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Gemcitabine

CAS No.
95058-81-4
Chemical Name:
Gemcitabine
Synonyms
GeMcitabin;gemicitabine;GEMCITABINE HCL USP;4-amino-1-[(2R,4R,5R)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2(1H)-one;4-Amino-1-((2R,4R,5R)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyrimidin-2(1H)-one;Zefei;Gemcel;GemLip;T11Base;LY-18011
CBNumber:
CB4438054
Molecular Formula:
C9H11F2N3O4
Molecular Weight:
263.2
MDL Number:
MFCD00869720
MOL File:
95058-81-4.mol
MSDS File:
SDS
Last updated:2024-03-16 17:36:18

Gemcitabine Properties

Melting point 168,64 C
alpha 365 +425.36°; D +71.51°
Boiling point 482.7±55.0 °C(Predicted)
Density 1.84±0.1 g/cm3(Predicted)
storage temp. Keep in dark place,Sealed in dry,Store in freezer, under -20°C
solubility Methanol (Slightly), Water (Slightly, Heated)
pka 11.65±0.70(Predicted)
form Solid
color White to Off-White
CAS DataBase Reference 95058-81-4(CAS DataBase Reference)
EWG's Food Scores 1
FDA UNII B76N6SBZ8R
ATC code L01BC05

Pharmacokinetic data

Protein binding Negligible
Excreted unchanged in urine <10%
Volume of distribution 12.4 Litres/m2 (women); 17.5 Litres/ m2 (men)
Biological half-life 42-94 minutes / -

SAFETY

Risk and Safety Statements

Symbol(GHS)  GHS hazard pictograms
GHS07
Signal word  Danger
Hazard statements  H312-H315-H319-H340-H361
Precautionary statements  P280-P308+P313
Hazard Codes  Xn,Xi
Risk Statements  21-36/38-46-62-63
Safety Statements  25-26-36/37-53
HS Code  29349990
Toxicity LD10 i.v. in rats: 200 mg/m2 (Abbruzzese)
NFPA 704
0
2 0

Gemcitabine price More Price(63)

Manufacturer Product number Product description CAS number Packaging Price Updated Buy
TCI Chemical G0544 Gemcitabine 95058-81-4 1G $64 2024-03-01 Buy
Cayman Chemical 11690 Gemcitabine ≥98% 95058-81-4 10mg $50 2024-03-01 Buy
Cayman Chemical 11690 Gemcitabine ≥98% 95058-81-4 25mg $88 2024-03-01 Buy
Cayman Chemical 11690 Gemcitabine ≥98% 95058-81-4 50mg $166 2024-03-01 Buy
Cayman Chemical 11690 Gemcitabine ≥98% 95058-81-4 100mg $292 2024-03-01 Buy
Product number Packaging Price Buy
G0544 1G $64 Buy
11690 10mg $50 Buy
11690 25mg $88 Buy
11690 50mg $166 Buy
11690 100mg $292 Buy

Gemcitabine Chemical Properties,Uses,Production

Description

Gemcitabine (2’,2’-difluorodeoxycytidine; dFdCyd) is a novel deoxycytidine analogue with both structural and metabolic similarities to cytarabine. It has a broad spectrum of antitumor activity in preclinical murine leukemia and solid tumor models. This drug requires intracellular phosphorylation that results in the accumulation of difluorodeoxycytidine triphosphate (dFdCTP). The dFdCTP competes with deoxycytidine triphosphate (dCTP) for incorporation into DNA, which in turn inhibits DNA synthesis and terminates DNA chain elongation. In addition, this drug reduces intracellular deoxynucleoside triphosphate pools, presumably through the inhibition of ribonucleotide reductase.
Gemcitabine is used alone or with other treatments/medications to treat certain types of cancer (including breast cancer, non-small cell lung cancer, ovarian cancer, pancreatic cancer, bladder cancer, bone cancer, Ewing’s sarcoma, mesenchymal chondrosarcoma osteosarcoma, dedifferentiated chondrosarcoma, head and neck cancers-cancer of the nasopharynx, hepatobiliary cancers including gallbladder cancer, Hodgkin lymphoma, kidney cancer, malignant pleural mesothelioma, non Hodgkin lymphoma, non-melanoma skin cancer – dermatofibrosarcoma protuberans (DFSP), occult primary, small cell lung cancer, soft tissue sarcoma, testicular cancer, thymic malignancies, uterine malignancies). It is a chemotherapy drug that works by slowing or stopping the growth of cancer cells. One commercial product of gemcitabine is Gemzar, which is supplied in a sterile form for intravenous use only.

