LY2334737: an orally available prodrug of gemcitabine for treatment of patients with advanced solid tumors [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]
| ID Source | ID |
|---|---|
| PubMed CID | 11646777 |
| CHEMBL ID | 577711 |
| SCHEMBL ID | 595762 |
| MeSH ID | M0569901 |
| Synonym |
|---|
| CHEMBL577711 |
| ly2334737 |
| ly-2334737 |
| unii-ylr364xysa |
| cytidine, 2'-deoxy-2',2'-difluoro-n-(1-oxo-2-propylpentyl)- |
| ylr364xysa , |
| 892128-60-8 |
| SCHEMBL595762 |
| HY-13672 |
| CS-1815 |
| 1-(2,2-difluoro-2-deoxy-beta-d-ribofuranosyl)-4-(2-propyl-1-oxopentyl)aminopyrimidin-2-one |
| AKOS030526967 |
| NCGC00378563-01 |
| DB12906 |
| n-[1-[(2r,4r,5r)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-2-oxopyrimidin-4-yl]-2-propylpentanamide |
| Q27294578 |
| MS-26471 |
| NCGC00378563-02 |
| jxrhgmjvkrflok-uxigcninsa-n |
| ly 2334737 |
| BL98401 |
| DTXSID001025742 |
| 2'-deoxy-2',2'-difluoro-n-(1-oxo-2-propylpentyl)-cytidine |
| n-(1-((2r,4r,5r)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-2-oxo-1,2-dihydropyrimidin-4-yl)-2-propylpentanamide |
| n-{1-[(2r,4r,5r)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-2-oxo-1,2-dihydropyrimidin-4-yl}-2-propylpentanamide |
LY2334737 is an orally available prodrug of gemcitabine.
| Excerpt | Reference | Relevance |
|---|---|---|
| "LY2334737 is an oral gemcitabine prodrug. " | ( Phase I study of oral gemcitabine prodrug (LY2334737) in Japanese patients with advanced solid tumors. Benhadji, KA; Makiuchi, T; Nokihara, H; Sekiguchi, R; Slapak, CA; Tamura, T; Uenaka, K; Yamada, Y; Yamamoto, N, 2013) | 2.1 |
| "LY2334737 is an orally available prodrug of gemcitabine. " | ( Phase I study of Oral gemcitabine prodrug (LY2334737) alone and in combination with erlotinib in patients with advanced solid tumors. Beijnen, JH; Benhadji, KA; Callies, S; Garcia-Ribas, I; Jansen, RS; Koolen, SL; Kronemeijer, RH; Langenberg, MH; Nol, A; Schellens, JH; Slapak, CA; Voest, EE; Witteveen, PO, 2011) | 2.07 |
| Excerpt | Reference | Relevance |
|---|---|---|
| "LY2334737 displays linear pharmacokinetics and the MTD is 40 mg with or without daily administration of 100 mg erlotinib. " | ( Phase I study of Oral gemcitabine prodrug (LY2334737) alone and in combination with erlotinib in patients with advanced solid tumors. Beijnen, JH; Benhadji, KA; Callies, S; Garcia-Ribas, I; Jansen, RS; Koolen, SL; Kronemeijer, RH; Langenberg, MH; Nol, A; Schellens, JH; Slapak, CA; Voest, EE; Witteveen, PO, 2011) | 2.07 |
PK data were consistent with the first-in-man study of LY2334737 and did not reveal any drug-drug interaction. This Phase 1b study aimed to determine the recommended Phase 2 dose of Ly 2334737, an oral pro-drug of gemcitabine.
