Onalespib (AT13387)

카탈로그 번호S1163 배치:S116304

인쇄

기술 자료

화학식

C24H31N3O3
분자량 409.52 CAS 번호 912999-49-6
용해도 (25°C)* 시험관 내(In vitro) DMSO 82 mg/mL (200.23 mM)
Water Insoluble
Ethanol Insoluble
생체 내(In Vivo) (개별적으로 순서대로 용매를 제품에 첨가하십시오.)
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
* <1 mg/ml은 약간 용해되거나 불용해됨을 의미합니다.
* Selleck은 모든 화합물의 용해도를 자체적으로 테스트하며, 실제 용해도는 게시된 값과 약간 다를 수 있습니다. 이는 정상적인 현상이며, 약간의 배치 간 변동으로 인해 발생합니다.
* 실온 배송 (안정성 테스트 결과 이 제품은 냉각 조치 없이 배송될 수 있음을 보여줍니다.)

원액 준비

생물학적 활성

설명 Onalespib (AT13387) is a selective potent Hsp90 inhibitor with IC50 of 18 nM in A375 cells, displays a long duration of anti-tumor activity. Phase 2.
표적
HSP90
(Cell-free assay)
18 nM
시험관 내(In vitro) The Kd for Onalespib (AT13387) binding is 0.7 nM. This compares to a Kd of 6.7 nM for the binding of the ansamycin 17-AAG to the same site. The mean stoichiometry of binding for this compound is 1.03. Its inhibition of a number of isolated kinases is also investigated, including CDK1, CDK2, CDK4, FGFR3, PKB-b, JAK2, VEGFR2, PDGFRβ and Aurora B. None of the tested kinases are significantly inhibited at concentrations below 30 μM. It is a potent inhibitor of the proliferation and survival of many different cell lines (such as MES-SA cell line) from a variety of different tumor types. Across a panel of 30 tumor cell lines, it potently inhibits cell proliferation with GI50 values in the range 13–260 nM. The compound also inhibits proliferation of the non-tumorigenic human prostate epithelial cell line PNT2 with a GI50 value of 480 nM.
생체 내(In Vivo) When given on an intermittent basis, Onalespib (AT13387) could be tolerated at doses of up to 70 mg/kg twice weekly or 90 mg/kg once weekly. Body weight loss in mice does not exceed 20% before recovering in all cases except one, and loss is highest following the second dose. Tumor growth inhibition is similar in NCI-H1975 for both dosing regimens. The maintenance of antitumor effects with such a prolonged off-treatment period is consistent with the extended pharmacodynamic action of this compound observed for mutant EGFR and other biomarkers in vitro and in vivo and the extended retention of it in tumors.

프로토콜 (참조)

키나아제 분석:[2]
  • HSP90 competition isothermal calorimetry

    Kd values for Onalespib (AT13387) binding to HSP90 are determined with a competition Isothermal Calorimetry (ITC) format. ITC experiments are performed on a Micro Cal VP-ITC at 25 °C in a buffer comprising 25 mM Tris, 100 mM NaCl, 1 mM MgCl2 and 1 mM Tris(2-carboxy- ethyl)phosphine at pH 7.4 in order to maintain the higher affinit
세포 분석:[2]
  • 세포주

    A375, 22RV1 and T474 cells

  • 농도

    1 μM

  • 배양 시간

    4 hours

  • 방법

    The human cell lines including A375, 22RV1, T474, DU1 45, LNCa P, MCF-7, DA-MB-468 are seeded into 96-well plates before the addition of Onalespib (AT13387) in 0.1% (v/v) DMSO. GI50 are determined using a 10-point dose response curve for three cell doubling times. After incubation with this compound at 10% (v/v), Alamar blue is added, and cells are incubated for a further 4 hours. Fluorescence is read.
동물 연구:[2]
  • 동물 모델

    Athymic BALB /c mice

  • 용량

    80 mg/kg

  • 투여

    Intraperitoneal adminis tration

참조

  • http://mct.aacrjournals.org/cgi/content/meeting_abstract/8/12_MeetingAbstracts/A217
  • https://pubmed.ncbi.nlm.nih.gov/22181674/

고객 제품 검증

IC50 determinations of compound S1 and S13 on heat shock poteins ATPase activity using ADP fluorescence assay. (A)inhibition of HSP70 (B) inhibition of HSP90 The test compounds were diluted from mother plates (10 mM in 100% (v/v) DMSO) into series ofconcentration (in 2.0% (v/v) DMSO). AT13387 and 17-DMAG were used as positive controls in each assay. Data were performed in triplicate andanalyzed by GraphPad.Prism.

