Home Cytoskeletal Signaling Antineoplastic and Immunosuppressive Antibiotics 억제제 Geldanamycin (NSC 122750)

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Geldanamycin (NSC 122750) HSP90 억제제

제품 번호S2713

Geldanamycin은 Kd 1.2 μM의 천연 HSP90 억제제로, 글루코코르티코이드 수용체(GR)/HSP 결합을 특이적으로 방해합니다. Geldanamycin은 숙주의 염증 반응을 줄임으로써 바이러스 감염으로 인한 ALI(급성 폐 손상)/ARDS(급성 호흡 곤란 증후군)를 완화합니다.
Geldanamycin (NSC 122750) Antineoplastic and Immunosuppressive Antibiotics 억제제 Chemical Structure

화학 구조

분자량: 560.64

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품질 관리

배치: 순도: 99.96%
99.96

세포 배양, 처리 및 작업 농도

세포주 분석 유형 농도 배양 시간 제형 활성 설명 PMID
A2780 cells Proliferation assay Compound was evaluated for antiproliferative activity against human ovarian carcinoma cell line A2780, IC50=3.4 μM 11514145
SW620 cell Growth inhibition assay Inhibitory concentration against human colorectal carcinoma SW620 cell lines, IC50=6.2 nM 15658879
MCF-7 cell Growth inhibition assay Inhibitory concentration against human breast cancer MCF-7 cell lines, IC50=6.5 nM 15658879
K562 cell Growth inhibition assay Inhibitory concentration against human leukemia K562 cell lines, IC50=22.1 nM 15658879
HT-29 cell Growth inhibition assay Inhibitory concentration against human colorectal carcinoma HT-29 cell lines, IC50=24.5 nM 15658879
SK-BR-3 Function assay 50 mg/kg Inhibition of oncogene product p185 erbB-2 from human breast cancer cells(SK-BR-3 cells) at 50 mg/kg dose, IC50=0.07μM 7562911
SK-BR-3 Function assay In vitro inhibition of p185 erbB-2 oncoprotein in human breast cancer SK-BR-3 cells, IC50=0.07μM 7562912
MCF-7 Function assay Inhibition of steady-state expression of HER2 in MCF-7 breast cancer cells, IC50=0.05μM 10340605
MCF-7 Function assay Inhibition of steady-state expression of ER in MCF-7 breast cancer cells, IC50=0.06μM 10340605
MCF-7 Function assay Inhibition of steady-state expression of Raf-1 in MCF-7 breast cancer cells, IC50=0.2μM 10340605
SKBR-3 Function assay Effective concentration for Her-2 degradation in SKBR-3 cells, Concentration=5μM 15713410
HEK293 Function assay Inhibition of HSP90 expressed in HEK293 cells assessed as effect on Akt1:p27 interaction complexes by EYFP and/or YFP Venus fragment based reporter gene assay 16680159
LS174T Cytotoxicity assay Cytotoxicity against human LS174T cells by MTS assay, IC50=0.45μM 17034135
rat neuronal cells Cytotoxicity assay 10 uM 24 hrs Cytotoxicity against rat neuronal cells at 10 uM after 24 hrs 17276679
P19 Cytotoxicity assay 18 hrs Cytotoxicity against mouse P19 cells after 18 hrs, IC50=0.1μM 17442565
MCF7 Growth inhibition assay Growth inhibition of human MCF7 cells after days by SRB assay, GI50=35.6μM 17869098
HCT116 Growth inhibition assay Growth inhibition of human HCT116 cells, GI50=0.021μM 18243703
DLD1 Growth inhibition assay Growth inhibition of human DLD1 cells, GI50=0.037μM 18243703
KPL4 Growth inhibition assay Growth inhibition of human KPL4 cells, GI50=0.059μM 18243703
A549 Growth inhibition assay Growth inhibition of human A549 cells, GI50=0.064μM 18243703
KPL4 Function assay 40 hrs Inhibition of Hsp90 in human KPL4 cells assessed as depletion of ErbB2 level after 40 hrs, MEC=0.11μM 18243703
KPL4 Function assay 40 hrs Inhibition of Hsp90 in human KPL4 cells assessed as depletion of Raf-1 level after 40 hrs, MEC=0.33μM 18243703
Jurkat Function assay 1 uM Inhibition of to HSP90 in FADD deficient human Jurkat cells assessed as RIP protein degradation at 1 uM by Western blot 18408713
HEK293T Function assay Inhibition of TNF-alpha-induced NF-kappaB activation expressed in HEK293T cells by luciferase reporter gene assay 18408713
