Home Metabolism PPAR agonist Pioglitazone (U-72107)

연구용

Pioglitazone (U-72107) PPARγ Agonist

제품 번호: S2590

Pioglitazone is a selective peroxisome proliferator-activated receptor-gamma (PPARγ) agonist, used to treat diabetes; A weak activator for full-length hPPARα, but not full-length hPPARδ.
Pioglitazone (U-72107) PPAR agonist Chemical Structure

화학 구조

분자량: 356.44

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품질 관리 (Quality Control)

배치: 순도: 99.83%
99.83

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

세포주 분석 유형 농도 배양 시간 제형 활성 설명 PMID
CV-1 Function assay In vitro transcriptional activation of Peroxisome proliferator activated receptor gamma (PPAR) expressed in CV-1 cells, EC50=0.69μM 8576907
3T3-L1 Function assay Effective concentration for 50% enhancement of insulin-induced triglyceride accumulation in 3T3-L1 cells, EC50=0.16μM 9599241
CV-1 Function assay Activation of peroxisome proliferator activated receptor gamma measured by induction of 50% of maximum alkaline phosphatase activity, transfection assay in CV-1 cells, EC50=0.58884μM 9836620
CV-1 Function assay Maximal reporter activity against human Peroxisome proliferator activated receptor gamma Gal4 chimeric in transiently transfected CV-1 cells by functional assay., EC50=0.58μM 11720854
HEK293 Function assay Agonist activity at PPARgamma expressed in HEK293 cells assessed as induction of receptor interaction with steroid receptor coactivator-1 by EYFP based reporter gene assay 16680159
HEK293 Function assay Agonist activity at PPARgamma expressed in HEK293 cells assessed as induction of receptor interaction with retinoid X-receptor alpha by EYFP based reporter gene assay 16680159
CV1 Function assay Transactivation of PPARgamma in CV1 cells, EC50=0.55μM 16821769
Cos7 Function assay 14 hrs Transactivation of human PPARgamma LBD expressed in african green monkey Cos7 cells co-transfected with fused GAL4-DBD after 14 hrs by Dual-Glo Luciferase reporter gene assay, EC50=0.3μM 20307981
3T3L1 Function assay 100 umol/L Increase in PPARgamma mRNA levels in mouse 3T3L1 cells at 100 umol/L by RT-PCR 20392645
CHO Function assay Activation of Gal4-tagged human PPARgamma expressed in CHO cells by luciferase reporter gene assay, EC50=0.14μM 20656494
HEK293T Function assay 1 uM 24 hrs Partial agonist activity at human PPARgamma-LBD expressed in HEK293T cells assessed as induction of receptor transactivation at 1 uM after 24 hrs by luciferase reporter gene assay 21030263
COS-1 Function assay Agonist activity at human PPARgamma ligand binding domain expressed in COS-1 cells co-transfected with Gal4 by luciferase reporter gene assay, EC50=0.39μM 21130649
CHO Function assay 24 hrs Partial agonist activity at human PPARgamma expressed in CHO cells co-transfected with Gal4-responsive luciferase reporter plasmid after 24 hrs by transactivation assay, EC50=0.39μM 21377875
COS7 Function assay Modulation of human PPARgamma-LBD expressed in african green monkey COS7 cells co-transfected with Gal4 assessed as activation of transactivation activity by luciferase assay, EC50=0.3μM 21873070
Sf21 Function assay Inhibition of human BSEP expressed in plasma membrane vesicles of Sf21 cells assessed as inhibition of ATP-dependent [3H]taurocholate uptake, IC50=0.3μM 21965623
Sf21 Function assay Inhibition of Sprague-Dawley rat Bsep expressed in plasma membrane vesicles of Sf21 cells assessed as inhibition of ATP-dependent [3H]taurocholate uptake, IC50=2μM 21965623
HepG2 Function assay 20 hrs Agonist activity at GAL4-tagged human PPARgamma ligand binding domain expressed in HepG2 cells assessed as transactivation after 20 hrs by beta-galactosidase reporter gene assay, EC50=0.57μM 22341573
HEK293 Function assay 18 hrs Transactivation of human GAL4-fused PPARgamma ligand binding domain transfected in HEK293 cells after 18 hrs by dual luciferase reporter gene assay, EC50=0.8μM 23102891
COS7 Function assay Transactivation of GAL4-fused human PPARgamma ligand binding domain transfected in african green monkey COS7 cells by luciferase reporter gene assay, EC50=0.2μM 23130964
THP1 Antiinflammatory assay 1 hr Antiinflammatory activity in human THP1 cells assessed as inhibition of PMA-induced MCP-1 secretion preincubated for 1 hr prior PMA-challenge measured after 48 hrs by ELISA, IC50=18.84μM 23811092
THP1 Antiinflammatory assay 2 hrs Antiinflammatory activity in human THP1 cells assessed as inhibition of PMA-induced MCP-1 secretion incubated for 2 hrs prior to PMA challenge measured after 72 hrs by ELISA, IC50=18.6μM 24531227
HEK293 Function assay 10 uM 24 hrs Transactivation of PPAR-gamma (unknown origin) expressed in HEK293 cells at 10 uM after 24 hrs by luciferase reporter gene assay 24890090
HEK293 Function assay 18 hrs Agonist activity at human PPARgamma expressed in HEK293 cells incubated for 18 hrs by luciferase reporter gene assay, EC50=0.21μM 25333853
COS7 Function assay Transactivation of human PPARgamma expressed in African green monkey COS7 cells incubated overnight by dual-glo luciferase reporter gene assay, EC50=0.2μM 26595749
THP1 Function assay 10 uM 24 hrs Upregulation of ABCA1 mRNA expression in human THP1 cells at 10 uM after 24 hrs by qPCR method relative to control 27220065
