Sibiromycin

Sibiromycin is a naturally produced glycosylated pyrrolobenzodiazepines (PBDs). Sibiromycin is also a potent antitumor antibiotic that binds covalently to DNA in the minor groove at the NH2 of guanine[1][2].

Research Areas >> Cancer

Signaling Pathways >> Cell Cycle/DNA Damage >> DNA Alkylator/Crosslinker

Pyrrolobenzodiazepines (PBDs) are sequence selective DNA alkylating agents with remarkable antineoplastic activity[1]. Alkylation of DNA by anthramycin, sibiromycin and tomaymycin is sequence specific with the following trend for binding preference 5′-Pu-G-Pu>5′-Py-G-Pu>5′-Pu-G-Py>5′-Py-G-Py[1]. Sibiromycin shows cytotoxicity against L1210 (leukemia), ADJ/PC6 (plasmacytoma) and CH1 (ovarian) cells with IC50s of ranging 0.000017 ~0.0029 μM[1].

[1]. Gerratana B. Biosynthesis, synthesis, and biological activities of pyrrolobenzodiazepines. Med Res Rev. 2012;32(2):254-293.

[2]. Li W, et al. Biosynthesis of sibiromycin, a potent antitumor antibiotic. Appl Environ Microbiol. 2009;75(9):2869-2878.

MOLECULAR FORMULA :

C24-H31-N3-O7

MOLECULAR WEIGHT :

473.58

WISWESSER LINE NOTATION :

T C576 BVN IM HHJ E1U2 HQ KQ L1 MO- BT6OTJ CQ DQ D1 EM1 F1

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

6 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 :

Intravenous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

29 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 :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

459 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 :

32 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 :

84 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 :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

58 ug/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD10 - Lethal Dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

5 ug/kg

TOXIC EFFECTS :

Cardiac - pericarditis Cardiac - other changes

TYPE OF TEST :

LD10 - Lethal Dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rabbit

DOSE/DURATION :

12 ug/kg

TOXIC EFFECTS :

Blood - other changes

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

98 ug/kg/4D-I

TOXIC EFFECTS :

Related to Chronic Data - death

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

22500 ng/kg/30D-I

TOXIC EFFECTS :

Cardiac - cardiomyopathy including infarction Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol) Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - transaminases

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rabbit

DOSE/DURATION :

30 ug/kg/15D-I

TOXIC EFFECTS :

Kidney, Ureter, Bladder - other changes Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol) Related to Chronic Data - death

MUTATION DATA

TYPE OF TEST :

Mutation test systems - not otherwise specified

TEST SYSTEM :

Rodent - mouse Ascites tumor

DOSE/DURATION :

1 ug/L

REFERENCE :

NEOLA4 Neoplasma. (Karger-Libri, P.O. Box, CH-4009 Basel, Switzerland) V.4- 1957- Volume(issue)/page/year: 22,105,1975