Jurkat Function assay Inhibition of TNF-alpha-induced NF-kappaB activation expressed in FADD deficient human Jurkat cells by luciferase reporter gene assay 18408713
SKBR3 Function assay 24 hrs Inhibition of Hsp90-mediated HER2 degradation in human SKBR3 cells after 24 hrs by Western blot 18816111
SKBR3 Function assay 24 hrs Inhibition of Hsp90-mediated Raf degradation in human SKBR3 cells after 24 hrs by Western blot 18816111
HuH7 Antiviral assay 3 days Antiviral activity against Hepatitis C virus genotype 1b Con1 infected in human HuH7 cells assessed as GAPDH RNA or 18S rRNA level after 3 days by qRT-PCR analysis, EC50=0.00025μM 18936191
HuH7 Antiviral assay 3 days Antiviral activity against Hepatitis C virus genotype 1b Con1 infected in human HuH7 cells assessed as GAPDH RNA or 18S rRNA level after 3 days selected with 40 nM HCV-796 and 800 nM boceprevir by qRT-PCR analysis, EC50=0.0012μM 18936191
SH-SY5Y Neuroprotection assay Neuroprotection against beta-amyloid peptide 1-42-induced toxicity in human SH-SY5Y cells assessed as lactate dehydrogenase release, EC50=0.04269μM 19138859
SH-SY5Y Neuroprotection assay 10 nM Neuroprotection against beta-amyloid peptide 1-42-induced toxicity in retinoic acid-differentiated human SH-SY5Y cells assessed as lactate dehydrogenase release at 10 nM 19138859
SKBR3 Cytotoxicity assay 72 hrs Cytotoxicity against human SKBR3 cells after 72 hrs by celltiter-glo assay, IC50=0.041μM 19405528
MCF7 Cytotoxicity assay Cytotoxicity against human MCF7 cells by SRB assay, IC50=9.6μM 19560353
SK-BR-3 Antiproliferative assay Antiproliferative activity against human SK-BR-3 cells, IC50=0.0158μM 19896848
MCF7 Antiproliferative assay Antiproliferative activity against human MCF7 cells, IC50=0.0161μM 19896848
A431 Antiproliferative assay 72 hrs Antiproliferative activity against human A431 cells after 72 hrs, IC50=0.2μM 20655237
PP30 Function assay 100 uM 3 hrs Inhibition of human HSP90alpha expressed in yeast PP30 cells co-expressing HSF-lacZ reporter assessed as induction of heat shock response at 100 uM after 3 hrs 21129982
MCF7 Function assay 0.5 uM Inhibition of Hsp90 in human MCF7 cells assessed as Akt degradation at 0.5 uM by Western blot analysis 21273068
MCF7 Function assay 0.5 uM Inhibition of Hsp90 in human MCF7 cells assessed as Raf degradation at 0.5 uM by Western blot analysis 21273068
MCF7 Function assay 0.5 uM Inhibition of Hsp90 in human MCF7 cells assessed as Hsp90 degradation at 0.5 uM by Western blot analysis 21273068
MCF7 Function assay 0.5 uM Inhibition of Hsp90 in human MCF7 cells assessed as Her2 degradation at 0.5 uM by Western blot analysis 21273068
HCT116 Antiproliferative assay 4 days Antiproliferative activity against human HCT116 cells measured on day 4 by Cell titer-glo assay, EC50=0.03μM 21420297
HCT116 Antiproliferative assay Antiproliferative activity against human HCT116 cells by luminescence assay, EC50=0.03μM 21605975
U87 Antiproliferative assay Antiproliferative activity against human U87 cells by luminescence assay, EC50=0.089μM 21605975
HCT116 Antiproliferative assay Antiproliferative activity against human HCT116 cells, IC50=0.03μM 21715165
NCI-H1975 Antiproliferative assay Antiproliferative activity against human NCI-H1975 cells, IC50=0.036μM 21715165
U87MG Antiproliferative assay Antiproliferative activity against human U87MG cells, IC50=0.089μM 21715165
MCF7 Function assay 500 nM 24 hrs Inhibition of Hsp90 in human MCF7 cells assessed as induction of Her2 degradation at 500 nM after 24 hrs by Western blot method 21861487
MCF7 Function assay 500 nM 24 hrs Inhibition of Hsp90 in human MCF7 cells assessed as induction of Raf degradation at 500 nM after 24 hrs by Western blot method 21861487
