Home Epigenetics HDAC 억제제 Ricolinostat (ACY-1215)

연구용

Ricolinostat (ACY-1215) HDAC 억제제

제품 번호: S8001

Ricolinostat (ACY-1215, Rocilinostat)은 무세포 분석에서 5 nM의 IC50을 갖는 선택적 HDAC6 억제제입니다. 이는 HDAC1/2/3(class I HDAC)보다 HDAC6에 대해 10배 이상 더 선택적이며, HDAC8에 대해서는 약간의 활성을, HDAC4/5/7/9/11, Sirtuin1 및 Sirtuin2에 대해서는 최소한의 활성을 나타냅니다. Ricolinostat (ACY-1215)은 세포 증식을 억제하고 Apoptosis related를 촉진합니다. 임상 2상.
Ricolinostat (ACY-1215) HDAC 억제제 Chemical Structure

화학 구조

분자량: 433.5

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품질 관리 (Quality Control)

배치: 순도: 99.96%
99.96

함께 자주 사용되는 제품 Ricolinostat (ACY-1215)

(+)-JQ1

It and JQ1 increase apoptosis, diminish the expression of c-MYC and BCL-2, and lower multiple myeloma cells proliferation.

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

세포주 분석 유형 농도 배양 시간 제형 활성 설명 PMID
A-172 Growth Inhibition Assay 10 nM 24/48 h inhibits cell growth time dependently 26150340
U87MG Growth Inhibition Assay 10 nM 24/48 h inhibits cell growth time dependently 26150340
Hbl-1 Growth Inhibition Assay 48 h IC50=1.6 μM 26116270
OCI-Ly10 Growth Inhibition Assay 48 h IC50=0.9 μM 26116270
Riva Growth Inhibition Assay 48 h IC50=2.2 μM 26116270
Su-DHL2 Growth Inhibition Assay 48 h IC50=3.3 μM 26116270
OCI-Ly1 Growth Inhibition Assay 48 h IC50=2.4 μM 26116270
OCI-Ly7 Growth Inhibition Assay 48 h IC50=1.2 μM 26116270
Su-DHL4 Growth Inhibition Assay 48 h IC50=4.7 μM 26116270
Su-DHL6 Growth Inhibition Assay 48 h IC50=3.2 μM 26116270
Hbl-2 Growth Inhibition Assay 48 h IC50=1.9 μM 26116270
Jeko-1 Growth Inhibition Assay 48 h IC50=1.5 μM 26116270
Jvm-2 Growth Inhibition Assay 48 h IC50=4.0 μM 26116270
Rec-1  Growth Inhibition Assay 48 h IC50=2.3 μM 26116270
CCL-119 Growth Inhibition Assay 48 h IC50=1.7 μM 26116270
H9 Growth Inhibition Assay 48 h IC50=1.2 μM 26116270
HH Growth Inhibition Assay 48 h IC50=2.5 μM 26116270
Sup-T1 Growth Inhibition Assay 48 h IC50=1.6 μM 26116270
MM.1S Function Assay 0-5μM 6 h increases acetylated α-tubulin 22262760
MM.1S Function Assay 0.25/1μM 18 h increases acetylated α-tubulin 22262760
MM.1R Function Assay 0.25/1μM 18 h increases acetylated α-tubulin 22262760
RPMI8226  Function Assay 0.25/1μM 18 h increases acetylated α-tubulin 22262760
MM.1S Cell Viability Assay 0-8μM 48 h decreases MM-cell viability in a dose-dependent manner 22262760
OPM1 Cell Viability Assay 0-8μM 48 h decreases MM-cell viability in a dose-dependent manner 22262760
RPMI Cell Viability Assay 0-8μM 48 h decreases MM-cell viability in a dose-dependent manner 22262760
MM.1R Cell Viability Assay 0-8μM 48 h decreases MM-cell viability in a dose-dependent manner 22262760
LR5 Cell Viability Assay 0-8μM 48 h decreases MM-cell viability in a dose-dependent manner 22262760
OPM2 Cell Viability Assay 0-8μM 48 h decreases MM-cell viability in a dose-dependent manner 22262760
Sf9 Function assay 10 mins Inhibition of full length human recombinant N-terminal GST-tagged HDAC6 expressed in Sf9 cells using FTS as substrate preincubated for 10 mins followed by substrate addition measured over 30 mins, IC50 = 0.0047 μM. 28038324