THP1 Function assay 10 uM 24 hrs Upregulation of ABCG1 mRNA expression in human THP1 cells at 10 uM after 24 hrs by qPCR method relative to control 27220065
COS7 Function assay 42 hrs Transactivation of GAL4-fused human PPARgamma ligand binding domain expressed in African green monkey COS7 cells after 42 hrs by dual luciferase reporter gene assay, EC50=0.5μM 27560282
COS7 Function assay 42 hrs Transactivation at Gal4 fused PPARgamma LBD (unknown origin) expressed in African green monkey COS7 cells after 42 hrs by luciferase assay, EC50=0.32μM 27569195
COS7 Function assay 42 hrs Transactivation of Gal4 fused human PPARgamma LBD expressed in African green monkey COS7 cells after 42 hrs by dual luciferase reporter gene assay, EC50=0.38μM 27918994
PC3 Function assay 50 uM 24 hrs Increase in p21(WAF1) protein expression in human PC3 cells at 50 uM incubated for 24 hrs by Western blot analysis 28395220
MDA-MB-231 Function assay 50 uM 24 hrs Increase in p21(WAF1) protein expression in human MDA-MB-231 cells at 50 uM incubated for 24 hrs by Western blot analysis 28395220
HEK293 Function assay 24 hrs Transactivation activity at Gal4 fused full length human PPARgamma LBD expressed in HEK293 cells after 24 hrs by luciferase reporter gene assay, EC50=1.1μM 28465099
HEK293 Function assay 4 hrs Transrepression activity at human PPARgamma expressed in HEK293 cells assessed as inhibition of TNFalpha induced NF-kappaB promoter activity pretreated for 4 hrs followed by TNFalpha stimulation after 3 hrs by luciferase reporter gene assay, IC50=22μM 28465099
SCC15 Cytotoxicity assay 50 uM 24 hrs Cytotoxicity against human SCC15 cells transfected with PPARalpha siRNA assessed as reduction in cell viability at 50 uM after 24 hrs by resazurin reduction assay 29031063
SCC15 Cytotoxicity assay 50 uM 24 hrs Cytotoxicity against human SCC15 cells transfected with PPARbeta siRNA assessed as reduction in cell viability at 50 uM after 24 hrs by resazurin reduction assay 29031063
HepG2 Function assay 24 hrs Agonist activity at PPARgamma in human HepG2 cells assessed as activation of PPRE incubated for 24 hrs by dual luciferase reporter gene assay, EC50=0.24μM 30001846
HEK293BENA Function assay 24 hrs Transactivation of GAL4-fused human PPARgamma transfected in HEK293BENA cells after 24 hrs by steady glo-luciferase reporter gene assay, EC50=2.053μM 30351933
HEK293 Function assay 18 hrs Transactivation of human full length PPARgamma expressed in HEK293 cells after 18 hrs by luciferase reporter gene based luminescence assay, EC50=0.1μM 30362739
293H Function assay 16 hrs Transactivation of GAL4-DBD fused human PPARgamma ligand binding domain expressed in UAS-bla HEL 293H cells preincubated for 16 hrs followed by FRET substrate addition and measured after 2 hrs by TR-FRET assay, EC50=0.098μM 30429097
3T3L1 Function assay 10 uM 24 hrs Agonist activity at PPARgamma in mouse 3T3L1 cells assessed as increase in AP1 mRNA expression at 10 uM after 24 hrs by SYBR green dye based RT-PCR analysis 30594432
3T3L1 Function assay 10 uM 24 hrs Agonist activity at PPARgamma in mouse 3T3L1 cells assessed as increase in CD36 mRNA expression at 10 uM after 24 hrs by SYBR green dye based RT-PCR analysis 30594432
3T3L1 Function assay 10 uM 24 hrs Agonist activity at PPARgamma in mouse 3T3L1 cells assessed as increase in Glut4 mRNA expression at 10 uM after 24 hrs by SYBR green dye based RT-PCR analysis 30594432
3T3L1 Function assay 10 uM 24 hrs Agonist activity at PPARgamma in mouse 3T3L1 cells assessed as increase in adiponectin mRNA expression at 10 uM after 24 hrs by SYBR green dye based RT-PCR analysis 30594432
stem cells Function assay 5 days Induction of adipogenesis in human bone marrow-derived mesenchymal stem cells assessed as increase in adiponectin production measured on day 5 in presence of IDX by ELISA, EC50=0.35μM 30672698
HEK293T Function assay 18 hrs Transactivation of full length human PPARgamma2 expressed in HEK293T cells co-expressing PPRE after 18 hrs by luciferase reporter gene assay, EC50=0.25μM 30676741
HEK293T Function assay 18 hrs Transactivation of chimeric Gal4 yeast DBD fused-PPARgamma LBD (unknown origin) expressed in HEK293T cells co-expressing PPRE after 18 hrs by luciferase reporter gene assay, EC50=0.35μM 30676741
HepG2 Function assay 30 uM Binding affinity to NAF1 (unknown origin) expressed in human HepG2 cells assessed as inhibition of mitochondrial respiration at 30 uM 30770154
HepG2 Function assay 30 uM Binding affinity to NAF1 in human HepG2 cells assessed as inhibition of mitochondrial respiration at 30 uM 30770154
COS7 Function assay 39 hrs Transactivation of Gal4-fused human PPARgamma transfected in COS7 cells co-transfected with pGAL5-TK-pGL3 and pRennilla-CMV incubated for 39 hrs by dual luciferase reporter assay, EC50=1.4μM 31648125
K562-IMA[r] Function assay 10 uM 72 hrs Induction of sensitization to imatinib-induced cytotoxicity in imatinib-resistant human K562-IMA[r] cells assessed as induction of cell death at 10 uM after 72 hrs in presence of 1 uM imatinib by propidium iodide/Triton-X100 dye based FACS analysis 31648125
클릭하여 더 많은 세포주 실험 데이터 보기

