Intoplicine dimesylate

• CAT Number: I029391
• CAS Number: 133711-99-6
• Molecular Formula: C23H32N4O7S2
• Molecular Weight: 540.65
• Purity: ≥95%
• Synonyms: 16-[3-(dimethylamino)propylamino]-13-methyl-11,15-diazatetracyclo[8.7.0.02,7.012,17]heptadeca-1(10),2(7),3,5,8,12(17),13,15-octaen-5-ol;methanesulfonic acid
• InChI: InChI=1S/C21H24N4O.2CH4O3S/c1-13-12-23-21(22-9-4-10-25(2)3)19-18-16-7-6-15(26)11-14(16)5-8-17(18)24-20(13)19;2*1-5(2,3)4/h5-8,11-12,24,26H,4,9-10H2,1-3H3,(H,22,23);2*1H3,(H,2,3,4)
• InChIKey: JAUYMMJDKJISLX-UHFFFAOYSA-N
• SMILES: CC1=CN=C(C2=C1NC3=C2C4=C(C=C3)C=C(C=C4)O)NCCCN(C)C.CS(=O)(=O)O.CS(=O)(=O)O

Intoplicine (RP 60475) dimesylate, an antitumor derivative in the 7H-benzo[e]pyrido[4,3-b]indole series, is a DNA topoisomerase I and II inhibitor. Intoplicine dimesylate strongly binds DNA (KA = 2 x 105 /M) and thereby increases the length of linear DNA[1][2].
With 1-hour exposure to Intoplicine dimesylate at final concentrations of 2.5 micrograms/mL and 10.0 micrograms/mL, 26% and 54% of the assessable specimens shows positive in vitro responses, respectively[2].
With continuous exposure to Intoplicine dimesylate at concentrations of 0.25 micrograms/mL and 2.5 micrograms/mL, 16% and 71% of the assessable specimens showed positive responses, respectively[2].
Activity is seen against breast (71%), non-small-cell lung (69%), and ovarian (45%) cancer colony-forming units at a Intoplicine dimesylate concentration of 10.0 micrograms/mL after 1-hour exposure[2].
At the highest non-toxic dose (HNTD) (6 mg/kg/injection, total dose, 36 mg/kg), intoplicine dimesylate shows highly active with a T/C of 0% and a corresponding total log cell kill of 3[3].

Reference

[1]. Riou JF, et al. Intoplicine (RP 60475) and its derivatives, a new class of antitumor agents inhibiting both topoisomerase I and II activities. Cancer Res. 1993;53(24):5987-5993.
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[2]. Eckardt JR, et al. Activity of intoplicine (RP60475), a new DNA topoisomerase I and II inhibitor, against human tumor colony-forming units in vitro. J Natl Cancer Inst. 1994;86(1):30-33.
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[3]. Bissery MC, et al. Antitumor activity of intoplicine (RP 60475, NSC 645008), a new benzo-pyrido-indole: evaluation against solid tumors and leukemias in mice. Invest New Drugs. 1993;11(4):263-277.
 [Content Brief]