Sf9 Function assay 15 mins Inhibition of full length recombinant human N-terminal GST-tagged HDAC6 expressed in baculovirus infected sf9 cells using Boc-Lys-(Ac)-AMC as substrate preincubated for 15 mins followed by substrate addition measured after 60 mins by fluorescence assay, IC50 = 0.009 μM. 29500130
Sf9 Function assay 15 mins Inhibition of full length recombinant human C-terminal His-tagged HDAC3/N-terminal GST-tagged NCOR2 (395 to 489 residues) expressed in baculovirus infected sf9 cells using Boc-Lys-(Ac)-AMC as substrate preincubated for 15 mins followed by substrate additi, IC50 = 0.037 μM. 29500130
Sf9 Function assay 10 mins Inhibition of full length human recombinant C-terminal FLAG-tagged HDAC2 expressed in Sf9 cells using FTS as substrate preincubated for 10 mins followed by substrate addition measured over 30 mins, IC50 = 0.048 μM. 28038324
Sf9 Function assay 10 mins Inhibition of full length human recombinant C-terminal FLAG-His-tagged HDAC1 expressed in Sf9 cells using FTS as substrate preincubated for 10 mins followed by substrate addition measured over 30 mins, IC50 = 0.058 μM. 28038324
Sf9 Function assay 15 mins Inhibition of full length recombinant human C-terminal His-tagged HDAC2 expressed in baculovirus infected sf9 cells using Boc-Lys-(Ac)-AMC as substrate preincubated for 15 mins followed by substrate addition measured after 60 mins by fluorescence assay, IC50 = 0.066 μM. 29500130
Sf9 Function assay 15 mins Inhibition of full length recombinant human C-terminal FLAG/His-tagged HDAC1 expressed in baculovirus infected sf9 cells using Boc-Lys-(Ac)-AMC as substrate preincubated for 15 mins followed by substrate addition measured after 60 mins by fluorescence ass, IC50 = 0.1 μM. 29500130
BCP-ALL Cytotoxicity assay 72 hrs Cytotoxicity against human BCP-ALL cells derived from patient 1 after 72 hrs by CellTiter-Glo luminescent cell viability assay, IC50 = 0.29 μM. 30365892
BCP-ALL Cytotoxicity assay 72 hrs Cytotoxicity against human BCP-ALL cells derived from patient 4 after 72 hrs by CellTiter-Glo luminescent cell viability assay, IC50 = 0.54 μM. 30365892
BCP-ALL Cytotoxicity assay 72 hrs Cytotoxicity against human BCP-ALL cells derived from patient 2 after 72 hrs by CellTiter-Glo luminescent cell viability assay, IC50 = 0.58 μM. 30365892
RPMI8226 Cytotoxicity assay 72 hrs Cytotoxicity against human RPMI8226 cells after 72 hrs by MTT assay, IC50 = 1.468 μM. 26443078
SEM Cytotoxicity assay 72 hrs Cytotoxicity against human SEM cells after 72 hrs by CellTiter-Glo luminescent cell viability assay, IC50 = 1.61 μM. 30365892
SUP-B15 Cytotoxicity assay 72 hrs Cytotoxicity against human SUP-B15 cells after 72 hrs by CellTiter-Glo luminescent cell viability assay, IC50 = 1.92 μM. 30365892
RPMI18226 Cytotoxicity assay 72 hrs Cytotoxicity against human RPMI18226 cells after 72 hrs by CellTiter-Glo luminescent cell viability assay, IC50 = 1.97 μM. 30365892
HL60 Cytotoxicity assay 72 hrs Cytotoxicity against human HL60 cells after 72 hrs by CellTiter-Glo luminescent cell viability assay, IC50 = 2.36 μM. 30365892
