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Pioglitazone HCl P450 (e.g. CYP17) remmer

Name: Pioglitazone HCl
Brand: Selleck Chemicals
SKU: S2046
Rating: 5 (11 reviews)

Cat.nr.S2046

Pioglitazone HCl (AD-4833, U-72107E) is een remmer van cytochrome P450 (CYP)2C8 en CYP3A4 enzymen. Deze verbinding remt CYP2C8, CYP3A4 en CYP2C9 met Ki-waarden van respectievelijk 1,7 μM, 11,8 μM en 32,1 μM. Het is ook een selectieve peroxisome proliferator-activated receptor-gamma (PPARγ) agonist met een EC50 van respectievelijk 0,93 μM en 0,99 μM voor humaan PPARγ en muis-PPARγ. Deze chemische stof remt mitochondriale ijzeropname, lipideperoxidatie en daaropvolgende ferroptosis.

Pioglitazone HCl P450 (e.g. CYP17) remmer Chemical Structure

Chemische structuur

Molecuulgewicht: 392.9

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Kwaliteitscontrole

Batch: Zuiverheid: 99.88%

99.88

Gerelateerde doelwitten	Dehydrogenase HSP Transferase PDE phosphatase PPAR Vitamin Carbohydrate Metabolism Mitochondrial Metabolism Drug Metabolite
Overig P450 (e.g. CYP17) Inhibitoren	Apigenin Baicalein Avasimibe Naringenin Diosmetin Alizarin Orteronel Benzbromarone Sodium Danshensu Naringin

Celkweek, behandeling & werkzame concentratie

Cellijnen	Assaytype	Concentratie	Incubatietijd	Activiteitsbeschrijving	PMID
COS cells	Function assay			Transcriptional activation in COS cells expressing PPAR gamma and RXR alpha; values in the parentheses indicates 95% confidence interval, EC50=0.49 μM	11906293
HepG2 cells	Function assay			Peroxisome proliferator activated receptor gamma agonistic activity in HepG2 cells, EC50=7.6 μM	10714503
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	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
Klik om meer experimentele gegevens over cellijnen te bekijken

Chemische informatie, opslag en stabiliteit

Molecuulgewicht	392.9	Formule	C₁₉H₂₀N₂O₃S.HCl	Opslag (vanaf de datum van ontvangst)	3 jaar-20°Cpoeder
CAS-nr.	112529-15-4	SDF downloaden		Opslag van stamoplossingen	1 jaar-80°Cin oplosmiddel 1 maand-20°Cin oplosmiddel
Synoniemen	AD-4833, U-72107E			Smiles	CCC1=CN=C(C=C1)CCOC2=CC=C(C=C2)CC3C(=O)NC(=O)S3.Cl

Oplosbaarheid

In vitro
Batch:

DMSO : 79 mg/mL (201.06 mM)
(Met vocht verontreinigd DMSO kan de oplosbaarheid verminderen. Gebruik verse, watervrije DMSO.)

Ethanol : 4 mg/mL

Water : Insoluble

Molariteitscalculator

Massa	Concentratie	Volume	Molecuulgewicht
=	×	×

Verdunningscalculator Molecuulgewichtcalculator

In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 Corn oil Gevalideerd door Selleck labs. Mocht u aanpassingen aan deze formulering nodig hebben, neem dan contact op met ons verkoopteam voor aangepaste tests.	5.000mg/ml (12.73mM)	Taking the 1 mL working solution as an example, add 50 μL of 100 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Gevalideerd door Selleck labs. Mocht u aanpassingen aan deze formulering nodig hebben, neem dan contact op met ons verkoopteam voor aangepaste tests.	5.000mg/ml (12.73mM)	Taking the 1 mL working solution as an example, add 50 μL of 100 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Gevalideerd door Selleck labs. Mocht u aanpassingen aan deze formulering nodig hebben, neem dan contact op met ons verkoopteam voor aangepaste tests.	2.000mg/ml (5.09mM)	Taking the 1 mL working solution as an example, add 50 μL of 40 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to make it clear; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.

