Home Cytoskeletal Signaling HSP inhibitor Ganetespib (STA-9090)

연구용

Ganetespib (STA-9090) HSP90 Inhibitor

제품 번호: S1159

Ganetespib (STA-9090) is an HSP90 inhibitor with IC50 of 4 nM in OSA 8 cells, induces apoptosis of OSA cells while normal osteoblasts are not affected; active metabolite of STA-1474. Phase 3.
Ganetespib (STA-9090) HSP inhibitor Chemical Structure

화학 구조

분자량: 364.4

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품질 관리 (Quality Control)

배치: 순도: 99.97%
99.97

세포 배양, 처리 및 작업 농도
(Cell Culture, Treatment & Working Concentration)

세포주 분석 유형 농도 배양 시간 제형 활성 설명 PMID
NCI-H1975 Growth Inhibition Assay 72 h IC50=8 nM 22144665
NCI-H1975 Growth Inhibition Assay 48 h IC50=16 nM 22144665
Calu-6 Growth Inhibition Assay IC50=64 nM 23012248
Calu-1 Growth Inhibition Assay IC50=58 nM 23012248
H2122 Growth Inhibition Assay IC50=53 nM 23012248
A549 Growth Inhibition Assay IC50=43 nM 23012248
H358 Growth Inhibition Assay IC50=29 nM 23012248
H1734 Growth Inhibition Assay IC50=28 nM 23012248
H727 Growth Inhibition Assay IC50=28 nM 23012248
COR-L23 Growth Inhibition Assay IC50=22 nM 23012248
H1792 Growth Inhibition Assay IC50=20 nM 23012248
H2009 Growth Inhibition Assay IC50=19 nM 23012248
SK-LU-1 Growth Inhibition Assay IC50=18 nM 23012248
H2212 Growth Inhibition Assay IC50=17 nM 23012248
H441 Growth Inhibition Assay IC50=14 nM 23012248
H2030 Growth Inhibition Assay IC50=12 nM 23012248
H23 Growth Inhibition Assay IC50=11 nM 23012248
HOP-62 Growth Inhibition Assay IC50=11 nM 23012248
IA-LM Growth Inhibition Assay IC50=10 nM 23012248
H460 Growth Inhibition Assay IC50=8 nM 23012248
H157 Growth Inhibition Assay IC50=7 nM 23012248
H1355 Growth Inhibition Assay IC50=5 nM 23012248
VCaP Growth Inhibition Assay IC50=7 nM 23152004
LNCaP Growth Inhibition Assay IC50=8 nM 23152004
Ramos-RA1 Growth Inhibition Assay IC50=7.4 nM 23303741
Karpas-299 Growth Inhibition Assay IC50=9.6 nM 23303741
Kasumi-1 Growth Inhibition Assay IC50=5.8 nM 23303741
CCRF-CEM (2) Growth Inhibition Assay IC50=7.2 nM 23303741
CCRF-CEM (1) Growth Inhibition Assay IC50=12.5 nM 23303741
MOLT-4 Growth Inhibition Assay IC50=10.6 nM 23303741
RS4;11 Growth Inhibition Assay IC50=13.5 nM 23303741
COG-LL-317 Growth Inhibition Assay IC50=4.4 nM 23303741
NALM-6 Growth Inhibition Assay IC50=11.7 nM 23303741
CHLA-136 Growth Inhibition Assay IC50=23.2 nM 23303741
CHLA-90 Growth Inhibition Assay IC50=22.3 nM 23303741
NB-EBc1 Growth Inhibition Assay IC50=16.8 nM 23303741
NB-1643 Growth Inhibition Assay IC50=7.4 nM 23303741
SJ-GBM2 Growth Inhibition Assay IC50=12.9 nM 23303741
CHLA-258 Growth Inhibition Assay IC50=6.4 nM 23303741
CHLA-10 Growth Inhibition Assay IC50=5.7 nM 23303741
CHLA-9 Growth Inhibition Assay IC50=4.6 nM 23303741
TC-71 Growth Inhibition Assay IC50=4.5 nM 23303741
CHLA-266 Growth Inhibition Assay IC50=27.1 nM 23303741
BT-12 Growth Inhibition Assay IC50=14.3 nM 23303741
Rh30 Growth Inhibition Assay IC50=5.6 nM 23303741
Rh18 Growth Inhibition Assay IC50=6.2 nM 23303741
Rh41 Growth Inhibition Assay IC50=10.4 nM 23303741
RD Growth Inhibition Assay IC50=8 nM 23303741
K033 Apoptosis Assay 100 nM 72 h significantly induces apoptosis 23418523
M23 Apoptosis Assay 100 nM 72 h significantly induces apoptosis 23418523
K029 Apoptosis Assay 100 nM 72 h significantly induces apoptosis 23418523
K028 Apoptosis Assay 100 nM 72 h significantly induces apoptosis 23418523
