Home Cell Cycle CDK inhibitor Flavopiridol (Alvocidib, HMR-1275)

연구용

Flavopiridol (Alvocidib, HMR-1275) CDK inhibitor

제품 번호: S1230

Flavopiridol (Alvocidib) competes with ATP to inhibit CDKs including CDK1, CDK2, CDK4, CDK6, and CDK9 with IC50 values in the 20-100 nM range. It is more selective for CDK1, 2, 4, 6, 9 versus CDK7. Flavopiridol is initially found to inhibit EGFR and PKA. Flavopiridol induces autophagy and ER stress. Flavopiridol blocks HIV-1 replication. Phase 1/2.
Flavopiridol (Alvocidib, HMR-1275) CDK inhibitor Chemical Structure

화학 구조

분자량: 401.84

바로가기

품질 관리 (Quality Control)

배치: 순도: 99.92%
99.92

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

세포주 분석 유형 농도 배양 시간 제형 활성 설명 PMID
MCF-7 tumor cell Proliferation assay Inhibition of MCF-7 tumor cell proliferation 10843211
PC3 cell Function assay Inhibition of PC3 cell clonogenic assay, IC50=10 μM 11063609
HCT116 cell Function assay Inhibition of HCT116 cell clonogenic assay, IC50=13 μM 11063609
A2780 cell Function assay Inhibition of A2780 cell clonogenic assay， IC50=15 μM 11063609
Mia PaCa-2 cell Function assay Inhibition of Mia PaCa-2 cell clonogenic assay, IC50=36 μM 11063609
LNCaP human prostate carcinoma cell Proliferation assay Inhibition of LNCaP human prostate carcinoma cell proliferation 12190313
HCT116/VP35 human colon carcinoma cell Proliferation assay Inhibition of HCT116/VP35 human colon carcinoma cell proliferation, IC50=17 nM 12190313
HCT116 human colon carcinoma cell Proliferation assay Inhibition of HCT116 human colon carcinoma cell proliferation, IC50=18 nM 12190313
HCT116/VM46 human colon carcinoma cell Proliferation assay Inhibition of HCT116/VM46 human colon carcinoma cell proliferation, IC50=21 nM 12190313
A2780/DDP-R human ovarian carcinoma cell Proliferation assay Inhibition of A2780/DDP-R human ovarian carcinoma cell proliferation, IC50=38 nM 12190313
ABAE human fibroblast cell Proliferation assay Inhibition of ABAE human fibroblast cell proliferation, IC50=45 nM 12190313
HL60 human leukemia cell Proliferation assay Inhibition of HL60 human leukemia cell proliferation, IC50=46 nM 12190313
Hs 27 human fibroblast cell Proliferation assay Inhibition of Hs 27 human fibroblast cell proliferation, IC50=51 nM 12190313
CCRF-CEM human leukemia cell Proliferation assay Inhibition of CCRF-CEM human leukemia cell proliferation, IC50=52 nM 12190313
OVCAR-3 human ovarian carcinoma cell Proliferation assay Inhibition of OVCAR-3 human ovarian carcinoma cell proliferation, IC50=54 nM 12190313
A2780/DDP-S human ovarian carcinoma cell Proliferation assay Inhibition of A2780/DDP-S human ovarian carcinoma cell proliferation, IC50=56 nM 12190313
A2780/TAX-S human ovarian carcinoma cell Proliferation assay Inhibition of A2780/TAX-S human ovarian carcinoma cell proliferation, IC50=65 nM 12190313
LS174T human colon carcinoma cell Proliferation assay Inhibition of LS174T human colon carcinoma cell proliferation, IC50=65 nM 12190313
MCF-7 human breast carcinoma cell Proliferation assay Inhibition of MCF-7 human breast carcinoma cell proliferation, IC50=66 nM 12190313
PC3 human prostate carcinoma cell Proliferation assay Inhibition of PC3 human prostate carcinoma cell proliferation, IC50=66 nM 12190313
MLF mouse lung fibroblast cell Proliferation assay Inhibition of MLF mouse lung fibroblast cell proliferation, IC50=72 nM 12190313
