Campathecin

Names

[ Name ]:
Campathecin

[Synonym ]:
EINECS 444-280-6
Camptothecin
d-Camptothecin
1H-Pyrano(3',4':6,7)indolizino(1,2-b)quinoline-3,14(4H,12H)-dione, 4-ethyl-4-hydroxy-, (S)-
(S)-4-ethyl-4-hydroxy-1H-Pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione
(S)-4-ethyl-4-hydroxy-1H-Pyrano(3',4':6,7)indolizino(1,2-b)quinoline-3,14(4H,12H)-dione
CaMpathecin
1H-Pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione, 4-ethyl-4-hydroxy-, (4S)-
(S)-(+)-Camptothecin
(4S)-4-Ethyl-4-hydroxy-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione
1H-Pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione, 4-ethyl-4-hydroxy-, (S)-
Camptohecin
MFCD00081076
Baicalin std.
CAMPTOTHECINE
1H-Pyrano(3',4':6,7)indolizino(1,2-b)quinoline-3,14(4H,12H)-dione, 4-ethyl-4-hydroxy-, (4S)-
(S)-4-ethyl-4-hydroxy-1H-pyrano-[3',4':6,7]indolizinol[1,2-b]quinoline-3,14(4H,12H)-dione
(+)-Camptothecin
(+)-Camptothecine

Biological Activity

[Description]:

Campathecin is a potent DNA enzyme topoisomerase I inhibitor, with an IC50 of 679 nM.

[Related Catalog]:

Signaling Pathways >> Antibody-drug Conjugate >> ADC Cytotoxin

Signaling Pathways >> Cell Cycle/DNA Damage >> Topoisomerase

Research Areas >> Cancer

[Target]

Topoisomerase I:679 nM (IC50)

[In Vitro]

[3H]BrCPT labeling of topoisomerase I is enhanced greatly by the presence of DNA; very little labeling of isolated topoisomerase I or isolated DNA occurrs. Even in the presence of DNA, [3H]BrCPT labeling of topoisomerase I is inhibited by camptothecin, suggesting that both CPT and BrCPT bind to the same site on the DNA-topoisomerase I binary complex[1]. With increasing concentrations of camptothecin, closed circular pRR322 DNA (form I) is converted to nicked circular DNA (form 11). This apparent nicking activitv of camptothecin required DNA topoisomerase I[2].

[Kinase Assay]

Each reaction mixture (200 μL, total volume) contained 2 μg of supercoiled pDPT2789 DNA (2.4 nM plasmid concentration), 50 mM Tris-HCl, pH 7.5, 120 mM KCl, 10 mM MgCl2, 0.5 mM EDTA, 0.05% dimethyl sulfoxide, 1% methanol, 100 μg/mL BSA, 4.3 ng of calf thymus topoisomerase I (0.26 nM), and a CPT derivative. The reaction mixture is incubated at 37°C, and at the indicated times 20-μL aliquots are removed and terminated by the addition of 5 μL of SDS/Ficoll stop mix (final concentrations, 0.5% SDS, 2% Ficoll, 0.025% bromphenol blue). The samples are loaded onto a 1% agarose gel and analyzed by electrophoresis.

[References]

[1]. Hertzberg RP, et al. Irreversible trapping of the DNA-topoisomerase I covalent complex. Affinity labeling of the camptothecin binding site. J Biol Chem. 1990 Nov 5;265(31):19287-95.

[2]. Hsiang YH, et al. Camptothecin induces protein-linked DNA breaks via mammalian DNA topoisomerase I. J Biol Chem. 1985 Nov 25;260(27):14873-8.

[3]. Luzzio MJ, et al. Synthesis and antitumor activity of novel water soluble derivatives of camptothecin as specific inhibitors of topoisomerase I. Synthesis and antitumor activity of novel water soluble derivatives of camptothecin as specific inhibitors of topoisomerase I.

[Related Small Molecules]

Chemical & Physical Properties

[ Density]:
1.5±0.1 g/cm3

[ Boiling Point ]:
757.0±60.0 °C at 760 mmHg

[ Melting Point ]:
260 °C (dec.)(lit.)

[ Molecular Formula ]:
C₂₀H₁₆N₂O₄

[ Molecular Weight ]:
348.352

[ Flash Point ]:
411.6±32.9 °C

[ Exact Mass ]:
348.110992

[ PSA ]:
81.42000

[ LogP ]:
1.60

[ Vapour Pressure ]:
0.0±2.7 mmHg at 25°C

[ Index of Refraction ]:
1.746

[ Water Solubility ]:
insoluble

MSDS

Click to get detail MSDS

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: UQ0492000

CAS REGISTRY NUMBER :: 7689-03-4

LAST UPDATED :: 199706

DATA ITEMS CITED :: 29

MOLECULAR FORMULA :: C20-H16-N2-O4

MOLECULAR WEIGHT :: 348.38

WISWESSER LINE NOTATION :: T F6 D6 C566 BN HVO LVN NHT&&&&J GQ G2

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 50100 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 :: 64 mg/kg

TOXIC EFFECTS :: Tumorigenic - active as anti-cancer agent

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

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 38 mg/kg

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

TYPE OF TEST :: Cytogenetic analysis

MUTATION DATA

TYPE OF TEST :: DNA damage

TEST SYSTEM :: Primate - monkey Kidney

DOSE/DURATION :: 25 umol/L

REFERENCE :: CNREA8 Cancer Research. (Public Ledger Building, Suit 816, 6th & Chestnut Sts., Philadelphia, PA 19106) V.1- 1941- Volume(issue)/page/year: 48,1722,1988

Safety Information

[ Symbol ]:

GHS06

[ Signal Word ]:
Danger

[ Hazard Statements ]:
H301

[ Precautionary Statements ]:
Missing Phrase - N15.00950417

[ Personal Protective Equipment ]:
Eyeshields;Faceshields;Gloves;type P2 (EN 143) respirator cartridges

[ Hazard Codes ]:
T:Toxic;

[ Risk Phrases ]:
R25

[ Safety Phrases ]:
S45-S36/37/39-S26

[ RIDADR ]:
UN 1544 6.1/PG 3

[ WGK Germany ]:
3

[ RTECS ]:
UQ0492000

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

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