Onalespib free base
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MedKoo CAT#: 200317

CAS#: 912999-49-6 (free base)

Description: Onalespib, also known as AT13387 , is a synthetic, orally bioavailable, small-molecule inhibitor of heat shock protein 90 (Hsp90) with potential antineoplastic activity. Hsp90 inhibitor AT13387 selectively binds to Hsp90, thereby inhibiting its chaperone function and promoting the degradation of oncogenic signaling proteins involved in tumor cell proliferation and survival. Hsp90, a chaperone protein upregulated in a variety of tumor cells, regulates the folding, stability and degradation of many oncogenic signaling proteins.


Chemical Structure

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Onalespib free base
CAS# 912999-49-6 (free base)

Theoretical Analysis

MedKoo Cat#: 200317
Name: Onalespib free base
CAS#: 912999-49-6 (free base)
Chemical Formula: C24H31N3O3
Exact Mass: 409.23654
Molecular Weight: 409.52
Elemental Analysis: C, 70.39; H, 7.63; N, 10.26; O, 11.7

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10.0mg USD 150.0 Same Day
25.0mg USD 250.0 Same Day
50.0mg USD 350.0 Same Day
100.0mg USD 650.0 Same Day
200.0mg USD 950.0 Same Day
500.0mg USD 1650.0 Same Day
1.0g USD 2650.0 2 Weeks
2.0g USD 4650.0 2 Weeks
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Related CAS #: 912999-49-6 (free base)   1019889-35-0 (lactate)    

Synonym: AT13387; AT-13387; AT 13387; Onalespib; Onalespib lactate.

IUPAC/Chemical Name: (2,4-dihydroxy-5-isopropylphenyl)(5-((4-methylpiperazin-1-yl)methyl)isoindolin-2-yl)methanone

InChi Key: IFRGXKKQHBVPCQ-UHFFFAOYSA-N

InChi Code: InChI=1S/C24H31N3O3/c1-16(2)20-11-21(23(29)12-22(20)28)24(30)27-14-18-5-4-17(10-19(18)15-27)13-26-8-6-25(3)7-9-26/h4-5,10-12,16,28-29H,6-9,13-15H2,1-3H3

SMILES Code: O=C(C1=CC(C(C)C)=C(O)C=C1O)N2CC3=C(C=C(CN4CCN(C)CC4)C=C3)C2

Appearance: White 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, not in water

Shelf Life: >2 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

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 20.0 48.8

Preparing Stock Solutions

The following data is based on the product molecular weight 409.52 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

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1: Courtin A, Smyth T, Hearn K, Saini HK, Thompson NT, Lyons JF, Wallis NG. Emergence of resistance to tyrosine kinase inhibitors in non-small-cell lung cancer can be delayed by an upfront combination with the HSP90 inhibitor onalespib. Br J Cancer. 2016 Sep 27. doi: 10.1038/bjc.2016.294. [Epub ahead of print] PubMed PMID: 27673365.

2: Ferraldeschi R, Welti J, Powers MV, Yuan W, Smyth T, Seed G, Riisnaes R, Hedayat S, Wang H, Crespo M, Nava Rodrigues D, Figueiredo I, Miranda S, Carreira S, Lyons JF, Sharp S, Plymate SR, Attard G, Wallis N, Workman P, de Bono JS. Second-Generation HSP90 Inhibitor Onalespib Blocks mRNA Splicing of Androgen Receptor Variant 7 in Prostate Cancer Cells. Cancer Res. 2016 May 1;76(9):2731-42. doi: 10.1158/0008-5472.CAN-15-2186. PubMed PMID: 27197266; PubMed Central PMCID: PMC4874658.

3: Wagner AJ, Agulnik M, Heinrich MC, Mahadevan D, Riedel RF, von Mehren M, Trent J, Demetri GD, Corless CL, Yule M, Lyons JF, Oganesian A, Keer H. Dose-escalation study of a second-generation non-ansamycin HSP90 inhibitor, onalespib (AT13387), in combination with imatinib in patients with metastatic gastrointestinal stromal tumour. Eur J Cancer. 2016 Jul;61:94-101. doi: 10.1016/j.ejca.2016.03.076. Epub 2016 May 5. PubMed PMID: 27156227.

4: Spiegelberg D, Dascalu A, Mortensen AC, Abramenkovs A, Kuku G, Nestor M, Stenerlöw B. The novel HSP90 inhibitor AT13387 potentiates radiation effects in squamous cell carcinoma and adenocarcinoma cells. Oncotarget. 2015 Nov 3;6(34):35652-66. doi: 10.18632/oncotarget.5363. PubMed PMID: 26452257; PubMed Central PMCID: PMC4742132.

5: O'Neill S, Humphries D, Tse G, Marson LP, Dhaliwal K, Hughes J, Ross JA, Wigmore SJ, Harrison EM. Heat shock protein 90 inhibition abrogates TLR4-mediated NF-κB activity and reduces renal ischemia-reperfusion injury. Sci Rep. 2015 Aug 7;5:12958. doi: 10.1038/srep12958. PubMed PMID: 26248657; PubMed Central PMCID: PMC4528191.

6: Do K, Speranza G, Chang LC, Polley EC, Bishop R, Zhu W, Trepel JB, Lee S, Lee MJ, Kinders RJ, Phillips L, Collins J, Lyons J, Jeong W, Antony R, Chen AP, Neckers L, Doroshow JH, Kummar S. Phase I study of the heat shock protein 90 (Hsp90) inhibitor onalespib (AT13387) administered on a daily for 2 consecutive days per week dosing schedule in patients with advanced solid tumors. Invest New Drugs. 2015 Aug;33(4):921-30. doi: 10.1007/s10637-015-0255-1. Epub 2015 Jun 18. PubMed PMID: 26082332.