LX-1 human lung carcinoma Proliferation assay Inhibition of LX-1 human lung carcinoma proliferation, IC50=75 nM 12190313
A431 human squamous cell Proliferation assay Inhibition of A431 human squamous cell carcinoma cell proliferation, IC50=75 nM 12190313
SKBR-3 human breast carcinoma cell Proliferation assay Inhibition of SKBR-3 human breast carcinoma cell proliferation, IC50=77 nM 12190313
A2780/TAX-R human ovarian carcinoma cell Proliferation assay Inhibition of A2780/TAX-R human ovarian carcinoma cell proliferation, IC50=78 nM 12190313
M109 mouse lung carcinoma cell Proliferation assay Inhibition of M109 mouse lung carcinoma cell proliferation, IC50=80 nM 12190313
CACO-2 human colon carcinoma cell Proliferation assay Inhibition of CACO-2 human colon carcinoma cell proliferation, IC50=86 nM 12190313
A549 human lung carcinoma cell Proliferation assay Inhibition of A549 human lung carcinoma cell proliferation, IC50=96 nM 12190313
MIP human colon carcinoma cell Function assay Inhibition of MIP human colon carcinoma cell line, IC50=0.12 μM 12190313
K562 human leukemia cell Proliferation assay Inhibition of K562 human leukemia cell proliferation, IC50=0.13 μM 12190313
human A2780 cell line Proliferation assay 72 h Antiproliferative effect against human A2780 cell line was determined in a whole cell 72 hr cytotoxicity assay, IC50=71 nM 15027863
human ovarian (A2780) cancer cell Cytotoxic assay Cytotoxic effect on human ovarian (A2780) cancer cell line, IC50=71 nM 15125971
ID8 cells Proliferation assay Antiproliferative activity against ID8 cells, IC50=7 nM 17123821
MCF7 cells Proliferation assay Antiproliferative activity against MCF7 cells, IC50=26 nM 17123821
Sf9 cells Function assay Inhibition of recombinant cyclin A/CDK2 expressed in Sf9 cells, IC50=12 nM 17904366
human A2780 cells Function assay Inhibition of cdk-mediated NPM phosphorylation at thr199 in human A2780 cells 18469809
human A2780 cells Function assay 24 h Inhibition of cdk-mediated Rb phosphorylation at thr821 in human A2780 cells after 24 hrs 18469809
human NCI60 cells Proliferation assay 72 h Antiproliferative activity against human NCI60 cells after 72 hrs by sulforhodamine B assay, GI50=74.7 nM 21080703
human NCI60 cells Proliferation assay 72 h Antiproliferative activity against human NCI60 cells assessed as lethal effect after 72 hrs by sulforhodamine B assay, LC50=0.904 μM 21080703
human A2780 cells Cytotoxic assay 24 h Cytotoxicity against human A2780 cells after 24 hrs by MTT assay, GI50=23 nM 23301767
human MRC5 cells Cytotoxic assay 72 h Cytotoxicity against human MRC5 cells after 72 hrs by MTT assay, GI50=28 nM 23301767
human A2780 cells Cytotoxic assay 72 h Cytotoxicity against human A2780 cells after 72 hrs by MTT assay, GI50=29 nM 23301767
human A2780 cells Cytotoxic assay 48 h Cytotoxicity against human A2780 cells after 48 hrs by MTT assay, GI50=31 nM 23301767
human MRC5 cells Cytotoxic assay 48 h Cytotoxicity against human MRC5 cells after 48 hrs by MTT assay, GI50=39 nM 23301767
human MRC5 cells Cytotoxic assay 24 h Cytotoxicity against human MRC5 cells after 24 hrs by MTT assay, GI50=49 nM 23301767
human HMEC1 cells Cytotoxic assay 24 h Cytotoxicity against human HMEC1 cells after 24 hrs by MTT assay, GI50=61 nM 23301767
human HMEC1 cells Cytotoxic assay 48 h Cytotoxicity against human HMEC1 cells after 48 hrs by MTT assay, GI50=62 nM 23301767
