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MedKoo Cat#: 202950 | Name: Tanespimycin
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

Tanespimycin, also known as 17-AAG, is an orally bioavailable, small-molecule inhibitor of several receptor protein tyrosine kinases with potential antiangiogenic and antineoplastic activities. Telatinib binds to and inhibits the vascular endothelial growth factor receptors (VEGFRs) type 2 and 3, platelet-derived growth factor receptor beta (PDGFRb) and c-Kit, which may result in the inhibition of angiogenesis and cellular proliferation in tumors in which these receptors are upregulated. These telatinib-inhibited receptor protein tyrosine kinases are overexpressed or mutated in many tumor cell types and may play key roles in tumor angiogenesis and tumor cell proliferation.

Chemical Structure

Tanespimycin
Tanespimycin
CAS#75747-14-7

Theoretical Analysis

MedKoo Cat#: 202950

Name: Tanespimycin

CAS#: 75747-14-7

Chemical Formula: C31H43N3O8

Exact Mass: 585.3050

Molecular Weight: 585.69

Elemental Analysis: C, 63.57; H, 7.40; N, 7.17; O, 21.85

Price and Availability

Size Price Availability Quantity
5mg USD 90.00 Ready to ship
10mg USD 150.00 Ready to ship
25mg USD 350.00 Ready to ship
50mg USD 550.00 Ready to ship
100mg USD 950.00 Ready to ship
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Related CAS #
No Data
Synonym
17-AAG, 17 AAG, 17AAG, BAY 57-9352, BAY 579352, BAY579352, KOS-953, KOS-953, KOS-953, Tanespimycin
IUPAC/Chemical Name
(4E,6E,8S,9S,10E,12S,13R,14S,16R)-19-(allylamino)-13-hydroxy-8,14-dimethoxy-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.
InChi Key
AYUNIORJHRXIBJ-HTLBVUBBSA-N
InChi Code
InChI=1S/C31H43N3O8/c1-8-12-33-26-21-13-17(2)14-25(41-7)27(36)19(4)15-20(5)29(42-31(32)39)24(40-6)11-9-10-18(3)30(38)34-22(28(21)37)16-23(26)35/h8-11,15-17,19,24-25,27,29,33,36H,1,12-14H2,2-7H3,(H2,32,39)(H,34,38)/b11-9+,18-10+,20-15+/t17-,19+,24+,25+,27-,29+/m1/s1
SMILES Code
NC(O[C@@H](/C(C)=C/[C@H](C)[C@@H](O)[C@@H](OC)C[C@H](C)CC1=C2NCC=C)[C@@H](OC)/C=C/C=C(C)/C(NC(C1=O)=CC2=O)=O)=O
Appearance
Purple crystalline solid
Purity
>95% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, not in water
Shelf Life
>5 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
Phase I study of Telatinib: Telatinib (450 mg b.i.d.) combined with bevacizumab (1 mg/kg bi-weekly) shows antitumor activity, but accumulating constitutional toxicity impedes long-term treatment of patients. Therefore, this combination will not be pursued in a phase II setting.   (source: Ann Oncol. 2011 Nov;22(11):2508-15). Phase I study of Telatinib:   (source: Ann Oncol. 2011 Nov;22(11):2508-15). Phase I study of Telatinib (combo study):  Twenty-three patients were included in this phase I trial. Most frequently (>25%) reported adverse events of any grade were vomiting, nausea, fatigue, diarrhea, alopecia, and hand-foot syndrome. A silent myocardial infarction and two cases of decreased left ventricular ejection fraction were reported; both were reversible. Cardiac monitoring of the subsequent patients did not reveal other abnormalities. The study was terminated when the recommended single agent phase II doses of telatinib (900 mg twice daily) and capecitabine/irinotecan