GEMCITABINE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C9H11F2N3O4
Molecular Weight	263.1981
Optical Activity	UNSPECIFIED
Defined Stereocenters	3 / 3
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

NC1=NC(=O)N(C=C1)[C@@H]2O[C@H](CO)[C@@H](O)C2(F)F

InChI

InChIKey=SDUQYLNIPVEERB-QPPQHZFASA-N

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

HIDE SMILES / InChI

Molecular Formula	C9H11F2N3O4
Molecular Weight	263.1981
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	3 / 3
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: http://www.drugbank.ca/drugs/DB00441
Curator's Comment: Description was created based on several sources, including http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/020509s075lbl.pdf

Gemcitabine is a nucleoside analog used as chemotherapy. It is marketed as Gemzar® by Eli Lilly and Company. Gemcitabine inhibits thymidylate synthetase, leading to inhibition of DNA synthesis and cell death. Gemcitabine is a prodrug so activity occurs as a result of intracellular conversion to two active metabolites, gemcitabine diphosphate and gemcitabine triphosphate by deoxycitidine kinase. Gemcitabine diphosphate also inhibits ribonucleotide reductase, the enzyme responsible for catalyzing synthesis of deoxynucleoside triphosphates required for DNA synthesis. Finally, Gemcitabine triphosphate (diflurorodeoxycytidine triphosphate) competes with endogenous deoxynucleoside triphosphates for incorporation into DNA. Gemcitabine is indicated for the treatment of advanced ovarian cancer that has relapsed at least 6 months after completion of platinum-based therapy; metastatic ovarian cancer; inoperable, locally advanced (Stage IIIA or IIIB), or metastatic (Stage IV) non-small cell lung cancer; and locally advanced (nonresectable Stage II or Stage III) or metastatic (Stage IV) adenocarcinoma of the pancreas.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Ribonucleoside-diphosphate reductase M1 chain 4 Target ID: CHEMBL1830 Sources: http://www.drugbank.ca/drugs/DB00441	Inhibitor 8228
Target ID: DNA Sources: http://www.drugbank.ca/drugs/DB00441	Inhibitor 8228
T-24 2 Target ID: CHEMBL614774 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25833690	Inhibitor 8228	3.0 nM [IC50]
CAKI-1 3 Target ID: CHEMBL614067 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25833690	Inhibitor 8228	30.0 nM [IC50]
PANC-1 5 Target ID: CHEMBL614139 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25517919	Inhibitor 8228	10.0 nM [IC50]
MIA PaCa-2 2 Target ID: CHEMBL614725 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25517919	Inhibitor 8228	7.0 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Advanced ovarian cancer 5 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/020509s075lbl.pdf	Primary	Approved 8360	Gemzar Approved Use Gemzar is a nucleoside metabolic inhibitor indicated: • in combination with carboplatin, for the treatment of advanced ovarian cancer that has relapsed at least 6 months after completion of platinum- based therapy. • in combination with paclitaxel, for first-line treatment of metastatic breast cancer after failure of prior anthracycline-containing adjuvant chemotherapy, unless anthracyclines were clinically contraindicated. • in combination with cisplatin for the treatment of non-small cell lung cancer. • as a single agent for the treatment of pancreatic cancer. Launch Date 8.3203201E11
Metastatic breast cancer 6 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/020509s075lbl.pdf	Primary	Approved 8360	Gemzar Approved Use Gemzar is a nucleoside metabolic inhibitor indicated: • in combination with carboplatin, for the treatment of advanced ovarian cancer that has relapsed at least 6 months after completion of platinum- based therapy. • in combination with paclitaxel, for first-line treatment of metastatic breast cancer after failure of prior anthracycline-containing adjuvant chemotherapy, unless anthracyclines were clinically contraindicated. • in combination with cisplatin for the treatment of non-small cell lung cancer. • as a single agent for the treatment of pancreatic cancer. Launch Date 8.3203201E11
Pancreatic cancer 95 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/020509s075lbl.pdf	Primary	Approved 8360	Gemzar Approved Use Gemzar is a nucleoside metabolic inhibitor indicated: • in combination with carboplatin, for the treatment of advanced ovarian cancer that has relapsed at least 6 months after completion of platinum- based therapy. • in combination with paclitaxel, for first-line treatment of metastatic breast cancer after failure of prior anthracycline-containing adjuvant chemotherapy, unless anthracyclines were clinically contraindicated. • in combination with cisplatin for the treatment of non-small cell lung cancer. • as a single agent for the treatment of pancreatic cancer. Launch Date 8.3203201E11
Non-small cell lung cancer 201 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/020509s075lbl.pdf	Primary	Approved 8360	Gemzar Approved Use Gemzar is a nucleoside metabolic inhibitor indicated: • in combination with carboplatin, for the treatment of advanced ovarian cancer that has relapsed at least 6 months after completion of platinum- based therapy. • in combination with paclitaxel, for first-line treatment of metastatic breast cancer after failure of prior anthracycline-containing adjuvant chemotherapy, unless anthracyclines were clinically contraindicated. • in combination with cisplatin for the treatment of non-small cell lung cancer. • as a single agent for the treatment of pancreatic cancer. Launch Date 8.3203201E11

