CAS 51264-14-3|Amsacrine

Introduction：Basic information about CAS 51264-14-3|Amsacrine, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.

Table of Contents

1. Names
2. Amsacrine BiologicalActivity
3. Chemical & Physical Properties
4. Toxicological Information
CHEMICAL IDENTIFICATION
HEALTH HAZARD DATA
ACUTE TOXICITY DATA
MUTATION DATA
5. Safety Information
6. Customs
7. Synonyms

Common Name	Amsacrine
CAS Number	51264-14-3	Molecular Weight	393.459
Density	1.4±0.1 g/cm3	Boiling Point	563.0±60.0 °C at 760 mmHg
Molecular Formula	C₂₁H₁₉N₃O₃S	Melting Point	230-240ºC
MSDS	/	Flash Point	294.3±32.9 °C

Names

Name	amsacrine
Synonym	More Synonyms

Amsacrine BiologicalActivity

Description	Amsacrine is an inhibitor of topoisomerase II, and acts as an antineoplastic agent which can intercalates into the DNA of tumor cells.
Related Catalog	Signaling Pathways >>Autophagy >>AutophagySignaling Pathways >>Cell Cycle/DNA Damage >>TopoisomeraseResearch Areas >>Cancer
Target	Topoisomerase II
In Vitro	Amsacrine blocks HERG currents in HEK 293 cells and Xenopus oocytes in a concentration-dependent manner, with IC50 values of 209.4 nm and 2.0 μM, respectively. Amsacrine causes a negative shift in the voltage dependence of both activation (−7.6 mV) and inactivation (−7.6 mV). HERG current block by amsacrine is not frequency dependent[1]. In vitro studies of normal human lymphocytes with various concentrations of m-AMSA, show both increased levels of chromosomal aberrations, ranging from 8% to 100%, and increase SCEs, ranging from 1.5 times the normal at the lowest concentration studied (0.005 μg/mL) to 12 times the normal (0.25 μg/mL)[3]. Amsacrine-induced apoptosis of U937 cells is characterized by caspase-9 and caspase-3 activation, increased intracellular Ca2+ concentration, mitochondrial depolarization, and MCL1 down-regulation. Amsacrine induces MCL1 down-regulation by decreasing its stability. Further, amsacrine-treated U937 cells show AKT degradation and Ca2+-mediated ERK inactivation[4].
In Vivo	In animals treated with different doses of amsacrine (0.5-12 mg/kg), the frequencies of micronucleated polychromatic erythrocytes increase significantly after treatment with 9 and 12 mg/kg. Furthermore, the present study demonstrates for the first time that amsacrine has high incidences of clastogenicity and low incidences of aneugenicity whereas nocodazole has high incidences of aneugenicity and low incidences of clastogenicity during mitotic phases in vivo[2].
Animal Admin	Amsacrine is investigated in three separated experiments. In the first experiment, animals are treated by intraperitoneal injection with 0.5, 1.5 and 4.5 mg/kg of amsacrine and bone marrow is sampled 24 h after treatment. Preliminary negative MN results at this sampling time lead to the use of 30 h sampling time for amsacrine. Thus, in the second experiment, mice are treated with 0.5, 1.5 and 4.5 mg/kg of amsacrine and bone marrow is sampled 30 h after treatment. The doses and sampling times for amsacrine are chosen by reference to earlier studies and the selected doses are within the dose range used for human chemotherapy. The results again show that the micronuclei frequency in the bone marrow of mice is not affected by treatment with any of the selected doses of the test agent, at 30 h sampling time, thus, in the third experiment, mice are treated with 6, 9 and 12 mg/kg of amsacrine and bone marrow is sampled 24 and 30 h after treatment.
References	[1]. Thomas D, et al. Inhibition of cardiac HERG currents by the DNA topoisomerase II inhibitor amsacrine: mode of action. Br J Pharmacol. 2004 Jun;142(3):485-94. [2]. Attia SM. Molecular cytogenetic evaluation of the mechanism of genotoxic potential of amsacrine and nocodazole in mouse bone marrow cells. J Appl Toxicol. 2013 Jun;33(6):426-33. [3]. Kao-Shan CS, et al. Cytogenetic effects of amsacrine on human lymphocytes in vivo and in vitro. Cancer Treat Rep. 1984 Jul-Aug;68(7-8):989-97. [4]. Lee YC, et al. Amsacrine-induced apoptosis of human leukemia U937 cells is mediated by the inhibition of AKT- and ERK-induced stabilization of MCL1. Apoptosis. 2016 Oct 19

Chemical & Physical Properties

Density	1.4±0.1 g/cm3
Boiling Point	563.0±60.0 °C at 760 mmHg
Melting Point	230-240ºC
Molecular Formula	C₂₁H₁₉N₃O₃S
Molecular Weight	393.459
Flash Point	294.3±32.9 °C
Exact Mass	393.114716
PSA	88.70000
LogP	2.12
Vapour Pressure	0.0±1.5 mmHg at 25°C
Index of Refraction	1.723
InChIKey	XCPGHVQEEXUHNC-UHFFFAOYSA-N
SMILES	COc1cc(NS(C)(=O)=O)ccc1Nc1c2ccccc2nc2ccccc12

