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(-)-Irofulven

Names

[ CAS No. ]:
158440-71-2

[ Name ]:
(-)-Irofulven

[Synonym ]:
HMAF
Spiro(cyclopropane-1,5'(5H)-inden)-7'(6'H)-one,6'-hydroxy-3'-(hydroxymethyl)-2',4',6'-trimethyl-,(R)
[14C]-Irofulven
6-hydroxymethylacylfulvene
(-)-irofulven
Acylfulvene,6-(hydroxymethyl)
MGI 114

Biological Activity

[Description]:

(-)-Irofulven (MGI 114), an Illudin S analog, is a DNA alkylating agent. (-)-Irofulven inhibits the replication of DNA, induces tumor cells apoptosis, and has potent antitumor activity[1][2].

[Related Catalog]:

Signaling Pathways >> Apoptosis >> Apoptosis
Research Areas >> Cancer
Signaling Pathways >> Cell Cycle/DNA Damage >> DNA Alkylator/Crosslinker

[In Vitro]

(-)-Irofulven (2.8 μM; 1 hour) induces p53-dependent cell cycle arrest[1]. (-)-Irofulven (0.8 μM, 0.9 μM and 2.8 μM; 1 hour) induces CHK2 activation is related to p53 status in cells[1]. (-)-Irofulven inhibits DNA replication and induces chromosome aberrations (breaks and radials)[1]. Cell Cycle Analysis[1] Cell Line: A2780, CAOV3 and HCT116 cells Concentration: 2.8 μM Incubation Time: 1 hour Result: p53 wild-type cells mainly arrested at G1/S phases, while p53-mutated or p53-null cells arrested at S and G2/M phases. Western Blot Analysis[1] Cell Line: A2780, CAOV3 and HCT116 cells Concentration: 0.8 μM, 0.9 μM and 2.8 μM Incubation Time: 1 hour Result: Induced the Thr 68 phosphorylation of CHK2 kinase in cells.

[In Vivo]

(-)-Irofulven (7 mg/kg; i.p; on days 1-5 and 8-12) produces a statistically significant increase in the median survival of mice bearing tumor cells[2]. Animal Model: Male and female athymic BALB/c mice (nu/nu genotype, 6 weeks old or older) injected with human glioblastoma multiforme[2]. Dosage: 7 mg/kg Administration: i.p; on days 1-5 and 8-12 Result: Was active against all tumor lines.

[References]

[1]. Yutian Wang, et al. Irofulven induces replication-dependent CHK2 activation related to p53 status. Biochem Pharmacol. 2007 Feb 15;73(4):469-80.

[2]. H S Friedman, et al. Activity of irofulven (6-hydroxymethylacylfulvene) in the treatment of glioblastoma multiforme-derived xenografts in athymic mice. Cancer Chemother Pharmacol. 2001 Nov;48(5):413-6.

Chemical & Physical Properties

[ Density]:
1.28g/cm3

[ Boiling Point ]:
501ºC at 760 mmHg

[ Molecular Formula ]:
C15H18O3

[ Molecular Weight ]:
246.30200

[ Flash Point ]:
270.9ºC

[ Exact Mass ]:
246.12600

[ PSA ]:
57.53000

[ LogP ]:
1.66560

[ Vapour Pressure ]:
3.9E-12mmHg at 25°C

[ Index of Refraction ]:
1.617

[ Storage condition ]:
-20°C

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :
WH0204487
CHEMICAL NAME :
Spiro(cyclopropane-1,5'(5H)-inden)-7'(6'H)-one, 6'-hydroxy-3'-(hydroxymethyl)-2',4',6'- trimethyl-, (R)-
CAS REGISTRY NUMBER :
158440-71-2
LAST UPDATED :
199712
DATA ITEMS CITED :
4
MOLECULAR FORMULA :
C15-H18-O3
MOLECULAR WEIGHT :
246.33

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :
LD - Lethal dose
ROUTE OF EXPOSURE :
Intravenous
SPECIES OBSERVED :
Rodent - rat
DOSE/DURATION :
>6610 ug/kg
TOXIC EFFECTS :
Cardiac - other changes Blood - changes in bone marrow (not otherwise specified) Blood - changes in other cell count (unspecified)
REFERENCE :
FAATDF Fundamental and Applied Toxicology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1981- Volume(issue)/page/year: 36(1, Pt 2),180,1997
TYPE OF TEST :
LDLo - Lowest published lethal dose
ROUTE OF EXPOSURE :
Intravenous
SPECIES OBSERVED :
Mammal - dog
DOSE/DURATION :
2 mg/kg
TOXIC EFFECTS :
Blood - thrombocytopenia Blood - changes in bone marrow (not otherwise specified) Blood - changes in other cell count (unspecified)
REFERENCE :
FAATDF Fundamental and Applied Toxicology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1981- Volume(issue)/page/year: 36(1, Pt 2),180,1997 ** OTHER MULTIPLE DOSE TOXICITY DATA **
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Intravenous
SPECIES OBSERVED :
Rodent - rat
DOSE/DURATION :
20339 ug/kg/5D-I
TOXIC EFFECTS :
Cardiac - other changes Blood - changes in bone marrow (not otherwise specified) Blood - changes in other cell count (unspecified)
REFERENCE :
FAATDF Fundamental and Applied Toxicology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1981- Volume(issue)/page/year: 36(1, Pt 2),180,1997
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Intravenous
SPECIES OBSERVED :
Mammal - dog
DOSE/DURATION :
3 mg/kg/5D-I
TOXIC EFFECTS :
Blood - thrombocytopenia Blood - changes in bone marrow (not otherwise specified) Blood - changes in other cell count (unspecified)
REFERENCE :
FAATDF Fundamental and Applied Toxicology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1981- Volume(issue)/page/year: 36(1, Pt 2),180,1997

Synthetic Route

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Precursor & DownStream

Precursor

DownStream

Related Compounds

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