available prodrug of gemcitabine which is a nucleoside analog used as chemotherapy.IC50 Value:Target: Nucleoside analogin 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 [1].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) [1]. 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 [2]. 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 [3].

Name	N-[1-[(2R,4R,5R)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-2-oxopyrimidin-4-yl]-2-propylpentanamide
Synonym	More Synonyms

Description	LY2334737 is an orally available prodrug of gemcitabine which is a nucleoside analog used as chemotherapy.IC50 Value:Target: Nucleoside analogin 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 [1].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) [1]. 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 [2]. 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 [3].
Related Catalog	Signaling Pathways >> Cell Cycle/DNA Damage >> Nucleoside Antimetabolite/Analog Research Areas >> Cancer
References	[1]. Pratt SE, et al. 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. [2]. Koolen SL, et al. Phase I study of Oral gemcitabine prodrug (LY2334737) alone and in combination with erlotinib in patients with advanced solid tumors. Clin Cancer Res. 2011 Sep 15;17(18):6071-82. [3]. Francia G, et al. 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.

Description

Related Catalog

Signaling Pathways >> Cell Cycle/DNA Damage >> Nucleoside Antimetabolite/Analog

Research Areas >> Cancer

References

[1]. Pratt SE, et al. 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.

[2]. Koolen SL, et al. Phase I study of Oral gemcitabine prodrug (LY2334737) alone and in combination with erlotinib in patients with advanced solid tumors. Clin Cancer Res. 2011 Sep 15;17(18):6071-82.

[3]. Francia G, et al. 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.