human HMEC1 cells Cytotoxic assay 72 h Cytotoxicity against human HMEC1 cells after 72 hrs by MTT assay, GI50=66 nM 23301767
A2780 Function assay 330 nM 24 hr Percentage A2780 cells in sb-G1 after 24 hr r at 330 nM (IC50), Cell cycle = 0.001 μM. 12190313
A2780 Apoptosis assay 330 nM 24 hr Apoptotic A2780 cells after 24 hr r at 330 nM (IC50), Cell cycle = 0.001 μM. 12190313
A2780 Function assay 2980 nM 24 hr Percentage A2780 cells in sub-G1 after 24 hr r at 2980 nM (IC90), Cell cycle = 0.002 μM. 12190313
A2780 Apoptosis assay 2980 nM 24 hr Apoptotic A2780 cells after 24 hr r at 2980 nM (IC90), Cell cycle = 0.009 μM. 12190313
A2780 Function assay 2980 nM 24 hr Percentage A2780 cells in S-phase after 24 hr r at 2980 nM (IC90), Cell cycle = 0.012 μM. 12190313
A2780 Function assay 330 nM 24 hr Percentage A2780 cells in S-phase after 24 hr r at 330 nM (IC50), Cell cycle = 0.016 μM. 12190313
A2780 Function assay 330 nM 24 hr Percentage A2780 cells in G2/M after 24 hr r at 330 nM (IC50), Cell cycle = 0.023 μM. 12190313
A2780 Function assay 2980 nM 24 hr Percentage A2780 cells in G2/M after 24 hr r at 2980 nM (IC90), Cell cycle = 0.025 μM. 12190313
A2780 Function assay 330 nM 24 hr Percentage A2780 cells in G1 after 24 hr r at 330 nM (IC50), Cell cycle = 0.06 μM. 12190313
A2780 Function assay 2980 nM 24 hr Percentage A2780 cells in G1 after 24 hr r at 2980 nM (IC90), Cell cycle = 0.061 μM. 12190313
A2780 Function assay 24 hrs Inhibition of cdk-mediated Rb phosphorylation at ser807/811 in human A2780 cells after 24 hrs 18469809
A2780 Function assay 24 hrs Inhibition of cdk9-mediated RNA pol2 CTD phosphorylation at ser2 in human A2780 cells after 24 hrs 18469809
A2780 Function assay 24 hrs Inhibition of cdk7-mediated RNA pol2 CTD phosphorylation at ser5 in human A2780 cells after 24 hrs 18469809
A2780 Apoptosis assay 24 hrs Induction of apoptosis in human A2780 cells assessed as appearance of Mcl1 protein level after 24 hrs 18469809
DR-U2OS-GFP Function assay 0.1 uM 56 hrs Reduction of homologous recombination in human DR-U2OS-GFP cells expressing I-SceI nuclease assessed as reduction of RAD51 level at 0.1 uM after 56 hrs by immunoblotting 21417417
A2780 Function assay 24 hrs Inhibition of CDK9 in human A2780 cells assessed as reduction of RNAPII CTD phosphorylation at Ser2 at GI50 concentration after 24 hrs by Western blotting analysis 23301767
A2780 Cell cycle assay 24 hrs Cell cycle arrest in human A2780 cells assessed as accumulation at G2/M phase at less than GI50 after 24 hrs by flow cytometric analysis 23301767
A2780 Function assay 24 hrs Inhibition of CDK9 in human A2780 cells assessed as downregulation of MCL1 at GI50 to 5XGI50 concentration after 24 hrs by Western blotting analysis 23301767
A2780 Apoptosis assay 24 hrs Induction of apoptosis in human A2780 cells assessed as induction of PARP cleavage at GI50 to 5XGI50 concentration after 24 hrs by Western blotting analysis 23301767
A2780 Function assay 24 hrs Inhibition of CDK9 in human A2780 cells assessed as downregulation of HDM2 at GI50 to 5XGI50 concentration after 24 hrs by Western blotting analysis 23301767
MT4 Antiproliferative assay Antiviral activity against Human immunodeficiency virus 1 NL 4-3 infected in MT4 cells measured on day 4 post infection by p24 assay, EC50 = 0.015 μM. 25914804
