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MedKoo Cat#: 584518 | Name: Alvespimycin
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Description:

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

Alvespimycin is a heat shock protein 90 (Hsp90) inhibitor and promising therapeutic agent for cancer.

Chemical Structure

Alvespimycin
CAS#467214-20-6 (free base)

Theoretical Analysis

MedKoo Cat#: 584518

Name: Alvespimycin

CAS#: 467214-20-6 (free base)

Chemical Formula: C32H48N4O8

Exact Mass: 616.3472

Molecular Weight: 616.76

Elemental Analysis: C, 62.32; H, 7.84; N, 9.08; O, 20.75

Price and Availability

Size Price Availability Quantity
5mg USD 450.00 2 Weeks
10mg USD 750.00 2 Weeks
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Related CAS #
 467214-21-7(HCl) 467214-20-6 (free base)
Synonym
Alvespimycin; KOS 1022; KOS-1022; KOS1022; 17-DMAG; NSC 707545; NSC707545; NSC-707545
IUPAC/Chemical Name
((4E,6Z,8S,9S,10E,12S,13R,14S,16R)-19-(2-dimethylaminoethylamino)-13-hydroxy-8,14-dimethoxy-4,10,12,16-tetramethyl-3,20,22-trioxo-2-azabicyclo(16.3.1)docosa-4,6,10,18,21-pentaen-9-yl) carbamate
InChi Key
KUFRQPKVAWMTJO-LMZWQJSESA-N
InChi Code
InChI=1S/C32H48N4O8/c1-18-14-22-27(34-12-13-36(5)6)24(37)17-23(29(22)39)35-31(40)19(2)10-9-11-25(42-7)30(44-32(33)41)21(4)16-20(3)28(38)26(15-18)43-8/h9-11,16-18,20,25-26,28,30,34,38H,12-15H2,1-8H3,(H2,33,41)(H,35,40)/b11-9-,19-10+,21-16+/t18-,20+,25+,26+,28-,30+/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=C2NCCN(C)C)[C@@H](OC)/C=C\C=C(C)\C(NC(C1=O)=CC2=O)=O)=O
Appearance
Solid powder
Purity
>98% (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
Shelf Life
>3 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
2934.99.03.00
More Info
Product Data
Product Data
Certificate of Analysis
View CoA: current batch, Lot# C21M11C12
Safety Data Sheet (SDS)
View Safety Data Sheet (SDS)
Instruction
View handling instruction
Biological target:
Alvespimycin (17-DMAG) is a potent inhibitor of Hsp90, binding to Hsp90 with an EC50 of 62 ± 29 nM.
In vitro activity:
Exposure of human SH-SY5Y neuroblastoma cells to 17-DMAG (10−11 to 10−8 m) for 24 h and 48 h did not affect cell viability as measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. However, 17-DMAG at concentrations of 10−7 to 10−5 m caused significant reductions in cell viability for 24 h and 48 h (P < 0.001) (Fig. 5A). In the subsequent experiments, concentrations of 17-DMAG were below 10 nm. As shown in Fig. 5B, after exposure to 2 μm rotenone for 48 h, the cell viability decreased by 30% compared to the control group (P < 0.001). Pretreatment with 17-DMAG at concentrations of 1 nm and 3 nm significantly attenuated rotenone-induced cell death (P < 0.05 and P < 0.01). This result suggested that 17-DMAG was effective in inhibiting rotenone-induced cell death. Reference: FEBS J. 2014 Feb;281(4):1110-22. https://pubmed.ncbi.nlm.nih.gov/24304935/
In vivo activity:
Consistent with past reports, this study found that hyperglycemia led to extensive HT in ischemic areas of the brain in MCAO model rats at 24 h post-MCAO. Relative to animals injected with vehicle control, animals administered 17-DMAG exhibited significant reductions in both infarct size and hemorrhage volume at 24 h post-MCAO (Figures 1(b)–1(d)). There was also a clear correlation between infarct size and hemorrhage volume in these animals (Figures 1(b)–1(d)). Relative to sham controls, MCAO model animals exhibited clear neurological deficits that were partially reversed in MCAO model animals that had been treated with 17-DMAG (Figure 1(e)). Reference: Biomed Res Int. 2021; 2021: 6668442. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7878095/