was reached. Pharmacokinetic profiles showed no clinically relevant changes upon coadministration of the three drugs. (Circulating) endothelial (progenitor) cell levels stabilized during treatment. Five of 23 patients had partial remission and 9 of 23 patients showed stable disease. CONCLUSIONS:  Continuous administration of 900 mg telatinib twice daily can be safely combined with irinotecan (180 mg/m(2)) and capecitabine (1,000 mg/m(2) twice daily, day 1-14) and is the recommended schedule for further phase II studies. Tumor shrinkage and disease stabilization was observed. Cardiac toxicity needs further investigation in following studies. (source: Clin Cancer Res. 2010 Apr 1;16(7):2187-97 .). Phase I study of Telatinib (combo study):  
Product Data
Product Data
Certificate of Analysis
View CoA: current batch, Lot#LC61026
Safety Data Sheet (SDS)
View Safety Data Sheet (SDS)
Instruction
View handling instruction
Biological target:
Tanespimycin (17-AAG, CP127374, NSC-330507, KOS 953) 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.
In vitro activity:
17-AAG inhibited cell growth and induced G2/M cell cycle arrest and apoptosis in CCA cells together with the down-regulation of Bcl-2, Survivin and Cyclin B1, and the up-regulation of cleaved PARP. Moreover, increased caspase-3 activity was also observed in CCA cells treated with 17-AAG. To examine the role of HSP90 in CCA cells, RBE and HCCC-9810 cells were treated with DMSO or increasing concentrations of 17-AAG (0.25, 0.5, 1.0, 2.0, and 4.0 μM) for different intervals (24, 48, and 72 h). As shown in Fig. 1, cells displayed a time- and dose-dependent manner reduction in cell proliferation, and a maximal reduction of proliferation was achieved after treatment with 1.0 μM 17-AAG for 72 h, where RBE and HCCC-9810 cells showed 89.10 and 78.94 % inhibition, respectively. Moreover, the apparent IC50s of 17-AAG for RBE and HCCC-9810 cells at 72 h were 0.608 and 0.613 μM, respectively. Subsequent experiments were then performed using IC50 values of 0.6 μM for both cell lines. Flow cytometry was performed to investigate whether apoptosis contributes to cell growth inhibition by 17-AAG. As illustrated in Fig. 2a, after exposure to 17-AAG for 72 h and staining with Hoechst 33258, both RBE and HCCC-9810 cells exhibited typical apoptotic morphological changes, such as cytoplasmic blebbing, dense chromatin, and the formation of apoptotic bodies. Moreover, flow cytometry results showed that the percentages of apoptosis were 2.5 ± 0.9 % and 3.8 ± 1.1 % in DMSO-treated RBE and HCCC-9810 cells, respectively. After treating these cells with 0.6 μM 17-AAG for 72 h, the percentages of apoptosis increased to 18.5 ± 2.1 % and 25.5 ± 3.9 %, respectively (Fig. 2b). Furthermore, the activity of caspase-3 in RBE and HCCC-9810 cells was also markedly increased after treatment with 17-AAG (Fig. 2c). Consistently, after treatment with 0.6 μM 17-AGG for 72 h, the expression level of cleaved PARP was elevated in both cell lines. In addition, the expression levels of Bcl-2 and Survivin, two apoptosis inhibitors, were decreased in RBE and HCCC-9810 cells after 0.6 μM 17-AGG treatment for 72 h (Fig. 3). Taken together, these data suggest that 17-AAG may down-regulate Bcl-2 and Survivin expression in human CCA cells, leading to apoptosis. Reference: Clin Exp Med. 2013 Nov;13(4):323-8. https://link.springer.com/article/10.1007%2Fs10238-012-0208-3
