Ansamitocin P-3

Names

[ Name ]:
Ansamitocin P-3

[Synonym ]:
Ansamitosin P 3
Propanoic acid, 2-methyl-, (1S,2R,3S,5S,6S,16E,18E,20R,21S)-11-chloro-21-hydroxy-12,20-dimethoxy-2,5,9,16-tetramethyl-8,23-dioxo-4,24-dioxa-9,22-diazatetracyclo[19.3.1.1.0]hexacosa-10,12,1 4(26),16,18-pentaen-6-yl ester
ANSAMITOCIN P-3
Tam-330
(1S,2R,3S,5S,6S,16E,18E,20R,21S)-11-Chloro-21-hydroxy-12,20-dimethoxy-2,5,9,16-tetramethyl-8,23-dioxo-4,24-dioxa-9,22-diazatetracyclo[19.3.1.1.0]hexacosa-10(26),11,13,16,18-pentaen-6-yl 2- methylpropanoate
2'-De(acetylmethylamino)-2'-methylmaytansine
Propanoic acid, 2-methyl-, (1S,2R,3R,5S,6S,16E,18E,20R,21S)-11-chloro-21-hydroxy-12,20-dimethoxy-2,5,9,16-tetramethyl-8,23-dioxo-4,24-dioxa-9,22-diazatetracyclo[19.3.1.1.0]hexacosa-10,12,1 4(26),16,18-pentaen-6-yl ester
Anasamitocin P-3
(1S,2R,3R,5S,6S,16E,18E,20R,21S)-11-Chloro-21-hydroxy-12,20-dimethoxy-2,5,9,16-tetramethyl-8,23-dioxo-4,24-dioxa-9,22-diazatetracyclo[19.3.1.1.0]hexacosa-10(26),11,13,16,18-pentaen-6-yl 2- methylpropanoate
Maytansinol isobutyrate
O3-isobutyryl-maytansinol
(3E,5E,7R,84S)-14-chloro-10t,11c-epoxy-84-hydroxy-12c-isobutyryl-15,7r-dimethoxy-3,9c,11t,15-tetramethyl-(84r'H,86c'H)-15-aza-1(1,3)-benzena-8(4,6)-[1,3]oxazinana-cyclopentadecaphane-3,5-diene-82,14-dione

Biological Activity

[Description]:

Ansamitocin P-3 is a microtubule inhibitor. Ansamitocin P-3 is a macrocyclic antitumor antibiotic.

[Related Catalog]:

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

Signaling Pathways >> Cell Cycle/DNA Damage >> Microtubule/Tubulin

Signaling Pathways >> Cytoskeleton >> Microtubule/Tubulin

Natural Products >> Others

Research Areas >> Cancer

[Target]

Microtubule[1]

[In Vitro]

Ansamitocin P3 potently inhibits the proliferation of MCF-7, HeLa, EMT-6/AR1 and MDA-MB-231 cells in culture with a half-maximal inhibitory concentration of 20±3, 50±0.5, 140±17, and 150±1.1 pM, respectively. Further, Ansamitocin P3 is found to bind to purified tubulin in vitro with a dissociation constant (Kd) of 1.3±0.7 µM. The binding of Ansamitocin P3 induces conformational changes in tubulin. Ansamitocin P3 inhibits the proliferation of MCF-7, HeLa, EMT-6/AR1 and MDA-MB-231 cells in culture in a concentration dependent manner. Flow cytometric analysis of PI-stained cells suggests that Ansamitocin P3 inhibits the cell cycle progression of MCF-7 cells in G2/M phase. For example, 26, 50 and 70% of the cells are found to be in G2/M phase in the absence and presence of 50 and 100 pM Ansamitocin P3, respectively[2].

[Cell Assay]

MCF-7, EMT-6/AR1, HeLa and MDA-MB-231 cells are seeded in 96 well plates. Subsequently, cells are incubated with vehicle (0.1% DMSO) or different concentrations (1-1000 pM) of Ansamitocin P3 for 48 h in MCF-7 cells and 24 h for EMT-6/AR1, HeLa and MDA-MB-231 cells, respectively. The half maximal inhibitory concentration of cell proliferation (IC50) for Ansamitocin P3 is determined by sulforhodamine B assay. Four independent experiments are carried out in MCF-7 cells and three independent sets of experiments are performed in EMT-6/AR1, HeLa and MDA-MB-231 cells[2].