Solvent mg/mL mM comments
Solubility
DMSO 13.0 21.08
DMF 20.0 32.43
DMF:PBS (pH 7.2) (1:1) 0.5 0.81
Ethanol 2.0 3.24
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 616.76 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. Hu Y, Bobb D, He J, Hill DA, Dome JS. The HSP90 inhibitor alvespimycin enhances the potency of telomerase inhibition by imetelstat in human osteosarcoma. Cancer Biol Ther. 2015;16(6):949-57. doi: 10.1080/15384047.2015.1040964. Epub 2015 Apr 28. PMID: 25920748; PMCID: PMC4622625. 2. Gao L, Zhao G, Fang JS, Yuan TY, Liu AL, Du GH. Discovery of the neuroprotective effects of alvespimycin by computational prioritization of potential anti-Parkinson agents. FEBS J. 2014 Feb;281(4):1110-22. doi: 10.1111/febs.12672. Epub 2014 Jan 9. PMID: 24304935. 3. Zhang J, Wang K, Qi J, Cao X, Wang F. The Hsp90 Inhibitor 17-DMAG Attenuates Hyperglycemia-Enhanced Hemorrhagic Transformation in Experimental Stroke. Biomed Res Int. 2021 Feb 2;2021:6668442. doi: 10.1155/2021/6668442. PMID: 33614785; PMCID: PMC7878095. 4. Singh S, Abu-Zaid A, Lin W, Low J, Abdolvahabi A, Jin H, Wu Q, Cooke B, Fang J, Bowling J, Vaithiyalingam S, Currier D, Yun MK, Fernando DM, Maier J, Tillman H, Bulsara P, Lu Z, Das S, Shelat A, Li Z, Young B, Lee R, Rankovic Z, Murphy AJ, White SW, Davidoff AM, Chen T, Yang J. 17-DMAG dually inhibits Hsp90 and histone lysine demethylases in alveolar rhabdomyosarcoma. iScience. 2020 Dec 28;24(1):101996. doi: 10.1016/j.isci.2020.101996. PMID: 33490904; PMCID: PMC7811140.
In vitro protocol:
1. Hu Y, Bobb D, He J, Hill DA, Dome JS. The HSP90 inhibitor alvespimycin enhances the potency of telomerase inhibition by imetelstat in human osteosarcoma. Cancer Biol Ther. 2015;16(6):949-57. doi: 10.1080/15384047.2015.1040964. Epub 2015 Apr 28. PMID: 25920748; PMCID: PMC4622625. 2. Gao L, Zhao G, Fang JS, Yuan TY, Liu AL, Du GH. Discovery of the neuroprotective effects of alvespimycin by computational prioritization of potential anti-Parkinson agents. FEBS J. 2014 Feb;281(4):1110-22. doi: 10.1111/febs.12672. Epub 2014 Jan 9. PMID: 24304935.
In vivo protocol:
1. Zhang J, Wang K, Qi J, Cao X, Wang F. The Hsp90 Inhibitor 17-DMAG Attenuates Hyperglycemia-Enhanced Hemorrhagic Transformation in Experimental Stroke. Biomed Res Int. 2021 Feb 2;2021:6668442. doi: 10.1155/2021/6668442. PMID: 33614785; PMCID: PMC7878095. 2. Singh S, Abu-Zaid A, Lin W, Low J, Abdolvahabi A, Jin H, Wu Q, Cooke B, Fang J, Bowling J, Vaithiyalingam S, Currier D, Yun MK, Fernando DM, Maier J, Tillman H, Bulsara P, Lu Z, Das S, Shelat A, Li Z, Young B, Lee R, Rankovic Z, Murphy AJ, White SW, Davidoff AM, Chen T, Yang J. 17-DMAG dually inhibits Hsp90 and histone lysine demethylases in alveolar rhabdomyosarcoma. iScience. 2020 Dec 28;24(1):101996. doi: 10.1016/j.isci.2020.101996. PMID: 33490904; PMCID: PMC7811140.
