17-AAG Chemical Properties

Melting point:

201-203°C

Boiling point:

797.8±60.0 °C(Predicted)

Density 

1.21

RTECS 

LX8932000

Flash point:

>110°(230°F)

storage temp. 

Keep in dark place,Sealed in dry,Store in freezer, under -20°C

solubility 

DMSO: soluble

form 

solid

pka

8.62±0.70(Predicted)

color 

Purple or dark red

Water Solubility 

Soluble in DMSO at 150 mg/mL; soluble in ethanol at 5 mg/mL. Very poorly soluble in water

Sensitive 

Light Sensitive

Stability:

Stable for 1 year from date of purchase as supplied. Protect from moisture. Solutions in DMSO or ethanol may be stored at -20°C for up to 3 months.

InChIKey

AYUNIORJHRXIBJ-HTLBVUBBSA-N

SMILES

C12C(=O)C(=CC(=O)C=1NCC=C)NC(=O)C(C)=CC=C[C@H](OC)[C@@H](OC(=O)N)C(C)=C[C@H](C)[C@@H](O)[C@@H](OC)C[C@H](C)C2 |t:17,19,30|

CAS DataBase Reference

75747-14-7

Safety Information

Hazard Codes 

Xi

Risk Statements 

36/37/38

Safety Statements 

22-24/25-36-26

WGK Germany 

3

HS Code 

29419090

MSDS

• Language:English Provider:SigmaAldrich

17-AAG Usage And Synthesis

Description

Tanespimycin (17-AAG, CP127374, NSC-330507, KOS 953) (75747-14-7) is a potent HSP90 inhibitor with IC50 of 5 nM in a cell-free assay, having a 100-fold higher binding affinity for HSP90 derived from tumour cells than HSP90 from normal cells. Tanespimycin (17-AAG) induces apoptosis, necrosis, autophagy and mitophagy. Phase 3.

Targets

HSP90 5 nM.

In vitro

17-AAG, an analog of geldanamycin, exhibits greater than 100 times higher binding affinity for Hsp90 derived from HER-2-overexpressing cancer cells (BT474, N87, SKOV3 and SKBR3) or BT474 breast carcinoma cells with IC50 values of 5-6 nM. 17-AAG causes the degradation of HER2, HER3, Akt, and both mutant and wild-type androgen receptor (AR), leading to the RB-dependent G1 growth arrest of prostate cancer cells such as LNCaP, LAPC-4, DU-145, and PC-3 with IC50 values of 25-45 nM. [2] In addition to inducing apoptosis of Ba/F3 cells transformed with wild-type BCR-ABL with an IC50 of 5.2 μM, 17-AAG has the ability to induce apoptosis of cells transformed with imatinib mesylate-resistant T315I and E255K BCR-ABL mutants with IC50 values of 2.3 μM and 1.0 μM, respectively, by inducing the degradation of both wild-type BCR-ABL protein and mutants.

Description

17-AAG (75747-14-7) is a semi-synthetic analog of geldanamycin (Cat.# 10-1084) which is less toxic and more stable. 17-AAG selectively binds to and inhibits HSP90 from tumor cells. Anti-angiogenic activity. Cell permeable.

Chemical Properties

Dark Purple Solid

Uses

Geldanamycin is a potent inhibitor of Hsp90 that exhibits severe hepatotoxicity when used in vivo. 17-AAG is an analog of geldanamycin which has potent in vivo activity and reduced toxicity. Like other Hsp90 inhibitors, 17-AAG has diverse anti-tumor actions and has potential in treating certain types of cancer. 17-AAG inhibits the growth of prostate cancer cell lines (IC50 = 25-45 nM). 17-AAG promotes the degradation of HER2 and induces growth arrest and apoptosis in breast cancer cells overexpressing HER2 (IC50 = 4-72 nM).

Uses

17-(Allylamino)-17-demethoxygeldanamycin (17-AAG) inhibits heat shock protein 90 (Hsp90), the expression of heat shock factor-1, and the activity of oncogenic proteins such as N-ras, Ki-ras, c-Akt, and p185erB2. In addition to its anti-tumor effects, 17-AAG also induces apoptosis.

Uses

Potent inhibitor of heat shock protein 90 (Hsp90). 17-AAG is a less toxic analog than Geldanamycin. It induces apoptosis and displays antitumor effects. 17-AAG inhibits the activity of oncogenic proteins such as N-ras, Ki-ras, c-Akt, and p185erB2.

Definition

ChEBI: A 19-membered macrocyle that is geldanamycin in which the methoxy substituent attached to the benzoquinone moiety has been replaced by an allylamino group. It is a potent inhibitor of heat shock protein 90 (Hsp90). A less toxic analogue than geldanamycin, t induces apoptosis and displays antitumour effects.