K008 Apoptosis Assay 100 nM 72 h significantly induces apoptosis 23418523
K033 Function Assay 250 nM 24 h induces a modest increase in G1 population 23418523
M23 Function Assay 250 nM 24 h induces G1 and G2/M arrest 23418523
K029 Function Assay 250 nM 24 h induces G1 arrest 23418523
K028 Function Assay 250 nM 24 h induces G2 arrest 23418523
K008 Function Assay 250 nM 24 h induces G2 arrest 23418523
K033 Cell Viability Assay IC50=75.5 nM 23418523
M23 Cell Viability Assay IC50=37.5 nM 23418523
K029 Cell Viability Assay IC50=46 nM 23418523
K028 Cell Viability Assay IC50=84 nM 23418523
K008 Cell Viability Assay IC50=60 nM 23418523
H3122 Cell Viability Assay 0-1000 nM 72 h IC50=10 nM 23533265
H2228 Cell Viability Assay 0-1000 nM 72 h IC50=13 nM 23533265
A1847 Apoptosis Assay 10-100 nM 24/48/72 h induces apoptosis time and dose dependently 23900136
OVCAR-8 Apoptosis Assay 10-100 nM 24/48/72 h induces apoptosis time and dose dependently 23900136
OVCAR-5 Apoptosis Assay 10-100 nM 24/48/72 h induces apoptosis time and dose dependently 23900136
SKOV-3 Cell Viability Assay 0-1000 nM 72 h inhibits cell viability dose dependently 23900136
A1847 Cell Viability Assay 0-1000 nM 72 h inhibits cell viability dose dependently 23900136
OVCAR-8 Cell Viability Assay 0-1000 nM 72 h inhibits cell viability dose dependently 23900136
OVCAR-5 Cell Viability Assay 0-1000 nM 72 h inhibits cell viability dose dependently 23900136
H146  Function Assay 30 nM 72 h induces persistent G2/M phase arrest 24166505
GLC4 Function Assay 30 nM 72 h induces persistent G2/M phase arrest 24166505
H82 Function Assay 30 nM 72 h induces persistent G2/M phase arrest 24166505
AC3 Growth Inhibition Assay IC50=25.9 nM 24166505
H1173 Growth Inhibition Assay IC50=12.62 nM 24166505
H792 Growth Inhibition Assay IC50=45.07 nM 24166505
H620 Growth Inhibition Assay IC50=32.67 nM 24166505
N592 Growth Inhibition Assay IC50=14.12 nM 24166505
H526 Growth Inhibition Assay IC50=21.64 nM 24166505
H187 Growth Inhibition Assay IC50=24.99 nM 24166505
H146 Growth Inhibition Assay IC50=28.51 nM 24166505
H128 Growth Inhibition Assay IC50=69.55 nM 24166505
H69 Growth Inhibition Assay IC50=83.36 nM 24166505
GLC4 Growth Inhibition Assay IC50=20.47 nM 24166505
H82 Growth Inhibition Assay IC50=30.27 nM 24166505
MDA-MB-231 Function Assay 100 nM 24 h inhibits the migratory and invasive capacity  24173541
BT-20  Function Assay 100/250 nM 24 h resulted in a dose-dependent destabilization of EGFR, IGF-IR, MET, and CRAF 24173541
MDA-MB-435 Function Assay 100 nM 30 min inhibits accumulation of HIF-1α 24248265
MDA-MB-231 Function Assay 100 nM 30 min inhibits accumulation of HIF-1α 24248265
HCC2998 Growth Inhibition Assay IC50=128 nM 24682747
SK-CO-1 Growth Inhibition Assay IC50=81 nM 24682747
LS-123 Growth Inhibition Assay IC50=73 nM 24682747
SNU-C2B Growth Inhibition Assay IC50=45 nM 24682747
LS-1034 Growth Inhibition Assay IC50=31 nM 24682747
LoVo Growth Inhibition Assay IC50=22 nM 24682747
COLO-678 Growth Inhibition Assay IC50=21 nM 24682747
NCI-H747 Growth Inhibition Assay IC50=17 nM 24682747
COLO-205 Growth Inhibition Assay IC50=14 nM 24682747
HCT 116 Growth Inhibition Assay IC50=14 nM 24682747
HuTu-80 Growth Inhibition Assay IC50=13 nM 24682747
HCT-15 Growth Inhibition Assay IC50=8 nM 24682747
SW620 Growth Inhibition Assay IC50=8 nM 24682747