1: Hu ZY, Lu J, Zhao Y. A physiologically based pharmacokinetic model of alvespimycin in mice and extrapolation to rats and humans. Br J Pharmacol. 2014 Jun;171(11):2778-89. doi: 10.1111/bph.12609. PubMed PMID: 24471734; PubMed Central PMCID: PMC4243854. 2: Hu Y, Bobb D, He J, Hill DA, Dome JS. The HSP90 inhibitor alvespimycin enhances the potency of telomerase inhibition by imetelstat in human osteosarcoma. Cancer Biol Ther. 2015;16(6):949-57. doi: 10.1080/15384047.2015.1040964. Epub 2015 Apr 28. PubMed PMID: 25920748; PubMed Central PMCID: PMC4622625. 3: Gao L, Zhao G, Fang JS, Yuan TY, Liu AL, Du GH. Discovery of the neuroprotective effects of alvespimycin by computational prioritization of potential anti-Parkinson agents. FEBS J. 2014 Feb;281(4):1110-22. doi: 10.1111/febs.12672. Epub 2014 Jan 9. PubMed PMID: 24304935. 4: Schulze K, Imbeaud S, Letouzé E, Alexandrov LB, Calderaro J, Rebouissou S, Couchy G, Meiller C, Shinde J, Soysouvanh F, Calatayud AL, Pinyol R, Pelletier L, Balabaud C, Laurent A, Blanc JF, Mazzaferro V, Calvo F, Villanueva A, Nault JC, Bioulac-Sage P, Stratton MR, Llovet JM, Zucman-Rossi J. Exome sequencing of hepatocellular carcinomas identifies new mutational signatures and potential therapeutic targets. Nat Genet. 2015 May;47(5):505-511. doi: 10.1038/ng.3252. Epub 2015 Mar 30. PubMed PMID: 25822088; PubMed Central PMCID: PMC4587544. 5: Jhaveri K, Miller K, Rosen L, Schneider B, Chap L, Hannah A, Zhong Z, Ma W, Hudis C, Modi S. A phase I dose-escalation trial of trastuzumab and alvespimycin hydrochloride (KOS-1022; 17 DMAG) in the treatment of advanced solid tumors. Clin Cancer Res. 2012 Sep 15;18(18):5090-8. doi: 10.1158/1078-0432.CCR-11-3200. Epub 2012 Jul 10. PubMed PMID: 22781552. 6: Maddocks K, Hertlein E, Chen TL, Wagner AJ, Ling Y, Flynn J, Phelps M, Johnson AJ, Byrd JC, Jones JA. A phase I trial of the intravenous Hsp90 inhibitor alvespimycin (17-DMAG) in patients with relapsed chronic lymphocytic leukemia/small lymphocytic lymphoma. Leuk Lymphoma. 2016 Sep;57(9):2212-5. doi: 10.3109/10428194.2015.1129536. Epub 2016 Jan 14. PubMed PMID: 26764527; PubMed Central PMCID: PMC5455147. 7: Lancet JE, Gojo I, Burton M, Quinn M, Tighe SM, Kersey K, Zhong Z, Albitar MX, Bhalla K, Hannah AL, Baer MR. Phase I study of the heat shock protein 90 inhibitor alvespimycin (KOS-1022, 17-DMAG) administered intravenously twice weekly to patients with acute myeloid leukemia. Leukemia. 2010 Apr;24(4):699-705. doi: 10.1038/leu.2009.292. Epub 2010 Jan 28. PubMed PMID: 20111068. 8: Pacey S, Wilson RH, Walton M, Eatock MM, Hardcastle A, Zetterlund A, Arkenau HT, Moreno-Farre J, Banerji U, Roels B, Peachey H, Aherne W, de Bono JS, Raynaud F, Workman P, Judson I. A phase I study of the heat shock protein 90 inhibitor alvespimycin (17-DMAG) given intravenously to patients with advanced solid tumors. Clin Cancer Res. 2011 Mar 15;17(6):1561-70. doi: 10.1158/1078-0432.CCR-10-1927. Epub 2011 Jan 28. PubMed PMID: 21278242; PubMed Central PMCID: PMC3060938. 9: Smith MA, Morton CL, Phelps DA, Kolb EA, Lock R, Carol H, Reynolds CP, Maris JM, Keir ST, Wu J, Houghton PJ. Stage 1 testing and pharmacodynamic evaluation of the HSP90 inhibitor alvespimycin (17-DMAG, KOS-1022) by the pediatric preclinical testing program. Pediatr Blood Cancer. 2008 Jul;51(1):34-41. doi: 10.1002/pbc.21508. PubMed PMID: 18260120. 10: Yang DS. Novel prediction of anticancer drug chemosensitivity in cancer cell lines: evidence of moderation by microRNA expressions. Conf Proc IEEE Eng Med Biol Soc. 2014;2014:4780-6. doi: 10.1109/EMBC.2014.6944693. PubMed PMID: 25571061. 