| Excerpt | Reference | Relevance |
|---|---|---|
| " Valproate amide 3 is orally bioavailable and releases gemcitabine into the systemic circulation after passing through the intestinal mucosa." | ( Synthesis, crystallization, and biological evaluation of an orally active prodrug of gemcitabine. Bao, J; Bender, DM; Dantzig, AH; Diseroad, WD; Law, KL; Magnus, NA; McCarthy, JR; Perkins, EJ; Peterson, JA; Pu, YJ; Remick, DM; Reutzel-Edens, SM; Starling, JJ; Stephenson, GA; Vaid, RK; Zhang, D, 2009) | 0.35 |
| "The ATP-binding cassette transporter P-glycoprotein (P-gp) is known to limit both brain penetration and oral bioavailability of many chemotherapy drugs." | ( A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein. Ambudkar, SV; Brimacombe, KR; Chen, L; Gottesman, MM; Guha, R; Hall, MD; Klumpp-Thomas, C; Lee, OW; Lee, TD; Lusvarghi, S; Robey, RW; Shen, M; Tebase, BG, 2019) | 0.51 |
| Excerpt | Relevance | Reference |
|---|---|---|
| " Oral dosing of mice results in absorption of intact prodrug with slow systemic hydrolysis yielding higher plasma levels of LY2334737 than gemcitabine and prolonged gemcitabine exposure." | ( Efficacy of low-dose oral metronomic dosing of the prodrug of gemcitabine, LY2334737, in human tumor xenografts. Dantzig, AH; Donoho, GP; Durland-Busbice, S; Perkins, EJ; Pratt, SE; Shepard, RL; Starling, JJ; Wickremsinhe, ER, 2013) | 0.83 |
| " The toxicities observed at the 40 mg dose may require the development of alternative dosing schedules." | ( Phase I study of oral gemcitabine prodrug (LY2334737) in Japanese patients with advanced solid tumors. Benhadji, KA; Makiuchi, T; Nokihara, H; Sekiguchi, R; Slapak, CA; Tamura, T; Uenaka, K; Yamada, Y; Yamamoto, N, 2013) | 0.65 |
| Protein | Taxonomy | Measurement | Average (µ) | Min (ref.) | Avg (ref.) | Max (ref.) | Bioassay(s) |
|---|---|---|---|---|---|---|---|
| cytochrome P450 family 3 subfamily A polypeptide 4 | Homo sapiens (human) | Potency | 23.9185 | 0.0123 | 7.9835 | 43.2770 | AID1645841 |
| G | Vesicular stomatitis virus | Potency | 8.4866 | 0.0123 | 8.9648 | 39.8107 | AID1645842 |
| Interferon beta | Homo sapiens (human) | Potency | 8.4866 | 0.0033 | 9.1582 | 39.8107 | AID1645842 |
| HLA class I histocompatibility antigen, B alpha chain | Homo sapiens (human) | Potency | 8.4866 | 0.0123 | 8.9648 | 39.8107 | AID1645842 |
| Inositol hexakisphosphate kinase 1 | Homo sapiens (human) | Potency | 8.4866 | 0.0123 | 8.9648 | 39.8107 | AID1645842 |
| cytochrome P450 2C9, partial | Homo sapiens (human) | Potency | 8.4866 | 0.0123 | 8.9648 | 39.8107 | AID1645842 |
| [prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023] | |||||||
| Assay ID | Title | Year | Journal | Article |
|---|---|---|---|---|
| AID1346987 | P-glycoprotein substrates identified in KB-8-5-11 adenocarcinoma cell line, qHTS therapeutic library screen | 2019 | Molecular pharmacology, 11, Volume: 96, Issue:5 | A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein. |
| AID1346986 | P-glycoprotein substrates identified in KB-3-1 adenocarcinoma cell line, qHTS therapeutic library screen | 2019 | Molecular pharmacology, 11, Volume: 96, Issue:5 | A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein. |
| AID1296008 | Cytotoxic Profiling of Annotated Libraries Using Quantitative High-Throughput Screening | 2020 | SLAS discovery : advancing life sciences R & D, 01, Volume: 25, Issue:1 | Cytotoxic Profiling of Annotated and Diverse Chemical Libraries Using Quantitative High-Throughput Screening. |
| AID1347159 | Primary screen GU Rhodamine qHTS for Zika virus inhibitors: Unlinked NS2B-NS3 protease assay | 2020 | Proceedings of the National Academy of Sciences of the United States of America, 12-08, Volume: 117, Issue:49 | Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors. |
| AID1347160 | Primary screen NINDS Rhodamine qHTS for Zika virus inhibitors | 2020 | Proceedings of the National Academy of Sciences of the United States of America, 12-08, Volume: 117, Issue:49 | Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors. |
| AID1347411 | qHTS to identify inhibitors of the type 1 interferon - major histocompatibility complex class I in skeletal muscle: primary screen against the NCATS Mechanism Interrogation Plate v5.0 (MIPE) Libary | 2020 | ACS chemical biology, 07-17, Volume: 15, Issue:7 | High-Throughput Screening to Identify Inhibitors of the Type I Interferon-Major Histocompatibility Complex Class I Pathway in Skeletal Muscle. |