LS-411 N Growth Inhibition Assay IC50=5 nM 24682747
RKO Growth Inhibition Assay IC50=4 nM 24682747
SW780 Growth Inhibition Assay IC50=3451 nM 24784839
RT4 Growth Inhibition Assay IC50=1733 nM 24784839
TCCSUP Growth Inhibition Assay IC50=142 nM 24784839
MGH-U3 Growth Inhibition Assay IC50=53 nM 24784839
HT-1197 Growth Inhibition Assay IC50=53 nM 24784839
5637 Growth Inhibition Assay IC50=44 nM 24784839
35612 Growth Inhibition Assay IC50=38 nM 24784839
KU-19-19 Growth Inhibition Assay IC50=36 nM 24784839
LB831-BLC Growth Inhibition Assay IC50=34 nM 24784839
UM-UC3 Growth Inhibition Assay IC50=33 nM 24784839
647-V Growth Inhibition Assay IC50=27 nM 24784839
HT-1376 Growth Inhibition Assay IC50=21 nM 24784839
J82 Growth Inhibition Assay IC50=18 nM 24784839
BFTC Growth Inhibition Assay IC50=17 nM 24784839
SCaBER Growth Inhibition Assay IC50=10 nM 24784839
639-V Growth Inhibition Assay IC50=10 nM 24784839
RT112 Growth Inhibition Assay IC50=9 nM 24784839
T24 Growth Inhibition Assay IC50=7 nM 24784839
SW-1710 Growth Inhibition Assay IC50=6 nM 24784839
DSH1 Growth Inhibition Assay IC50=6 nM 24784839
CAL27 Cytoxicity Assay 10/50 nM 24 h decreases cell proliferation dose dependently 25205430
Detroit562 Cytoxicity Assay 10/50 nM 24 h decreases cell proliferation dose dependently 25205430
FUDA Cytoxicity Assay 10/50 nM 24 h decreases cell proliferation dose dependently 25205430
SCC25 Cytoxicity Assay 10/50 nM 24 h decreases cell proliferation dose dependently 25205430
HT-29 Function Assay 50nM 24 h DMSO induced G0/G1 arrest 25210794
HCT-116 Function Assay 50nM 24 h DMSO induced G0/G1 arrest 25210794
MGC-803 Function Assay 0.1-1000 nM 24 h induces G2/M cell-cycle arrest 25590805
MKN-28 Cell Viability Assay 0.1-1000 nM 72 h inhibits cell viability dose dependently 25590805
SGC-7901 Cell Viability Assay 0.1-1000 nM 72 h inhibits cell viability dose dependently 25590805
MGC-803 Cell Viability Assay 0.1-1000 nM 72 h inhibits cell viability dose dependently 25590805
MV411 Apoptosis Assay 30/80/150/250 nM 24/48/72 h induces dose dependant induction of apoptosis 25882550
HL60 Apoptosis Assay 30/80/150/250 nM 24/48/72 h induces dose dependant induction of apoptosis 25882550
TC32 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells 29435139
A673 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells 29435139
Saos-2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells 29435139
BT-37 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells 29435139
RD qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells 29435139
SK-N-SH qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells 29435139
NB1643 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells 29435139
OHS-50 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells 29435139
A673 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for A673 cells) 29435139
SJ-GBM2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells 29435139
SK-N-MC qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells 29435139
NB-EBc1 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells 29435139
LAN-5 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells 29435139
Rh18 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 cells 29435139
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화학 정보, 보관 및 안정성 (Chemical Information, Storage & Stability)

