Synonym
LY-188011; LY 188011; LY188011; Abbreviations: dFdC; dFdCyd; gemcitabine;Gemzar.
IUPAC/Chemical Name
4-amino-1-((2R,4R,5R)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyrimidin-2(1H)-one
InChi Key
SDUQYLNIPVEERB-QPPQHZFASA-N
InChi Code
InChI=1S/C9H11F2N3O4/c10-9(11)6(16)4(3-15)18-7(9)14-2-1-5(12)13-8(14)17/h1-2,4,6-7,15-16H,3H2,(H2,12,13,17)/t4-,6-,7-/m1/s1
SMILES Code
O=C1N=C(N)C=CN1[C@@H]2O[C@H](CO)[C@@H](O)C2(F)F
Purity
>98% (or refer to the Certificate of Analysis)
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
>2 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
Biological target:
DNA synthesis & repair inhibitor
In vitro activity:
To test the antiviral activity of gemcitabine and 2FdC against SARS-CoV-2, the image-based antiviral assay was carried out by addition of 3-fold serial dilutions (from 300 to 0.02 μM at 10 concentration points) of each compound to Vero cells for 30 min before infection (MOI, 0.02), in which remdesivir was used as a control. The resulting microscopic images from the viral S protein and nuclear condensation represented antiviral efficacy and cytotoxicity, respectively (Figure 2A). Gemcitabine potently suppressed viral infection in a dose-dependent manner with little cytotoxicity at the maximal concentration (300 μM), equating to EC50 of 1.2 ± 1.1 μM, CC50 > 300 μM, and an SI value > 250.0 (Figure 2B). In contrast, 2FdC exhibited weaker antiviral activity with EC50 of 175.2 ± 1.3 μM, CC50 > 300.0 μM, and SI > 1.7. As expected, remdesivir induced a considerable antiviral effect (EC50 of 35.4 ± 1.0 μM, CC50 > 300.0 μM, and SI > 8.5), confirming the reliability of the antiviral assay system. The results suggested that gemcitabine is a highly potent antiviral compound inhibiting SARS-CoV-2 replication in vitro, while deletion of one fluorine from gemcitabine causes drastic reduction of antiviral efficacy, stressing that difluoro substitution on position 2′ of the deoxycytidine nucleoside analogue confers antiviral efficacy.
In vivo activity:
To test the additive effects of NUCB1 with GEM (gemcitabine) in vivo, SW1990 cells overexpressing NUCB1 or control vector were injected subcutaneously into nude mice (n = 6 mice per group) and GEM was injected intraperitoneally (50 mg/kg). Tumor volume was monitored and measured for 24 days. As shown in Figure 3, tumor grafts formed from SW1990 cells overexpressing NUCB1 showed additive effects with GEM treatment, as indicated by decreased tumor volumes (Figure 3A) and decreased tumor weights (Figures 3B,C). Moreover, TUNEL staining confirmed induction of apoptosis upon NUCB1 overexpression, and GEM treatment resulted in further increase in apoptosis (Figure 3D). Collectively, these data reinforce that NUCB1 suppresses proliferation and enhances the anti-tumor effects of GEM in pancreatic cancer cells in vivo.
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
5.0 |
19.00 |
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
263.20
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. Jang Y, Shin JS, Lee MK, Jung E, An T, Kim UI, Kim K, Kim M. Comparison of Antiviral Activity of Gemcitabine with 2'-Fluoro-2'-Deoxycytidine and Combination Therapy with Remdesivir against SARS-CoV-2. Int J Mol Sci. 2021 Feb 4;22(4):1581. doi: 10.3390/ijms22041581. PMID: 33557278; PMCID: PMC7915419.
2. Hua YQ, Zhang K, Sheng J, Ning ZY, Li Y, Shi WD, Liu LM. NUCB1 Suppresses Growth and Shows Additive Effects With Gemcitabine in Pancreatic Ductal Adenocarcinoma via the Unfolded Protein Response. Front Cell Dev Biol. 2021 Mar 29;9:641836. doi: 10.3389/fcell.2021.641836. PMID: 33855021; PMCID: PMC8041069.
In vitro protocol:
1. Jang Y, Shin JS, Lee MK, Jung E, An T, Kim UI, Kim K, Kim M. Comparison of Antiviral Activity of Gemcitabine with 2'-Fluoro-2'-Deoxycytidine and Combination Therapy with Remdesivir against SARS-CoV-2. Int J Mol Sci. 2021 Feb 4;22(4):1581. doi: 10.3390/ijms22041581. PMID: 33557278; PMCID: PMC7915419.