In vivo activity:
Mice bearing CWR22 or CWRSA6 (androgen-independent) tumors were treated with 25 or 50 mg/kg 17-AAG or EPL diluent for 4 days. After the final dose (8 h), the mice were sacrificed and the tumors removed. Four days of 17-AAG treatment resulted in a dose-dependent reduction in the expression of AR, HER2, HER3, and Akt (Fig. 5A⇓ ; CWR22 DNS). A dose of 50 mg/kg resulted in an 87% decline in AR, a 85% decline in HER2, a 50% decline in HER3, and a 60% decline in Akt expression in CWRSA6 tumors. Treatment was also associated with an 8-fold increase in Hsp70 and a 1.5-fold increase in Hsp90 levels. No change in the expression of PI3k was noted. Reference: Clin Cancer Res. 2002 May;8(5):986-93. https://clincancerres.aacrjournals.org/content/8/5/986.long
Solvent mg/mL mM
Solubility
DMSO 100.0 170.74
Ethanol 33.0 56.34
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 585.69 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
1. Zhang J, Zheng Z, Zhao Y, Zhang T, Gu X, Yang W. The heat shock protein 90 inhibitor 17-AAG suppresses growth and induces apoptosis in human cholangiocarcinoma cells. Clin Exp Med. 2013 Nov;13(4):323-8. doi: 10.1007/s10238-012-0208-3. Epub 2012 Sep 7. PMID: 22955701. 2. Solit DB, Zheng FF, Drobnjak M, Münster PN, Higgins B, Verbel D, Heller G, Tong W, Cordon-Cardo C, Agus DB, Scher HI, Rosen N. 17-Allylamino-17-demethoxygeldanamycin induces the degradation of androgen receptor and HER-2/neu and inhibits the growth of prostate cancer xenografts. Clin Cancer Res. 2002 May;8(5):986-93. PMID: 12006510. 3. Solit DB, Zheng FF, Drobnjak M, Münster PN, Higgins B, Verbel D, Heller G, Tong W, Cordon-Cardo C, Agus DB, Scher HI, Rosen N. 17-Allylamino-17-demethoxygeldanamycin induces the degradation of androgen receptor and HER-2/neu and inhibits the growth of prostate cancer xenografts. Clin Cancer Res. 2002 May;8(5):986-93. PMID: 12006510. 4. Newman B, Liu Y, Lee HF, Sun D, Wang Y. HSP90 inhibitor 17-AAG selectively eradicates lymphoma stem cells. Cancer Res. 2012 Sep 1;72(17):4551-61. doi: 10.1158/0008-5472.CAN-11-3600. Epub 2012 Jun 29. PMID: 22751135; PMCID: PMC3443561.
In vitro protocol:
1. Zhang J, Zheng Z, Zhao Y, Zhang T, Gu X, Yang W. The heat shock protein 90 inhibitor 17-AAG suppresses growth and induces apoptosis in human cholangiocarcinoma cells. Clin Exp Med. 2013 Nov;13(4):323-8. doi: 10.1007/s10238-012-0208-3. Epub 2012 Sep 7. PMID: 22955701. 2. Solit DB, Zheng FF, Drobnjak M, Münster PN, Higgins B, Verbel D, Heller G, Tong W, Cordon-Cardo C, Agus DB, Scher HI, Rosen N. 17-Allylamino-17-demethoxygeldanamycin induces the degradation of androgen receptor and HER-2/neu and inhibits the growth of prostate cancer xenografts. Clin Cancer Res. 2002 May;8(5):986-93. PMID: 12006510.
In vivo protocol:
1. Solit DB, Zheng FF, Drobnjak M, Münster PN, Higgins B, Verbel D, Heller G, Tong W, Cordon-Cardo C, Agus DB, Scher HI, Rosen N. 17-Allylamino-17-demethoxygeldanamycin induces the degradation of androgen receptor and HER-2/neu and inhibits the growth of prostate cancer xenografts. Clin Cancer Res. 2002 May;8(5):986-93. PMID: 12006510. 2. Newman B, Liu Y, Lee HF, Sun D, Wang Y. HSP90 inhibitor 17-AAG selectively eradicates lymphoma stem cells. Cancer Res. 2012 Sep 1;72(17):4551-61. doi: 10.1158/0008-5472.CAN-11-3600. Epub 2012 Jun 29. PMID: 22751135; PMCID: PMC3443561.
