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Amadis Chemical offer CAS#121032-29-9;CAT#A804639
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121032-29-9 Usage

Uses

A chemotherapy drug used in the treatment of relapsed/refractory T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL).

Uses

antineoplastic

Usage and dosage

Nelarabine is mainly used for patients who have received at least two chemotherapy regimens but still have no response, or have occurred recurrent acute T-cell lymphoblastic leukemia and T-cell lymphoblastic lymphoma.
Adult patients received nelarabine i.v. over 2 hours on days 1, 3 and 5 in every 21 days with the recommendation dose of 1500mg/m2 in every 21 days and without dilution; pediatric patients received this regimen over 1 hour for 5 consecutive days with the recommendation dose of 650mg/m2 in every 21 days, without dilution.  The recommended treatment period for adults and children is unspecified. In clinical trials, unless the patient get worse and cannot tolerate toxicity. They should treated with bone marrow transplant immediately or no longer be treated.

Pharmacology and pharmacokinetics

Nelarabine is a prodrug for deoxyguanosine analogue 9-β-arabinosyl guanine (ara-G). Ara-G has poor water solubility and can become Nelarabine with methoxy group in vivo. It was mono-phosphorylated into 5'-triphosphate ara-G, when catalyzed by adenosine deaminase and deoxycytidine kinase. Ara cells-GTP is accumulated in leukemia. PNP deficiency leads to the selective accumulation of dGTP in T cells, whereas dGTP rapidly degrades in B cells without accumulation in B cells. Intracellular accumulation of dGTP can inhibit DNA synthesis. Arabinosyl guanine can selectively kill cells with T cell leukemia, leading to cell death. Other mechanisms may be cytotoxicity and systemic toxicity of Nelarabine.
Recurrent pharmacokinetic study of leukemia or lymphoma in patients found that Nelarabine and ara-G can eliminated in plasma quickly. the two half-life were 30 minutes and 3 hour when giving 1500mg/m2 dose of Nelarabine. The study also found that ara-G usually reached the peak concentration at the end of Nelarabine administration, and its peak concentration value is usually greater than the peak concentration of Nelarabine, indicating that Nelarabine in the body can be quickly and completely transformed into ara-G. Nelarabine and ara-G were partially abolished by the kidneys, and the mean renal excretion rates of Nelarabine and ara-G measured 24 hours after administration of Nelarabine in 28 adult patients were 6.6 ± 4.7% and 27 ± 15% .

Physical properties

White or almost white crystalline powder. This product is slightly soluble in water, the solubility in water is about 8-9mg/ml (25 ℃, PH = 4~10).

Note

Nelarabine-induced neurotoxicity is a dose-limiting toxic reaction. Patients should pay close attention during the medication whether there is confusion, drowsiness, convulsions, ataxia, paresthesia and hypoesthesia and other symptoms. Patients who had undergone intrathecal chemotherapy or cranial radiotherapy had an increased risk of neurotoxic response after Nelarabine administration.
Nelarabine may also cause leukopenia, thrombocytopenia, anemia and neutropenia (including febrile neutropenia), so the application of Nelarabine should be routine for patients with complete blood count (including platelet count).According to standard treatment regimen, Nelarabine used in patients with tumor lysis syndrome complicated by hyperuricemia, can be relieved by intravenous hydration; in the presence of hyperuricemia risk patients may also consider taking allopurinol for treatment. Immunodeficient patients receiving Nelarabine should avoid live vaccines.

Definition

ChEBI: A purine nucleoside in which O-methylguanine is attached to arabinofuranose via a beta-N9-glycosidic bond. Inhibits DNA synthesis and causes cell death; a prodrug of 9-beta /stereo>-D-arabinofuranosylguanine (ara-G).

Clinical trials

A large amount of clinical trials have shown that results of Nelarabine’s treatment of T-cell lymphocytic leukemia (T-PLL) and peripheral T-cell lymphoma are encouraging.
The potential indications for Nelarabine also include non-T-cell disease with high levels of nucleotide kinases in the target tissue. In fact, phase I and II clinical trials have shown that Nelarabine alone or in combination with other drugs also have a certain effect on the treatment of B-cell chronic lymphocytic leukemia.
Intracellular levels of ara-GTP can predict whether patients respond to Nelarabine. And the combination of Nelarabine and other drugs can be used to further expand the use of the product range.
In addition, this drugs can be improved in the administration method. Now the administration method is 1-2 hours intravenous infusion. Patients receive Nelarabine daily for 5 days or Nelarabine was administered on days 1, 3, and 5. Finally, since the product selectively acts on T-cells without the bone marrow toxicity of headache, the development of myelosuppression can be exploited.
At present, there are three institutes declare the right of raw materials and preparation of Nelarabine: Beijing Fu Ruikang Pharmaceutical Technology Research Institute, Hangzhou Rong Li Pharmaceutical Technology Co., Ltd., Jiangsu Aokang medicine.

Developed by GlaxoSmithKline

Nelarabine is a prodrug for deoxyguanosine analogue ——9-beta-D-arabinofuranosyl guanine (ara-G). Nelarabine demethylates in the role of adenosine deaminase (ADA) and turns into ara-G. Then, It turns into active ara-G triphosphate (ara-GTP) in the role of the deoxyguanosine kinase and deoxycytidine kinase and under the action of the monophosphorylation pathway. Ara-GTP can accumulate in leukemia cells, and bind to DNA to inhibit DNA synthesis, and accelerate leukemia cell death. In addition, the anti-cancer mechanism of Nelarabine may also be related to its cytotoxicity and somatic toxicity.
Nelarabine was first successfully developed by GlaxoSmithKline. On October 28, 2005 under the approval of the US Food and Drug Administration, it became a new drug for curing T-cell acute lymphoblastic leukemia (T-ALL) and T-Cells lymphoblasticlymphoma (T-LBL) which are resistant to at least two types of chemotherapy regimens or relapsed after initial treatment. This new drug officially listed in the United States in 2006. This product didn’t apply for patent and administrative protection in China, so the development of this product does not exist intellectual property issues.

Brand name

Arranon (SmithKline Beecham).
InChI:InChI=1/C11H15N5O5/c1-20-9-5-8(14-11(12)15-9)16(3-13-5)10-7(19)6(18)4(2-17)21-10/h3-4,6-7,10,17-19H,2H2,1H3,(H2,12,14,15)/t4-,6-,7+,10-/m1/s1

121032-29-9SDS

SAFETY DATA SHEETS

According to Globally Harmonized System of Classification and Labelling of Chemicals (GHS) - Sixth revised edition

Version: 1.0

Creation Date: Aug 19, 2017

Revision Date: Aug 19, 2017

1.Identification

1.1 GHS Product identifier

Product name nelarabine

1.2 Other means of identification

Product number -
Other names 2-Amino-6-methoxypurinribonucleosid

1.3 Recommended use of the chemical and restrictions on use

Identified uses For industry use only.
Uses advised against no data available

1.4 Supplier's details

1.5 Emergency phone number

Emergency phone number -
Service hours Monday to Friday, 9am-5pm (Standard time zone: UTC/GMT +8 hours).

More Details:121032-29-9 SDS

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