분자량 364.4 화학식

C20H20N4O3

 보관 (수령일로부터)
CAS 번호 888216-25-9 SDF 다운로드 원액 보관

동의어 N/A Smiles CC(C)C1=C(C=C(C(=C1)C2=NNC(=O)N2C3=CC4=C(C=C3)N(C=C4)C)O)O

용해도 (Solubility)

In vitro
배치:

DMSO : 40 mg/mL (109.76 mM)
(수분으로 오염된 DMSO는 용해도를 감소시킬 수 있습니다. 신선하고 무수 DMSO를 사용하십시오.)

Ethanol : 9 mg/mL

Water : Insoluble

몰농도 계산기

질량 농도 부피 분자량
희석 계산기 분자량 계산기

In vivo
배치:

생체 내 제형 계산기 (투명한 용액)

1단계: 아래 정보 입력 (권장: 실험 중 손실을 고려하여 추가 동물 포함)

mg/kg g μL

2단계: 생체 내 제형 입력 (이것은 계산기일 뿐 제형이 아닙니다. 용해도 섹션에 생체 내 제형이 없는 경우 먼저 당사에 문의하십시오.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

계산 결과:

작업 농도: mg/ml;

DMSO 원액 준비 방법: mg 약물 사전 용해 μL DMSO ( 원액 농도 mg/mL, 농도가 해당 약물 배치의 DMSO 용해도를 초과하는 경우 먼저 당사에 문의하십시오. )

생체 내 제형 준비 방법: 취하다 μL DMSO 원액, 다음 추가μL PEG300, 혼합하고 투명하게 한 다음 추가μL Tween 80, 혼합하고 투명하게 한 다음 추가 μL ddH2O, 혼합하고 투명하게 합니다.

생체 내 제형 준비 방법: 취하다 μL DMSO 원액, 다음 추가 μL 옥수수 기름, 혼합하고 투명하게 합니다.

참고: 1. 다음 용매를 추가하기 전에 액체가 투명한지 확인하십시오.
2. 용매를 순서대로 추가해야 합니다. 다음 용매를 추가하기 전에 이전 추가에서 얻은 용액이 투명한 용액인지 확인해야 합니다. 와동, 초음파 또는 뜨거운 물 중탕과 같은 물리적 방법을 사용하여 용해를 도울 수 있습니다.

작용 메커니즘 (Mechanism of Action)