1: Chen SZ, Chen XM, Li YQ, Yang S, Mo XY, Zhang F, Mo KL, Ding Y. [Inhibitory effect of 17-AAG combined with paclitaxel on proliferation of esophageal squamous cell carcinoma Eca-109 cells in vitro]. Nan Fang Yi Ke Da Xue Xue Bao. 2015 Jun 20;35(6):844-7. Chinese. PubMed PMID: 26111682. 2: Yun IS, Lee MH, Rah DK, Lew DH, Park JC, Lee WJ. Heat Shock Protein 90 Inhibitor (17-AAG) Induces Apoptosis and Decreases Cell Migration/Motility of Keloid Fibroblasts. Plast Reconstr Surg. 2015 Jul;136(1):44e-53e. doi: 10.1097/PRS.0000000000001362. PubMed PMID: 26111331. 3: Xiao Y, Guan J. 17-AAG enhances the cytotoxicity of flavopiridol in mantle cell lymphoma via autophagy suppression. Neoplasma. 2015;62(3):391-7. doi: 10.4149/neo_2015_047. PubMed PMID: 25866220. 4: Li J, Yang F, Guo J, Zhang R, Xing X, Qin X. 17-AAG post-treatment ameliorates memory impairment and hippocampal CA1 neuronal autophagic death induced by transient global cerebral ischemia. Brain Res. 2015 Jun 12;1610:80-8. doi: 10.1016/j.brainres.2015.03.051. Epub 2015 Apr 7. PubMed PMID: 25858486. 5: Ye XY, Luo QQ, Xu YH, Tang NW, Niu XM, Li ZM, Shen SP, Lu S, Chen ZW. 17-AAG suppresses growth and invasion of lung adenocarcinoma cells via regulation of the LATS1/YAP pathway. J Cell Mol Med. 2015 Mar;19(3):651-63. doi: 10.1111/jcmm.12469. PubMed PMID: 25712415; PubMed Central PMCID: PMC4369821. 6: Xu Y, Zhu Q, Chen D, Shen Z, Wang W, Ning G, Zhu Y. The HSP90 inhibitor 17-AAG exhibits potent antitumor activity for pheochromocytoma in a xenograft model. Tumour Biol. 2015 Feb 15. [Epub ahead of print] PubMed PMID: 25682284. 7: Desale SS, Raja SM, Kim JO, Mohapatra B, Soni KS, Luan H, Williams SH, Bielecki TA, Feng D, Storck M, Band V, Cohen SM, Band H, Bronich TK. Polypeptide-based nanogels co-encapsulating a synergistic combination of doxorubicin with 17-AAG show potent anti-tumor activity in ErbB2-driven breast cancer models. J Control Release. 2015 Jun 28;208:59-66. doi: 10.1016/j.jconrel.2015.02.001. Epub 2015 Feb 3. PubMed PMID: 25660204; PubMed Central PMCID: PMC4430376. 8: Lee KH, Jang AH, Yoo CG. 17-AAG Enhances PS-341-Induced Lung Cancer Cell Death by Blocking the NF-κB and PI3K/Akt Pathways. Am J Respir Cell Mol Biol. 2015 Jan 29. [Epub ahead of print] PubMed PMID: 25633180. 9: Mayor-López L, Tristante E, Carballo-Santana M, Carrasco-García E, Grasso S, García-Morales P, Saceda M, Luján J, García-Solano J, Carballo F, de Torre C, Martínez-Lacaci I. Comparative Study of 17-AAG and NVP-AUY922 in Pancreatic and Colorectal Cancer Cells: Are There Common Determinants of Sensitivity? Transl Oncol. 2014 Oct 24;7(5):590-604. doi: 10.1016/j.tranon.2014.08.001. eCollection 2014 Oct. PubMed PMID: 25389454; PubMed Central PMCID: PMC4225658. 10: Santos DM, Petersen AL, Celes FS, Borges VM, Veras PS, de Oliveira CI. Chemotherapeutic potential of 17-AAG against cutaneous leishmaniasis caused by Leishmania (Viannia) braziliensis. PLoS Negl Trop Dis. 2014 Oct 23;8(10):e3275. doi: 10.1371/journal.pntd.0003275. eCollection 2014 Oct. PubMed PMID: 25340794; PubMed Central PMCID: PMC4207694. 