529488-28-6

529488-28-6 - Names and Identifiers

Name	2,3-dimethoxy-12-(2-(methylamino)ethyl)-[1,3]dioxolo[4',5':4,5]benzo[1,2-h]benzo[c][1,6]naphthyridin-13(12H)-one
Synonyms	GENZ644282 GNZ-644282 Genz644282 GENZ 644282 Genz-644282 GENZ-644282 GENZ 644282 8,9-dimethoxy-2,3-methylenedioxy-5-[2-(N-methylamino)ethyl]-5H-dibenzo[c,h]1,6-naphthyridin-6-one 2,3-Dimethoxy-12-[2-(methylamino)ethyl]benzo[c][1,3]benzodioxolo[5,6-h][1,6]naphthyridin-13(12H)-one 2,3-Dimethoxy-12-[2-(methylamino)ethyl]benzo[c][1,3]benzodioxolo[5,6-h][1,6]naphthyridin-13(12H)-one GENZ-644282
CAS	529488-28-6

529488-28-6 - Physico-chemical Properties

Molecular Formula	C22H21N3O5
Molar Mass	407.42
Density	1.344±0.06 g/cm3(Predicted)
Melting Point	254-257℃ (Decomposition)
Boling Point	665.5±55.0 °C(Predicted)
Solubility	Soluble in DMSO
Appearance	Solid
Color	Off-White to Pale Yellow
pKa	9.59±0.10(Predicted)
Storage Condition	-20°C Freezer
Use	Genz-644282, also known as SAR402674, is a non-camptothecin inhibitor of topoisomerase I with potential antineoplastic activity. Topoisomerase I inhibitor Genz-644282 binds to and inhibits the enzyme topoisomerase I, which may result in the inhibition of repair of single-strand DNA breaks, DNA replication, and tumor cell growth in susceptible tumor cell populations.
Target	Topoisomerase

529488-28-6 - Reference

Reference

1: Sooryakumar D, Dexheimer TS, Teicher BA, Pommier Y. Molecular and cellular pharmacology of the novel noncamptothecin topoisomerase I inhibitor Genz-644282. Mol Cancer Ther. 2011 Aug;10(8):1490-9. Epub 2011 Jun 2. PubMed PMID: 21636699; PubMed Central PMCID: PMC3155218.
2: Houghton PJ, Lock R, Carol H, Morton CL, Gorlick R, Anders Kolb E, Keir ST, Reynolds CP, Kang MH, Maris JM, Billups CA, Zhang MX, Madden SL, Teicher BA, Smith MA. Testing of the topoisomerase 1 inhibitor Genz-644282 by the pediatric preclinical testing program. Pediatr Blood Cancer. 2011 May 5. doi: 10.1002/pbc.23016. [Epub ahead of print] PubMed PMID: 21548007; PubMed Central PMCID: PMC3154998.
3: Kurtzberg LS, Roth S, Krumbholz R, Crawford J, Bormann C, Dunham S, Yao M, Rouleau C, Bagley RG, Yu XJ, Wang F, Schmid SM, Lavoie EJ, Teicher BA. Genz-644282, a novel non-camptothecin topoisomerase I inhibitor for cancer treatment. Clin Cancer Res. 2011 May 1;17(9):2777-87. Epub 2011 Mar 17. PubMed PMID: 21415217.

529488-28-6 - Preparation solution concentration reference

	1mg	5mg	10mg
1 mM	2.454 ml	12.272 ml	24.545 ml
5 mM	0.491 ml	2.454 ml	4.909 ml
10 mM	0.245 ml	1.227 ml	2.454 ml
5 mM	0.049 ml	0.245 ml	0.491 ml

Last Update：2024-01-02 23:10:35

529488-28-6 - Cell Experiment

Colony-forming assays were conducted with mouse and human bone marrow and eight human tumor cell lines. In addition, 29 human tumor cell lines representing a range of histology and potential resistance mechanisms were assayed for sensitivity to Genz-644282 in a 72-hour exposure assay. The efficacy of Genz-644282 was compared with standard anticancer drugs (i.e., irinotecan, docetaxel, and dacarbazine) in human tumor xenografts of colon cancer, renal cell carcinoma, non-small cell lung cancer, and melanoma.

Last Update：2023-08-16 21:32:38

529488-28-6 - Animal Experiment

Genz-644282 was tested against the PPTP in vitro panel (0.1 nM to 1 μM), and in vivo using three times per week × 2 schedule repeated at day 21 at its maximum tolerated dose (MTD) of 4 mg/kg. Subsequently Genz-644282 was tested at 4, 3, 2, and 1 mg/kg in 3 models to assess the dose-response relationship. mRNA gene signatures predictive for Genz-644282 response in vitro were applied to select 15 tumor models that were evaluated prospectively.

Last Update：2023-08-16 21:32:38

529488-28-6 - Reference Information

use	GENZ-644282 is used to synthesize ARC-111 analogs to improve the anti-tumor activity of the parent compound.
biological activity	Genz-644282 is a non-camptothecin topoisomerase I (Topo I) inhibitor with strong cytotoxicity, with an average IC50 value of 1.2 nM (range is 0.2 nM-21.9 nM). Genz-644282 can be used for cancer research.
target	TargetValue Topo I (Cell-free assay) 1.2 nM
Target	Value
Topo I (Cell-free assay)	1.2 nM

Last Update：2024-04-09 21:54:55