MT4 Cytotoxicity assay Cytotoxicity against human MT4 cells, IC50 = 0.067 μM. 25914804
Sf9 Function assay 15 mins Inhibition of CDK2/cyclin E1 (unknown origin) expressed in Sf9 insect cells using UlightCFFKNIVTPRTPPPSQGK-amide substrate after 15 mins by autoradiography, IC50 = 0.13 μM. 25914804
A549 Antiproliferative assay 3 days Antiproliferative activity against human A549 cells after 3 days by SRB method, GI50 = 0.14 μM. 25914804
DU145 Antiproliferative assay 3 days Antiproliferative activity against human DU145 cells after 3 days by SRB method, GI50 = 0.15 μM. 25914804
KB Antiproliferative assay 3 days Antiproliferative activity against human KB cells after 3 days by SRB method, GI50 = 0.16 μM. 25914804
KBVIN Antiproliferative assay 3 days Antiproliferative activity against human KBVIN cells after 3 days by SRB method, GI50 = 0.18 μM. 25914804
HCT116 Antiproliferative assay 72 hrs Antiproliferative activity against human HCT116 cells after 72 hrs by Celltiter-Glo reagent based assay in presence of 10% fetal bovine serum, EC50 = 0.034 μM. 26985305
HCT116 Antiproliferative assay 72 hrs Antiproliferative activity against human HCT116 cells after 72 hrs by Celltiter-Glo reagent based assay in presence of 0.625% fetal bovine serum, EC50 = 0.059 μM. 26985305
Sf9 Function assay 10 mins Inhibition of human His6-tagged CDK9/cyclin T1 expressed in baculovirus infected sf9 cells using GST-CTD as substrate after 10 mins in presence of [gamma-32P]ATP by SDS-PAGE analysis, IC50 = 0.0025 μM. 27171036
Sf21 Function assay Inhibition of recombinant human full length C-terminal His6-tagged CDK9/cyclin T1 expressed in baculovirus infected Sf21 insect cells using PDKtide as substrate, IC50 = 0.011 μM. 27171036
HeLa Cytotoxicity assay 72 hrs Cytotoxicity against human HeLa cells assessed as decrease in cell viability after 72 hrs by MTT assay, CC50 = 0.12 μM. 27171036
sf21 Function assay Inhibition of full length human N-terminal His6-tagged CDK6/N-terminal GST-tagged cyclin D3 expressed in sf21 cells using histone H1 substrate, IC50 = 0.395 μM. 27171036
Sf21 Function assay Inhibition of recombinant human full length C-terminal His6-tagged CDK7/cyclin H/N-terminal GST-tagged MAT1 expressed in baculovirus infected Sf21 insect cells using cdk7 substrate peptide, IC50 = 0.514 μM. 27171036
HepG2 Antiproliferative assay 72 hrs Antiproliferative activity against human HepG2 cells after 72 hrs by CelTiter-Glo assay, EC50 = 0.1464 μM. 29407975
KOPN8 Antiproliferative assay 72 hrs Antiproliferative activity against human KOPN8 cells after 72 hrs by CelTiter-Glo assay, EC50 = 0.1926 μM. 29407975
SEM Antiproliferative assay 72 hrs Antiproliferative activity against human SEM cells after 72 hrs by CelTiter-Glo assay, EC50 = 0.2043 μM. 29407975
UOCB1 Antiproliferative assay 72 hrs Antiproliferative activity against human UOCB1 cells after 72 hrs by CelTiter-Glo assay, EC50 = 0.2084 μM. 29407975
KOPN8 Apoptosis assay 0.5 uM 3 to 24 hrs Induction of apoptosis in human KOPN8 cells assessed as upregulation of cleaved PARP level at 0.5 uM after 3 to 24 hrs by Western blot analysis 29407975
KOPN8 Apoptosis assay 0.5 uM 1 hr Induction of apoptosis in human KOPN8 cells assessed as upregulation of cleaved PARP level at 0.5 uM pre-treated with NAC for 1 hr and measured after 3 to 24 hrs by Western blot analysis 29407975
클릭하여 더 많은 세포주 실험 데이터 보기