In vivo formulatiecalculator (heldere oplossing)

Stap 1: Voer onderstaande informatie in (Aanbevolen: een extra dier om rekening te houden met verlies tijdens het experiment)

Dosering: mg/kg Gemiddeld gewicht van dieren: g Doseervolume per dier:μL Aantal dieren:

Stap 2: Voer de in vivo formulering in (Dit is alleen de calculator, geen formulering. Neem eerst contact met ons op als er geen in vivo formulering is in de sectie oplosbaarheid.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Berekeningsresultaten:

Werkconcentratie: mg/ml;

Methode voor het bereiden van DMSO-moedervloeistof: mg geneesmiddel vooropgelost in μL DMSO ( Concentratie moedervloeistof mg/mL, Neem eerst contact met ons op als de concentratie de DMSO-oplosbaarheid van de batch van het geneesmiddel overschrijdt. )

Methode voor het bereiden van in vivo formulering: Neem μL DMSO moedervloeistof, voeg daarna toeμL PEG300, mengen en verhelderen, daarna toevoegenμL Tween 80, mengen en verhelderen, daarna toevoegen μL ddH₂O, mengen en verhelderen.

Methode voor het bereiden van in vivo formulering: Neem μL DMSO moedervloeistof, voeg daarna toe μL Maïsolie, mengen en verhelderen.

Opmerking: 1. Zorg ervoor dat de vloeistof helder is voordat u het volgende oplosmiddel toevoegt.
2. Zorg ervoor dat u het/de oplosmiddel(en) in de juiste volgorde toevoegt. U moet ervoor zorgen dat de verkregen oplossing, bij de vorige toevoeging, een heldere oplossing is voordat u verdergaat met het toevoegen van het volgende oplosmiddel. Fysieke methoden zoals vortexen, ultrasoon of een warmwaterbad kunnen worden gebruikt om het oplossen te bevorderen.

Werkingsmechanisme

Targets/IC₅₀/Ki	Ferroptosis hPPARγ (Cell-free assay) 0.93 μM(EC50) rPPARγ (Cell-free assay) 0.99 μM(EC50) CYP2C8 (Cell-free assay) 1.7 μM(Ki) CYP3A4 (Cell-free assay) 11.8 μM(Ki) CYP2C9 (Cell-free assay) 32.1 μM(Ki)
In vitro	Pioglitazone HCl remt LPS-geïnduceerde iNOS-expressie en NO-generatie, en remming van iNOS is voldoende om dopaminerge neuronen te beschermen tegen LPS-letsel. Deze verbinding beschermt dopaminerge neuronen tegen LPS-letsel, althans via remming van iNOS-expressie en NO-generatie, wat potentieel gemedieerd wordt via remming van p38 MAPK-activiteit. Het remt LPS-geïnduceerde fosforylering van p38 MAPK.
In vivo	Oraal toegediend Pioglitazone HCl (0,3-3 mg/kg/dag gedurende 7 dagen) vermindert dosisafhankelijk hyperglycemie, hyperlipidemie en hyperinsulinemie bij mannelijke vette ratten. Deze verbinding verbetert de glucosetolerantie en verhoogt de glycemische respons op exogeen insuline en de klaring van plasma-triglyceriden bij ratten. Transgene muizen die met deze verbinding zijn behandeld, vertonen verbeterde spierkracht en lichaamsgewicht, een vertraagd begin van de ziekte en overleven significant langer dan onbehandelde SOD1-G93A-muizen. Deze chemische stof vermindert significant hyperglycemie, hyperlipidemie, hyperinsulinemie en glucose-intolerantie gekarakteriseerd als insulineresistente toestanden bij deze ratten en muizen. Het potentiëert insuline-gemedieerd glucose-Metabolism in het diafragma en vetweefsels van gele KK-muizen en verhoogt de glycemische respons op exogeen insuline bij Zucker-vette ratten. Dit middel resulteert in een vermindering van het aantal geactiveerde microglia en reactieve astrocyten in de hippocampus en cortex van APPV717I-transgene muizen. Het verlaagt de bèta-secretase-1 (BACE1) mRNA- en eiwitniveaus in APPV717I-transgene muizen.
Referenties	[1] https://pubmed.ncbi.nlm.nih.gov/18205920/ [2] https://pubmed.ncbi.nlm.nih.gov/2189419/ [3] https://pubmed.ncbi.nlm.nih.gov/16120782/ [4] https://pubmed.ncbi.nlm.nih.gov/2334455/ [5] https://pubmed.ncbi.nlm.nih.gov/8767349/ [6] https://pubmed.ncbi.nlm.nih.gov/14982965/ [7] https://pubmed.ncbi.nlm.nih.gov/12642470/ [8] https://pubmed.ncbi.nlm.nih.gov/27510639/

Informatie over klinische proeven

(gegevens van https://clinicaltrials.gov, bijgewerkt op 2024-05-22)

NCT-nummer	Werving	Aandoeningen	Sponsor/medewerkers	Startdatum	Fasen
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

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