Geldanamycin

Names

[ Name ]:
Geldanamycin

[Synonym ]:
GELDANAMYCIN,STREPTOMYCES HYGROSCOPICUS
Streptomyces hygroscopicus
GELDANAMYCIN FROM STRE
(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%

Articles

The induction of heme oxygenase-1 suppresses heat shock protein 90 and the proliferation of human breast cancer cells through its byproduct carbon monoxide.

Toxicol. Appl. Pharmacol. 274(1) , 55-62, (2014)

Heme oxygenase (HO)-1 is an oxidative stress-response enzyme which catalyzes the degradation of heme into bilirubin, ferric ion, and carbon monoxide (CO). Induction of HO-1 was reported to have antitu...

Bioreduction of aryl azides during mutasynthesis of new ansamitocins.

Org. Lett. 15(17) , 4442-5, (2013)

Supplementing a culture of a mutant strain of Actinosynnema pretiosum that is unable to biosynthesize aminohydroxy benzoic acid (AHBA), with 3-azido-5-hydroxy-benzoic acid and 3-azido-5-amino-benzoic ...

Flotillin depletion affects ErbB protein levels in different human breast cancer cells.

Biochim. Biophys. Acta 1843(9) , 1987-96, (2014)

The ErbB3 receptor is an important regulator of cell growth and carcinogenesis. Among breast cancer patients, up to 50-70% have ErbB3 overexpression and 20-30% show overexpressed or amplified ErbB2. E...

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.