C_max

Value	Dose	Analyte	Population
229 nM EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/19556122	75 mg/m² 1 times / week multiple, intravenous dose: 75 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	GEMCITABINE blood	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
263.6 nM EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/19556122	135 mg/m² 1 times / week multiple, intravenous dose: 135 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	GEMCITABINE blood	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
292.5 nM EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/19556122	180 mg/m² 1 times / week multiple, intravenous dose: 180 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	GEMCITABINE blood	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
3526.4 nM × h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/19556122	75 mg/m² 1 times / week multiple, intravenous dose: 75 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	GEMCITABINE blood	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
4818.5 nM × h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/19556122	135 mg/m² 1 times / week multiple, intravenous dose: 135 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	GEMCITABINE blood	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
4863.4 nM × h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/19556122	180 mg/m² 1 times / week multiple, intravenous dose: 180 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	GEMCITABINE blood	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
5700 mg/m2 1 times / 2 weeks multiple, intravenous MTD Dose: 5700 mg/m2, 1 times / 2 weeks Route: intravenous Route: multiple Dose: 5700 mg/m2, 1 times / 2 weeks Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/020509s082lbl.pdf https://pubmed.ncbi.nlm.nih.gov/17434832	unhealthy, 55 years (range: 34-71 years) n = 4 Health Status: unhealthy Age Group: 55 years (range: 34-71 years) Sex: M+F Population Size: 4 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/020509s082lbl.pdf https://pubmed.ncbi.nlm.nih.gov/17434832	Other AEs: Myelosuppression, Paresthesia... Other AEs: Myelosuppression Paresthesia Rash (severe) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/020509s082lbl.pdf https://pubmed.ncbi.nlm.nih.gov/17434832
2200 mg/m2 3 times / 4 weeks multiple, intravenous MTD Dose: 2200 mg/m2, 3 times / 4 weeks Route: intravenous Route: multiple Dose: 2200 mg/m2, 3 times / 4 weeks Sources: https://pubmed.ncbi.nlm.nih.gov/8996158	unhealthy, 58 years (range: 40-77 years) n = 6 Health Status: unhealthy Condition: Non-Small-Cell Lung Cancer Age Group: 58 years (range: 40-77 years) Sex: M+F Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/8996158	Other AEs: Neutropenia, AST increased... Other AEs: Neutropenia (grade 2, 1 patient) AST increased (grade 2, 1 patient) ALT increased (grade 2, 1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/8996158
2800 mg/m2 3 times / 4 weeks multiple, intravenous Dose: 2800 mg/m2, 3 times / 4 weeks Route: intravenous Route: multiple Dose: 2800 mg/m2, 3 times / 4 weeks Sources: https://pubmed.ncbi.nlm.nih.gov/8996158	unhealthy, 58 years (range: 40-77 years) n = 5 Health Status: unhealthy Condition: Non-Small-Cell Lung Cancer Age Group: 58 years (range: 40-77 years) Sex: M+F Population Size: 5 Sources: https://pubmed.ncbi.nlm.nih.gov/8996158	DLT: Hepatotoxicity, Neutropenic infection... Dose limiting toxicities: Hepatotoxicity (grade 3, 2 patients) Neutropenic infection (grade 4, 1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/8996158
1000 mg/m2 3 times / 4 weeks multiple, intravenous Recommended Dose: 1000 mg/m2, 3 times / 4 weeks Route: intravenous Route: multiple Dose: 1000 mg/m2, 3 times / 4 weeks Sources: https://pubmed.ncbi.nlm.nih.gov/30397477	unhealthy, 74 years n = 1 Health Status: unhealthy Age Group: 74 years Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/30397477	Disc. AE: Necrosis skin... AEs leading to discontinuation/dose reduction: Necrosis skin (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/30397477
800 mg/m2 3 times / 4 weeks multiple, intravenous Dose: 800 mg/m2, 3 times / 4 weeks Route: intravenous Route: multiple Dose: 800 mg/m2, 3 times / 4 weeks Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/020509s082lbl.pdf	unhealthy, adult n = 979 Health Status: unhealthy Condition: malignancies Age Group: adult Sex: M+F Population Size: 979 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/020509s082lbl.pdf	Disc. AE: Myocardial infarction, Cerebrovascular accident... AEs leading to discontinuation/dose reduction: Myocardial infarction (2%) Cerebrovascular accident (2%) Arrhythmia (2%) Hypertension (2%) Anemia (<1%) Thrombocytopenia (<1%) Hepatic dysfunction NOS (<1%) Kidney dysfunction (<1%) Nausea (<1%) Vomiting (<1%) Fever (<1%) Rash (<1%) Dyspnea (<1%) Hemorrhage (<1%) Infection (<1%) Stomatitis (<1%) Somnolence (<1%) Flu syndrome (<1%) Edema (<1%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/020509s082lbl.pdf

