Rabacfosadine (GS-9219), a novel prodrug of the nucleotide analogue PMEG, is designed as a cytotoxic agent that preferentially targets lymphoid cells.

In lymphocytes, Rabacfosadine (GS-9219) is converted to its active metabolite, 9-(2-phosphonylmethoxyethyl)guanine (PMEG) diphosphate, via enzymatic hydrolysis, deamination, and phosphorylation. GS-9219 has substantial antiproliferative activity against activated lymphocytes and hematopoietic tumor cell lines. The ability of Rabacfosadine to inhibit the proliferation of activated lymphocytes and of tumor cells of hematopoietic origin is investigated. Rabacfosadine inhibits the proliferation of mitogen-stimulated T and B lymphocytes with EC₅₀ values of 135 and 42 nM, respectively, as determined by BrdUrd incorporation. To compare the activity of GS-9219 in dividing and nondividing cells, Rabacfosadine is evaluated in these populations using a metabolism-based sodium XTT assay instead of BrdUrd assays. Results from the XTT assay shows a 127-fold difference between the EC₅₀ values of Rabacfosadine in quiescent (EC₅₀=17.2 μM) and proliferating (EC₅₀=135 nM) cells. These results indicate a substantial selectivity of Rabacfosadine toward actively replicating lymphoblasts^[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Rabacfosadine (RAB) has substantial single-agent activity in dogs with lymphoma, and a different mechanism of action than Doxorubicin (DOX). Open-label, multicenter prospective clinical trial. Dogs receive alternating Rabacfosadine (1.0 mg/kg IV weeks 0, 6, 12) and Doxorubicin (30 mg/m² IV weeks 3, 9, 15). Dogs that achieved complete response (CR) are followed by monthly evaluations. Complete clinicopathological evaluation and assessment of remission and adverse event (AEs) are performed every 21 days. Acute AEs, occurring within 21 days after administration of the first dose of each agent, are compared between Rabacfosadine and Doxorubicin in 46 dogs receiving at least 1 dose of each agent^[2].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

526.53

C₂₁H₃₅N₈O₆P

859209-74-8

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Reiser H, et al. GS-9219–a novel acyclic nucleotide analogue with potent antineoplastic activity in dogs with spontaneous non-Hodgkin’s lymphoma. Clin Cancer Res. 2008 May 1;14(9):2824-32.

  [2]. Thamm DH, et al. Alternating Rabacfosadine/Doxorubicin: Efficacy and Tolerability in Na?ve Canine Multicentric Lymphoma. J Vet Intern Med. 2017 May;31(3):872-878.

Twenty million PHA-stimulated T cells are incubated with 10 μM[¹⁴C]GS-9219 for 24 h. Cells are washed once with tissue culture medium and twice with PBS, incubated in 80% methanol overnight, and centrifuged at 14,000 rpm for 15 min to remove denatured proteins. The methanol extracts are lyophilized and dissolved in the high-performance liquid chromatography (HPLC) loading buffer. A portion of each sample is used for scintillation counting to calculate the total pmoles, and the rest is used for HPLC analysis to calculate the ratio of metabolites. HPLC analysis is done by gradient elution using a Phenomenex Prodigy column (5 μm, ODS3 150×4 mm), where buffer A is 25 mM K₂HPO₄ (pH 6.0) and 5 mM Tetrabutylammonium bromide and buffer B is 25 mM K₂HPO₄ (pH 6.0), 70% Acetonitrile, and 5 mM Tetrabutylammonium bromide^[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Dogs^[2]
Dogs are given alternating doses of Rabacfosadine and Doxorubicin every 3 weeks. Rabacfosadine is administered at a dosage of 1.0 mg/kg as a 30-minute IV infusion on weeks 0, 6, and 12. Doxorubicin is administered at a dosage of 30 mg/m² (1.0 mg/kg for dogs weighing <15 kg) as an approximately 20-minute iv infusion on weeks 3, 9, and 15. concurrent cytotoxic chemotherapy of any kind corticosteroids are not allowed. a cbc is performed 1 week after the first rabacfosadine doxorubicin treatments (weeks 4). all dogs have physical examination with lymph node measurements, owner history, cbc, serum biochemistry profile (sbc), urinalysis at each visit. thoracic radiographs recommended 15 every 2 months thereafter in responding dogs. dose delays, reductions, or both, supportive treatment for aes carried out discretion attending clinician. that experienced complete response (cr) followed monthly examinations until relapse, when they considered off study. partial (pr) stable disease (sd) study censored from analysis time. time withdrawal, eligible additional clinician.

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

• [1]. Reiser H, et al. GS-9219–a novel acyclic nucleotide analogue with potent antineoplastic activity in dogs with spontaneous non-Hodgkin’s lymphoma. Clin Cancer Res. 2008 May 1;14(9):2824-32.

  [2]. Thamm DH, et al. Alternating Rabacfosadine/Doxorubicin: Efficacy and Tolerability in Na?ve Canine Multicentric Lymphoma. J Vet Intern Med. 2017 May;31(3):872-878.