| AID1066254 | Cytostatic activity against human MCF7 cells after 2 days by coulter counter analysis | 2014 | Journal of medicinal chemistry, Jan-09, Volume: 57, Issue:1 | Synthesis and cytostatic evaluation of 4-N-alkanoyl and 4-N-alkyl gemcitabine analogues. |
| AID438469 | Antitumor activity in human HCT116 cells xenografted CD1 mouse assessed as maximum tumor reduction at 3.77 mg/kg, po administered daily for 14 days measured after 6 weeks | 2009 | Journal of medicinal chemistry, Nov-26, Volume: 52, Issue:22 | Synthesis, crystallization, and biological evaluation of an orally active prodrug of gemcitabine. |
| AID438452 | Solubility in buffer solution at pH 1 after 4 hrs at 40 degC | 2009 | Journal of medicinal chemistry, Nov-26, Volume: 52, Issue:22 | Synthesis, crystallization, and biological evaluation of an orally active prodrug of gemcitabine. |
| AID1066258 | Cytostatic activity against mouse L1210 cells after 2 days by coulter counter analysis | 2014 | Journal of medicinal chemistry, Jan-09, Volume: 57, Issue:1 | Synthesis and cytostatic evaluation of 4-N-alkanoyl and 4-N-alkyl gemcitabine analogues. |
| AID438459 | Stability in CD1 mouse small intestine homogenate assessed as hydrolysis rate after 30 mins at 96 uM | 2009 | Journal of medicinal chemistry, Nov-26, Volume: 52, Issue:22 | Synthesis, crystallization, and biological evaluation of an orally active prodrug of gemcitabine. |
| AID438455 | Solubility in buffer solution at pH 6 after 4 hrs at 40 degC | 2009 | Journal of medicinal chemistry, Nov-26, Volume: 52, Issue:22 | Synthesis, crystallization, and biological evaluation of an orally active prodrug of gemcitabine. |
| AID1066257 | Cytostatic activity against human CEM cells after 3 days by coulter counter analysis | 2014 | Journal of medicinal chemistry, Jan-09, Volume: 57, Issue:1 | Synthesis and cytostatic evaluation of 4-N-alkanoyl and 4-N-alkyl gemcitabine analogues. |
| AID438456 | Solubility in buffer solution at pH 8 after 4 hrs at 40 degC | 2009 | Journal of medicinal chemistry, Nov-26, Volume: 52, Issue:22 | Synthesis, crystallization, and biological evaluation of an orally active prodrug of gemcitabine. |
| AID438468 | Tmax in po dosed CD1 mouse | 2009 | Journal of medicinal chemistry, Nov-26, Volume: 52, Issue:22 | Synthesis, crystallization, and biological evaluation of an orally active prodrug of gemcitabine. |
| AID438449 | Chemical stability in buffer solution assessed as hydrolysis at pH 4 after 4 hrs at 40 degC | 2009 | Journal of medicinal chemistry, Nov-26, Volume: 52, Issue:22 | Synthesis, crystallization, and biological evaluation of an orally active prodrug of gemcitabine. |
| AID438466 | AUC in po dosed CD1 mouse | 2009 | Journal of medicinal chemistry, Nov-26, Volume: 52, Issue:22 | Synthesis, crystallization, and biological evaluation of an orally active prodrug of gemcitabine. |
| AID438458 | Stability in human small intestine homogenate assessed as hydrolysis rate at 96 uM | 2009 | Journal of medicinal chemistry, Nov-26, Volume: 52, Issue:22 | Synthesis, crystallization, and biological evaluation of an orally active prodrug of gemcitabine. |
| AID438447 | Chemical stability in buffer solution assessed as hydrolysis at pH 1 after 4 hrs at 40 degC | 2009 | Journal of medicinal chemistry, Nov-26, Volume: 52, Issue:22 | Synthesis, crystallization, and biological evaluation of an orally active prodrug of gemcitabine. |
| AID438461 | Stability in human liver S9 fraction assessed as hydrolysis rate at 100 uM | 2009 | Journal of medicinal chemistry, Nov-26, Volume: 52, Issue:22 | Synthesis, crystallization, and biological evaluation of an orally active prodrug of gemcitabine. |
| AID1066255 | Cytostatic activity against human HeLa cells after 4 days by coulter counter analysis | 2014 | Journal of medicinal chemistry, Jan-09, Volume: 57, Issue:1 | Synthesis and cytostatic evaluation of 4-N-alkanoyl and 4-N-alkyl gemcitabine analogues. |
| AID438465 | Gemcitabine Cmax in CD1 mouse at 14.3 mg/kg, po | 2009 | Journal of medicinal chemistry, Nov-26, Volume: 52, Issue:22 | Synthesis, crystallization, and biological evaluation of an orally active prodrug of gemcitabine. |
