158440-71-2

158440-71-2 structure

Name: (-)-Irofulven
Chemical Name: (5'R)-5'-hydroxy-1'-(hydroxymethyl)-2',5',7'-trimethylspiro[cyclopropane-1,6'-indene]-4'-one
CAS Number: 158440-71-2
Molecular Formula: C₁₅H₁₈O₃
Molecular Weight: 246.30200
Catalog: Signaling Pathways Apoptosis Apoptosis
Create Date: 2017-06-14 12:52:33
Modify Date: 2024-01-09 12:04:24
(-)-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].

Name	(5'R)-5'-hydroxy-1'-(hydroxymethyl)-2',5',7'-trimethylspiro[cyclopropane-1,6'-indene]-4'-one
Synonyms	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

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.

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

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

50-00-0

33781-60-1

~75%

158440-71-2

Literature: McMorris, Trevor C.; Hu, Yi; Yu, Jian; Kelner, Michael J. Chemical Communications, 1997 , # 3 p. 315 - 316

1149-99-1

158440-71-2

Literature: Journal of Labelled Compounds and Radiopharmaceuticals, , vol. 41, # 4 p. 279 - 285

Precursor 3
50-00-0 33781-60-1 1149-99-1
DownStream 0

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