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Belinostat (PXD101) HDAC 억제제

제품 번호: S1085

Belinostat (PXD101)은 세포 무함유 분석에서 27 nM의 IC50을 보이는 새로운 HDAC 억제제이며, 시스플라틴 내성 종양에서 활성이 입증되었습니다. Belinostat (PXD101)은 autophagy를 유도합니다.
Belinostat (PXD101) HDAC 억제제 Chemical Structure

화학 구조

분자량: 318.35

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품질 관리 (Quality Control)

배치: 순도: 99.74%
99.74

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

세포주 분석 유형 농도 배양 시간 제형 활성 설명 PMID
HCT116 Function Assay 0.9 μM  24 h down-regulats TS protein levels after 6 h incubation 17124594
HCT116 Growth Inhibition Assay 48 h EC50=0.28 μM 17124594
Granta-519 Growth Inhibition Assay 24 h IC50=56.3 μM 20068080
Jeko-1 Growth Inhibition Assay 24 h IC50=0.2 μM 20068080
HBL-2 Growth Inhibition Assay 24 h IC50=0.4 μM 20068080
Panc-1  Apoptosis Assay 100/500/1000 nM 48 h induces dose dependent apoptosis 22681698
AsPC-1 Apoptosis Assay 100/500/1000 nM 48 h induces dose dependent apoptosis 22681698
T3M4 Apoptosis Assay 100/500/1000 nM 48 h induces dose dependent apoptosis 22681698
Panc-1  Growth Inhibition Assay 0-800 nM 48 h inhibits cell proliferation in a dose dependent manner 22681698
AsPC-1 Growth Inhibition Assay 0-800 nM 48 h inhibits cell proliferation in a dose dependent manner 22681698
T3M4 Growth Inhibition Assay 0-800 nM 48 h inhibits cell proliferation in a dose dependent manner 22681698
MiaPaCa2 Function Assay 1/10 μM 24 h induces growth arrested in G2/M 23475695
AsPc1 Function Assay 1/10 μM 24 h induces growth arrested in G2/M 23475695
Panc0403 Apoptosis Assay 1 μM 24 h induces apoptosis 23475695
Panc1005 Apoptosis Assay 1 μM 24 h induces apoptosis 23475695
Panc0327 Apoptosis Assay 1 μM 24 h induces apoptosis 23475695
Panc0203 Growth Inhibition Assay 48 h EC50=22.2 μM 23475695
PL45 Growth Inhibition Assay 48 h EC50=20.8 μM 23475695
Panc1005 Growth Inhibition Assay 48 h EC50=1.1 μM 23475695
Panc0403 Growth Inhibition Assay 48 h EC50=1.1 μM 23475695
BxPc3 Growth Inhibition Assay 48 h EC50=1.0 μM 23475695
MiaPaCa2 Growth Inhibition Assay 48 h EC50=0.7 μM 23475695
Panc0327 Growth Inhibition Assay 48 h EC50=0.5 μM 23475695
AsPc1 Growth Inhibition Assay 48 h EC50=0.3 μM 23475695
PC9 Function Assay 0.5/1/2 μM 4 h DMSO inhibits the levels of Akt (p-Akt) and EGFR 23515752
H1650 Function Assay 0.5/1/2 μM 4 h DMSO inhibits the levels of Akt (p-Akt) and EGFR 23515752
H460 Function Assay 0.5/1/2 μM 4 h DMSO inhibits the levels of Akt (p-Akt) and EGFR 23515752
PC9 Function Assay 500 nM 24 h DMSO decreases EGFR expression 23515752
H1650 Function Assay 500 nM 24 h DMSO decreases EGFR expression 23515752
H460 Function Assay 500 nM 24 h DMSO decreases EGFR expression 23515752
HCC4006 Growth Inhibition Assay 72 h DMSO IC50=0.46 μM 23515752
HCC2935 Growth Inhibition Assay 72 h DMSO IC50=0.97 μM 23515752
HCC827 Growth Inhibition Assay 72 h DMSO IC50=0.29 μM 23515752
HCC2279 Growth Inhibition Assay 72 h DMSO IC50=0.4 μM 23515752
PC9 Growth Inhibition Assay 72 h DMSO IC50=0.29 μM 23515752
H820 Growth Inhibition Assay 72 h DMSO IC50=0.4 μM 23515752
H1650 Growth Inhibition Assay 72 h DMSO IC50=0.88 μM 23515752
H1975 Growth Inhibition Assay 72 h DMSO IC50=0.68 μM 23515752
H520 Growth Inhibition Assay 72 h DMSO IC50=0.75 μM 23515752
H1299 Growth Inhibition Assay 72 h DMSO IC50=1.2 μM 23515752
H460 Growth Inhibition Assay 72 h DMSO IC50=0.86 μM 23515752
H1666 Growth Inhibition Assay 72 h DMSO IC50>10 μM 23515752
PANC-1 Function Assay 10 μM 2/4 h DMSO increases intracellular ROS level 23743198
