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121032-29-9 , Nelarabine, CAS:121032-29-9

121032-29-9 , Nelarabine,
CAS:121032-29-9
C11H15N5O5 / 297.27
MFCD00871078

奈拉滨 , Nelarabine

Nelarabine is a purine nucleoside analog that is used as a cytotoxic agent in hematological malignancies. Nelarabine is converted into arabinosyl-guanine (ara-G) in the blood, and ara-G is selectively accumulated in T cells and malignant T-lymphoid cells, where it is phosphorylated to produce ara-GTP and incorporated into DNA. This leads to DNA breaks, increased expression of Fas ligand, and apoptosis. Ara-G is accumulated most effectively by acute lymphoid leukemia and chronic myeloid leukemia blasts.

Nelarabine is an arabinonucleoside antimetabolite with antineoplastic activity. Nelarabine is demethoxylated by adenosine deaminase to become biologically active 9-beta-D-arabinosylguanine (ara-G); ara-G incorporates into DNA, thereby inhibiting DNA synthesis and inducing an S phase-dependent apoptosis of tumor cells. (NCI04)

Nelarabine is a purine analogue and antineoplastic agent used in the therapy of T cell lymphoblastic leukemia or lymphoma. Nelarabine is associated with a low rate of transient serum enzyme elevations during therapy and has been linked to rare instances of clinically apparent acute liver injury with jaundice.

Nelarabine, also known as arranon or compound 506U78, belongs to the class of organic compounds known as purine nucleosides. Purine nucleosides are compounds comprising a purine base attached to a ribosyl or deoxyribosyl moiety. Nelarabine is a drug which is used for the treatment of pediatric and adult patients with acute t-cell lymphoblastic leukemia and t-cell lymphoblastic lymphoma whose disease has not responded to or has relapsed following treatment with at least two chemotherapy regimens. Nelarabine exists as a solid, soluble (in water), and a very weakly acidic compound (based on its pKa). Nelarabine has been detected in multiple biofluids, such as urine and blood. Within the cell, nelarabine is primarily located in the cytoplasm. Nelarabine can be biosynthesized from guanine and 9-beta-D-arabinofuranosylguanine.

Nelarabine is a drug that prevents the growth of cells by inhibiting the bcr-abl kinase, which is an intracellular target. This drug has been shown to be effective against pediatric patients with t-cell acute lymphoblastic leukemia and adults with chronic myeloid leukemia. Nelarabine has minimal toxicity in humans and is not toxic to healthy cells. It has been shown to have anti-inflammatory properties and may be used as a biomarker for autoimmune diseases. Nelarabine also inhibits angiogenesis, which may be due to its effects on nuclear DNA.

Title: Nelarabine

CAS Registry Number: 121032-29-9

CAS Name: 9-b-D-Arabinofuranosyl-6-methoxy-9H-purin-2-amine

Additional Names: 2-amino-9-b-D-arabinofuranosyl-6-methoxy-9H-purine

Manufacturers' Codes: GW-506U78; 506U

Trademarks: Arranon (GSK)

Molecular Formula: C11H15N5O5

Molecular Weight: 297.27

Percent Composition: C 44.44%, H 5.09%, N 23.56%, O 26.91%

Literature References: Purine nucleoside; prodrug of guanine arabinoside. Prepn: T. A. Krenitsky et al., EP 294114 (1988 to Wellcome Foundation); idem, D. J. T. Porter, US 5424295 (1995 to Burroughs Wellcome); D. R. Averett et al., Antimicrob. Agents Chemother. 35, 851 (1991). HPLC determn of active metabolites in leukemia cells: C. O. Rodriguez Jr. et al., J. Chromatogr. B 745, 421 (2000). Mechanism of action study: idem, et al., Blood 102, 1842 (2003). Clinical pharmacokinetics: D. F. Kisor et al., J. Clin. Oncol. 18, 995 (2000). Clinical evaluation in T-cell malignancies: S. L. Berg et al., ibid. 23, 3376 (2005). Review of pharmacology and clinical experience: D. F. Kisor, Ann. Pharmacother. 39, 1056-1063 (2005).

Properties: mp 209-217° (dec). uv max (50 mM potassium phosphate buffer (pH 7.0)-ethanol (9:1, v/v)): 247.5, 279 nm (e 9100, 9300). [a]D20 +55.9° (c = 0.27 in DMF). Slightly sol to sol in water.

Melting point: mp 209-217°

Optical Rotation: [a]D20 +55.9° (c = 0.27 in DMF)

Absorption maximum: uv max (50 mM potassium phosphate buffer (pH 7.0)-ethanol (9:1, v/v)): 247.5, 279 nm (e 9100, 9300)

Therap-Cat: Antineoplastic.

Keywords: Antineoplastic; Antimetabolites; Purine Analogs.

CAS Number

121032-29-9

Product Name

Nelarabine

IUPAC Name

(3S,4S,5R)-2-(2-amino-6-methoxypurin-9-yl)-5-(hydroxymethyl)oxolane-3,4-diol

Molecular Formula

C11H15N5O5

Molecular Weight

297.27 g/mol

InChI

InChI=1S/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

InChI Key

IXOXBSCIXZEQEQ-XJCFNFQFSA-N

SMILES

COC1=NC(=NC2=C1N=CN2C3C(C(C(O3)CO)O)O)N

Solubility

Slightly soluble to soluble in water
1.39e+01 g/L

Synonyms

2-amino-6-methoxypurine arabinoside, 2-amino-9-beta-D-arabinofuranosyl-6-methoxy-9H-purine, 506U78, Arranon, compound 506U78, GW506U78, nelarabine

Canonical SMILES

COC1=NC(=NC2=C1N=CN2C3C(C(C(O3)CO)O)O)N

Isomeric SMILES

COC1=NC(=NC2=C1N=CN2[C@H]3[C@H]([C@@H]([C@H](O3)CO)O)O)N

CAS No: 121032-29-9 Synonyms: 9-b-D-Arabinofuranosyl-6-methoxy-9H-purin-2-amine506uArranon MDL No: MFCD00871078 Chemical Formula: C11H15N5O5 Molecular Weight: 297.27

References: 1. Cohen, M.H. et al., Oncologist, 13, 709 (2008)2. Hernandez-Ilizaliturri, F.J. et al., Clin. Med. Therap., 1, 505 (2009)3. Sigalas, P. et al., Leuk. Res., 33, e61 (2009)


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