Cytochalasin B

Names

[ Name ]:
Cytochalasin B

[Synonym ]:
EINECS 239-000-2
2H-Oxacyclotetradecino[2,3-d]isoindole-2,18(5H)-dione, 6,7,8,9,10,12a,13,14,15,15a,16,17-dodecahydro-5,13-dihydroxy-9,15-dimethyl-14-methylene-16-(phenylmethyl)-, (3E,5R,9R,11E,12aS,13S,15S,15aS,16S,18aS)-
(3E,5R,9R,11E,12aS,13S,15S,15aS,16S,18aS)-16-Benzyl-5,13-dihydroxy-9,15-dimethyl-14-methylene-6,7,8,9,10,12a,13,14,15,15a,16,17-dodecahydro-2H-oxacyclotetradecino[2,3-d]isoindole-2,18(5H)-dione
Phomin
(3E,5R,9R,11E,12aS,13S,15S,15aS,16S,18aS)-16-benzyl-5,13-dihydroxy-9,15-dimethyl-14-methylidene-6,7,8,9,10,12a,13,14,15,15a,16,17-dodecahydro-2H-oxacyclotetradecino[2,3-d]isoindole-2,18(5H)-dione
Cytochalasin B
MFCD00077704

Biological Activity

[Description]:

Cytochalasin B is a cell-permeable mycotoxin binding to the barbed end of actin filaments, disrupting the formation of actin polymers, with Kd value of 1.4-2.2 nM for F-actin.

[Related Catalog]:

Signaling Pathways >> Cytoskeleton >> Arp2/3 Complex

Research Areas >> Cancer

Natural Products >> Others

[Target]

Kd: 2.2 nM (F-actin, with Mg2+), 1.4 nM (F-actin, with Mg2+/K+)[1]

[In Vitro]

Cytochalasin B is a cell-permeable mycotoxin binding to the barbed end of actin filaments, inhibits the enlongation and shortening of actin filaments, with Kds of 2.2 nM and 1.4 nM for F-actin in the presence of MgCl2 (2 mM) or MgCl2 (2 mM) plus KCl, respectively[1]. Cytochalasin B (0.1-10 μM) shows inhibitory effect on multiple murine cancer cell lines, with IC50s of 2.56 μM (M109c), 10.46 μM (B16BL6), 105.5 μM (P388/ADR), 51.9 μM (P388/S) and IC80s of 12.23 μM (M109c), 44.86 μM (B16BL6), 188.4 μM (P388/ADR), 84.1 μM (P388/S) after treatment for 3 h, with IC50s of 0.25 μM (M109c), 0.37 μM (B16F10), 0.87 μM (B16BL6), and IC80s of 0.75 μM (M109c), 1.21 μM (B16F10), 10.41 μM (B16BL6) after treatment for 4 days[2]. Cytochalasin B (6 μM) increases the myofibrillar fragmentation index (MFI), which is attributed to the intensely breaking of myofibrillar proteins into short segments. Cytochalasin B also accelerates the disruption of actin filaments. In addition, Cytochalasin B accelerates the transformation from F-actin to G-actin, lowering the content of F-actin and significantly increasing G-actin bands during postmortem conditioning[3].

[In Vivo]

Cytochalasin B (10, 25, 50 mg/kg, i.p.) dose-dependently increases the life expectancy of Balb/c mice bearing with P388/ADR leukemias. Cytochalasin B at 50 mg/kg produces 10 % long-term survival in the multidrug resistant P388/ADR cohort, and 40 % long-term survival in the drug sensitive P388/S cohort[2].

[Cell Assay]

The attached cell lines M109c, B16BL6, and B16F10 are seeded at 1 to 4 × 104 cells/mL in 2 mL volumes in 24-well culture plates 1 day prior to treatment with Cytochalasin B. The suspension culture of P388/ADR cells is seeded at 5 × 104 cells/mL and allowed to grow overnight before Cytochalasin B treatment. Cells are treated with Cytochalasin B for 3 h, as well as 2, 3, or 4 days. In the case of continuous exposure for 2, 3, or 4 days, attached cells are trypsinized and counted with a hemacytometer. Leukemia cell suspensions are counted with a Coulter Counter. In the case of short-term exposure, cells are washed twice with fresh medium, then trypsinized (except for P388/ADR cells), reseeded, and allowed to regrow for 3 days, at which time they are counted. Growth results are calculated as the number of cells generated above the seeding density compared to the untreated control cells and graphically presented as percent of control increase[2].