References

[1] H. A. Burris, M. J. Moore, J. Andersen, M. R. Green, M. L. Rothenberg, M. R. Modiano, M. C. Cripps, R. K. Portenoy, A. M. Storniolo, P. Tarassoff, R. Nelson, F. A. Dorr, C. D. Stephens, D. D. Von Hoff (1997) Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial, 15, 2403-2413
[2] http://www.webmd.com/drugs/2/drug-13451/gemcitabine-intravenous/details

Description

Gemcitabine is an anticancer nucleoside analog that inhibits the growth of HL-60 promyelocytic leukemia cells with an LC50 value of 40 nM. It inhibits the growth of MX-1 mammary, CX-1, HC-1, GC3, and VRC5 colon, LX-1, Calu-6, and NCI-H460 lung, and HS766T, PaCa-2, PANC-1, and BxPC-3 pancreatic cancer tumors in mouse xenograft models (45-93% inhibition). Gemcitabine is a prodrug that is metabolized to a diphosphate and triphosphate form in cells. The triphosphate form is incorporated into DNA which induces masked chain termination and cell death. By specifically inhibiting growth arrest and DNA damage inducible protein 45 a (Gadd45a), a key mediator of active DNA demethylation, gemcitabine, at concentrations ranging from 34 to 134 nM, inhibits repair-mediated DNA demethylation in a methylation-sensitive reporter assay. Gemcitabine also has broad antiretroviral activity, decreasing MuLV cell infectivity, a murine AIDS model, in cell culture (EC50 = ~1.5 nM) and inhibits the progression of murine AIDS in vivo at a dose of 1-2 mg/kg per day.

Originator

Gemzar,Lilly Co.

Uses

Gemcitabine is used for breast cancer treatment. First-line treatment for locally advanced pancreatic cancer.

Uses

Gemcitabine(Gemzar) belongs to the group of medicines called antimetabolites. It is used alone or in combination with other medicines to treat cancer of the breast, ovary, pancreas, and lung. Gemcitabine interferes with the growth of cancer cells, which a

Definition

ChEBI: Gemcitabine is a 2'-deoxycytidine having geminal fluoro substituents in the 2'-position. An inhibitor of ribonucleotide reductase, gemcitabine is used in the treatment of various carcinomas, particularly non-small cell lung cancer, pancreatic cancer, bladder cancer and breast cancer. It has a role as a photosensitizing agent, a DNA synthesis inhibitor, a prodrug, an EC 1.17.4.1 (ribonucleoside-diphosphate reductase) inhibitor, an environmental contaminant, a xenobiotic, a radiosensitizing agent, an antineoplastic agent, an antimetabolite, an antiviral drug and an immunosuppressive agent. It is an organofluorine compound and a pyrimidine 2'-deoxyribonucleoside.

Indications

Gemcitabine (Gemzar), an antimetabolite, undergoes metabolic activation to difluorodeoxycytidine triphosphate, which interferes with DNA synthesis and repair. It is the single most active agent for the treatment of metastatic pancreatic cancer, and it is used as a first-line treatment for both pancreatic and small cell lung cancer. It is administered by intravenous infusion. The dose-limiting toxicity is bone marrow suppression.