| AID438454 | Solubility in buffer solution at pH 4 after 4 hrs at 40 degC | 2009 | Journal of medicinal chemistry, Nov-26, Volume: 52, Issue:22 | Synthesis, crystallization, and biological evaluation of an orally active prodrug of gemcitabine. |
| AID438451 | Chemical stability in buffer solution assessed as hydrolysis at pH 8 after 4 hrs at 40 degC | 2009 | Journal of medicinal chemistry, Nov-26, Volume: 52, Issue:22 | Synthesis, crystallization, and biological evaluation of an orally active prodrug of gemcitabine. |
| AID438462 | Drug level in CD1 mouse portal blood at 14.3 mg/kg, po after 5 mins | 2009 | Journal of medicinal chemistry, Nov-26, Volume: 52, Issue:22 | Synthesis, crystallization, and biological evaluation of an orally active prodrug of gemcitabine. |
| AID438464 | Gemcitabine AUC in CD1 mouse at 14.3 mg/kg, po | 2009 | Journal of medicinal chemistry, Nov-26, Volume: 52, Issue:22 | Synthesis, crystallization, and biological evaluation of an orally active prodrug of gemcitabine. |
| AID438472 | Stability in CD1 mouse liver S9 fraction assessed as hydrolysis rate at 100 uM | 2009 | Journal of medicinal chemistry, Nov-26, Volume: 52, Issue:22 | Synthesis, crystallization, and biological evaluation of an orally active prodrug of gemcitabine. |
| AID438467 | Cmax in po dosed CD1 mouse | 2009 | Journal of medicinal chemistry, Nov-26, Volume: 52, Issue:22 | Synthesis, crystallization, and biological evaluation of an orally active prodrug of gemcitabine. |
| AID438460 | Stability in human small intestine homogenate assessed as hydrolysis rate after 30 mins at 96 uM | 2009 | Journal of medicinal chemistry, Nov-26, Volume: 52, Issue:22 | Synthesis, crystallization, and biological evaluation of an orally active prodrug of gemcitabine. |
| AID438448 | Chemical stability in buffer solution assessed as hydrolysis at pH 2 after 4 hrs at 40 degC | 2009 | Journal of medicinal chemistry, Nov-26, Volume: 52, Issue:22 | Synthesis, crystallization, and biological evaluation of an orally active prodrug of gemcitabine. |
| AID438453 | Solubility in buffer solution at pH 2 after 4 hrs at 40 degC | 2009 | Journal of medicinal chemistry, Nov-26, Volume: 52, Issue:22 | Synthesis, crystallization, and biological evaluation of an orally active prodrug of gemcitabine. |
| AID438470 | Antitumor activity in human HCT116 cells xenografted CD1 mouse assessed as maximum tumor reduction at 7.55 mg/kg, po administered daily for 14 days measured after 6 weeks | 2009 | Journal of medicinal chemistry, Nov-26, Volume: 52, Issue:22 | Synthesis, crystallization, and biological evaluation of an orally active prodrug of gemcitabine. |
| AID438450 | Chemical stability in buffer solution assessed as hydrolysis at pH 6 after 4 hrs at 40 degC | 2009 | Journal of medicinal chemistry, Nov-26, Volume: 52, Issue:22 | Synthesis, crystallization, and biological evaluation of an orally active prodrug of gemcitabine. |
| AID1066256 | Cytostatic activity against human dCK-deficient CEM cells after 3 days by coulter counter analysis | 2014 | Journal of medicinal chemistry, Jan-09, Volume: 57, Issue:1 | Synthesis and cytostatic evaluation of 4-N-alkanoyl and 4-N-alkyl gemcitabine analogues. |
| AID438457 | Stability in CD1 mouse small intestine homogenate assessed as hydrolysis rate minute at 96 uM | 2009 | Journal of medicinal chemistry, Nov-26, Volume: 52, Issue:22 | Synthesis, crystallization, and biological evaluation of an orally active prodrug of gemcitabine. |
| [information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||||
| Timeframe | Studies, This Drug (%) | All Drugs % |
|---|---|---|
| pre-1990 | 0 (0.00) | 18.7374 |
| 1990's | 0 (0.00) | 18.2507 |
| 2000's | 1 (7.14) | 29.6817 |
| 2010's | 10 (71.43) | 24.3611 |
| 2020's | 3 (21.43) | 2.80 |
| [information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||
According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be moderate demand-to-supply ratio for research on this compound.
| This Compound (20.54) All Compounds (24.57) |
| Publication Type | This drug (%) | All Drugs (%) |
|---|---|---|
| Trials | 5 (35.71%) | 5.53% |
| Reviews | 0 (0.00%) | 6.00% |
| Case Studies | 0 (0.00%) | 4.05% |
| Observational | 0 (0.00%) | 0.25% |
| Other | 9 (64.29%) | 84.16% |
| [information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||