11: Ambade A, Catalano D, Lim A, Kopoyan A, Shaffer SA, Mandrekar P. Inhibition of heat shock protein 90 alleviates steatosis and macrophage activation in murine alcoholic liver injury. J Hepatol. 2014 Oct;61(4):903-11. doi: 10.1016/j.jhep.2014.05.024. Epub 2014 May 22. PubMed PMID: 24859453; PubMed Central PMCID: PMC4169725. 12: Nanduri P, Hao R, Fitzpatrick T, Yao TP. Chaperone-mediated 26S proteasome remodeling facilitates free K63 ubiquitin chain production and aggresome clearance. J Biol Chem. 2015 Apr 10;290(15):9455-64. doi: 10.1074/jbc.M114.627950. Epub 2015 Feb 24. PubMed PMID: 25713068; PubMed Central PMCID: PMC4392251. 13: Lazaro I, Oguiza A, Recio C, Mallavia B, Madrigal-Matute J, Blanco J, Egido J, Martin-Ventura JL, Gomez-Guerrero C. Targeting HSP90 Ameliorates Nephropathy and Atherosclerosis Through Suppression of NF-κB and STAT Signaling Pathways in Diabetic Mice. Diabetes. 2015 Oct;64(10):3600-13. doi: 10.2337/db14-1926. Epub 2015 Jun 26. PubMed PMID: 26116697. 14: Iguchi N, Malykhina AP, Wilcox DT. Inhibition of HIF Reduces Bladder Hypertrophy and Improves Bladder Function in Murine Model of Partial Bladder Outlet Obstruction. J Urol. 2016 Apr;195(4 Pt 2):1250-6. doi: 10.1016/j.juro.2015.08.001. Epub 2016 Feb 28. PubMed PMID: 26926557; PubMed Central PMCID: PMC5505069. 15: Safavi S, Järnum S, Vannas C, Udhane S, Jonasson E, Tomic TT, Grundevik P, Fagman H, Hansson M, Kalender Z, Jauhiainen A, Dolatabadi S, Stratford EW, Myklebost O, Eriksson M, Stenman G, Schneider-Stock R, Ståhlberg A, Åman P. HSP90 inhibition blocks ERBB3 and RET phosphorylation in myxoid/round cell liposarcoma and causes massive cell death in vitro and in vivo. Oncotarget. 2016 Jan 5;7(1):433-45. doi: 10.18632/oncotarget.6336. PubMed PMID: 26595521; PubMed Central PMCID: PMC4808009. 16: Tsai YC, Lam KK, Peng YJ, Lee YM, Yang CY, Tsai YJ, Yen MH, Cheng PY. Heat shock protein 70 and AMP-activated protein kinase contribute to 17-DMAG-dependent protection against heat stroke. J Cell Mol Med. 2016 Oct;20(10):1889-97. doi: 10.1111/jcmm.12881. Epub 2016 May 31. PubMed PMID: 27241357; PubMed Central PMCID: PMC5020632. 17: Wang YL, Shen HH, Cheng PY, Chu YJ, Hwang HR, Lam KK, Lee YM. 17-DMAG, an HSP90 Inhibitor, Ameliorates Multiple Organ Dysfunction Syndrome via Induction of HSP70 in Endotoxemic Rats. PLoS One. 2016 May 25;11(5):e0155583. doi: 10.1371/journal.pone.0155583. eCollection 2016. PubMed PMID: 27224288; PubMed Central PMCID: PMC4880344. 18: Yang WL, Lee YE, Chen MH, Chao KM, Huang CY. In-silico drug screening and potential target identification for hepatocellular carcinoma using Support Vector Machines based on drug screening result. Gene. 2013 Apr 10;518(1):201-8. doi: 10.1016/j.gene.2012.11.030. Epub 2012 Dec 6. PubMed PMID: 23220021. 19: Liu Y, Yu Y, Chu H, Bing D, Wang S, Zhou L, Chen J, Chen Q, Pan C, Sun Y, Cui Y. 17-DMAG induces Hsp70 and protects the auditory hair cells from kanamycin ototoxicity in vitro. Neurosci Lett. 2015 Feb 19;588:72-7. doi: 10.1016/j.neulet.2014.12.060. Epub 2014 Dec 31. PubMed PMID: 25556684. 20: Seo YH. Organelle-specific Hsp90 inhibitors. Arch Pharm Res. 2015 Sep;38(9):1582-90. doi: 10.1007/s12272-015-0636-1. Epub 2015 Jul 22. Review. PubMed PMID: 26195286.