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	TK2 3 hCNT1 2 hCNT2 2 hCNT3 2 MRP5 40

Drug as victim

Target	Modality	Activity
MRP5 40	substrate 3326 Sources: https://www.nature.com/articles/6601011/ Page: -	yes
TK2 3	substrate 3326 Sources: https://www.sciencedirect.com/science/article/pii/S0923753419381785 Page: -	yes
hCNT1 2	substrate 3326 Sources: https://www.sciencedirect.com/science/article/pii/S0923753419381785 Page: -	yes
hCNT2 2	substrate 3326 Sources: https://www.sciencedirect.com/science/article/pii/S0923753419381785 Page: -	yes
hCNT3 2	substrate 3326 Sources: https://www.sciencedirect.com/science/article/pii/S0923753419381785 Page: -	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:175901	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:175901
ChemicalBook	CB4438054	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB4438054
MolPort	MolPort-003-987-478	https://www.molport.com/shop/molecule-link/MolPort-003-987-478
Selleck Chemicals	Gemcitabine(Gemzar)	http://www.selleckchem.com/products/Gemcitabine(Gemzar).html
ZINC	ZINC000018279854	http://zinc15.docking.org/substances/ZINC000018279854

PubMed

Title	Date	PubMed
Treatment of classical Kaposi's sarcoma with gemcitabine.	2001	11306832
Noncardiogenic pulmonary edema: an unusual and serious complication of anticancer therapy.	2001	11306727
Chemotherapy of metastatic breast cancer: what to expect in 2001 and beyond.	2001	11306725
Excellent response to gemcitabine in a massively pre-treated woman with extensive cutaneous involvement after recurrence of breast cancer.	2001	11291839
Achievement of complete remission in refractory Hodgkin's disease with prolonged infusion of gemcitabine.	2001	11291828
Recent advances in bladder cancer chemotherapy.	2001	11291559
Neoadjuvant, adjuvant, and palliative treatment of pancreatic cancer.	2001 Apr	11276380
2'-C-cyano-2'-deoxy-1-beta-D-arabino-pentofuranosylcytosine: a novel anticancer nucleoside analog that causes both DNA strand breaks and G(2) arrest.	2001 Apr	11259616
Gemcitabine following radiotherapy with concurrent 5-fluorouracil for nonmetastatic adenocarcinoma of the pancreas.	2001 Apr 20	11291097
Phase II trial of two-weekly gemcitabine in patients with advanced biliary tract cancer.	2001 Feb	11300321
[Medical treatment of pulmonary neoplasms].	2001 Feb	11294106
Challenging the platinum combinations: docetaxel (Taxotere) combined with gemcitabine or vinorelbine in non-small cell lung cancer.	2001 Feb	11284620
[Palliative therapy of pancreatic adenocarcinoma].	2001 Feb	11253511
Biweekly gemcitabine, doxorubicin, and paclitaxel as first-line treatment in metastatic breast cancer. Final results from a phase II trial.	2001 Feb	11252890
The gemcitabine/epirubicin/paclitaxel trials in advanced breast cancer.	2001 Feb	11252889
Gemcitabine, paclitaxel, and trastuzumab in metastatic breast cancer.	2001 Feb	11252888
Gemcitabine and Pemetrexed disodium in treating breast cancer.	2001 Feb	11252887
Gemcitabine plus cisplatin in breast cancer.	2001 Feb	11252886
Gemcitabine and paclitaxel as salvage therapy in metastatic breast cancer.	2001 Feb	11252885
Docetaxel/gemcitabine: salvage chemotherapy in anthracycline-pretreated patients with advanced breast cancer.	2001 Feb	11252884
Treatment of advanced breast cancer with gemcitabine and vinorelbine.	2001 Feb	11252883