Targets/IC50/Ki
HSP90
(OSA 8 cells)
4 nM
시험관 내(In vitro)
The 50% inhibitory concentrations (IC50) for Ganetespib (STA-9090) against malignant mast cell lines are 10-50 times lower than that for 17-AAG, indicating that triazolone class of HSP90 inhibitors likely exhibits greater potency than geldanamycin based inhibitors. This compound inhibits MG63 cell lines with IC50 of 43 nM. It binds to the ATP-binding domain at the N-terminus of Hsp90 and serves as a potent Hsp90 inhibitor by causing degradation of multiple oncogenic Hsp90 client proteins including HER2/neu, mutated EGFR, Akt, c-Kit, IGF-1R, PDGFRα, Jak1, Jak2, STAT3, STAT5, HIF-1α, CDC2 and c-Met as well as Wilms' tumor 1. At low nanomolar concentrations, it potently arrests cell proliferation and induces apoptosis in a wide variety of human cancer cell lines, including many receptor tyrosine kinase inhibitor- and tanespimycin-resistant cell lines. It exhibits potent cytotoxicity in a range of solid and hematologic tumor cell lines, including those that express mutated kinases that confer resistance to small-molecule tyrosine kinase inhibitors. Its treatment rapidly caused the degradation of known Hsp90 client proteins, exhibits superior potency to the ansamycin inhibitor 17-AAG, and shows sustained activity even with short exposure times. In anohter study, it induces apoptosis of malignant canine mast cell lines. It is active at significantly lower concentrations for C2 and BR canine malignant mast cells with IC50 of 19 and 4 nM, respectively, while 17-AAG inhibits C2 and BR canine malignant mast cells with IC50 of 958 and 44 nM, respectively. Both the expression of WT and mutant Kit are downregulated by 100 nM of this compound after 24 hours in all lines treated including C2 and BMCMCs cells. However, no effects on PI3K or HSP90 expression are observed following treatment with it.
생체 내(In vivo)
Administration of Ganetespib (STA-9090) leads to significant tumor shrinkage in several tumor xenograft models in mice and appears to be less toxic. Furthermore, this compound demonstrated better tumor penetration compared with tanespimycin. It inhibits in vivo tumor growth in both malignant mast cell and OSA xenograft models. Ganetespib significantly inhibits tumor growth when dosed with two repeating cycles of 25 mg/kg/day for 3 days, with a %T/C value of 18. It is well-tolerated, with the vehicle and Ganetespib groups having average bodyweight changes relative to the start of the study of +0.3% and -8.1% on day 17, respectively.
참조
  • [4] https://pubmed.ncbi.nlm.nih.gov/18657349/

적용 분야 (Applications)

방법 바이오마커 이미지 PMID
Western blot EGFR / c-Met / IGF-1Rβ/ Akt / p-Akt / ERK / p-ERK p27(Kip1) / p21 (Cip1) / Cyclin D1 / Cyclin E / Cyclin B1 / CDK1 / CDK2 / CDK4 Survivin / Bcl-2 / Bcl-xl / Mcl-1 B-RAF / C-RAF / N-RAS HER2 / p-STAT3 / BIM CDK1 / Cyclin D1 / Cyclin B1 / p27 c-PARP / c-caspase 3 / caspase 8 / c-caspase 8 / caspase 9 / c-caspase 9 ErbB2 / pErbB2 / Src / pSrc / mTOR / pmTOR / Bad / pBad / GSK3 / pGSK3 Wee1 / p-Wee1 / Chk1 / p-Chk1
S1159-WB1
23418523
Growth inhibition assay Cell viability
S1159-viability1
23418523

임상시험 정보 (Clinical Trial Information)

(데이터 출처 https://clinicaltrials.gov, 업데이트 날짜 2024-05-22)

NCT 번호 모집 조건 스폰서/협력자 시작일 단계
NCT02192541 Terminated
Neoplasms
National Cancer Institute (NCI)|National Institutes of Health Clinical Center (CC)
 December 2 2014 Phase 1
NCT02008877 Completed
Malignant Peripheral Nerve Sheath Tumors (MPNST)|Sarcoma
Sarcoma Alliance for Research through Collaboration|Synta Pharmaceuticals Corp.|United States Department of Defense
 December 2013 Phase 1|Phase 2

자주 묻는 질문 (Frequently Asked Questions)

질문 1:
Does this inhibitor inhibit both isoforms of HSP90?

답변:
We don't have the information now and it is not very clear in the literature either. From following two references, it indicates that it might be specific to the alpha form “It binds to the ATP binding site of Hsp90 alpha with a Kd of 110 nM” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3477583/