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

Product information

CAS Number: 859209-74-8

Molecular Weight: 526.53

Formula: C21H35N8O6P

Chemical Name: ethyl (2S)-2-{[({2-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]ethoxy}methyl)({[(2S)-1-ethoxy-1-oxopropan-2-yl]amino})phosphoryl]amino}propanoate

Smiles: C[C@H](NP(=O)(COCCN1C=NC2=C1N=C(N)N=C2NC1CC1)N[C@@H](C)C(=O)OCC)C(=O)OCC

InChiKey: ANSPEDQTHURSFQ-KBPBESRZSA-N

InChi: InChI=1S/C21H35N8O6P/c1-5-34-19(30)13(3)27-36(32,28-14(4)20(31)35-6-2)12-33-10-9-29-11-23-16-17(24-15-7-8-15)25-21(22)26-18(16)29/h11,13-15H,5-10,12H2,1-4H3,(H2,27,28,32)(H3,22,24,25,26)/t13-,14-/m0/s1

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

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.

In Vivo:

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.

Products are for research use only. Not for human use.