[References]

[1]. Kiso T, et al. Screening for microtubule-disrupting antifungal agents by using a mitotic-arrest mutant of Aspergillus nidulans and novel action of phenylalanine derivatives accompanying tubulin loss. Antimicrob Agents Chemother. 2004 May;48(5):1739-48.

[2]. Venghateri JB, et al. Ansamitocin P3 depolymerizes microtubules and induces apoptosis by binding to tubulin at thevinblastine site. PLoS One. 2013 Oct 4;8(10):e75182.

[Related Small Molecules]

Chemical & Physical Properties

[ Density]:
1.3±0.1 g/cm3

[ Boiling Point ]:
833.1±65.0 °C at 760 mmHg

[ Melting Point ]:
190-192℃

[ Molecular Formula ]:
C₃₂H₄₃ClN₂O₉

[ Molecular Weight ]:
635.145

[ Flash Point ]:
457.7±34.3 °C

[ Exact Mass ]:
634.265686

[ PSA ]:
136.16000

[ LogP ]:
5.09

[ Vapour Pressure ]:
0.0±3.2 mmHg at 25°C

[ Index of Refraction ]:
1.583

[ Storage condition ]:
2-8°C

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: OQ2291000

CHEMICAL NAME :: Maytansine, 2'-de(acetylmethylamino)-2'-methyl-

CAS REGISTRY NUMBER :: 66584-72-3

LAST UPDATED :: 199401

DATA ITEMS CITED :: 4

MOLECULAR FORMULA :: C32-H43-Cl-N2-O9

MOLECULAR WEIGHT :: 635.22

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 625 ug/kg

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

MUTATION DATA

TYPE OF TEST :: Cytogenetic analysis

TEST SYSTEM :: Rodent - mouse Ascites tumor

DOSE/DURATION :: 4 ug/kg

REFERENCE :: CNREA8 Cancer Research. (Public Ledger Building, Suit 816, 6th & Chestnut Sts., Philadelphia, PA 19106) V.1- 1941- Volume(issue)/page/year: 40,1707,1980

Safety Information

[ Symbol ]:

GHS07

[ Signal Word ]:
Warning

[ Hazard Statements ]:
H302-H315-H319-H332-H335

[ Precautionary Statements ]:
P261-P305 + P351 + P338

[ Personal Protective Equipment ]:
dust mask type N95 (US);Eyeshields;Gloves

[ Hazard Codes ]:
Xn

[ Risk Phrases ]:
20/22-36/37/38

[ Safety Phrases ]:
26-36

[ RIDADR ]:
NONH for all modes of transport

[ RTECS ]:
OQ2293000

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Articles

Enhanced production of ansamitocin P-3 by addition of isobutanol in fermentation of Actinosynnema pretiosum.

Bioresour. Technol. 102 , 1863-1868, (2011)

Supply of isobutanol to enhance the production of anti-tumor agent ansamitocin P-3 (AP-3) in medium containing agro-industrial residues was investigated with analysis of gene transcription, enzyme act...

Amide N-glycosylation by Asm25, an N-glycosyltransferase of ansamitocins.

Chem. Biol. 15(8) , 863-74, (2008)

Ansamitocins are potent antitumor maytansinoids produced by Actinosynnema pretiosum. Their biosynthesis involves the initial assembly of a macrolactam polyketide, followed by a series of postpolyketid...

Determination of the cryptic stereochemistry of the first PKS chain-extension step in ansamitocin biosynthesis by Actinosynnema pretiosum.

ChemBioChem. 7(8) , 1221-5, (2006)

The biosynthesis of the antitumor antibiotic, ansamitocin, involves the assembly of a linear octaketide on the ansamitocin (asm) polyketide synthase (PKS), which is then cyclized to proansamitocin and...

Related Compounds

The content on this webpage is sourced from various professional data sources. If you have any questions or concerns regarding the content, please feel free to contact service1@chemsrc.com.