MCF7 Function assay 500 nM 24 hrs Inhibition of Hsp90 in human MCF7 cells assessed as induction of Akt degradation at 500 nM after 24 hrs by Western blot method 21861487
MCF7 Cytotoxicity assay 72 hrs Cytotoxicity against human MCF7 cells at 72 hrs by MTS assay, IC50=0.053μM 22162786
HepG2 Cytotoxicity assay Cytotoxicity against human HepG2 cells, IC50=0.37μM 22849774
SKBR3 Antiproliferative assay 72 hrs Antiproliferative activity against estrogen receptor deficient human SKBR3 cells after 72 hrs, IC50=0.0085μM 23648180
MCF7 Antiproliferative assay 72 hrs Antiproliferative activity against human MCF7 cells expressing estrogen receptor after 72 hrs, IC50=0.0098μM 23648180
HepG2 Cytotoxicity assay Cytotoxicity against human HepG2 cells by MTT assay, IC50=0.3μM 23656556
SKBR3 Function assay 0.5 uM 18 hrs Inhibition of HSP90 in human SKBR3 cells assessed as aggregation of intracellular HER2 at 0.5 uM after 18 hrs by DAPI staining-based immunofluorescence microscopic analysis 23859777
A549 Cytotoxicity assay 2 days Cytotoxicity against human A549 cells after 2 days by AlamarBlue assay, IC50=0.15μM 23947794
CL1-5 Function assay 2 uM 16 hrs Inhibition of HSP90 in human CL1-5 cells assessed as reduction of total Akt at 2 uM after 16 hrs by Western blotting analysis 24428777
L6 Cytotoxicity assay 72 hrs Cytotoxicity against rat L6 cells after 72 hrs by Alamar Blue assay, IC50=6μM 24580531
Sf9 Function assay 16 hrs Displacement of GM-BODIPY from human full length HSP90 alpha expressed in baculovirus-infected Sf9 cells after 16 hrs by fluorescence polarization assay, IC50=0.074μM 24751441
MDA-kb2 Function assay 18 hrs Inhibition of HSP90 in human MDA-kb2 cells assessed as reduction in glucocorticoid receptor-dependent luciferase expression after 18 hrs by firefly luciferase reporter gene assay, IC50<0.01μM 24984936
MCF7 Antiproliferative assay 72 hrs Antiproliferative activity against human MCF7 cells assessed as growth inhibition after 72 hrs by MTS/PMS assay, IC50=0.04μM 25075762
MDA-MB-231 Cytotoxicity assay 72 hrs Cytotoxicity against human MDA-MB-231 cells after 72 hrs by MTT assay, IC50=0.05μM 25105924
LNCAP Cytotoxicity assay 72 hrs Cytotoxicity against human LNCAP cells after 72 hrs by MTT assay, IC50=0.43μM 25105924
MDA-MB 231 Function assay 0.5 and 5 uM Inhibition of HSP90 in human MDA-MB 231 cells assessed increase in HSP70 protein levels at 0.5 and 5 uM by Western blot method 25105924
HUVEC Cytotoxicity assay 72 hrs Cytotoxicity against HUVEC cells after 72 hrs by MTT assay, IC50=0.019μM 25277067
A431 Cytotoxicity assay 72 hrs Cytotoxicity against human A431 cells after 72 hrs by MTT assay, IC50=0.04μM 25277067
BGC823 Cytotoxicity assay 72 hrs Cytotoxicity against human BGC823 cells after 72 hrs by MTT assay, IC50=0.04μM 25277067
HepG2 Cytotoxicity assay 72 hrs Cytotoxicity against human HepG2 cells after 72 hrs by MTT assay, IC50=0.04μM 25277067
MDA-MB-231 Cytotoxicity assay 72 hrs Cytotoxicity against human MDA-MB-231 cells after 72 hrs by MTT assay, IC50=0.05μM 25277067
A549 Cytotoxicity assay 72 hrs Cytotoxicity against human A549 cells after 72 hrs by MTT assay, IC50=0.097μM 25277067
HL7702 Cytotoxicity assay 72 hrs Cytotoxicity against human HL7702 cells after 72 hrs by MTT assay, IC50=0.141μM 25277067
SW480 Cytotoxicity assay 72 hrs Cytotoxicity against human SW480 cells after 72 hrs by MTT assay, IC50=0.31μM 25277067
HeLa Cytotoxicity assay 72 hrs Cytotoxicity against human HeLa cells after 72 hrs by MTT assay, IC50=0.798μM 25277067
MDA-MB 231 Function assay 0.5 uM 24 hrs Inhibition Hsp90 in human MDA-MB 231 cells assessed as increase in HSP70 protein level at 0.5 uM incubated for 24 hrs by Western blot method 25277067