[Animal admin]

Mice[2] For chemotherapy testing, Balb/c mice under isoflurane anesthesia are challenged with 2 × 105 trypan blue negative P388/S or P388/ADR cells subcutaneously (s.c.) in a volume of 200 μL. Untreated mice are kept in order to determine the lethality of the challenge without chemotherapeutic intervention. Long-term survival is defined as challenged mice that survive the duration of the observation period. Cytochalasins B and D are prepared in suspension form in 2 % carboxymethyl cellulose 1 % tween 20 (CMC/Tw) for intraperitoneal (i.p.) administration. The congeners or the vehicle are administered to leukemia-challenged mice on Days 1-8 following the initial challenge[2].

[References]

[1]. Theodoropoulos PA, et al. Cytochalasin B may shorten actin filaments by a mechanism independent of barbed end capping. Biochem Pharmacol. 1994 May 18;47(10):1875-81.

[2]. Trendowski M, et al. Chemotherapy with cytochalasin congeners in vitro and in vivo against murine models. Invest New Drugs. 2015 Apr;33(2):290-9.

[3]. Zhou C, et al. The effect of Cytochalasin B and Jasplakinolide on depolymerization of actin filaments in goose muscles during postmortem conditioning. Food Res Int. 2016 Dec;90:1-7.

[Related Small Molecules]

CK-636 | CK869

Chemical & Physical Properties

[ Density]:
1.2±0.1 g/cm3

[ Boiling Point ]:
740.6±60.0 °C at 760 mmHg

[ Melting Point ]:
218-223ºC

[ Molecular Formula ]:
C₂₉H₃₇NO₅

[ Molecular Weight ]:
479.608

[ Flash Point ]:
401.7±32.9 °C

[ Exact Mass ]:
479.267181

[ PSA ]:
95.86000

[ LogP ]:
3.71

[ Vapour Pressure ]:
0.0±2.6 mmHg at 25°C

[ Index of Refraction ]:
1.596

[ Storage condition ]:
−20°C

[ Water Solubility ]:
ethanol: 20 mg/mL

MSDS

Click to get detail MSDS

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: RO0205000

CHEMICAL NAME :: 2H-Oxacyclotetradec(2,3-d)isoindole-2,18(5H)-dione, 16-benzyl-6,7,8,9,10,12a,13,14,15,15a, 16,17-dodecahydro-5,13-dihydroxy-9,15-dimethyl-14-met hylene-, (E)-(5S,9R,12aS,13S,15S,15aS, 16aS,18aS)-

CAS REGISTRY NUMBER :: 14930-96-2

LAST UPDATED :: 199612

DATA ITEMS CITED :: 18

MOLECULAR FORMULA :: C29-H37-N-O5

MOLECULAR WEIGHT :: 479.67

WISWESSER LINE NOTATION :: T56-14- 1A U AXVM GY TVO JU RUTJ D1R& F1 GU1 HQ M1 QQ

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 :: 11 mg/kg

TOXIC EFFECTS :: Behavioral - ataxia Behavioral - coma Lungs, Thorax, or Respiration - cyanosis

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

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 30 mg/kg

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

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 1500 ug/kg

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

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - Central Nervous System Reproductive - Specific Developmental Abnormalities - musculoskeletal system

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 5 mg/kg

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

TOXIC EFFECTS :: Reproductive - Effects on Embryo or Fetus - fetal death Reproductive - Specific Developmental Abnormalities - Central Nervous System

MUTATION DATA

TYPE OF TEST :: Cytogenetic analysis

TEST SYSTEM :: Mammal - species unspecified Bone marrow

DOSE/DURATION :: 1 gm/L

REFERENCE :: TSITAQ Tsitologiya. Cytology. (V/O Mezhdunarodnaya Kniga, 113095 Moscow, USSR) V.1- 1959- Volume(issue)/page/year: 24,814,1982

Safety Information

[ Symbol ]:

GHS06

[ Signal Word ]:
Danger

[ Hazard Statements ]:
H302-H330

[ Precautionary Statements ]:
P260-P284-P310

[ Personal Protective Equipment ]:
Eyeshields;Faceshields;full-face respirator (US);Gloves;multi-purpose combination respirator cartridge (US);type ABEK (EN14387) respirator filter

[ Hazard Codes ]:
T+: Very toxic;

[ Risk Phrases ]:
R26/27/28;R63

[ Safety Phrases ]:
28-36/37-45

[ RIDADR ]:
UN 1544 6

[ WGK Germany ]:
3

[ RTECS ]:
RO0205000

[ Packaging Group ]:
I

[ Hazard Class ]:
6.1(a)

[ HS Code ]:
29349990

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

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