General Description

Chemical structure: benzenoid

Biological Activity

Inhibitor of heat shock protein 90 (Hsp90) chaperone activity, and an analog of geldanamycin (9,13-Dihydroxy-8,14,19-trimethoxy-4,10,12,16-tetramethyl-2-azabicyclo[16.3.1]docosa-4,6,10,18,21-pentaene-3,20,22-trione, 9-carbamate ). Subsequently inhibits the activity of oncogenic proteins such as p185 erbB-2 (IC 50 = 31 nM), N-ras, Ki-ras and c-Akt. Antitumor in vivo .

Biochem/physiol Actions

17-(Allylamino)-17-demethoxygeldanamycin (17-AAG) is a benzoquinone and is an analog of geldanamycin.

Synthesis

The reaction of (+)-geldanamycin (5.1 mg, 9.0 μmol) with allylamine (10.0 μL, 0.13 mmol) was dissolved in chloroform (1.5 mL) at room temperature and stirred. The progress of the reaction was monitored by thin-layer chromatography (TLC), and complete conversion of geldanamycin was confirmed after 18 hours. The reaction mixture was subsequently washed with saturated saline, dried over anhydrous sodium sulfate and concentrated under reduced pressure to remove the solvent. Purification was carried out by rapid column chromatography on silica gel, the eluent being a mixed petroleum ether/ethyl acetate solvent, to give the target product as a purple solid (5.3 mg, 99% yield). The product characterization data were as follows: IR (KBr, cm?1) 3464, 3333, 2958, 2929, 2825, 1728, 1691, 1652, 1571, 1485, 1372, 1323, 1189, 1101, 1057; UV (95% ethanol, λmax/nm) 332 (ε=2.0×10?); 1H NMR (CDCl?, 500 MHz) δ 9.14 (s, 1H), 7.28 (s, 1H), 6.93 (bd, J=11.5 Hz, 1H), 6.56 (bdd, J=11.5, 11.0 Hz, 1H), 6.38 (bt, J=6.0 Hz, 1H), 5.94-5.81 (m, 3H), 5.30- 5.24 (m, 2H), 5.17 (s, 1H), 4.82 (bs, 2H), 4.29 (bd, J=10.0 Hz, 1H), 4.21 (bs, 1H), 4.18-4.08 (m, 2H), 3.55 (ddd, J=9.0, 6.5, 2.0 Hz, 1H), 3.43 (ddd, J=9.0, 3.0 , 3.0 Hz, 1H), 3.34 (s, 3H), 3.25 (s, 3H), 2.72 (dqd, J=9.5, 7.0, 2.0 Hz, 1H), 2.63 (d, J=14.0 Hz, 1H), 2.34 (dd, J=14.0, 11.0 Hz, 1H), 2.00 (bs, 3H), 1.78 (d, J= 1.0 Hz, 3H), 1.78-1.74 (m, 2H), 1.74-1.67 (m, 1H), 0.99-0.95 (m, 6H); 13C NMR (CDCl?, 125 MHz) δ 183.8 (18-C), 180.9 (21-C), 168.4 (1-C), 156.0 (7-O?CNH?), 144.6 (17-C), 141.2 (20-C), 135.8 (5-C), 134.9 (2-C), 133.7 (9-C), 132.7 (8-C), 132.5 (3'-C), 126.9 (4-C), 126.5 (3-C), 118.5 (3'-C), 108.8 (19-C), 108.7 (16-C), 81.6 (7-C), 81.4 (12-C), 81.2 (6-C), 72.6 (11-C), 57.1 (6- or 12-OCH?), 56.7 (6- or 12-OCH?), 47.8 (1'-C), 35.0 (13-C), 34.3 (15-C), 32.3 (10-C ), 28.4 (14-C), 22.9 (14-CH?), 12.8 (8-CH?), 12.6 (2-CH?), 12.3 (10-CH?); HRMS (FAB) m/z 586.3120 [M+H]? (calculated value of 586.3129 for C??H??N?O?).

storage

-20°C

References

[1] T W SCHULTE  L M N. The benzoquinone ansamycin 17-allylamino-17-demethoxygeldanamycin binds to HSP90 and shares important biologic activities with geldanamycin.[J]. Cancer Chemotherapy and Pharmacology, 1998, 42 4: 273-279. DOI:10.1007/s002800050817
[2] ADEELA KAMAL. A high-affinity conformation of Hsp90 confers tumour selectivity on Hsp90 inhibitors[J]. Nature, 2003, 425 6956: 407-410. DOI:10.1038/nature01913
[3] ADEELA KAMAL  Francis J B  Marcus F Boehm. Therapeutic and diagnostic implications of Hsp90 activation.[J]. Trends in molecular medicine, 2004, 10 6: 283-290. DOI:10.1016/j.molmed.2004.04.006

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