11: Ghalhar MG, Akbarzadeh A, Rahmati M, Mellatyar H, Dariushnejad H, Zarghami N, Barkhordari A. Comparison of inhibitory effects of 17-AAG nanoparticles and free 17-AAG on HSP90 gene expression in breast cancer. Asian Pac J Cancer Prev. 2014;15(17):7113-8. PubMed PMID: 25227799. 12: Wang B, Chen L, Ni Z, Dai X, Qin L, Wu Y, Li X, Xu L, Lian J, He F. Hsp90 inhibitor 17-AAG sensitizes Bcl-2 inhibitor (-)-gossypol by suppressing ERK-mediated protective autophagy and Mcl-1 accumulation in hepatocellular carcinoma cells. Exp Cell Res. 2014 Nov 1;328(2):379-87. doi: 10.1016/j.yexcr.2014.08.039. Epub 2014 Sep 6. PubMed PMID: 25196280. 13: Pradhan R, Poudel BK, Choi JY, Choi IS, Shin BS, Choi HG, Yong CS, Kim JO. Erratum to: Preparation and evaluation of 17-allyamino-17-demethoxygeldanamycin (17-AAG)-loaded poly(lactic acid-co-glycolic acid) nanoparticles. Arch Pharm Res. 2015 May;38(5):930-1. doi: 10.1007/s12272-014-0463-9. PubMed PMID: 25098423. 14: Faingold D, Filho VB, Fernandes B, Jagan L, de Barros AM Jr, Orellana ME, Antecka E, Burnier MN Jr. Expression of focal adhesion kinase in uveal melanoma and the effects of Hsp90 inhibition by 17-AAG. Pathol Res Pract. 2014 Nov;210(11):739-45. doi: 10.1016/j.prp.2014.06.023. Epub 2014 Jul 1. PubMed PMID: 25041838. 15: Hadley KE, Hendricks DT. Use of NQO1 status as a selective biomarker for oesophageal squamous cell carcinomas with greater sensitivity to 17-AAG. BMC Cancer. 2014 May 15;14:334. doi: 10.1186/1471-2407-14-334. PubMed PMID: 24886060; PubMed Central PMCID: PMC4032580. 16: Wang S, Wang X, Du Z, Liu Y, Huang D, Zheng K, Liu K, Zhang Y, Zhong X, Wang Y. SNX-25a, a novel Hsp90 inhibitor, inhibited human cancer growth more potently than 17-AAG. Biochem Biophys Res Commun. 2014 Jul 18;450(1):73-80. doi: 10.1016/j.bbrc.2014.05.076. Epub 2014 May 28. PubMed PMID: 24879994. 17: Pradhan R, Poudel BK, Choi JY, Choi IS, Shin BS, Choi HG, Yong CS, Kim JO. Preparation and evaluation of 17-allyamino-17-demethoxygeldanamycin (17-AAG)-loaded poly(lactic acid-co-glycolic acid) nanoparticles. Arch Pharm Res. 2015 May;38(5):734-41. doi: 10.1007/s12272-014-0404-7. Epub 2014 May 15. PubMed PMID: 24824337. 18: Ortega L, Calvillo M, Luna F, Pérez-Severiano F, Rubio-Osornio M, Guevara J, Limón ID. 17-AAG improves cognitive process and increases heat shock protein response in a model lesion with Aβ25-35. Neuropeptides. 2014 Aug;48(4):221-32. doi: 10.1016/j.npep.2014.04.006. Epub 2014 Apr 29. PubMed PMID: 24819277. 19: Choi YE, Battelli C, Watson J, Liu J, Curtis J, Morse AN, Matulonis UA, Chowdhury D, Konstantinopoulos PA. Sublethal concentrations of 17-AAG suppress homologous recombination DNA repair and enhance sensitivity to carboplatin and olaparib in HR proficient ovarian cancer cells. Oncotarget. 2014 May 15;5(9):2678-87. PubMed PMID: 24798692; PubMed Central PMCID: PMC4058036. 20: Chen Y, Wang B, Liu D, Li JJ, Xue Y, Sakata K, Zhu LQ, Heldt SA, Xu H, Liao FF. Hsp90 chaperone inhibitor 17-AAG attenuates Aβ-induced synaptic toxicity and memory impairment. J Neurosci. 2014 Feb 12;34(7):2464-70. doi: 10.1523/JNEUROSCI.0151-13.2014. PubMed PMID: 24523537; PubMed Central PMCID: PMC3921421.