Name: Dapagliflozin (BMS-512148)
Brand: Selleck Chemicals
SKU: S1548
Rating: 5 (44 reviews)

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Controllo Qualità

Lotto: Purezza: 99.99%

99.99

Target correlati	CXCR Hedgehog/Smoothened PKA Adrenergic Receptor AChR 5-HT Receptor Histamine Receptor Dopamine Receptor Ras KRas
Altro SGLT Inibitori	Sotagliflozin (LX4211) Phlorizin Phloretin (RJC 02792) Tofogliflozin(CSG 452) Ipragliflozin (ASP1941) KGA-2727 Mizagliflozin (KWA 0711, DSP-3235 free base) Ipragliflozin L-Proline Bexagliflozin (EGT1442) Swertisin

Coltura cellulare, trattamento e concentrazione di lavoro

Linee cellulari	Tipo di saggio	Tempo di incubazione	Descrizione dellattività	PMID
CHO cells	Function assay	2 h	Inhibition of human SGLT2 expressed in CHO cells assessed as [14C]alpha-methyl-D-glucopyranoside uptake after 2 hrs by liquid scintillation counting, IC50=0.00049 μM	20434909
CHOK1 cells	Function assay	3 h	Inhibition of human SGLT2 expressed in CHOK1 cells assessed as inhibition of [14C]-AMG uptake after 3 hrs by microbeta scintillation counting analysis, IC50=0.001 μM	24842618
HEK293.ETN cells	Function assay	1.5 h	Inhibition of human SGLT2 transfected in HEK293.ETN cells assessed as AMG uptake after 1.5 hrs by scintillation counting, IC50=0.0067 μM	19896374
COS-7 cells	Function assay	2 h	Inhibition of human SGLT1 transfected in COS-7 cells assessed as AMG uptake after 2 hrs by scintillation counting, IC50=0.89 μM	19896374
CHO	Function assay		Inhibition of human SGLT2 expressed in CHO cells assessed as inhibition of [14C]AMG accumulation, EC50 = 0.0011 μM.	18260618
CHO	Function assay		Inhibition of rat SGLT2 expressed in CHO cells assessed as inhibition of [14C]AMG accumulation, EC50 = 0.003 μM.	18260618
CHO	Function assay		Inhibition of human SGLT1 expressed in CHO cells assessed as inhibition of [14C]AMG accumulation, EC50 = 1.39 μM.	18260618
HEK293.ETN	Function assay		Inhibition of human SGLT2 expressed in HEK293.ETN cells assessed as methyl-alpha-D-[U-14C]glucopyranoside uptake by scintillation counting, IC50 = 0.0067 μM.	19700318
COS7	Function assay		Inhibition of human SGLT1 expressed in african green monkey COS7 cells assessed as methyl-alpha-D-[U-14C]glucopyranoside uptake by scintillation counting, IC50 = 0.885 μM.	19700318
HEK293	Function assay		Inhibition of human SGLT1 expressed in HEK293 cells assessed as inhibition of [14C]alpha-methylglucopyranoside uptake, IC50 = 0.81 μM.	19785435
CHO	Function assay	2 hrs	Inhibition of human SGLT2 expressed in CHO cells assessed as inhibition of sodium-dependent methyl-alpha-D-[U-14C]glucopyranoside uptake after 2 hrs, IC50 = 0.0014 μM.	20149653
CHO	Function assay	2 hrs	Inhibition of human SGLT1 expressed in CHO cells assessed as inhibition of sodium-dependent methyl-alpha-D-[U-14C]glucopyranoside uptake after 2 hrs, IC50 = 1.2 μM.	20149653
CHO	Function assay		Inhibition of human recombinant SGLT2 expressed in CHO cells by liquid scintillation counting, IC50 = 0.00049 μM.	20181486
HEK293	Function assay	1.5 hrs	Inhibition of human SGLT2 expressed in HEK293 cells assessed as inhibition of [14C]alpha-methyl-D-glucopyranoside uptake after 1.5 hrs by liquid scintillation counting, IC50 = 0.0067 μM.	20576578
COS7	Function assay	2 hrs	Inhibition of human SGLT1 expressed in african green monkey COS7 cells assessed as inhibition of [14C]alpha-methyl-D-glucopyranoside uptake after 2 hrs by liquid scintillation counting, IC50 = 0.89 μM.	20576578
CHO	Function assay	2 hrs	Inhibition of human SGLT2 expressed in CHO cells assessed as sodium-dependent [14C]-alpha-methyl-D-glucopyranoside uptake after 2 hrs by liquid scintillation counting, EC50 = 0.003 μM.	21128592
CHO	Function assay	2 hrs	Inhibition of human SGLT1 expressed in CHO cells assessed as sodium-dependent [14C]-alpha-methyl-D-glucopyranoside uptake after 2 hrs by liquid scintillation counting, EC50 = 0.4285 μM.	21128592
CHO	Function assay	2 hrs	Inhibition of human SGLT2 expressed in CHO cells assessed as inhibition of [14C]alpha-methyl-D-glucopyranoside uptake after 2 hrs by liquid scintillation counting, IC50 = 0.00049 μM.	21193308
CHO	Function assay	60 mins	Inhibition of human SGLT2 expressed in CHO cells assessed as inhibition of [14C]-alpha-methyl-D-glucopyranoside transport after 60 mins by scintillation counting, IC50 = 0.004 μM.	21398124
CHO	Function assay	60 mins	Inhibition of human SGLT2 expressed in CHO cells assessed as inhibition of [14C]-alpha-methyl-D-glucopyranoside transport after 60 mins by scintillation counting in presence of 100% plasma, IC50 = 0.022 μM.	21398124
CHO	Function assay	60 mins	Inhibition of human SGLT1 expressed in CHO cells assessed as inhibition of [14C]-alpha-methyl-D-glucopyranoside transport after 60 mins by scintillation counting, IC50 = 0.37 μM.	21398124