Manufacturing Process

Benzyl 4,6-O-benzylidene-2-O-benzyl-3-oxo-α-D-gluco-pyranoside was obtained by 4 steps from glucose.
0.53 ml (4.0 mmol) of DAST (fluorinaiting agent) was added to asolution of 300 mg (0.67 mmol) of benzyl 4,6-O-benzylidene-2-O-benzyl-3-oxo-α-Dgluco-pyranoside in anhydrous dichloromethane (4 ml). The solution was then stirred at room temperature for 2 h, and the excess of DAST was neutralized by careful addition of saturated aqueous NaHCO3. The resulting mixture was extracted with CH2Cl2, and organic phase was dried and evaporated. The residue was purified by CC (Hexane/Ethyl acetate 7:1) to afford benzyl 4,6-Obenzylidene-2-O-benzyl-3-deoxy-3,3-difluoro-α-D-gluco-pyranoside (189 mg, 60%), melting point 118°-119°C.
Benzyl 4,6-O-benzylidene-2-O-benzyl-3-deoxy-3,3-difluoro-α-D-glucopyranoside (77 mg, 0.16 mmol) was dissolved in a 0.1 N solution of HCl in ethanol and stirred at room temperature for 40 h. The solution was then neutralized with solid NaHCO3, filtered and evaporated to give an oily product that was dissolved in 2 ml of CH2Cl2 and 0.5 ml of pyridine. After cooling to 0°C, 0.40 ml (1.6 mmol) of benzoyl chloride was added and the solution was stirred for 1 h and poured into ice and water (200 ml) containing NaHCO3, extracted several times with CH2Cl2, dried and evaporated to give 86 mg (0.14 mmol, 90%) of benzyl 4,6-di-O-benzoyl-2-O-benzyl-3-deoxy-3,3- difluoro-α-D-gluco-pyranoside.
Benzyl 4,6-di-O-benzoyl-2-O-benzyl-3-deoxy-3,3-difluoro-α-D-glucopyranoside (220 mg, 0.44 mmol) was dissolved in methanol in the presence of 200 mg of palladium on activated charcoal (10% Pd content). The suspension was stirred at room temperature under hydrogen pressure (10 bar) for 16 h. The suspension was then filtered through a thin silica gel pad, and evaporated. The residue was purified by CC to give 105 mg (59%) of 4,6- di-O-benzoyl-3-deoxy-3,3-difluoro-α/β-D-gluco-pyranoside as an inseparable anomeric mixture (ratio α/β = 5:1).
To a solution of 46 mg (0.11 mmol) of 4,6-di-O-benzoyl-3-deoxy-3,3-difluoro- α/β-D-gluco-pyranoside in water-dioxane 1:2 (2 ml) was added 120 mg (0.56 mmol) of sodium periodate. This resulting solution was stirred at room temperature for 20 h. Then, more sodium periodate (55 mg, 0.26 mmol) was added and stirring was continued for 6 h. After that, the solvents were evaporated and the solid was repeatedly extracted with ethyl acetate (total volume 70 ml). The solvent was then evaporated to give a solid that was treated for 15 min with a diluted (0.1%) methanolic solution of ammonia. THE solution was evaporated and the crude purified by preparative TLC (hexane/ethyl acetate 2:1) to yield 18 mg (0.04 mmol, 43%) of α-3,5-di-Obenzoyl-2-deoxy-2,2-difluoro-D-ribose.

Therapeutic Function

Antineoplastic, Antiviral

General Description

The drug is available as the hydrochloride salt in 200- and1,000-mg lyophilized single-dose vials for IV use.Gemcitabine is used to treat bladder cancer, breast cancer,pancreatic cancer, and NSCLC. Gemcitabine is a potent radiosensitizer,and it increases the cytotoxicity of cisplatin.The mechanism of action of this fluorine-substituted deoxycytidineanalog involves inhibition of DNA synthesis andfunction via DNA chain termination. The triphosphatemetabolite is incorporated into DNA inhibiting severalDNA polymerases and incorporated into RNA inhibitingproper function of mRNA. Resistance can occur because ofdecreased expression of the activation enzyme deoxycytidinekinase or decreased drug transport as well as increasedexpression of catabolic enzymes. Drug oral bioavailabilityis low because of deamination within the GI tract, and thedrug does not cross the blood-brain barrier. Metabolism bydeamination to 2', 2'-difluorouridine (dFdU) is extensive.Drug toxicity includes myelosuppression, fever, malaise,chills, headache, myalgias, nausea, and vomiting.

Hazard

Human systemic effects

Mechanism of action

Gemcitabine shows good activity against human leukemic cell lines, a number of murine solid tumors, and human tumor xenografts. Gemcitabine was significantly more cytotoxic than cytarabine in Chinese hamster ovary cells. The major cellular metabolite is the 5'-triphosphate of gemcitabine. The cytotoxicity was competitively reversed by deoxycytidine, suggesting that the biological activity required phosphorylation by deoxycytidine kinase. Tumor-bearing mice were treated with either gemcitabine or cytarabine (20 mg/kg). DNA synthesis reached 1 % of control levels upon administration of gemcitabine. The greater accumulation of gemcitabine-5'-triphosphate compared with cytarabine-5'-triphosphate may cause greater cytotoxicity and therapeutic activity. Further gemcitabine may enhance its own cytotoxic effects by self-potentiation mechanisms that act on, e. g., deoxycytidine monophosphate deaminase, deoxycytidine kinase or on DNA synthesis.

Clinical Use

Antineoplastic agent:

Palliative treatment, or first-line treatment with cisplatin, of locally advanced or metastatic non-small cell lung cancer

Pancreatic, ovarian and breast cancer

Bladder cancer in combination with cisplatin

Drug interactions

Potentially hazardous interactions with other drugs
Antipsychotics: avoid with clozapine, increased risk of agranulocytosis.