데이터 출처 [ PLoS One , 2013 , 8, e59315 ]

Relative effect of pharmacological HSP90 inhibition by (B) onalespib (AT13387, 10-40 nM) on the viability of FANCA wild-type and FANCA null cells under normal conditions or with increasing concentrations of MMC. Left panels indicate the effects of the indicated inhibitor on cell growth; middle panels the effects onMMCtolerance in FANCA-wild-type cells; right panels the effects onMMCtolerance in FANCA null cells Data presented as the mean ± SEM from 2 independent experiments.

데이터 출처 [ , , Cell, 2017, 168(5):856-866 ]

The cultured cells were pretreated with the indicated doses of onalespib for 60 min, and then stimulated by 10 μM of PGF2α or vehicle for 10 min. The cell extracts were then subjected to SDS-PAGE with subsequent Western blot analysis with antibodies against phospho-specific p38 MAP kinase or p38 MAP kinase. The histogram shows the quantitative representations of the levels of phosphorylated p38 MAP kinase after normalization with respect to p38 MAP kinase obtained from laser densitometric analysis. The levels were expressed as the fold increase to the basal levels presented as lane 1. Each value represents the mean ± S.E.M. of triplicate determinations from three independent cell preparations. *p<0.05 compared to the value of control. **p<0.05 compared to the value of PGF2α alone.

데이터 출처 [ , , PLoS One, 2017, 12(5):e0177878 ]

Selleck's Onalespib (AT13387) 인용됨 34 출판물

In Vivo Visualization and Quantification of Brain Heat Shock Protein 90 with [11C]HSP990 in Healthy Aging and Neurodegeneration [ J Nucl Med, 2025, jnumed.124.268961] PubMed: 40306968
Enhancing glioblastoma therapy: unveiling synergistic anticancer effects of Onalespib - radiotherapy combination therapy [ Front Oncol, 2025, 15:1451156] PubMed: 39949745
Radiosynthesis and Evaluation of [18F]FEHSP990 as Novel PET Tracer for Hsp90 PET Imaging [ J Labelled Comp Radiopharm, 2025, 68(4):e4144] PubMed: 40219580
The HSP90 inhibitor HVH-2930 exhibits potent efficacy against trastuzumab-resistant HER2-positive breast cancer [ Theranostics, 2024, 14(6):2442-2463] PubMed: 38646654
ARF suppression by MYC but not MYCN confers increased malignancy of aggressive pediatric brain tumors [ Nature Communications, 2023, 1221-2023)] PubMed: None
ARF suppression by MYC but not MYCN confers increased malignancy of aggressive pediatric brain tumors [ Nat Commun, 2023, 14(1):1221] PubMed: 36869047
Enhanced Therapeutic Effects of 177Lu-DOTA-M5A in Combination with Heat Shock Protein 90 Inhibitor Onalespib in Colorectal Cancer Xenografts [ Cancers (Basel), 2023, 15(17)4239] PubMed: 37686514
Combination therapy of tyrosine kinase inhibitor sorafenib with the HSP90 inhibitor onalespib as a novel treatment regimen for thyroid cancer [ Sci Rep, 2023, 10.1038/s41598-023-43486-z] PubMed: 37803074
Combination therapy of tyrosine kinase inhibitor sorafenib with the HSP90 inhibitor onalespib as a novel treatment regimen for thyroid cancer [ Sci Rep, 2023, 13(1):16844] PubMed: 37803074
Radiosynthesis and preclinical evaluation of [11C]SNX-ab as an Hsp90α,β isoform-selective PET probe for in vivo brain and tumour imaging [ EJNMMI Radiopharm Chem, 2023, 8(1):2] PubMed: 36715827

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