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

분자량 401.84 화학식

C21H20ClNO5

 보관 (수령일로부터)
CAS 번호 146426-40-6 SDF 다운로드 원액 보관

동의어 NSC 649890, HMR-1275, L86-8275 Smiles CN1CCC(C(C1)O)C2=C(C=C(C3=C2OC(=CC3=O)C4=CC=CC=C4Cl)O)O

용해도 (Solubility)

In vitro
배치:

DMSO : 80 mg/mL (199.08 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
First CDK inhibitor to be used in human clinical trials.
Targets/IC50/Ki
CDK9
(Cell-free assay)
20 nM
CDK1
(Cell-free assay)
30 nM
CDK4
(Cell-free assay)
20-40 nM
CDK2
(Cell-free assay)
40 nM
CDK6
(Cell-free assay)
60 nM
CDK7
(Cell-free assay)
875 nM
시험관 내(In vitro)
Flavopiridol (Alvocidib)은 MAP, PAK, PKC 및 EGFR과 같은 관련 없는 키나아제에 대해 14 μM 초과의 IC50으로 더 낮은 활성을 나타냅니다. 이는 HCT116, A2780, PC3 및 Mia PaCa-2 세포의 집락 성장을 각각 13 nM, 15 nM, 10 nM 및 36 nM의 IC50으로 유의미하게 억제합니다. 이 화합물은 또한 280 nM의 IC50으로 Glycogen synthase kinase-3 (GSK-3)의 활성을 강력하게 억제합니다. 다른 CDK와 비교했을 때, 875 nM의 IC50으로 CDK7의 활성을 덜 강력하게 억제합니다. 0.5 μM 농도에서 pSer807/811 Rb와 pThr199 NPM을 모두 억제하는 반면, pThr821 Rb에서는 경미한 변화가 관찰됩니다. 또한 전체 RNA polymerase II 수준과 Ser2 Ser5의 CTD 반복에서 RNA polymerase II의 인산화를 감소시킵니다. 광범위한 CDK 억제제로서 G1 또는 G2에서 Cell Cycle 진행을 억제할 수 있습니다. 0.3 μM 농도에서 CDK4 또는 CDK2 키나아제 활성 억제를 통해 MCF-7 또는 MDA-MB-468 세포의 G1 정지를 유도합니다. 이는 LNCAP의 16 nM에서 K562의 130 nM에 이르는 IC50 값으로 다양한 종양 세포주에 대해 강력한 세포 독성을 나타냅니다.
키나아제 분석
CDK 키나아제 분석
CDK1/cyclin B1 키나아제 분석을 위해, 키나아제 반응은 100 ng의 바큘로바이러스로 발현된 GST-CDK1/cyclin B1(인간) 복합체, 1 μg histone HI, 0.2 μCi [γ-33P]ATP, 25 μM ATP를 50 μL 키나아제 완충액(50 mM Tris, pH 8.0, 10 mM MgCl2, 1 mM EGTA, 0.5 mM DTT)에 포함하여 구성됩니다. CDK2/cyclin E 키나아제 분석을 위해, 키나아제 반응은 5 ng의 바큘로바이러스로 발현된 GST-CDK2/cyclin E(인간) 복합체, 0.5 μg GST-RB 융합 단백질(retinoblastoma 단백질의 아미노산 776-928), 0.2 μCi [γ-33P]ATP, 25 μM ATP를 50 μL 키나아제 완충액(50 mM Hepes, pH 8.0, 10 mM MgCl2, 1 mM EGTA, 2 mM DTT)에 포함하여 구성됩니다. CDK4/cyclin D1 키나아제 분석을 위해, 키나아제 반응은 150 ng의 바큘로바이러스로 발현된 GST-CDK4/cyclin D1(인간), 280 ng의 Stag-cyclin D1, 0.5 μg GST-RB 융합 단백질(retinoblastoma 단백질의 아미노산 776-928), 0.2 μCi [γ-33P]ATP, 25 μM ATP를 50 μL 키나아제 완충액(50 mM Hepes, pH 8.0, 10 mM MgCl2, 1 mM EGTA, 2 mM DTT)에 포함하여 구성됩니다. 반응액은 CDK1 및 CDK2의 경우 45분 동안, CDK4의 경우 1시간 동안 30°C에서 배양하며, 냉각된 트리클로로아세트산(TCA)을 최종 농도 15%가 되도록 첨가하여 반응을 정지시킵니다. TCA 침전물은 Filtermate 범용 수확기를 사용하여 GF/C 유니필터 플레이트에 수집되며, 필터는 TopCount 96웰 액체 섬광 계수기를 사용하여 정량화됩니다. Flavopiridol (Alvocidib)은 dimethylformamide(DMF)에 10 mM 농도로 용해되며, 각 3회 반복하여 6가지 농도에서 평가됩니다. 분석 시 DMF의 최종 농도는 2%입니다. IC50 값은 비선형 회귀 분석으로부터 도출되며 변동 계수는 16%입니다. CDK6에 대한 활성을 분석하기 위해 필터 결합 분석법이 확립되었습니다. 