Gemcitabine hydrochloride

SKU: G0063

Category: API's & Intermediates

Synonyms: 2'-Deoxy-2',2'-difluorocytidine , dFdC , Gemzar (Lilly) , LY-188011 , dFdC , dFdCyd , NSC613327; 122111-03-9
CAS-Number: C₉H₁₁F₂N₃O₄ · HCl
Molecular Formula: 299.66
Molecular Weight

Product Data
Handling
Safety Information
Details

Specifications

Purity: ≥98% (HPLC)
Identity: 1H-NMR
Appearance: White to off-white powder

Properties

Solvents: water (20mg/ml), DMSO (slightly), ethanol (insoluble)

Handling Advice: Protect from light and moisture.
Use / Stability: This product should not be used if colour has changed or if there are
Long Term Storage: RT
Short Term Storage: RT
Shipping: AMBIENT

Transportation: Not dangerous goods
Signal word: Danger
GHS Symbol: GHS08
Precautionary statements: P201-P308 + P313
Hazard statements: H360

Description: Widely used antitumor agent in vitro and in vivo. Deoxycytidine analog with cytotoxic effects. Inhibits DNA synthesis and induces apoptosis through inhibition of ribonucleotide reductase (R1 and R2). Following the uptake of this prodrug into cells by nucleoside transporters it is phosphorylated to its mono(dFdCMP), di(dFdCDP), and triphosphorylated(dFdCTP) forms by deoxycytidine kinase. dFdCDP and dFdCTP are reported to inhibit the activity of ribonucleotide reductase and impede DNA synthesis and repair mechanisms and induce cell death. 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, inhibits repair-mediated DNA demethylation in a methylation-sensitive reporter assay at concentrations ranging from 34-134nM. This anticancer nucleoside analog inhibits the growth of HL-60 promyelocytic leukemia cells with an LC50 value of 40nM. 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). Also shown to block mitochondrial DNA polymerase ?. Works synergistically with other chemotherapeutic agents to enhance their cytotoxicity. Has also broad antiretroviral activity, decreasing MuLV cell infectivity, a murine AIDS model, in cell culture (EC50 = ~1.5nM) and inhibits the progression of murine AIDS in vivo at a dose of 1-2 mg/kg per day.
References: (1) L.W. Hertel, et al., Cancer Res. 50, 4417 (1990) , (2) V. Heinemann, et al., Cancer Res. 52, 533 (1992) , (3) D.D. Ross & D.P. Cuddy, Biochem. Pharmacol. 48, 1619 (1994) , (5) W. Plunkett, et al., Se≥ Oncol. 22, 3 (1995) , (6) R.L. Merriman, et al., New Drugs 14, 243 (1996) , (7) J.R. Mackey, et al., Cancer Res. 58, 4349 (1998) , (8) R.P. McGeary, et al., Mini Rev. Med. Chem. 8, 1384 (2008) , (9) C.L. Clouser, et al., PLoS One 6, 1 (2011) , (10) S.W. Hung, et al., Cancer Lett. 320, 138 (2012)
InChi Key: OKKDEIYWILRZIA-OSZBKLCCSA-N
Smiles: OC[C@@H]1[C@@H](O)C(F)(F)[C@H](N2C=CC([NH3+])=NC2=O)O1.[Cl-]

Widely used antitumor agent in vitro and in vivo. Deoxycytidine analog with cytotoxic effects. Inhibits DNA synthesis and induces apoptosis through inhibition of ribonucleotide reductase (R1 and R2). Following the uptake of this prodrug into cells by nucleoside transporters it is phosphorylated to its mono(dFdCMP), di(dFdCDP), and triphosphorylated(dFdCTP) forms by deoxycytidine kinase. dFdCDP and dFdCTP are reported to inhibit the activity of ribonucleotide reductase and impede DNA synthesis and repair mechanisms and induce cell death. 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, inhibits repair-mediated DNA demethylation in a methylation-sensitive reporter assay at concentrations ranging from 34-134nM. This anticancer nucleoside analog inhibits the growth of HL-60 promyelocytic leukemia cells with an LC50 value of 40nM. 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). Also shown to block mitochondrial DNA polymerase ?. Works synergistically with other chemotherapeutic agents to enhance their cytotoxicity. Has also broad antiretroviral activity, decreasing MuLV cell infectivity, a murine AIDS model, in cell culture (EC50 = ~1.5nM) and inhibits the progression of murine AIDS in vivo at a dose of 1-2 mg/kg per day.

SKU: G0063 Category: API's & Intermediates

Additional information

Additional information

Synonyms	2'-Deoxy-2',2'-difluorocytidine, dFdC, Gemzar (Lilly), LY-188011, dFdC, dFdCyd, NSC613327
Purity	≥98% (HPLC)
Appearance	White to off-white powder
CAS-Number	122111-03-9
Molecular Formula	C9H11F2N3O4 · HCl
Molecular Weight	299.66
Identity	1H-NMR
Solvents	water (20mg/ml), DMSO (slightly), ethanol (insoluble)
Smiles	OC[C@@H]1[C@@H](O)C(F)(F)[C@H](N2C=CC([NH3+])=NC2=O)O1.[Cl-]
InChi Key	OKKDEIYWILRZIA-OSZBKLCCSA-N
Shipping	AMBIENT
Short Term Storage	RT
Long Term Storage	RT
Handling Advice	Protect from light and moisture.
Use / Stability	This product should not be used if colour has changed or if there are
Hazard statements	H360
Precautionary statements	P201-P308 + P313
GHS Symbol	GHS08
Signal word	Danger
Transportation	Not dangerous goods
References	(1) L.W. Hertel, et al., Cancer Res. 50, 4417 (1990), (2) V. Heinemann, et al., Cancer Res. 52, 533 (1992), (3) D.D. Ross & D.P. Cuddy, Biochem. Pharmacol. 48, 1619 (1994), (5) W. Plunkett, et al., Se≥ Oncol. 22, 3 (1995), (6) R.L. Merriman, et al., New Drugs 14, 243 (1996), (7) J.R. Mackey, et al., Cancer Res. 58, 4349 (1998), (8) R.P. McGeary, et al., Mini Rev. Med. Chem. 8, 1384 (2008), (9) C.L. Clouser, et al., PLoS One 6, 1 (2011), (10) S.W. Hung, et al., Cancer Lett. 320, 138 (2012)
Quantity	10 mg, 50 mg, Bulk