7: Smyth T, Paraiso KH, Hearn K, Rodriguez-Lopez AM, Munck JM, Haarberg HE, Sondak VK, Thompson NT, Azab M, Lyons JF, Smalley KS, Wallis NG. Inhibition of HSP90 by AT13387 delays the emergence of resistance to BRAF inhibitors and overcomes resistance to dual BRAF and MEK inhibition in melanoma models. Mol Cancer Ther. 2014 Dec;13(12):2793-804. doi: 10.1158/1535-7163.MCT-14-0452. Epub 2014 Oct 27. PubMed PMID: 25349308; PubMed Central PMCID: PMC4263034.

8: Shapiro GI, Kwak E, Dezube BJ, Yule M, Ayrton J, Lyons J, Mahadevan D. First-in-human phase I dose escalation study of a second-generation non-ansamycin HSP90 inhibitor, AT13387, in patients with advanced solid tumors. Clin Cancer Res. 2015 Jan 1;21(1):87-97. doi: 10.1158/1078-0432.CCR-14-0979. Epub 2014 Oct 21. PubMed PMID: 25336693.

9: Pillai RN, Ramalingam SS. Heat shock protein 90 inhibitors in non-small-cell lung cancer. Curr Opin Oncol. 2014 Mar;26(2):159-64. doi: 10.1097/CCO.0000000000000047. Review. PubMed PMID: 24463348.

10: Chan KC, Ting CM, Chan PS, Lo MC, Lo KW, Curry JE, Smyth T, Lee AW, Ng WT, Tsao GS, Wong RN, Lung ML, Mak NK. A novel Hsp90 inhibitor AT13387 induces senescence in EBV-positive nasopharyngeal carcinoma cells and suppresses tumor formation. Mol Cancer. 2013 Oct 24;12(1):128. doi: 10.1186/1476-4598-12-128. PubMed PMID: 24156782; PubMed Central PMCID: PMC3834878.

11: Patel BH, Barrett AG. Total synthesis of resorcinol amide Hsp90 inhibitor AT13387. J Org Chem. 2012 Dec 21;77(24):11296-301. doi: 10.1021/jo302406w. Epub 2012 Dec 6. PubMed PMID: 23186098.

12: Ahsan A, Ramanand SG, Whitehead C, Hiniker SM, Rehemtulla A, Pratt WB, Jolly S, Gouveia C, Truong K, Van Waes C, Ray D, Lawrence TS, Nyati MK. Wild-type EGFR is stabilized by direct interaction with HSP90 in cancer cells and tumors. Neoplasia. 2012 Aug;14(8):670-7. PubMed PMID: 22952420; PubMed Central PMCID: PMC3431175.

13: Smyth T, Van Looy T, Curry JE, Rodriguez-Lopez AM, Wozniak A, Zhu M, Donsky R, Morgan JG, Mayeda M, Fletcher JA, Schöffski P, Lyons J, Thompson NT, Wallis NG. The HSP90 inhibitor, AT13387, is effective against imatinib-sensitive and -resistant gastrointestinal stromal tumor models. Mol Cancer Ther. 2012 Aug;11(8):1799-808. doi: 10.1158/1535-7163.MCT-11-1046. Epub 2012 Jun 19. PubMed PMID: 22714264; PubMed Central PMCID: PMC3992119.

14: Graham B, Curry J, Smyth T, Fazal L, Feltell R, Harada I, Coyle J, Williams B, Reule M, Angove H, Cross DM, Lyons J, Wallis NG, Thompson NT. The heat shock protein 90 inhibitor, AT13387, displays a long duration of action in vitro and in vivo in non-small cell lung cancer. Cancer Sci. 2012 Mar;103(3):522-7. doi: 10.1111/j.1349-7006.2011.02191.x. Epub 2012 Feb 9. PubMed PMID: 22181674.

15: Liu J, Wang F, Ma Z, Wang X, Wang Y. Structural determination of three different series of compounds as Hsp90 inhibitors using 3D-QSAR modeling, molecular docking and molecular dynamics methods. Int J Mol Sci. 2011 Jan 30;12(2):946-70. doi: 10.3390/ijms12020946. PubMed PMID: 21541036; PubMed Central PMCID: PMC3083683.

16: Kang MH, Reynolds CP, Houghton PJ, Alexander D, Morton CL, Kolb EA, Gorlick R, Keir ST, Carol H, Lock R, Maris JM, Wozniak A, Smith MA. Initial testing (Stage 1) of AT13387, an HSP90 inhibitor, by the pediatric preclinical testing program. Pediatr Blood Cancer. 2012 Jul 15;59(1):185-8. doi: 10.1002/pbc.23154. Epub 2011 Apr 29. PubMed PMID: 21538821; PubMed Central PMCID: PMC3154460.

17: Woodhead AJ, Angove H, Carr MG, Chessari G, Congreve M, Coyle JE, Cosme J, Graham B, Day PJ, Downham R, Fazal L, Feltell R, Figueroa E, Frederickson M, Lewis J, McMenamin R, Murray CW, O'Brien MA, Parra L, Patel S, Phillips T, Rees DC, Rich S, Smith DM, Trewartha G, Vinkovic M, Williams B, Woolford AJ. Discovery of (2,4-dihydroxy-5-isopropylphenyl)-[5-(4-methylpiperazin-1-ylmethyl)-1,3-dihydrois oindol-2-yl]methanone (AT13387), a novel inhibitor of the molecular chaperone Hsp90 by fragment based drug design. J Med Chem. 2010 Aug 26;53(16):5956-69. doi: 10.1021/jm100060b. PubMed PMID: 20662534.



Additional Information

Related CAS#
CAS#912999-49-6 (AT13387 free base),
CAS#1019889-35-0 (AT13387 lactate)