반응 혼합물에는 2 μL의 CDK6(0.7 mg/μL), 5 μL의 histone H1(6 mg/mL), 14 μL의 키나아제 완충액(60 mM β-glycerophosphate, 30 mM p-nitrophenyl phosphate, 25 mM MOPS (pH 7.0), 5 mM EGTA, 15 mM MgCl2, 1 mM DTT, 0.1 mM Na-vanadate), 50% DMSO에 희석된 이 화합물의 증가하는 농도 3 μL, 그리고 90 μM 농도(최종 농도: 15 μM)의 비방사성 ATP 내 6 μL의 33P-ATP(1 mCi/mL)가 혼합됩니다. 분석은 33P-ATP 첨가로 시작됩니다. 반응액은 30°C에서 20분간 배양됩니다. 그 후 상층액 25 μL를 Whatman P81 인산셀룰로오스 종이에 점적합니다. 필터를 1% 인산 용액으로 5회 세척합니다. 젖은 필터는 1 mL의 섬광 유체 존재 하에 계수됩니다. Cdk9 활성은 50 mM HEPES pH 7.5, 10 mM MgCl2, 1 mM DTT, 3 μM Na3VO4, 150 μM RNA polymerase CDT 펩타이드 및 80 μM ATP 내에서 50 nM의 재조합 Cdk9/cyclin T를 사용하여 측정됩니다. Cdk7 분석은 동일한 완충액에서 200 μM ATP와 기질로서 10 μM myelin binding protein 존재 하에 37 nM의 정제된 키나아제를 사용하여 수행됩니다. CDK9 및 CDK7에 대한 효능은 강한 음이온 교환제(Dowex 1-X8 수지, 포름산염 형태) 기반 분석 또는 섬광 근접 분석(scintillation proximity assay)을 사용하여 결정됩니다. IC50 값은 용량-반응 곡선으로부터 계산됩니다.
생체 내(In vivo)
S1230을 7일 동안 7.5 mg/kg의 용량으로 투여했을 때 P388 쥐 백혈병에 대해 경미한 항종양 활성을 보였으며, 그 결과 %T/C 값은 110이었고, 누드 마우스에 sc 이식된 인간 A2780 난소암에 대해 활성을 나타내어 1.5 log cell kill (LCK)을 유도했다. S1230을 10일 동안 1-2.5 mg/kg의 용량으로 투여하면 활막 과형성 및 관절 파괴를 억제함으로써 마우스의 콜라겐 유발 관절염을 용량 의존적으로 유의하게 억제하는 반면, 항-콜라겐 제II형(CII) 항체(Abs)의 혈청 농도 및 CII에 대한 증식 반응은 유지된다. p21-온전한 Hct116 이종이식 누드 마우스 모델에서, CPT-11(100 mg/kg)을 투여한 후 7시간 및 16시간 뒤에 S1230(3 mg/kg)을 투여했을 때 종양 퇴행이 각각 86% 및 82% 유의하게 억제되었으며, 이는 CPT-11 단독 투여(40%)와 비교하여 2배 이상의 억제 효과를 나타냈다. 이 병용 요법은 CPT-11 단독 투여 시 완전 반응(CR)이 전혀 나타나지 않은 것과 대조적으로 약 30%의 완전 반응률(CR)을 보였다.
참조
  • [4] https://pubmed.ncbi.nlm.nih.gov/8674031/
  • [5] https://pubmed.ncbi.nlm.nih.gov/12190313/
  • [6] https://pubmed.ncbi.nlm.nih.gov/18209094/
  • [7] https://pubmed.ncbi.nlm.nih.gov/11751522/
  • [8] https://pubmed.ncbi.nlm.nih.gov/18469809/
  • [9] https://pubmed.ncbi.nlm.nih.gov/11311660/

적용 분야 (Applications)

방법 바이오마커 이미지 PMID
Western blot Cleaved caspase-8 / Cleaved caspase-9 / Cleaved caspase-3 p-RNAPII / p-eIF4E / Mnk1 p-ERK / ERK / p-p38 / p-4EBP1 / 4EBP1 / p-S6 CDK2 / CDK4 / Cyclin A / p21 / p27 / Rb
S1230-WB1
31193061
Growth inhibition assay Cell viability
S1230-viability1
31193061

임상시험 정보 (Clinical Trial Information)

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

NCT 번호 모집 조건 스폰서/협력자 시작일 단계
NCT03441555 Completed
Acute Myeloid Leukemia (AML)
AbbVie|Sumitomo Pharma America Inc.
 May 30 2018 Phase 1
NCT03298984 Completed
Acute Myeloid Leukemia
Sumitomo Pharma America Inc.
 September 25 2017 Phase 1