PANC-1 Cell Viability Assay 1/10 μM 48 h DMSO decreases cell viability in a dose dependent manner 23743198
PANC-1 Function Assay 10 μM 2/4/6 h DMSO induces AMPK activation 23743198
HL-60  Function Assay 0.2 μM 24/48/72 h enhances RA-induced granulocytic differentiation 25864732
NB4 Function Assay 0.2 μM 24/48/72 h enhances RA-induced granulocytic differentiation 25864732
HL-60  Function Assay 2 μM 24/48 h blocks cell cycle in S phase 25864732
NB4 Function Assay 2 μM 24/48 h blocks cell cycle in S phase 25864732
HL-60  Cell Viability Assay 0.2/2 μM 24/48/72 h decreases cell viability in both time and dose dependent manner 25864732
NB4 Cell Viability Assay 0.2/2 μM 24/48/72 h decreases cell viability in both time and dose dependent manner 25864732
RAW264.7 Anti-inflammatory assay 1 hr Anti-inflammatory activity in LPS-stimulated mouse RAW264.7 cells assessed as suppression of IL6 production pre-incubated for 1 hr before LPS stimulation for 24 hrs by ELISA method, IC50 = 0.000059 μM. 25113875
HEK293 Function assay Inhibition of HDAC6 in HEK293 cells, IC50 = 0.015 μM. 18308563
HEK293 Function assay Inhibition of HDAC1 in HEK293 cells, IC50 = 0.018 μM. 18308563
HeLa Function assay 30 mins Inhibition of HDAC in human HeLa cells nuclear extracts incubated for 30 mins by fluorescent assay, IC50 = 0.0264 μM. 25113875
HeLa Function assay Inhibition of HDAC in human HeLa cells using Fluor de Lys as substrate by fluorescence assay, IC50 = 0.027 μM. 23639537
HeLa Function assay Inhibition of HDAC from human HeLa cells, IC50 = 0.028 μM. 18247554
HEK293 Function assay Inhibition of HDAC3 in HEK293 cells, IC50 = 0.046 μM. 18308563
MDA-MB-231 Antiproliferative assay 72 hrs Antiproliferative activity against human MDA-MB-231 cells after 72 hrs by resazurin dye based fluorescence assay, IC50 = 0.062 μM. 29456804
Jurkat Antiproliferative assay 48 hrs Antiproliferative activity against human Jurkat cells after 48 hrs by MTT assay, IC50 = 0.07 μM. 29533873
A549 Antiproliferative assay 72 hrs Antiproliferative activity against human A549 cells after 72 hrs by resazurin dye based fluorescence assay, IC50 = 0.077 μM. 29456804
HeLa Antiproliferative assay 72 hrs Antiproliferative activity against human HeLa cells after 72 hrs by resazurin dye based fluorescence assay, IC50 = 0.087 μM. 29456804
MCF7 Antiproliferative assay 72 hrs Antiproliferative activity against human MCF7 cells after 72 hrs by resazurin dye based fluorescence assay, IC50 = 0.096 μM. 29456804
HEL Antiproliferative assay 48 hrs Antiproliferative activity against human HEL cells after 48 hrs by MTT assay, IC50 = 0.1 μM. 29533873
Huh7 Antiviral assay 3 days Antiviral activity against HCV genotype 1b infected in human Huh7 cells after 3 days by luciferase reporter gene assay, EC50 = 0.12 μM. 25490700
HCT116 Antiproliferative assay 48 hrs Antiproliferative activity against human HCT116 cells after 48 hrs by SRB assay, GI50 = 0.13 μM. 27344487
MOLT4 Antiproliferative assay 48 hrs Antiproliferative activity against human MOLT4 cells after 48 hrs by MTT assay, IC50 = 0.14 μM. 29533873
HCT116 Antiproliferative assay Antiproliferative activity against human HCT116 cells assessed as growth inhibition, IC50 = 0.16 μM. 21650221
HCT116 Antiproliferative assay Antiproliferative activity against human HCT116 cells, IC50 = 0.16 μM. 21742496
SK-N-BE(2) Antiproliferative assay 48 hrs Antiproliferative activity against human SK-N-BE(2) cells after 48 hrs by MTT assay, IC50 = 0.31 μM. 29533873