MCF7 Cytotoxicity assay 72 hrs Cytotoxicity against human MCF7 cells assessed as growth inhibition after 72 hrs by MTS/PMS assay, IC50=0.0427μM 25756299
MCF7 Function assay 24 hrs Inhibition of HSP90 in human MCF7 cells assessed as pAkt degradation at 5 times IC50 after 24 hrs by Western blot analysis 25756299
MCF7 Function assay 24 hrs Inhibition of HSP90 in human MCF7 cells assessed as Her2 degradation at 5 times IC50 after 24 hrs by Western blot analysis 25756299
MCF7 Function assay 24 hrs Inhibition of HSP90 in human MCF7 cells assessed as Cdk6 degradation at 5 times IC50 after 24 hrs by Western blot analysis 25756299
MCF7 Function assay 24 hrs Inhibition of HSP90 in human MCF7 cells assessed as Raf degradation at 5 times IC50 after 24 hrs by Western blot analysis 25756299
MCF7 Function assay 24 hrs Change in Cdc37 expression in human MCF7 cells at 5 times IC50 after 24 hrs by Western blot analysis 25756299
MCF7 Function assay 24 hrs Change in p23 expression in human MCF7 cells at 5 times IC50 after 24 hrs by Western blot analysis 25756299
MCF7 Function assay 24 hrs Inhibition of HSP90 in human MCF7 cells assessed as induction of heat shock response-mediated HSP90 production at 5 times IC50 after 24 hrs by Western blot analysis relative to vehicle-treated control 25756299
MCF7 Function assay 24 hrs Inhibition of HSP90 in human MCF7 cells assessed as induction of heat shock response-mediated HSP70 production at 5 times IC50 after 24 hrs by Western blot analysis relative to vehicle-treated control 25756299
MCF7 Function assay 24 hrs Inhibition of HSP90 in human MCF7 cells assessed as induction of heat shock response-mediated HSP27 production at 5 times IC50 after 24 hrs by Western blot analysis relative to vehicle-treated control 25756299
PC12 Function assay 10 uM 3 to 16 hrs Inhibition of D-aspartate biosynthesis in rat PC12 cells assessed as reduction of intracellular D-aspartate content at 10 uM measured at 3 to 16 hrs by O-phthalaldehyde/N-acetyl-L-cysteine derivatization technique-based HPLC analysis relative to vehicle-t 26642769
PC12 Function assay 10 uM 6 to 16 hrs Inhibition of D-aspartate biosynthesis in rat PC12 cells assessed as reduction of total D-aspartate content at 10 uM measured at 6 to 16 hrs by O-phthalaldehyde/N-acetyl-L-cysteine derivatization technique-based HPLC analysis relative to vehicle-treated c 26642769
PC12 Function assay 24 hrs Inhibition of D-aspartate biosynthesis in rat PC12 cells assessed as reduction of intracellular D-aspartate level up to 10 uM after 24 hrs by O-phthalaldehyde/N-acetyl-L-cysteine derivatization technique-based HPLC analysis 26642769
PC12 Function assay up to 10 uM 24 hrs Inhibition of D-aspartate biosynthesis in rat PC12 cells assessed as reduction of D-aspartate level in cell culture medium up to 10 uM after 24 hrs by O-phthalaldehyde/N-acetyl-L-cysteine derivatization technique-based HPLC analysis 26642769
A549 Function assay 12 to 24 hrs Inhibition of Hsp90 in human A549 cells assessed as decrease in EGFR levels at five times IC50 value after 12 to 24 hrs by Western blot analysis 26745854
A549 Function assay 12 to 24 hrs Inhibition of Hsp90 in human A549 cells assessed as decrease in Her2 levels at five times IC50 value after 12 to 24 hrs by Western blot analysis 26745854
A549 Function assay 12 to 24 hrs Inhibition of Hsp90 in human A549 cells assessed as decrease in C-Raf levels at five times IC50 value after 12 to 24 hrs by Western blot analysis 26745854
SKBR3 Function assay Inhibition of Hsp90 in human SKBR3 cells, IC50=0.07μM 26844689
BA/F3 Function assay 48 hrs Inhibition of imatinib-resistant BCR-ABL T315I mutant (unknown origin) expressed in mouse BA/F3 cells assessed as decrease in cell viability after 48 hrs by trypan blue exclusion assay, IC50=1μM 26844689