HL60 Antiproliferative assay 48 hrs Antiproliferative activity against human HL60 cells after 48 hrs in presence of JAK2 inhibitor CYT-387 by CCK-8 assay, IC50 = 2.54 μM. 29940115
K562 Antiproliferative assay 48 hrs Antiproliferative activity against human K562 cells after 48 hrs in presence of JAK2 inhibitor CYT-387 by CCK-8 assay, IC50 = 2.54 μM. 29940115
HEL Antiproliferative assay 48 hrs Antiproliferative activity against human HEL cells after 48 hrs in presence of JAK2 inhibitor CYT-387 by CCK-8 assay, IC50 = 2.54 μM. 29940115
KCL22 Cytotoxicity assay 72 hrs Cytotoxicity against imatinib-resistant human KCL22 cells after 72 hrs by CellTiter-Glo luminescent cell viability assay, IC50 = 3.38 μM. 30365892
U266 Cytotoxicity assay 72 hrs Cytotoxicity against human U266 cells after 72 hrs by CellTiter-Glo luminescent cell viability assay, IC50 = 3.52 μM. 30365892
SUP-B15 Cytotoxicity assay 72 hrs Cytotoxicity against imatinib-resistant human SUP-B15 cells after 72 hrs by CellTiter-Glo luminescent cell viability assay, IC50 = 3.54 μM. 30365892
KCL22 Cytotoxicity assay 72 hrs Cytotoxicity against human KCL22 cells after 72 hrs by CellTiter-Glo luminescent cell viability assay, IC50 = 3.75 μM. 30365892
HL60 Antiproliferative assay 48 hrs Antiproliferative activity against human HL60 cells after 48 hrs by CCK-8 assay, IC50 = 3.75 μM. 29940115
K562 Antiproliferative assay 48 hrs Antiproliferative activity against human K562 cells after 48 hrs by CCK-8 assay, IC50 = 3.75 μM. 29940115
HEL Antiproliferative assay 48 hrs Antiproliferative activity against human HEL cells after 48 hrs by CCK-8 assay, IC50 = 3.75 μM. 29940115
BCP-ALL Cytotoxicity assay 72 hrs Cytotoxicity against human BCP-ALL cells derived from patient 3 after 72 hrs by CellTiter-Glo luminescent cell viability assay, IC50 = 4.45 μM. 30365892
MV4-11 Function assay 1000 nM 6 hrs Inhibition of HDAC1/2/3 in human MV4-11 cells assessed as upregulation of histone H3 acetylation at 1000 nM after 6 hrs by Western blot analysis 26443078
TC32 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells 29435139
DAOY qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY 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
A673 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 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
BT-37 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 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
Saos-2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 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
LAN-5 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells 29435139
BT-12 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 cells 29435139
Rh18 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 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
RD qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells 29435139
MG 63 (6-TG R) qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for MG 63 (6-TG R) cells 29435139