Metabolism

After intravenous doses gemcitabine is rapidly cleared from the blood and metabolised by cytidine deaminase in the liver, kidney, blood, and other tissues. Clearance is about 25% lower in women than in men.
Almost all (99%) of the dose is excreted in urine as 2′-deoxy-2′,2′-difluorouridine (dFdU), only about 1% being found in the faeces. Intracellular metabolism produces mono-, di-, and triphosphate metabolites, the latter two active. The active intracellular metabolites have not been detected in plasma or urine.

References

[1] karnitz lm, flatten ks, wagner jm, et al. gemcitabine-induced activation of checkpoint signaling pathways that affect tumor cell survival. mol pharmacol, 2005, 68 (6): 1636-1644.
[2] ando t, ichikawa j, okamoto a, et al. gemcitabine inhibits viability, growth, and metastasis of osteosarcoma cell lines. j orthop res, 2005, 23 (4): 964-969.
[3] clouser cl, holtz cm, mullett m, et al. analysis of the ex vivo and in vivo antiretroviral activity of gemcitabine. plos one, 2011, 6 (1): e15840.

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View Lastest Price from Gemcitabine manufacturers

Image Update time Product Price Min. Order Purity Supply Ability Manufacturer
Gemcitabine pictures 2023-06-15 Gemcitabine
95058-81-4
US $50.00 / g 1g 99% 1000KG Baoji Guokang Bio-Technology Co., Ltd.
Gemcitabine pictures 2023-03-06 Gemcitabine
95058-81-4
US $10.00 / Kg/Drum 1KG 98% 10 ton Hebei Guanlang Biotechnology Co,.LTD
Gemcitabine pictures 2021-12-23 Gemcitabine
95058-81-4
US $0.00 / g 1g 99% 500kg WUHAN CIRCLE POWDER TECHNOLOGY CO.,LTD
  • Gemcitabine pictures
  • Gemcitabine
    95058-81-4
  • US $50.00 / g
  • 99%
  • Baoji Guokang Bio-Technology Co., Ltd.
  • Gemcitabine pictures
  • Gemcitabine
    95058-81-4
  • US $10.00 / Kg/Drum
  • 98%
  • Hebei Guanlang Biotechnology Co,.LTD
  • Gemcitabine pictures
  • Gemcitabine
    95058-81-4
  • US $0.00 / g
  • 99%
  • WUHAN CIRCLE POWDER TECHNOLOGY CO.,LTD

Gemcitabine Spectrum

2'-Deoxy-2',2'-difluoro-D-cytidine 2''-DEOXY-2'',2''-DIFLUOROCYTIDINE(GEMCITABINE) 2',2'-Difluorodeoxycytidine Cytidine, 2'-deoxy-2',2'-difluoro- NSC 613327 gencitabine base 2'-Deoxy-2',2'-difluro cytidine Hydrochloride GEMCITABINE (2''-DEOXY-2'', 2''-DIFLUOROCYTIDINE) LY-18011 3-Deoxy-2,2-difluoro-D-ribofuranose-3,5-dibenzoate Gecitabine base Folfugem Gamcitabine Gemcel GemLip Zefei 2',2'-Difluorodeoxycytidine (Gemcitabine base) 4-amino-1-[3,3-difluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one (Gemcitabine base) GeMcitabine T8 GeMcitabine API 122111-11-9 D-erythro-pentofuranose GeMictabine dFdC, dFdCyd, LY-188011 2'-Deoxy-2',2'-difluorocytidine, >=99% Gemcitabine free base 1-(4-Amino-2-oxo-1H-pyrimidin-1-yl)-2-deoxy-2,2-difluoro-beta-D-ribofuranose 2'-Deoxy-2',2'-difluro cytidine 2'-DEOXY-2',2'-DIFLUOROCYTIDINE 4-amino-1-[3,3-difluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one GEMCITABINE 4-Amino-1-[(2R,4R,5R)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one 2'-Deoxy-2',2'-difluro cytidine, Gemcitabine, Gemzar Gemcitabine USP/EP/BP Gemcitabine baseQ: What is Gemcitabine base Q: What is the CAS Number of Gemcitabine base Q: What is the storage condition of Gemcitabine base GEMCITABINE HCL USP gemicitabine GeMcitabin 4-amino-1-[(2R,4R,5R)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2(1H)-one 4-Amino-1-((2R,4R,5R)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyrimidin-2(1H)-one Gemcitabine (LY-188011) T11Base inhibit,LY 188011,LY-188011,Autophagy,Nucleoside Antimetabolite/Analog,Inhibitor,DNA/RNA Synthesis,Gemcitabine,Apoptosis 95058-81-4 C9H11F2N3O4 Inhibitors Antineoplastic API Antineoplastic drug, difluorine nucleoside analog