BA/F3 Function assay 48 hrs Inhibition of imatinib-resistant BCR-ABL E255K mutant (unknown origin) expressed in mouse BA/F3 cells assessed as decrease in cell viability after 48 hrs by trypan blue exclusion assay, IC50=1μM 26844689
BA/F3 Function assay 48 hrs Inhibition of BCR-ABL (unknown origin) expressed in mouse BA/F3 cells assessed as decrease in cell viability after 48 hrs by trypan blue exclusion assay, IC50=5μM 26844689
MDA-MB-231 Antiproliferative assay 72 hrs Antiproliferative activity against human MDA-MB-231 cells after 72 hrs by MTS/PMS assay, Activity=0.06μM 27003516
MDA-MB-231 Antiproliferative assay 72 hrs Antiproliferative activity against human MDA-MB-231 cells after 72 hrs by SRB assay, IC50=0.03μM 27266997
HeLa Antiproliferative assay 72 hrs Antiproliferative activity against human HeLa cells after 72 hrs by SRB assay, IC50=0.06μM 27266997
SNU638 Anticancer assay 72 hrs Anticancer activity against human SNU638 cells measured after 72 hrs by SRB assay, IC50=0.03μM 27283788
Caki1 Anticancer assay 72 hrs Anticancer activity against human Caki1 cells measured after 72 hrs by SRB assay, IC50=0.056μM 27283788
A549 Anticancer assay 72 hrs Anticancer activity against human A549 cells measured after 72 hrs by SRB assay, IC50=0.109μM 27283788
MDA-MB-231 Anticancer assay 72 hrs Anticancer activity against human MDA-MB-231 cells measured after 72 hrs by SRB assay, IC50=0.11μM 27283788
HCT116 Anticancer assay 72 hrs Anticancer activity against human HCT116 cells measured after 72 hrs by SRB assay, IC50=0.15μM 27283788
SKBR3 Antiproliferative assay 1 to 3 days Antiproliferative activity against Her2-overexpressing human SKBR3 cells after 1 to 3 days by MTS assay, GI50=0.43μM 27783977
NCI-H1975 Antiproliferative assay 1 to 3 days Antiproliferative activity against gefitinib-resistant human NCI-H1975 cells after 1 to 3 days by MTS assay, GI50=0.56μM 27783977
RPMI8226 Growth inhibition assay 72 hrs Growth inhibition of human RPMI8226 cells after 72 hrs by MTS/PMS assay, GI50=0.003μM 29057043
MDA-MB-231 Antiproliferative assay 72 hrs Antiproliferative activity against human MDA-MB-231 cells after 72 hrs by SRB assay, IC50=0.06μM 29172085
A549 Antiproliferative assay 72 hrs Antiproliferative activity against human A549 cells after 72 hrs by SRB assay, IC50=0.1μM 29172085
NCI-H1975 Antiproliferative assay 72 hrs Antiproliferative activity against human NCI-H1975 cells after 72 hrs by Cell Titer 96 Aqueous One Solution cell proliferation assay, GI50=0.56μM 29202402
A549 Function assay 5 to 10 uM 24 hrs Inhibition of HSP90alpha in human A549 cells assessed as upregulation of HSP90alpha expression at 5 to 10 uM after 24 hrs by Western blot analysis 29486954
A549 Function assay 5 to 10 uM 24 hrs Inhibition of HSP90beta in human A549 cells assessed as upregulation of HSP90beta expression at 5 to 10 uM after 24 hrs by Western blot analysis 29486954
SKBR3 Function assay 24 hrs Inhibition of HSP90 at N-terminus in human SKBR3 cells assessed as induction of Raf1 protein degradation incubated for 24 hrs by Western blot analysis 31591016
SKBR3 Function assay 24 hrs Inhibition of HSP90 at N-terminus in human SKBR3 cells assessed as induction of CDK4 protein degradation incubated for 24 hrs by Western blot analysis 31591016
SKBR3 Function assay 24 hrs Inhibition of HSP90 at N-terminus in human SKBR3 cells assessed as induction of Her2 protein degradation incubated for 24 hrs by Western blot analysis 31591016
SKBR3 Function assay 24 hrs Inhibition of HSP90 at N-terminus in human SKBR3 cells assessed as induction of AKT protein degradation incubated for 24 hrs by Western blot analysis 31591016
클릭하여 더 많은 세포주 실험 데이터 보기