CHO	Function assay	60 mins	Inhibition of SGLT6 expressed in CHO cells assessed as inhibition of [14C]-alpha-methyl-D-glucopyranoside transport after 60 mins by scintillation counting, IC50 = 0.38 μM.	21398124
CHO	Function assay	2 hrs	Inhibition of human SGLT2 expressed in CHO cells assessed as [14C]-alpha-methyl-D-glucopyranoside uptake after 2 hrs by liquid scintillation counter, IC50 = 0.00049 μM.	21514014
CHO	Function assay	60 mins	Inhibition of human SGLT2 expressed in CHO cells assessed as inhibition of [14C]-Glucose uptake using [14C]-methyl glucopyranoside after 60 mins by microbeta plate counting, IC50 = 0.003 μM.	21565497
CHO	Function assay		Inhibition of human SGLT2 expressed in CHO cells using methyl-alpha-D-glucopyranoside by liquid scintillation counting, IC50 = 0.00135 μM.	21592794
COS7	Function assay	2 hrs	Inhibition of human SGLT2 expressed in african green monkey COS7 cells assessed as inhibition of [14C]-methyl-alpha-D-glucopyranoside uptake after 2 hrs by scintillation counting in presence of 25 % human plasma, IC50 = 0.0032 μM.	21737266
293	Function assay	1.5 hrs	Inhibition of human SGLT1 expressed in human 293 cells assessed as inhibition of [14C]-methyl-alpha-D-glucopyranoside uptake after 1.5 hrs by scintillation counting in presence of 25 % human plasma, IC50 = 3.1 μM.	21737266
CHO	Function assay	2 hrs	Inhibition of human SGLT2 expressed in CHO cells assessed as reduction of [14C]-labeled AMG after 2 hrs by liquid scintillation counting, IC50 = 0.00135 μM.	21868239
CHO	Function assay	2 hrs	Inhibition of human SGLT2 expressed in CHO cells assessed as [14C]-alpha-methyl-D-glucopyranoside uptake after 2 hrs by liquid scintillation counting, IC50 = 0.00049 μM.	21906953
CHO-K1	Function assay		Inhibition of human SGLT2 expressed in CHO-K1 cells by [14C]AMG uptake assay, IC50 = 0.0013 μM.	22652255
CHO-K1	Function assay		Inhibition of human SGLT1 expressed in CHO-K1 cells by [14C]AMG uptake assay, IC50 = 0.8 μM.	22652255
CHO-K1	Function assay	120 mins	Inhibition of human SGLT2 expressed in CHO-K1 cells incubated for 120 mins at 37 degC by [14C]-AMG uptake assay, EC50 = 0.0024 μM.	22818040
CHO-K1	Function assay	120 mins	Inhibition of human SGLT1 expressed in CHO-K1 cells incubated for 120 mins at 37 degC by [14C]-AMG uptake assay, EC50 = 0.593 μM.	22818040
CHO	Function assay	45 mins	Inhibition of human SGLT2 expressed in CHO cells assessed as inhibition of sodium-dependent [14C]methyl-alpha-D-glucopyranoside uptake after 45 mins, IC50 = 0.0013 μM.	22889351
CHO	Function assay	45 mins	Inhibition of human SGLT1 expressed in CHO cells assessed as inhibition of sodium-dependent [14C]methyl-alpha-D-glucopyranoside uptake after 45 mins, IC50 = 0.8 μM.	22889351
CHOK1	Function assay	3 hrs	Inhibition of human SGLT1 expressed in CHOK1 cells assessed as inhibition of [14C]-AMG uptake after 3 hrs by microbeta scintillation counting analysis, IC50 = 0.891 μM.	24842618
CHO	Function assay	2 hrs	Inhibition of human SGLT2 expressed in CHO cells assessed as [14C]-alpha-methyl-D-glucopyranoside uptake after 2 hrs by liquid scintillation counting, IC50 = 0.00049 μM.	24900297
CHO	Function assay	2 hrs	Competitive inhibition of full-length human SGLT2 expressed in CHO cells assessed as inhibition of sodium-dependent [14C]-alpha-methyl-D-glucopyranoside uptake after 2 hrs by scintillation counting, IC50 = 0.005 μM.	25650254
CHO	Function assay	120 mins	Inhibition of human SGLT2 expressed in CHO cells assessed as decrease in uptake of [14C]AMG after 120 mins by TopCount method, IC50 = 0.0015 μM.	28447791
CHO	Function assay	120 mins	Inhibition of human SGLT1 expressed in CHO cells assessed as decrease in uptake of [14C]AMG after 120 mins by TopCount method, IC50 = 0.629 μM.	28447791
CHO	Function assay	1 hr	Inhibition of human SGLT2 expressed in CHO cells assessed as reduction in [14C]AMG uptake after 1 hr by microbeta counting method, EC50 = 0.002 μM.	29216560
CHO	Function assay	1 hr	Inhibition of human SGLT1 expressed in CHO cells assessed as reduction in [14C]AMG uptake after 1 hr by microbeta counting method, EC50 = 0.86 μM.	29216560
CHO	Function assay	1 hr	Inhibition of full-length human SGLT2 expressed in CHO cells assessed as decrease in [14C]-methyl alpha-D-glucopyranoside uptake after 1 hr by liquid scintillation counting method, IC50 = 0.00105 μM.	29764742
HEK293	Function assay	10 mins	Inhibition of human SGLT2 expressed in HEK293 cells assessed as decrease in [14C]-AMG uptake preincubated for 10 mins followed by [14C]-AMG addition and measured after 2 hrs by liquid scintillation counting method, IC50 = 0.0014 μM.	29954682
HEK293	Function assay	10 mins	Inhibition of human SGLT1 expressed in HEK293 cells assessed as decrease in [14C]-AMG uptake preincubated for 10 mins followed by [14C]-AMG addition and measured after 2 hrs by liquid scintillation counting method, IC50 = 1.83 μM.	29954682
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Informazioni chimiche, conservazione e stabilità

