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| 100mg |
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Purity: ≥98%
Onalespib (formerly also known as AT13387; AT-13387) is an orally bioavailable small-molecule Hsp90 inhibitor (IC50 = 18 nM in A375 cells) with long-lasting anti-tumor activity. 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.
| ln Vitro |
Glioma cell migration, survival, and proliferation are inhibited by onalespib lactate (0-0.4 µM; 72 h, 48 h) [2]. AKT, P-AKT, ERK1/2, P-ERK1/2, S6, and P-S6 protein expression are all decreased in a dose-dependent manner by onalespib lactate (0-0.4 µM; 48 h)[2].
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| ln Vivo |
In 6-week-old ICR mice, onalespib lactate (30 mg/kg; intraperitoneal; once) passes the blood-brain barrier (BBB) and results in long-lasting inhibition of HSP90 [2]. In zebrafish embryos, onalespib lactate (0.5 µM; 5 to 10 days after transplanting) and TMZ (10 µM) inhibit tumor growth and increase survival [2]. In HCT116 and A431 xenografts, onalespib lactate (5, 10 mg/kg for HCT116 xenografts, 20 mg/kg for A431 xenografts; i.p.; once daily for 3 days) showed anticancer efficacy [3].
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| Cell Assay |
Cell Proliferation Assay[2]
Cell Types: LN229, U251 and A172 cells Tested Concentrations: 0.1, 0.2, 0.4 µM Incubation Duration: 72 h Experimental Results: Inhibited cell proliferation in a dose-dependent manner. Western Blot Analysis[2] Cell Types: LN229, U251 and A172 cells Tested Concentrations: 0.1, 0.2, 0.4 µM Incubation Duration: 48 h Experimental Results: diminished the expression of EGFR, p-EGFR, AKT, P-AKT, ERK1/2, P-ERK1/2, S6, P- S6 protein in a dose-dependent manner. |
| Animal Protocol |
Animal/Disease Models: Female nu/nu balb/c (Bagg ALBino) mouse (HCT116 and A431 xenografts)[3]
Doses: 5, 10 mg/kg for HCT116 xenografts, 20 mg/kg for A431 xenografts Route of Administration: Ip; on day 1, 2, and 3 days Experimental Results: Inhibited tumor growth and had a median survival of 9.5 days and the maximum survival was 14 days in HCT116 xenografts, decreased the tumor size Dramatically by 32% in A431 xenografts. |
| References |
[1]. Riess JW, et al. Erlotinib and Onalespib Lactate Focused on EGFR Exon 20 Insertion Non-Small Cell Lung Cancer (NSCLC): A California Cancer Consortium Phase I/II Trial (NCI 9878). Clin Lung Cancer. 2021 Nov;22(6):541-548.
[2]. Canella A, et al. Efficacy of Onalespib, a Long-Acting Second-Generation HSP90 Inhibitor, as a Single Agent and in Combination with Temozolomide against Malignant Gliomas. Clin Cancer Res. 2017 Oct 15;23(20):6215-6226. [3]. Spiegelberg D, et al. The HSP90 inhibitor Onalespib exerts synergistic anti-cancer effects when combined with radiotherapy: an in vitro and in vivo approach. Sci Rep. 2020 Apr 3;10(1):5923. [4]. Woodhead AJ, et al. Discovery of (2,4-dihydroxy-5-isopropylphenyl)-[5-(4-methylpiperazin-1-ylmethyl)-1,3-dihydroisoindol-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. |
| Molecular Formula |
C27H37N3O6
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|---|---|
| Molecular Weight |
499.599187612534
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| CAS # |
1019889-35-0
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| Related CAS # |
Onalespib;912999-49-6
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| SMILES |
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
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| InChi Key |
VYRWEWHOAMGLLW-WNQIDUERSA-N
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| 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
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| Chemical Name |
(2,4-dihydroxy-5-isopropylphenyl)(5-((4-methylpiperazin-1-yl)methyl)isoindolin-2-yl)methanone (S)-2-hydroxypropanoate
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| Synonyms |
Onalespib lactate; AT-13387 lactate; ATI 13387; ATI-13387A; ATI-13387; ATI-13387AU; ATI13387.
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0016 mL | 10.0080 mL | 20.0160 mL | |
| 5 mM | 0.4003 mL | 2.0016 mL | 4.0032 mL | |
| 10 mM | 0.2002 mL | 1.0008 mL | 2.0016 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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