PC3 Antiproliferative assay 48 hrs Antiproliferative activity against human PC3 cells after 48 hrs by SRB assay, GI50 = 0.39 μM. 27344487
PC3 Antiproliferative assay 96 hrs Antiproliferative activity against human PC3 cells after 96 hrs by celltiter 96 assay, IC50 = 0.45 μM. 21634430
H1299 Antiproliferative assay Antiproliferative activity against human H1299 cells, IC50 = 0.46 μM. 21650221
HeLa Antiproliferative assay 48 hrs Antiproliferative activity against human HeLa cells after 48 hrs by MTT assay, IC50 = 0.51 μM. 29533873
HCT116 Antiproliferative assay 96 hrs Antiproliferative activity against human HCT116 cells after 96 hrs by celltiter 96 assay, IC50 = 0.6 μM. 21634430
A2780 Antiproliferative assay 96 hrs Antiproliferative activity against human A2780 cells after 96 hrs by celltiter 96 assay, IC50 = 0.67 μM. 21634430
HuH7 Cytotoxicity assay 3 days Cytotoxicity against human HuH7 cells assessed as inhibition of cell viability after 3 days by CellTiter 96 assay, CC50 = 0.68 μM. 25490700
COLO205 Antiproliferative assay 96 hrs Antiproliferative activity against human COLO205 cells after 96 hrs by celltiter 96 assay, IC50 = 0.7 μM. 21634430
A549 Antiproliferative assay 48 hrs Antiproliferative activity against human A549 cells after 48 hrs by SRB assay, GI50 = 0.78 μM. 27344487
HL60 Antiproliferative assay 48 hrs Antiproliferative activity against human HL60 cells after 48 hrs by SRB assay, GI50 = 1.09 μM. 27344487
K562 Antiproliferative assay 48 hrs Antiproliferative activity against human K562 cells after 48 hrs by MTT assay, IC50 = 1.1 μM. 29533873
PC3 Antiproliferative assay 48 hrs Antiproliferative activity against human PC3 cells after 48 hrs by MTT assay, IC50 = 1.3 μM. 29533873
NFF Cytotoxicity assay 72 hrs Cytotoxicity against human NFF cells after 72 hrs by SRB assay, IC50 = 1.4 μM. 28241112
HEK293 Cytotoxicity assay 48 hrs Cytotoxicity against HEK293 cells after 48 hrs by resazurin assay, IC50 = 1.4 μM. 28241112
NFF Cytotoxicity assay 72 hrs Cytotoxicity against human NFF cells after 72 hrs by sulforhodamine B assay, IC50 = 1.42 μM. 30245402
HEK293 Cytotoxicity assay 48 hrs Cytotoxicity against HEK293 cells after 48 hrs by resazurin dye based assay, IC50 = 1.42 μM. 30245402
RAW264.7 Anti-inflammatory assay 1 hr Anti-inflammatory activity in LPS-stimulated mouse RAW264.7 cells assessed as suppression of nitric oxide production pre-incubated for 1 hr before LPS stimulation for 24 hrs by Griess reagent based assay, IC50 = 2.2 μM. 25113875
RAW264.7 Anti-inflammatory assay 1 hr Anti-inflammatory activity in LPS-stimulated mouse RAW264.7 cells assessed as suppression of TNFalpha production pre-incubated for 1 hr before LPS stimulation for 24 hrs by ELISA method, IC50 = 4.7 μM. 25113875
RAW264.7 Anti-inflammatory assay 1 hr Anti-inflammatory activity in LPS-stimulated mouse RAW264.7 cells assessed as suppression of PGE2 production pre-incubated for 1 hr before LPS stimulation for 24 hrs by enzyme immunoassay method, IC50 = 8.28 μM. 25113875
Huh-luc/neo7 Function assay 1 uM 1 to 3 hrs Inhibition of HDAC class 1 in human Huh-luc/neo7 cells assessed as histone H3 acetylation at 1 uM after 1 to 3 hrs by Western blotting analysis 25937017
PC3 Function assay 0.3 uM 48 hrs Inhibition of HDAC in human PC3 cells assessed as increase in amount of acetylated histone H3 at 0.3 uM after 48 hrs by Western blot analysis 27344487
HCT116 Function assay 0.3 uM 48 hrs Inhibition of HDAC in human HCT116 cells assessed as increase in amount of acetylated histone H3 at 0.3 uM after 48 hrs by Western blot analysis 27344487
클릭하여 더 많은 세포주 실험 데이터 보기