화학 정보, 보관 및 안정성

분자량 560.64 화학식

C29H40N2O9

 보관 (수령일로부터)
CAS 번호 30562-34-6 SDF 다운로드 원액 보관

동의어 NSC 122750 Smiles CC1CC(C(C(C=C(C(C(C=CC=C(C(=O)NC2=CC(=O)C(=C(C1)C2=O)OC)C)OC)OC(=O)N)C)C)O)OC

용해도

In vitro
배치:

DMSO : 100 mg/mL (178.36 mM)
(수분으로 오염된 DMSO는 용해도를 감소시킬 수 있습니다. 신선하고 무수 DMSO를 사용하십시오.)

Water : Insoluble

Ethanol : 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

Targets/IC50/Ki
p185
(SKBr3 cells)
70 nM
HSP90 (N-terminal domain)
(Cell-free assay)
0.78 μM(Kd)
HSP90
(Cell-free assay)
1.2 μM(Kd)
시험관 내(In vitro)
Geldanamycin은 Hsp90의 N-말단 도메인(잔기 1-220)에 있는 ATP 결합 부위에 결합합니다. 이 화합물은 용량 의존적으로 Hsp90의 ATPase 활성을 억제합니다. 이는 A2780 인간 난소 세포주에서 용량 의존적인 G2기 정지 및 S기 진입의 가역적 억제를 유발합니다. 이러한 억제는 p53 증가를 동반하며 최종적으로 p53 의존적임이 입증되었습니다. 이 화학 물질은 p185 수용체 단백질-티로신 키나제의 폴리유비퀴틴화 및 프로테아좀 분해를 유발하며, IC50이 70 nM입니다. 이는 전형적인 항종양 시약으로, 60개 인간 종양 세포주 패널에 대해 평균 GI50이 0.18 μM입니다.
키나아제 분석
뉴클레오티드 결합의 등온 적정 열량측정(ITC)
적정 실험은 MSC 시스템을 사용하여 수행됩니다. 각 실험에서 15 μL의 Geldanamycin (1% DMSO에 300 μM) 16개 분취액이 1.3 mL의 단백질 (20 mM Tris-HCl, pH 7.5, 1 mM EDTA에 31 μM)에 25 °C에서 주입되었고, 희석열을 뺀 후 결과 데이터가 맞춰졌습니다. 희석열은 이 화합물을 완충액에 첨가하고 완충액을 단백질에 첨가하는 별도의 실험에서 결정되었습니다. 뉴클레오티드 결합 부위에서 DMSO 결합의 증거는 관찰되지 않았습니다. 적정 데이터는 세 가지 유동 변수(화학양론, 결합 상수 (Kb) 1/Kd), 및 상호작용 엔탈피 변화 (ΔH°))를 사용하여 비선형 최소 제곱 곡선 피팅 알고리즘으로 맞춰졌습니다. 이 화합물이 온전한 효모 Hsp90에 결합하는 해리 상수 추정치는 1.22 μM이며, Hsp90 N-말단 도메인에 결합하는 해리 상수는 0.78 μM입니다. C-말단 단편에 결합할 때는 의미 있는 열이 관찰되지 않았습니다.
생체 내(In vivo)
Geldanamycin (50 mg/kg)은 FRE/erbB-2 마우스에서 pl85 관련 포스포티로신 수준에 30% 억제를 보입니다.
참조
  • [4] https://pubmed.ncbi.nlm.nih.gov/7909494/
  • [5] https://pubmed.ncbi.nlm.nih.gov/7628050/
  • [6] https://pubmed.ncbi.nlm.nih.gov/7562911/

임상시험 정보

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

NCT 번호 모집 조건 스폰서/협력자 시작일 단계
NCT00003969 Completed
Unspecified Adult Solid Tumor Protocol Specific
Cancer Research UK|National Cancer Institute (NCI)
 August 1998 Phase 1

기술 지원

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