Gemcitabine as single-agent therapy in the management of advanced breast cancer.	2001 Feb	11252882
Chemotherapy agents in transitional cell carcinoma: the old and the new.	2001 Feb	11246730
Effects of gemcitabine on cisplatin-induced nephrotoxicity in rats: schedule-dependent study.	2001 Feb	11243722
End-joining deficiency and radiosensitization induced by gemcitabine.	2001 Feb 15	11245469
P53 modulates the effect of loss of DNA mismatch repair on the sensitivity of human colon cancer cells to the cytotoxic and mutagenic effects of cisplatin.	2001 Feb 15	11245458
Gemcitabine-associated posterior reversible encephalopathy syndrome: MR imaging and MR spectroscopy findings.	2001 Jan	11295355
Phase I trial of gemcitabine in patients with advanced pancreatic cancer.	2001 Jan	11256843
Second-line chemotherapy for non-small-cell lung cancer with monthly docetaxel and weekly gemcitabine: a phase II trial.	2001 Jan	11249055
High-dose thiotepa and melphalan with hemopoietic progenitor support following induction therapy with epirubicin-paclitaxel-containing regimens in metastatic breast cancer (MBC).	2001 Jan	11249051
Treatment of pancreatic cancer with a combination of docetaxel, gemcitabine and granulocyte colony-stimulating factor: a phase II study of the Greek Cooperative Group for Pancreatic Cancer.	2001 Jan	11249034
Combined use of gemcitabine and radiation in mice.	2001 Jan-Feb	11299753
Novel approaches in the treatment of non-small-cell lung cancer.	2001 Mar	11301850
Treatment of elderly patients with non-small-cell lung cancer.	2001 Mar	11301849
Optimizing chemoradiation in locally advanced non-small-cell lung cancer.	2001 Mar	11301848
Gemcitabine and cisplatin combination in early-stage non-small-cell lung cancer.	2001 Mar	11301847
Gemcitabine for the treatment of non-small-cell lung cancer.	2001 Mar	11301846
Triplet combination chemotherapy and targeted therapy regimens.	2001 Mar	11301845
Gemcitabine and nonplatinum combinations in non-small-cell lung cancer.	2001 Mar	11301844
Gemcitabine in combination with new platinum compounds: an update.	2001 Mar	11301843
Irinotecan/gemcitabine combination chemotherapy in pancreatic cancer.	2001 Mar	11301841
Unexpected severe myelotoxicity of gemcitabine in pretreated breast cancer patients.	2001 Mar	11290868
Gemcitabine and vinorelbine as first-line chemotherapy for advanced non-small cell lung cancer: a phase II trial.	2001 Mar	11290433
Latent hematopoietic stem cell toxicity associated with protracted drug administration.	2001 Mar	11274755
[A case of primary malignant hemangiopericytoma of the lung with marked response to combination chemotherapy with cisplatin, ifosfamide and gemcitabine].	2001 Mar	11265407
Neoadjuvant chemoradiotherapy for adenocarcinoma of the pancreas: treatment variables and survival duration.	2001 Mar	11258776
Phase I study of stealth liposomal doxorubicin in combination with gemcitabine in the treatment of patients with metastatic breast cancer.	2001 Mar 15	11251001
Steroids affect collateral sensitivity to gemcitabine of multidrug-resistant human lung cancer cells.	2001 Mar 23	11282108
Cotton-wool spots associated with pancreatic carcinoma.	2001 Mar 26	11309222
Akt, MAPK (Erk1/2), and p38 act in concert to promote apoptosis in response to ErbB receptor family inhibition.	2001 May 4	11278435