화학 정보, 보관 및 안정성 (Chemical Information, Storage & Stability)

분자량 318.35 화학식

C15H14N2O4S

 보관 (수령일로부터)
CAS 번호 866323-14-0 SDF 다운로드 원액 보관

동의어 PXD101,NSC726630, PX-105684 Smiles C1=CC=C(C=C1)NS(=O)(=O)C2=CC=CC(=C2)C=CC(=O)NO

용해도 (Solubility)

In vitro
배치:

DMSO : 64 mg/mL (201.03 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 (Mechanism of Action)

특징
Lead compound of Topotarget.
Targets/IC50/Ki
HDAC
(Cell-free assay)
27 nM
시험관 내(In vitro)
Belinostat inhibits the growth of tumor cells (A2780, HCT116, HT29, WIL, CALU-3, MCF7, PC3 and HS852) with IC50 from 0.2-0.66 μM. PD101 shows low activity in A2780/cp70 and 2780AD cells, which are cisplatin and doxorubicin-resistant derivatives of A2780 cells. This compound could induce apoptosis through PARP cleavage and acetylation of histones H3/H4. It inhibits bladder cancer cell growth, especially in 5637 cells, which shows accumulation of G0-G1 phase, decrease in S phase and increase in G2-M phase. The growth inhibitory activity of this chemical on cell lines is not strongly influenced by the multidrug-resistant phenotype, whereas the activity of docetaxel is clearly affected. It could enhance the growth inhibitory activity of docetaxel or carboplatin in OVCAR-3 and A2780 cells. This compound also shows enhanced tubulin acetylation in ovarian cancer cell lines. A recent study shows that it activates protein kinase A in a TGF-β signaling-dependent mechanism and decreases survivin mRNA.
키나아제 분석
HDAC 활성
Subconfluent 배양물을 수확하여 얼음처럼 차가운 PBS로 두 번 세척하고 200 × g에서 5분간 원심분리하여 펠릿을 만듭니다. 세포 펠릿을 2부피의 용해 완충액[30% 글리세롤 및 450 mM NaCl을 포함하는 60 mM Tris 완충액(pH 7.4)]에 재현탁하고 세 번의 동결(드라이아이스)-해동(30 °C 수조) 주기를 통해 용해합니다. 세포 파편은 1.2 × 104 g에서 5분간 원심분리하여 제거하고 상청액은 -80 °C에 보관합니다. Histone H4 펩타이드(20개의 NH2-말단 잔기에 해당하는 서열 SGRGKGGKGLGKGGAKRHRK)는 아세테이트 공급원으로 [3H]acetyl CoA를 사용하여 p300의 hypoxanthine-aminopterin-thymidine 도메인을 포함하는 재조합 단백질에 의해 아세틸화됩니다. H4 펩타이드(100 μg)를 hypoxanthine-aminopterin-thymidine 완충액(50 mM Tris HCl pH 8.0, 5% 글리세롤, 50 mM KCl, 0.1 mM EDTA), 1 mM DTT, 1 mM 4-(2-aminoethyl) benzenesulfonylfluoride, 1 × complete 프로테아제 억제제, 정제된 p300 50 μL 및 1.85 m [3H]acetyl CoA(4.50Ci/mmol)와 혼합하여 최종 부피 300 μL로 만들고 30 °C에서 45분간 배양합니다. p300 단백질은 4 °C에서 1시간 동안 50% Ni-agaroase 비드 20 μL와 함께 배양하고 원심분리하여 제거합니다. 상청액을 2 mL Sephadex G15 컬럼에 적용하고 통과액을 수집합니다. 증류수 1 mL를 천천히 가하고 3방울씩 분획을 수집합니다. 이 과정을 증류수 4~5 mL가 추가될 때까지 반복하여 약 40개의 분획을 수집합니다. 각 분획 3 μL를 섬광액 2 mL에 희석하고 섬광 계수기로 계수하여 표지된 펩타이드를 포함하는 분획을 식별합니다. 이 분획들을 합치고, 혼합된 샘플 1 μL를 측정하여 모든 펩타이드 배치(3-7×103 cpm/μL)의 방사능을 평가합니다. 활성 분석을 위해 반응은 2 μL의 세포 추출물과, 사용되는 경우 2 μL의 본 화합물을 포함하는 완충액[30% 글리세롤을 포함하는 60 mM Tris(pH 7.4)] 총 부피 150 μL에서 수행됩니다. 반응은 [3H] 표지된 기질(20개의 NH2-말단 잔기에 해당하는 아세틸화된 histone H4 펩타이드) 2 μL를 첨가하여 시작합니다. 샘플은 37 °C에서 45분간 배양하고 HCl 및 아세트산(최종 농도 각각 0.72 및 0.12 M)을 첨가하여 반응을 정지시킵니다. 방출된 [3H]acetate는 ethyl acetate 750 μL로 추출하고 샘플을 1.2× 104 g에서 5분간 원심분리합니다. 상층액(600 μL)을 섬광액 3 mL로 옮기고 계수합니다.
생체 내(In vivo)
Belinostat indicates significant tumor growth delay in A2780 and A2780/cp70 xenograft at a dose of 10mg/kg with no effects on the body weight. This compound also induces p21WAF1, HDAC core and cell communication genes in mouse bladder tumors. Its monotherapy induces dose-proportional antitumor effects with TGI of 47% at a dose of 100mg/kg in A2780 xenograft. The combination of this chemical (100 mg/kg) with carboplatin (40 mg/kg) could delay tumor growth from 18.6 days to 22.5 days. Combining with bortezomib, it results in great tumor inhibition and gastrointestinal toxicity in mice with bortezomib-resistant UMSCC-11A xenograft.
참조
  • [4] https://pubmed.ncbi.nlm.nih.gov/21757750/
  • [5] https://pubmed.ncbi.nlm.nih.gov/17237265/