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

분자량 356.44 화학식

C19H20N2O3S

 보관 (수령일로부터)
CAS 번호 111025-46-8 SDF 다운로드 원액 보관

동의어 AD-4833, U 72107 Smiles CCC1=CN=C(C=C1)CCOC2=CC=C(C=C2)CC3C(=O)NC(=O)S3

용해도 (Solubility)

In vitro
배치:

DMSO : 20 mg/mL (56.11 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)

Targets/IC50/Ki
PPARγ
시험관 내(In vitro)

Pioglitazone is metabolised mainly by CYP2C8 and to a lesser extent by CYP3A4 in vitro. 
생체 내(In vivo)

Pioglitazone significantly attenuates left ventricular (LV) cavity dilatation and dysfunction by echocardiography as well as LV end-diastolic pressure in mice with extensive anterior myocardial infarction. This compound partially normalizes LV dP/dt(max) and dP/dt(min), indices of LV contractile function, which are significantly reduced in MI mice.

This compound results in a reduced activation of microglia, reduced induction of iNOS-positive cells and less glial fibrillary acidic protein positive cells in both striatum and substantia nigra pars compacta of MPTP mouse model of Parkinson's disease. It almost completely blocks staining of TH-positive neurons for nitrotyrosine, a marker of NO-mediated cell damage. 

This chemical (approximately 20 mg/kg/day) attenuates the MPTP-induced glial activation and prevents the dopaminergic cell loss in the substantia nigra pars compacta (SNpc) in MPTP mouse model of Parkinson's disease.

It results in a reduction in the number of activated microglia and reactive astrocytes in the hippocampus and cortex of 10-month-old APPV717I transgenic mice. Treatment with this compound reduces the expression of the proinflammatory enzymes cyclooxygenase 2 (COX2) and inducible nitric oxide synthase (iNOS). It decreases beta-secretase-1 (BACE1) mRNA and protein levels, and also a 27% reduction in the levels of soluble Abeta1-42 peptide. 
참조
  • [4] https://pubmed.ncbi.nlm.nih.gov/12153485/
  • [5] https://pubmed.ncbi.nlm.nih.gov/15817521/
  • [6] https://pubmed.ncbi.nlm.nih.gov/34989130/

적용 분야 (Applications)

방법 바이오마커 이미지 PMID
Western blot p-VEGFR2 / VEGFR Phopsho-RB / RB
S2590-WB1
29972411

임상시험 정보 (Clinical Trial Information)

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

NCT 번호 모집 조건 스폰서/협력자 시작일 단계
NCT05946564 Not yet recruiting
ANCA Associated Vasculitis|Rapidly Progressive Glomerulonephritis|Crescentic Glomerulonephritis
Assistance Publique - Hôpitaux de Paris|Ministry of Health France
 July 2023 Phase 3
NCT05305287 Recruiting
Non-Alcoholic Fatty Liver Disease|Type 2 Diabetes|Mitochondrial Metabolism Disorders
The University of Texas Health Science Center at San Antonio|National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
 November 1 2022 Phase 4
NCT05411965 Completed
Diabetes Mellitus Type 2
Boryung Pharmaceutical Co. Ltd
 April 28 2022 Phase 1
NCT04501406 Recruiting
Type 2 Diabetes Mellitus (T2DM)|Nonalcoholic Steatohepatitis
University of Florida|National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
 December 15 2020 Phase 2
NCT04535700 Completed
Type 2 Diabetes
Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal
 September 18 2020 Phase 4
NCT00904046 Recruiting
Uric Acid Kidney Stone Disease
University of Texas Southwestern Medical Center|National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)|Takeda Pharmaceuticals North America Inc.
 September 5 2019 Not Applicable