Onalespib lactate
featured

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

MedKoo CAT#: 206740

CAS#: 1019889-35-0 (lactate)

Description: Onalespib lactate, also known as ATI-13387A, is a second-generation, potent and selective HSP90 Inhibitor. Onalespib Blocks mRNA Splicing of Androgen Receptor Variant 7 in Prostate Cancer Cells. 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. AT13387 induces senescence in EBV-positive nasopharyngeal carcinoma cells and suppresses tumor formation. AT13387, displays a long duration of action in vitro and in vivo in non-small cell lung cancer.


Chemical Structure

img
Onalespib lactate
CAS# 1019889-35-0 (lactate)

Theoretical Analysis

MedKoo Cat#: 206740
Name: Onalespib lactate
CAS#: 1019889-35-0 (lactate)
Chemical Formula: C27H37N3O6
Exact Mass: 0.00
Molecular Weight: 499.608
Elemental Analysis: C, 64.91; H, 7.47; N, 8.41; O, 19.21

Price and Availability

Size Price Availability Quantity
1g USD 3450 2-3 months
2g USD 5150 2-3 months
5g USD 8650 2-3 months
Bulk inquiry

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

Synonym: Onalespib lactate; AT-13387 lactate; ATI-13387A; ATI-13387AU; ATI-13387; ATI 13387; ATI13387.

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

InChi Key: VYRWEWHOAMGLLW-WNQIDUERSA-N

InChi Code: InChI=1S/C24H31N3O3.C3H6O3/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;1-2(4)3(5)6/h4-5,10-12,16,28-29H,6-9,13-15H2,1-3H3;2,4H,1H3,(H,5,6)/t;2-/m.0/s1

SMILES Code: C[C@H](O)C(O)=O.O=C(N1CC2=C(C=C(CN3CCN(C)CC3)C=C2)C1)C4=CC(C(C)C)=C(O)C=C4O

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: >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

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

Product Data:
Biological target: Onalespib lactate, also known as ATI-13387A, is a second-generation, potent and selective HSP90 Inhibitor.
In vitro activity: The effect of AT13387 on in vitro radio-sensitization was assessed using a clonogenic assay. The amplitude of the effects of 100 nM AT13387 on the global proteome was significantly lower than that of 3 μM AT13387. Interestingly, except for Hsp70, the abundance of any other protein did not reach beyond the 1.5-fold abundance (log scale) level. The magnitude observed on protein levels (total 2145 significantly affected protein out of 5086) suggests that the 3 μM AT13387 concentration would not be selective. Therefore, when given at a dose producing such drug levels in patients, it seems unlikely that the cumulative effect of the drug would be selective for cancer treatment. Altogether, the data suggest that a sub-toxic concentration of AT13387 can cause radio-sensitization regardless of the specific oncogenic driver(s) present in the cell lines. Clin Cancer Res. 2020 Oct 1; 26(19): 5246–5257. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7541797/
In vivo activity: Following the determination of the pharmacokinetic profile of AT13387, it was sought to determine the duration for which AT13387 can exert its effects in vivo. To investigate these effects, a single 40 mg/kg dose of AT13387 was administered at 0 hours, and a second 40 mg/kg dose at 96 hours, to mice bearing UMSCC74B xenografts. The expression of Hsp70 was analyzed in the tumor at the various time points as previously described. Following administration, pharmacodynamics studies showed that the expression of chaperone protein Hsp70, our biomarker for Hsp90 activity, was upregulated after AT13387 treatment (Figure 5B). This result was confirmed by densitometry analysis, which showed an 8-fold upregulation of Hsp70 expression at 24 and 120 hours (Figure 5B). Nearly 2 to 5-fold increased Hsp70 expression was demonstrated using immunohistochemistry (Figure 5C). This upregulation suggests that AT13387 treatment showed the desired inhibitory effect of Hsp90 inhibition in vivo.This indicates a potential role of the immune component in radiosensitization by AT13387. Clin Cancer Res. 2020 Oct 1; 26(19): 5246–5257. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7541797/

Preparing Stock Solutions

The following data is based on the product molecular weight 499.61 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. Lundsten S, Spiegelberg D, Stenerlöw B, Nestor M. The HSP90 inhibitor onalespib potentiates 177Lu‑DOTATATE therapy in neuroendocrine tumor cells. Int J Oncol. 2019 Dec;55(6):1287-1295. doi: 10.3892/ijo.2019.4888. Epub 2019 Sep 30. PMID: 31638190; PMCID: PMC6831206. 2. Mehta RK, Pal S, Kondapi K, Sitto M, Dewar C, Devasia T, Schipper MJ, Thomas DG, Basrur V, Pai MP, Morishima Y, Osawa Y, Pratt WB, Lawrence TS, Nyati MK. Low-Dose Hsp90 Inhibitor Selectively Radiosensitizes HNSCC and Pancreatic Xenografts. Clin Cancer Res. 2020 Oct 1;26(19):5246-5257. doi: 10.1158/1078-0432.CCR-19-3102. Epub 2020 Jul 27. PMID: 32718999; PMCID: PMC7541797.
In vitro protocol: 1. Lundsten S, Spiegelberg D, Stenerlöw B, Nestor M. The HSP90 inhibitor onalespib potentiates 177Lu‑DOTATATE therapy in neuroendocrine tumor cells. Int J Oncol. 2019 Dec;55(6):1287-1295. doi: 10.3892/ijo.2019.4888. Epub 2019 Sep 30. PMID: 31638190; PMCID: PMC6831206. 2. Mehta RK, Pal S, Kondapi K, Sitto M, Dewar C, Devasia T, Schipper MJ, Thomas DG, Basrur V, Pai MP, Morishima Y, Osawa Y, Pratt WB, Lawrence TS, Nyati MK. Low-Dose Hsp90 Inhibitor Selectively Radiosensitizes HNSCC and Pancreatic Xenografts. Clin Cancer Res. 2020 Oct 1;26(19):5246-5257. doi: 10.1158/1078-0432.CCR-19-3102. Epub 2020 Jul 27. PMID: 32718999; PMCID: PMC7541797.
In vivo protocol: 1. Lundsten S, Spiegelberg D, Stenerlöw B, Nestor M. The HSP90 inhibitor onalespib potentiates 177Lu‑DOTATATE therapy in neuroendocrine tumor cells. Int J Oncol. 2019 Dec;55(6):1287-1295. doi: 10.3892/ijo.2019.4888. Epub 2019 Sep 30. PMID: 31638190; PMCID: PMC6831206. 2. Mehta RK, Pal S, Kondapi K, Sitto M, Dewar C, Devasia T, Schipper MJ, Thomas DG, Basrur V, Pai MP, Morishima Y, Osawa Y, Pratt WB, Lawrence TS, Nyati MK. Low-Dose Hsp90 Inhibitor Selectively Radiosensitizes HNSCC and Pancreatic Xenografts. Clin Cancer Res. 2020 Oct 1;26(19):5246-5257. doi: 10.1158/1078-0432.CCR-19-3102. Epub 2020 Jul 27. PMID: 32718999; PMCID: PMC7541797.

Molarity Calculator

Calculate the mass, volume, or concentration required for a solution.
=
x
x
g/mol

*When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and SDS / CoA (available online).

Reconstitution Calculator

The reconstitution calculator allows you to quickly calculate the volume of a reagent to reconstitute your vial. Simply enter the mass of reagent and the target concentration and the calculator will determine the rest.

=
÷

Dilution Calculator

Calculate the dilution required to prepare a stock solution.
x
=
x

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.