적용 분야 (Applications)

방법 바이오마커 이미지 PMID
Western blot p-H2AX(Ser139) / KU70 / KU80 / RAD51 / RAD52 / ERCC1 Acetyl Histone H3 / Acetyl Histone H4 / Acetyl tubulin p21 / p27 SOS1 / SOS2 PARP / p-ERK / p-p38 / p38 / p-BRAF / p-MEK / MEK
S1085-WB6
24155971
Growth inhibition assay Cell viability IC50
S1085-viability1
24155971

임상시험 정보 (Clinical Trial Information)

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

NCT 번호 모집 조건 스폰서/협력자 시작일 단계
NCT06406465 Not yet recruiting
Carcinoma Neuroendocrine|Tumor Neuroendocrine|Tumors Neuroendocrine|Neuroendocrine; Carcinoma|Small Cell; Receptors
National Cancer Institute (NCI)|National Institutes of Health Clinical Center (CC)
 May 15 2024 Phase 2
NCT04315233 Recruiting
Metastatic Breast Cancer|Recurrent Ovarian Carcinoma
University of Utah|Novartis|Acrotech Biopharma
 May 3 2021 Phase 1
NCT04703920 Recruiting
Metastatic Breast Cancer|Metastatic Castration-resistant Prostate Cancer|Metastatic Ovarian Carcinoma
University of Michigan Rogel Cancer Center|Pfizer|Acrotech Biopharma Inc.
 March 4 2021 Phase 1
NCT03772925 Active not recruiting
Recurrent Acute Myeloid Leukemia|Recurrent Myelodysplastic Syndrome|Refractory Acute Myeloid Leukemia|Refractory Myelodysplastic Syndrome
National Cancer Institute (NCI)
 June 20 2019 Phase 1

자주 묻는 질문 (Frequently Asked Questions)

질문 1:
Could you please give some suggestions for the use of it in vivo (i.p. injection)?

답변:
For I.P. injection, it can be dissolved in 2% DMSO+30% PEG 300+ddH2O at 10 mg/ml clearly. When preparing the solution, please dissolve this compound in DMSO clearly first. Then add PEG, after they mixed well, then dilute with water. Hope this information is useful to you.