Peso molecolare	408.87	Formula	C₂₁H₂₅ClO₆	Conservazione (Dalla data di ricezione)	3 years -20°C powder (seal)
N. CAS	461432-26-8	Scarica SDF		Conservazione delle soluzioni stock	1 anno-80°Cin solvente 1 mese-20°Cin solvente
Sinonimi	BMS-512148			Smiles	CCOC1=CC=C(C=C1)CC2=C(C=CC(=C2)C3C(C(C(C(O3)CO)O)O)O)Cl

Solubilità

In vitro
Lotto:

DMSO : 100 mg/mL (244.57 mM)
(Il DMSO contaminato da umidità può ridurre la solubilità. Utilizzare DMSO fresco e anidro.)

Ethanol : 100 mg/mL

Water : Insoluble

Calcolatore di Molarità

Massa	Concentrazione	Volume	Peso molecolare
=	×	×

Calcolatore di Diluizione Calcolatore del Peso Molecolare

In vivo Lotto:
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.
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 40%PEG300 2 5%Tween80 3 50%ddH2O Validato dai laboratori Selleck. Se necessiti di modifiche a questa formulazione, contatta il nostro team di vendita per test personalizzati.	4.100mg/ml (10.03mM)	Taking the 1 mL working solution as an example, add 50 μL 82 mg/ml clarified DMSO stock solution to 400 μL PEG300, mix evenly to clarify it; add 50 μL Tween80 to the above system, mix evenly to clarify it; then continue to add 500 μL ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.