Patents

Sample Use Guides

In Vivo Use Guide

For intravenous use only. • Ovarian Cancer: 1000 mg/m2 over 30 minutes on Days 1 and 8 of each 21-day cycle. (2.1) • Breast Cancer: 1250 mg/m2 over 30 minutes on Days 1 and 8 of each 21-day cycle. (2.2) • Non-Small Cell Lung Cancer: 1000 mg/m2 over 30 minutes on Days 1, 8, and 15 of each 28-day cycle or 1250 mg/m2 over 30 minutes on Days 1 and 8 of each 21-day cycle. (2.3) • Pancreatic Cancer: 1000 mg/m2 over 30 minutes once weekly for the first 7 weeks, then one week rest, then once weekly for 3 weeks of each 28-day cycle

Route of Administration: Intravenous

In Vitro Use Guide

Treatment of PANC-1 cells with gemcitabine (10 nM) increased the percentage of cells in S phase to 60.1±6.0% and reduced the percentage in the G0/G1 phase to 28.7±4.2%

Substance Class	Chemical Created by `admin` on `Wed Jul 05 23:45:36 UTC 2023` Edited by `admin` on `Wed Jul 05 23:45:36 UTC 2023`
Record UNII	B76N6SBZ8R
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

GEMCITABINE

Official Name

English

GEMCITABINE [USAN]

Common Name

English

LY188011

Code

English

GEMCITABINE [MI]

Common Name

English

GEMCITABINE [HSDB]

Common Name

English

CYTIDINE, 2'-DEOXY-2',2'-DIFLUORO-

Systematic Name

English

LY-188011

Code

English

NSC-613327

Code

English

GEMCITABINE [VANDF]

Common Name

English

2'-DEOXY-2',2'-DIFLUOROCYTIDINE

Systematic Name

English

gemcitabine [INN]

Common Name

English

Gemcitabine [WHO-DD]

Common Name

English

Classification Tree Code System Code

WHO-VATC

QL01BC05