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: PB1080000

CHEMICAL NAME :: Methanesulfon-m-anisidide, 4'-(9-acridinylamino)-

CAS REGISTRY NUMBER :: 51264-14-3

BEILSTEIN REFERENCE NO. :: 0500176

LAST UPDATED :: 199801

DATA ITEMS CITED :: 58

MOLECULAR FORMULA :: C21-H19-N3-O3-S

MOLECULAR WEIGHT :: 393.49

WISWESSER LINE NOTATION :: T C666 BNJ IMR BO1 DMSW1

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 5405 ug/kg/3H-C

TOXIC EFFECTS :: Blood - changes in bone marrow (not otherwise specified)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Human

DOSE/DURATION :: 12 mg/kg

TOXIC EFFECTS :: Vascular - thrombosis distant from injection site Gastrointestinal - nausea or vomiting Blood - other changes

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 53420 ug/kg

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

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

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 15470 ug/kg

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

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

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 110 mg/kg

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

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

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 33700 ug/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - dyspnea

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 50 mg/kg

TOXIC EFFECTS :: Behavioral - food intake (animal) Gastrointestinal - hypermotility, diarrhea Gastrointestinal - nausea or vomiting

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

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 6250 ug/kg

TOXIC EFFECTS :: Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - dyspnea Nutritional and Gross Metabolic - weight loss or decreased weight gain

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Primate - monkey

DOSE/DURATION :: 10400 ug/kg

TOXIC EFFECTS :: Blood - changes in bone marrow (not otherwise specified)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 546 mg/kg/13W-I

TOXIC EFFECTS :: Blood - changes in bone marrow (not otherwise specified) Related to Chronic Data - death

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 90 mg/kg/24W-I

TOXIC EFFECTS :: Blood - changes in bone marrow (not otherwise specified) Nutritional and Gross Metabolic - weight loss or decreased weight gain Related to Chronic Data - changes in testicular weight

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 69250 ug/kg/5D-I

TOXIC EFFECTS :: Behavioral - muscle contraction or spasticity Blood - pigmented or nucleated red blood cells Related to Chronic Data - death

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 125 mg/kg/5D-I

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Blood - changes in bone marrow (not otherwise specified) Related to Chronic Data - death

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 1950 ug/kg/5D-I

TOXIC EFFECTS :: Blood - hemorrhage Blood - changes in bone marrow (not otherwise specified) Blood - changes in leukocyte (WBC) count

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Primate - monkey

DOSE/DURATION :: 13 mg/kg/5D-I

TOXIC EFFECTS :: Blood - changes in bone marrow (not otherwise specified) Blood - changes in leukocyte (WBC) count

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 30 mg/kg/24W-I

TOXIC EFFECTS :: Tumorigenic - Carcinogenic by RTECS criteria Gastrointestinal - tumors Skin and Appendages - tumors

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

DOSE :: 6486 ug/kg

SEX/DURATION :: male 3 week(s) pre-mating

TOXIC EFFECTS :: Reproductive - Paternal Effects - spermatogenesis (incl. genetic material, sperm morphology, motility, and count)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 8 mg/kg

SEX/DURATION :: female 6-9 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Fertility - litter size (e.g. # fetuses per litter; measured before birth) Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 15 mg/kg

SEX/DURATION :: male 1 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Paternal Effects - spermatogenesis (incl. genetic material, sperm morphology, motility, and count)

TYPE OF TEST :: Micronucleus test

TYPE OF TEST :: DNA damage

TYPE OF TEST :: Cytogenetic analysis

MUTATION DATA

TYPE OF TEST :: DNA damage

TEST SYSTEM :: Mammal - species unspecified Lymphocyte

DOSE/DURATION :: 54 umol/L

REFERENCE :: CNREA8 Cancer Research. (Public Ledger Building, Suit 816, 6th & Chestnut Sts., Philadelphia, PA 19106) V.1- 1941- Volume(issue)/page/year: 38,1300,1978 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X6337 No. of Facilities: 7 (estimated) No. of Industries: 1 No. of Occupations: 1 No. of Employees: 14 (estimated) No. of Female Employees: 14 (estimated)

Safety Information

RIDADR	UN 3249
Packaging Group	III
Hazard Class	6.1(b)
HS Code	2935009090

Customs

HS Code	2935009090
Summary	2935009090 other sulphonamides VAT:17.0% Tax rebate rate:9.0% Supervision conditions:none MFN tariff:6.5% General tariff:35.0%

Synonyms

m-AMSA

meta-Amsacrine

Methanesulfonamide, N-[4-(9-acridinylamino)-3-methoxyphenyl]-

Amsacrine

4'-(Acridinylamino)methanesulfon-m-anisidide

Amsidyl

AMSA P-D

Amekrin

EINECS 257-094-3

AMSA, M-

Methanesulfonamide, N-(4-(9-acridinylamino)-3-methoxyphenyl)-

Amsine

Amsidine

N-[4-(9-Acridinylamino)-3-methoxuphenyl]methanesulfonamide

N-[4-(9-Acridinylamino)-3-methoxyphenyl]methanesulfonamide

N-[4-(acridin-9-ylamino)-3-(methyloxy)phenyl]methanesulfonamide

N-[4-(acridin-9-ylamino)-3-methoxyphenyl]methanesulfonamide

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