Rh30 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh30 cells 29435139
Rh41 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells 29435139
HL60 Function assay 0.1 to 10 uM 24 hrs Inhibition of HDAC6 in human HL60 cells assessed as increase in acetyl-alpha tubulin expression at 0.1 to 10 uM after 24 hrs by immunoblot assay 30365892
SEM Function assay 0.1 to 10 uM 24 hrs Inhibition of HDAC6 in human SEM cells assessed as increase in acetyl-alpha tubulin expression at 0.1 to 10 uM after 24 hrs by immunoblot assay 30365892
SUP-B15 Function assay 0.1 to 10 uM 24 hrs Inhibition of HDAC6 in imatinib-resistant human SUP-B15 cells assessed as increase in acetyl-alpha tubulin expression at 0.1 to 10 uM after 24 hrs by immunoblot assay 30365892
HL60 Function assay 0.1 to 10 uM 24 hrs Inhibition of HDAC6 in human HL60 cells assessed as increase in acetyl-histone H3 expression at 0.1 to 10 uM after 24 hrs by immunoblot assay 30365892
SEM Function assay 0.1 to 10 uM 24 hrs Inhibition of HDAC6 in human SEM cells assessed as increase in acetyl-histone H3 expression at 0.1 to 10 uM after 24 hrs by immunoblot assay 30365892
SUP-B15 Function assay 0.1 to 10 uM 24 hrs Inhibition of HDAC6 in imatinib-resistant human SUP-B15 cells assessed as increase in acetyl-histone H3 expression at 0.1 to 10 uM after 24 hrs by immunoblot assay 30365892
HL60 Function assay 0.1 to 10 uM 24 hrs Inhibition of HDAC6 in human HL60 cells assessed as increase in cleaved PARP expression at 0.1 to 10 uM after 24 hrs by immunoblot assay 30365892
SEM Function assay 0.1 to 10 uM 24 hrs Inhibition of HDAC6 in human SEM cells assessed as increase in cleaved PARP expression at 0.1 to 10 uM after 24 hrs by immunoblot assay 30365892
SUP-B15 Function assay 0.1 to 10 uM 24 hrs Inhibition of HDAC6 in imatinib-resistant human SUP-B15 cells assessed as increase in cleaved PARP expression at 0.1 to 10 uM after 24 hrs by immunoblot assay 30365892
SEM Antiproliferative assay 24 to 72 hrs Antiproliferative activity against human SEM cells at IC50 to 2 times IC50 after 24 to 72 hrs by trypan exclusion method 30365892
HEL Cell cycle assay 1 to 10 uM 48 hrs Cell cycle arrest in human HEL cells assessed as accumulation at G1 phase at 1 to 10 uM after 48 hrs propidium iodide staining based flow cytometry 29940115
SEM Function assay 18 hrs Inhibition of HDAC6 in human SEM cells assessed as decrease in aggresome accumulation at IC50 after 18 hrs by fluorescence microscopic method 30365892
SEM Function assay 1.6 uM 18 hrs Inhibition of HDAC6 in human SEM cells assessed as decrease in aggresome accumulation at 1.6 uM after 18 hrs by FACS analysis 30365892
SH-SY5Y Function assay 0.1 to 1 uM 24 hrs Inhibition of HDAC6 in human SH-SY5Y cells assessed as increase in acetylation of alpha-tubulin at 0.1 to 1 uM after 24 hrs by Western blot analysis 30028616
SH-SY5Y Function assay 0.1 to 1 uM 24 hrs Inhibition of class 1 HDAC in human SH-SY5Y cells assessed as increase in acetylation of histone H3 at 0.1 to 1 uM after 24 hrs by Western blot analysis 30028616
클릭하여 더 많은 세포주 실험 데이터 보기

