Geldanamycin

Names

[ Name ]:
Geldanamycin

[Synonym ]:
2-Azabicyclo[16.3.1]docosa-4,6,10,18,21-pentaene-3,20,22-trione, 9-[(aminocarbonyl)oxy]-13-hydroxy-8,14,19-trimethoxy-4,10,12,16-tetramethyl-, (4E,6Z,8S,9S,10E,12S,13R,14S,16R)-
GELDANAMYCIN,STREPTOMYCES HYGROSCOPICUS
Streptomyces hygroscopicus
GELDANAMYCIN FROM STRE
2-Azabicyclo[16.3.1]docosa-4,6,10,18,21-pentaene-3,20,22-trione, 9-[(aminocarbonyl)oxy]-13-hydroxy-8,14,19-trimethoxy-4,10,12,16-tetramethyl-, (4Z,6Z,8S,9R,10Z,12R,14R,16R)-
(4Z,6Z,8S,9R,10Z,12R,14R,16R)-13-Hydroxy-8,14,19-trimethoxy-4,10,12,16-tetramethyl-3,20,22-trioxo-2-azabicyclo[16.3.1]docosa-1(21),4,6,10,18-pentaen-9-yl carbamate
Geldanamycin
MFCD00274570
Geldanamycin from Streptomyces hygroscopicus
(4E,6Z,8S,9S,10E,12S,13R,14S,16R)-13-Hydroxy-8,14,19-trimethoxy-4,10,12,16-tetramethyl-3,20,22-trioxo-2-azabicyclo[16.3.1]docosa-1(21),4,6,10,18-pentaen-9-yl carbamate
Geldanamycin (9CI)

Biological Activity

[Description]:

Geldanamycin is a Hsp90 inhibitor with antimicrobial activity against many Gram-positive and some Gram-negative bacteria.

[Related Catalog]:

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

Signaling Pathways >> Metabolic Enzyme/Protease >> HSP

Research Areas >> Cancer

Natural Products >> Others

[Target]

HSP90:1.2 μM (Kd)

[In Vitro]

Geldanamycin significantly delays and reduces viperin expression, indicating that IRF3 is involved in viperin induction in RAW264.7 cells[1]. Geldanamycin (GA), a benzoquinone ansamycin, protected against neuronal injury induced by oxygen-glucose deprivation (OGD)/zVAD treatment in cultured primary neurons. More importantly, Geldanamycin decreases RIP1 protein level in a time and concentration-dependent manner. Geldanamycin also decreases the Hsp90 protein level, which causes instability of RIP1 protein, resulting in decreased RIP1 protein level but not RIP1 mRNA level after Geldanamycin treatment[2]. Geldanamycin (GA) is identified as the first natural product inhibitor of Hsp90 that binds to the N-terminal ATPase domain of Hsp90 to inhibit its chaperone function, and significantly induces tumor cell death via an apoptotic mechanism[3].

[References]

[1]. Tang HB, et al. Viperin inhibits rabies virus replication via reduced cholesterol and sphingomyelin and is regulated upstream by TLR4. Sci Rep. 2016 Jul 26;6:30529

[2]. Chen WW, et al. RIP1 mediates the protection of Geldanamycin on neuronal injury induced by oxygen-glucosedeprivation combined with zVAD in primary cortical neurons. J Neurochem. 2012 Jan;120(1):70-7.

[3]. Lin Z, et al. 17-ABAG, a novel Geldanamycin derivative, inhibits LNCaP-cell proliferation through heat shock protein 90 inhibition. Int J Mol Med. 2015 Aug;36(2):424-32.

[4]. Roe SM, et al. Structural basis for inhibition of the Hsp90 molecular chaperone by the antitumor antibiotics radicicol and geldanamycin. J Med Chem. 1999 Jan 28;42(2):260-6.

[Related Small Molecules]

17-AAG | Ganetespib(STA-9090) | NVP-AUY922 | VER-155008 | AT13387 | 17-DMAG (Alvespimycin) HCl | BIIB021 | Apoptozole | IPI-504 | KNK437 | Teprenone | KRIBB11 | Debio-0932 | HSP-990 | PU-H71

Chemical & Physical Properties

[ Density]:
1.2±0.1 g/cm3

[ Boiling Point ]:
783.9±60.0 °C at 760 mmHg

[ Melting Point ]:
255 °C

[ Molecular Formula ]:
C₂₉H₄₀N₂O₉

[ Molecular Weight ]:
560.636

[ Flash Point ]:
427.9±32.9 °C

[ Exact Mass ]:
560.273376

[ PSA ]:
163.48000

[ LogP ]:
2.00

[ Vapour Pressure ]:
0.0±6.2 mmHg at 25°C

[ Index of Refraction ]:
1.559

[ Storage condition ]:
−20°C

[ Water Solubility ]:
DMSO: soluble

MSDS

Click to get detail MSDS

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: LX8920000

CHEMICAL NAME :: Geldanamycin

CAS REGISTRY NUMBER :: 30562-34-6

LAST UPDATED :: 199612

DATA ITEMS CITED :: 6

MOLECULAR FORMULA :: C29-H40-N2-O9

MOLECULAR WEIGHT :: 560.71

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 2500 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 :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 1 mg/kg

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

TYPE OF TEST :: LD - Lethal dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: >50 mg/kg

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

TYPE OF TEST :: LD - Lethal dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: >4200 ug/kg

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

MUTATION DATA

TYPE OF TEST :: DNA inhibition

TEST SYSTEM :: Rodent - mouse Lymphocyte

DOSE/DURATION :: 1 mg/L

REFERENCE :: JANTAJ Journal of Antibiotics. (Japan Antibiotics Research Assoc., 2-20-8 Kamiosaki, Shinagawa-ku, Tokyo, 141, Japan) V.2-5, 1948-52; V.21- 1968- Volume(issue)/page/year: 35,886,1982

Safety Information

[ Personal Protective Equipment ]:
Eyeshields;Gloves;type N95 (US);type P1 (EN143) respirator filter

[ Hazard Codes ]:
T: Toxic;

[ Risk Phrases ]:
R36/37/38

[ Safety Phrases ]:
26-27-36/37/39

[ RIDADR ]:
NONH for all modes of transport

[ WGK Germany ]:
2

[ RTECS ]:
LX8920000

[ HS Code ]:
2933990090

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Customs

[ HS Code ]: 2933990090

[ Summary ]:
2933990090. heterocyclic compounds with nitrogen hetero-atom(s) only. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%

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