Fraxinellone

Names

[ Name ]:
Fraxinellone

[Synonym ]:
(3R,3aR)-3-(furan-3-yl)-3a,7-dimethyl-3a,4,5,6-tetrahydro-2-benzofuran-1(3H)-one
(3R,3aR)-3-(3-Furyl)-3a,7-dimethyl-3a,4,5,6-tetrahydro-2-benzofuran-1(3H)-one
1(3H)-Isobenzofuranone, 3-(3-furanyl)-3a,4,5,6-tetrahydro-3a,7-dimethyl-, (3R,3aR)-

Biological Activity

[Description]:

Fraxinellone is isolated from the root bark of the Rutaceae plant, Dictamnus dasycarpus. Fraxinellone is a PD-L1 inhibitor and inhibits HIF-1α protein synthesis without affecting HIF-1α protein degradation. Fraxinellone has the potential to be a valuable candidate for cancer treatment by targeting PD-L1[1].

[Related Catalog]:

Signaling Pathways >> Stem Cell/Wnt >> STAT

Research Areas >> Cancer

Signaling Pathways >> JAK/STAT Signaling >> STAT

Signaling Pathways >> Immunology/Inflammation >> PD-1/PD-L1

[In Vitro]

Fraxinellone (0-100 μM；12 hours) decreases the percent of PD-L1 positive cells from 20.4% to 11.4% in A549 cells[1]. Cell Viability Assay[1] Cell Line: A549 cells Concentration: 0 μM, 10 μM, 30 μM, 100 μM Incubation Time: 12 hours Result: Inhibited the percent of PD-L1 positive cells.

[In Vivo]

Fraxinellone (oral gavage; 30 and 100 mg/kg; every three days; 30 days) significantly suppresses tumor growth, reduces HIF-1α, pTyr705 STAT3, PD-L1 and VEGF staining compared with the control group in female athymic BALB/c nude mice[1]. Animal Model: BALB/c nude mice[1] Dosage: 30 and 100 mg/kg Administration: Oral gavage; 30 and 100 mg/kg; every three days; 30 days Result: Significantly suppressed tumor growth.

[References]

[1]. Xing Y, et al. Fraxinellone has anticancer activity in vivo by inhibiting programmed cell death-ligand 1 expression by reducing hypoxia-inducible factor-1α and STAT3. Pharmacol Res. 2018 Sep;135:166-180.

Chemical & Physical Properties

[ Density]:
1.2±0.1 g/cm3

[ Boiling Point ]:
372.9±30.0 °C at 760 mmHg

[ Melting Point ]:
116ºC

[ Molecular Formula ]:
C₁₄H₁₆O₃

[ Molecular Weight ]:
232.275

[ Flash Point ]:
179.3±24.6 °C

[ Exact Mass ]:
232.109940

[ PSA ]:
39.44000

[ LogP ]:
2.85

[ Vapour Pressure ]:
0.0±0.8 mmHg at 25°C

[ Index of Refraction ]:
1.552

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: TI3767000

CHEMICAL NAME :: Phthalide, 3-(3-furyl)-3a,4,5,6-tetrahydro-3a,7-dimethyl-

CAS REGISTRY NUMBER :: 28808-62-0

LAST UPDATED :: 198910

DATA ITEMS CITED :: 5

MOLECULAR FORMULA :: C14-H16-O3

MOLECULAR WEIGHT :: 232.30

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 274 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: PLMEAA Planta Medica. (Georg Thieme Verlag, Postfach 732, D-7000 Stuttgart 1, Fed. Rep. Ger.) V.1- 1953- Volume(issue)/page/year: 53,399,1987

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 116 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: PLMEAA Planta Medica. (Georg Thieme Verlag, Postfach 732, D-7000 Stuttgart 1, Fed. Rep. Ger.) V.1- 1953- Volume(issue)/page/year: 53,399,1987

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 430 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: PLMEAA Planta Medica. (Georg Thieme Verlag, Postfach 732, D-7000 Stuttgart 1, Fed. Rep. Ger.) V.1- 1953- Volume(issue)/page/year: 53,399,1987

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 355 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: PLMEAA Planta Medica. (Georg Thieme Verlag, Postfach 732, D-7000 Stuttgart 1, Fed. Rep. Ger.) V.1- 1953- Volume(issue)/page/year: 53,399,1987 ** REPRODUCTIVE DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 424 mg/kg

SEX/DURATION :: female 5-8 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - female fertility index (e.g. # females pregnant per # sperm positive females; # females pregnant per # females mated)

REFERENCE :: PLMEAA Planta Medica. (Georg Thieme Verlag, Postfach 732, D-7000 Stuttgart 1, Fed. Rep. Ger.) V.1- 1953- Volume(issue)/page/year: 53,399,1987

Safety Information

[ Symbol ]:

GHS06

[ Signal Word ]:
Danger

[ Hazard Statements ]:
H301

[ Precautionary Statements ]:
P301 + P310

[ Hazard Codes ]:
Xn

[ Safety Phrases ]:
24/25

[ RIDADR ]:
UN 2811 6.1/PG III

[ RTECS ]:
TI3767000

[ Packaging Group ]:
III