In vivo protocol:
1. Hua YQ, Zhang K, Sheng J, Ning ZY, Li Y, Shi WD, Liu LM. NUCB1 Suppresses Growth and Shows Additive Effects With Gemcitabine in Pancreatic Ductal Adenocarcinoma via the Unfolded Protein Response. Front Cell Dev Biol. 2021 Mar 29;9:641836. doi: 10.3389/fcell.2021.641836. PMID: 33855021; PMCID: PMC8041069.
1: Park JO, Oh DY, Hsu C, Chen JS, Chen LT, Orlando M, Kim JS, Lim HY. Gemcitabine Plus Cisplatin for Advanced Biliary Tract Cancer: A Systematic Review. Cancer Res Treat. 2015 Jul;47(3):343-61. doi: 10.4143/crt.2014.308. Epub 2015 May 18. Review. PubMed PMID: 25989801.
2: Maeda T, Tsuchiya M, Ishii J, Koda T, Kubota Y, Katagiri T, Tamura A, Otsuka Y, Shibuya K, Kaneko H. [A case of pancreatic cancer with distant metastasis successfully resected after neoadjuvant chemotherapy with a combination of S-1 and gemcitabine]. Gan To Kagaku Ryoho. 2014 Nov;41(12):2184-6. Review. Japanese. PubMed PMID: 25731464.
3: Ding X, Chen W, Fan H, Zhu B. Cytidine deaminase polymorphism predicts toxicity of gemcitabine-based chemotherapy. Gene. 2015 Mar 15;559(1):31-7. doi: 10.1016/j.gene.2015.01.010. Epub 2015 Jan 10. Review. PubMed PMID: 25582275.
4: Wei MY, Zhuang YF, Wang WM. Gemcitabine for the treatment of patients with osteosarcoma. Asian Pac J Cancer Prev. 2014;15(17):7159-62. Review. PubMed PMID: 25227807.
5: de Sousa Cavalcante L, Monteiro G. Gemcitabine: metabolism and molecular mechanisms of action, sensitivity and chemoresistance in pancreatic cancer. Eur J Pharmacol. 2014 Oct 15;741:8-16. doi: 10.1016/j.ejphar.2014.07.041. Epub 2014 Jul 30. Review. PubMed PMID: 25084222.
6: Nordh S, Ansari D, Andersson R. hENT1 expression is predictive of gemcitabine outcome in pancreatic cancer: a systematic review. World J Gastroenterol. 2014 Jul 14;20(26):8482-90. doi: 10.3748/wjg.v20.i26.8482. Review. PubMed PMID: 25024604; PubMed Central PMCID: PMC4093699.
7: Li Q, Yuan Z, Yan H, Wen Z, Zhang R, Cao B. Comparison of gemcitabine combined with targeted agent therapy versus gemcitabine monotherapy in the management of advanced pancreatic cancer. Clin Ther. 2014 Jul 1;36(7):1054-63. doi: 10.1016/j.clinthera.2014.05.066. Epub 2014 Jun 27. Review. PubMed PMID: 24986485.
8: Khan MF, Gottesman S, Boyella R, Juneman E. Gemcitabine-induced cardiomyopathy: a case report and review of the literature. J Med Case Rep. 2014 Jun 23;8:220. doi: 10.1186/1752-1947-8-220. Review. PubMed PMID: 24957905; PubMed Central PMCID: PMC4086693.
9: Koga H, Miyoshi A, Nakamura J, Ide T, Kitahara K, Noshiro H. [A case of effective treatment with S-1/gemcitabine chemotherapy and resection for advanced pancreatic cancer with peritoneal dissemination]. Gan To Kagaku Ryoho. 2014 May;41(5):665-8. Review. Japanese. PubMed PMID: 24917019.
10: Borazanci E, Von Hoff DD. Nab-paclitaxel and gemcitabine for the treatment of patients with metastatic pancreatic cancer. Expert Rev Gastroenterol Hepatol. 2014 Sep;8(7):739-47. doi: 10.1586/17474124.2014.925799. Epub 2014 May 31. Review. PubMed PMID: 24882381.
1. Pattarawat P, Hunt JT, Poloway J, Archibald CJ, Wang HR. A triple combination gemcitabine + romidepsin + cisplatin to effectively control triple-negative breast cancer tumor development, recurrence, and metastasis. Cancer Chemother Pharmacol. 2021 May 27. doi: 10.1007/s00280-021-04298-y. Epub ahead of print. PMID: 34043046.
-5547.jpg "Voriconazole, (R,R)-")