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

분자량 433.5 화학식

C24H27N5O3

 보관 (수령일로부터)
CAS 번호 1316214-52-4 SDF 다운로드 원액 보관

동의어 Rocilinostat Smiles C1=CC=C(C=C1)N(C2=CC=CC=C2)C3=NC=C(C=N3)C(=O)NCCCCCCC(=O)NO

용해도 (Solubility)

In vitro
배치:

DMSO : 42 mg/mL (96.88 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
Induced less cytotoxicity in PHA-stimulated PBMCs from 4 healthy donors compared with the pan-HDAC inhibitor SAHA.
Targets/IC50/Ki
HDAC6
(Cell-free assay)
4.7 nM
HDAC2
(Cell-free assay)
48 nM
HDAC3
(Cell-free assay)
51 nM
HDAC1
(Cell-free assay)
58 nM
HDAC8
(Cell-free assay)
100 nM
시험관 내(In vitro)

ACY-1215 is a hydroxamic acid derivative. ACY-1215 is 12-, 10-, and 11-fold less active against HDAC1, HDAC2, and HDAC3 (class I HDACs), respectively. ACY-1215 has minimal activity (IC50 > 1μM) against HDAC4, HDAC5, HDAC7, HDAC9, HDAC11, Sirtuin1, and Sirtuin2, and has slight activity against HDAC8 (IC50 = 0.1μM). The IC50 values for ACY-1215 for T-cell toxicity is 2.5μM. ACY-1215 overcomes tumor cell growth and survival conferred by BMSCs and cytokines in the BM milieu.
키나아제 분석
HDAC 효소 분석
Ricolinostat (ACY-1215)를 용해한 후 분석 완충액[50 mM HEPES, pH 7.4, 100 mM KCl, 0.001% Tween-20, 0.05% BSA 및 20 μM tris(2-carboxyethyl)phosphine]으로 최종 농도의 6배가 되도록 희석합니다. HDAC 효소는 분석 완충액으로 최종 농도의 1.5배가 되도록 희석하고 기질을 첨가하기 전에 Ricolinostat (ACY-1215)와 10분 동안 사전 배양합니다. 각 효소에 사용되는 FTS (HDAC1, HDAC2, HDAC3 및 HDAC6) 또는 MAZ-1675 (HDAC4, HDAC5, HDAC7, HDAC8 및 HDAC9)의 양은 적정 곡선에 의해 결정된 미카엘리스 상수(Km)와 동일합니다. FTS 또는 MAZ-1675는 0.3μM 시퀀싱 등급 트립신과 함께 최종 농도의 6배가 되도록 분석 완충액에 희석합니다. 기질/트립신 혼합물을 효소/화합물 혼합물에 첨가하고 플레이트를 60초 동안 흔든 다음 SpectraMax M5 마이크로타이터 플레이트 리더에 넣습니다. 펩타이드 기질 내 라이신 측쇄의 탈아세틸화 이후 30분 동안 7-amino-4-methoxy-coumarin의 방출을 모니터링하여 효소 반응을 관찰하고 반응의 선형 속도를 계산합니다.
생체 내(In vivo)

ACY-1215 is readily absorbed by tumor tissue. Moreover, the drug does not accumulate in tumor tissue, as evidenced by the parallel decline of acetylated α-tubulin in blood cells and tumor tissue by 24 hours after dose.

참조

적용 분야 (Applications)

방법 바이오마커 이미지 PMID
Western blot Ac-α-tubulin / Ac-Histone H4 Survivin / P21 / CDC2 / p53 / p-p53(S392) / Cyclin A2 / Cyclin B1 Bax / Bim / Bcl2 / Cleaved caspase-3 / Cleaved caspase-9 / Cleaved PARP PI3K(p85) / AKT / p-AKT(S473) / PRAS40 / Rag C / mTOR / p-mTOR / ERK / p-ERK Ac-β-catenin(K49) / p-β-catenin / β-catenin
S8001-WB1
31015208
Immunofluorescence β-tubulin / β-catenin
S8001-IF1
25546293
Growth inhibition assay Cell viability
S8001-viability1
31015208

임상시험 정보 (Clinical Trial Information)

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

NCT 번호 모집 조건 스폰서/협력자 시작일 단계
NCT02632071 Completed
Metastatic Breast Cancer|Breast Carcinoma
Columbia University|Acetylon Pharmaceuticals Incorporated|National Cancer Institute (NCI)
 March 1 2016 Phase 1
NCT01583283 Completed
Multiple Myeloma
Celgene
 July 12 2012 Phase 1
NCT01323751 Completed
Multiple Myeloma
Celgene|The Leukemia and Lymphoma Society
 July 2011 Phase 1|Phase 2

자주 묻는 질문 (Frequently Asked Questions)

질문 1:
What would you suggest to obtain a clear solution of it?

답변:
It can be dissolved in 2% DMSO/30% PEG 300/ddH2O at 5 mg/ml clearly, while in 1% DMSO/30% polyethylene glycol/1% Tween 80 at 30 mg/ml it is a suspension for oral administration. Please note that the precipitation will go out from the clear solution after stayed for about half an hour, so it is recommended to prepare the solution just before use.