HMN-214 Chemical Properties

Boiling point:

663.1±65.0 °C(Predicted)

Density 

1.24

storage temp. 

Inert atmosphere,Store in freezer, under -20°C

solubility 

≥21.2 mg/mL in DMSO; insoluble in H2O; insoluble in EtOH

form 

solid

pka

0.86±0.10(Predicted)

HMN-214 Usage And Synthesis

Description

HMN-214 is an orally bioavailable prodrug form of HMN-176, an indirect inhibitor of polo-like kinase (PLK) activity that inhibits proliferation of a variety of cancer cells. HMN-214 decreases the expression of multidrug resistance gene 1 (MDR1) in AB-A.1 cells and in tumors isolated from mice bearing multidrug-resistant KB-A1 xenografts. HMN-214 (20 mg/kg per day) reduces tumor volume in PC3, WiDr, and A549 mouse xenograft models. It does not decrease nerve conduction velocity or compound action potential amplitude in rabbit sciatic nerves in vivo when administered at a concentration of 30 mg/kg per day.

Uses

HMN 214 is a novel oral stilbene derivative with polo-like kinase-1-interacting properties, in patients with advanced solid tumors. It is a prodrug of HMN 176, a stilbene derivative that interferes with the subcellular spatial location of polo-like kinase-1 (PLK1).

Definition

ChEBI: N-(4-methoxyphenyl)sulfonyl-N-[2-[2-(1-oxido-4-pyridin-1-iumyl)ethenyl]phenyl]acetamide is a sulfonamide.

in vitro

hmn-176 showed potent cytotoxicity, with a mean ic50 of 118 nm. the cytotoxic effecacy of hnm-176 was superior to that of adm, vp-16 and cddp, but inferior to that of taxol and vcr. hmn-176 showed less vaiance in log(ic50) than did the reference agents. in addition, judging by its low resistance indices, hmn-176 was more cytotoxic toward the drug-resistant phenotypes of tumor cells than were the other agents tested [1].

in vivo

pk studies showed that hnm-214 was an acceptable oral prodrug of hmn-176. in the in vivo analysis of the schedule-dependency of hmn-214, the repeated administration for over 5 days elicited potent antitumor activity, as expected from the exposure-dependency of the cytotoxicity of hmn-176 and from the cytometric studies. the antitumor activity of hmn-214 against human tumor xenografts was equal or superior to that of clinically avaiable agents, including cis-platinum, adriamycin, vincristine and uft without severe toxicity such as neurotoxicity [1].

target

PLK1

IC 50

hmn-176 showed potent cytotoxic activity against several tumor cell lines with an average ic50 of 118 nmol/l

References

[1] takagi m, honmura t, watanabe s, yamaguchi r, nogawa m, nishimura i, katoh f, matsuda m, hidaka h. in vivo antitumor activity of a novel sulfonamide, hmn-214, against human tumor xenografts in mice and the spectrum of cytotoxicity of its active metabolite, hmn-176. invest new drugs. 2003 nov;21(4):387-99.
[2] garland ll, taylor c, pilkington dl, cohen jl, von hoff dd. a phase i pharmacokinetic study of hmn-214, a novel oral stilbene derivative with polo-like kinase-1-interacting properties, in patients with advanced solid tumors. clin cancer res. 2006 sep 1;12(17):5182-9.

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