Calcolatore di formulazione in vivo (Soluzione chiara)

Passo 1: Inserire le informazioni di seguito (Consigliato: Un animale aggiuntivo per tenere conto della perdita durante lesperimento)

Dosaggio: mg/kg Peso medio degli animali: g Volume di dosaggio per animale:μL Numero di animali:

Passo 2: Inserire la formulazione in vivo (Questo è solo il calcolatore, non la formulazione. Contattateci prima se non cè una formulazione in vivo nella sezione Solubilità.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Risultati del calcolo:

Concentrazione di lavoro: mg/ml;

Metodo per preparare il liquido master di DMSO: mg farmaco predissolto in μL DMSO ( Concentrazione del liquido master mg/mL, Vi preghiamo di contattarci prima se la concentrazione supera la solubilità del DMSO del lotto del farmaco. )

Metodo per preparare la formulazione in vivo: Prendere μL DMSO liquido master, quindi aggiungereμL PEG300, mescolare e chiarire, quindi aggiungereμL Tween 80, mescolare e chiarire, quindi aggiungere μL ddH₂O, mescolare e chiarire.

Metodo per preparare la formulazione in vivo: Prendere μL DMSO liquido master, quindi aggiungere μL Olio di mais, mescolare e chiarire.

Nota: 1. Si prega di assicurarsi che il liquido sia limpido prima di aggiungere il solvente successivo.
2. Assicurarsi di aggiungere il/i solvente/i in ordine. È necessario assicurarsi che la soluzione ottenuta, nellaggiunta precedente, sia una soluzione limpida prima di procedere allaggiunta del solvente successivo. Metodi fisici come il vortex, gli ultrasuoni o il bagno dacqua calda possono essere utilizzati per facilitare la dissoluzione.

Meccanismo dazione

Caratteristiche	More potent stimulator of glucosuria than other SGLT2 inhibitors.
Targets/IC₅₀/Ki	hSGLT2 (CHO cells) 1.1 nM(EC50)
In vitro	Dapagliflozin non è sensibile a hSGLT1 con un IC50 1200 volte superiore. Questo composto è 32 volte più potente della florizina contro hSGLT2 ma 4 volte meno potente della florizina contro hSGLT1. È altamente selettivo verso i trasportatori GLUT e mostra un'inibizione dell'8-9% in tampone senza proteine a 20 μM e praticamente nessuna inibizione in presenza del 4% di albumina sierica bovina. Questa sostanza chimica ha una buona permeabilità attraverso le membrane delle cellule Caco-2 ed è un substrato per la P-glicoproteina (P-gp) ma non un inibitore significativo della P-gp. È stabile nel siero di ratto, cane, scimmia e umano a 10 μM. Non mostra risposte inibitorie o induzione agli enzimi P450 umani. Le vie metaboliche in vitro di questo composto sono la glucuronidazione, l'idrossilazione e la O-deetilazione.
Saggio chinasico	Saggi di legame SGLT
Saggio chinasico	Le cellule di ovaio di criceto cinese (CHO) che esprimono stabilmente SGLT2 umano (hSGLT2) e SGLT1 umano (hSGLT1) sono utilizzate per lo sviluppo di saggi di trasporto utilizzando il substrato selettivo di SGLT α-metil-D-glucopiranoside (AMG). Dapagliflozin viene saggiato per la capacità di inibire l'assorbimento di [¹⁴C]AMG in un tampone privo di proteine per un periodo di incubazione di 2 ore. La curva di risposta è adattata a un modello empirico a quattro parametri per determinare la concentrazione dell'inibitore alla risposta massima dimezzata, riportata come EC50. Il tampone privo di proteine viene utilizzato per simulare le condizioni a basso contenuto proteico del filtrato glomerulare, che bagna i bersagli SGLT sulla superficie luminale del tubulo prossimale nel rene.
In vivo	Dapagliflozin riduce i livelli di glucosio nel sangue del 55% dopo una dose orale di 0,1 mg/kg in ratti diabetici indotti da streptozotocina (STZ), in parte grazie alla stabilità metabolica conferita dal legame C-glicosidico. Questo composto presenta un profilo favorevole di assorbimento, distribuzione, metabolismo ed escrezione (ADME) ed è biodisponibile per via orale. Questa sostanza chimica (1 mg/kg) provoca una glicosuria dose-dipendente significativa e un aumento del volume urinario in ratti normali entro 24 ore dalla somministrazione. Induce un aumento del glucosio urinario e dell'escrezione del volume urinario a 6 ore dalla somministrazione in ratti Zucker diabetici grassi (ZDF). Questo agente abbassa i livelli di glucosio a digiuno e post-pasto nei ratti ZDF anche dopo 2 settimane di trattamento, senza alcun indicatore di tossicità renale o epatica. Riduce significativamente lo sviluppo dell'iperglicemia, con un abbassamento della glicemia. Questo composto potrebbe migliorare la sensibilità all'insulina, ridurre la massa delle cellule β e lo sviluppo di una funzione pancreatica compromessa.
Riferimenti	[1] https://pubmed.ncbi.nlm.nih.gov/18260618/ [2] https://pubmed.ncbi.nlm.nih.gov/18356408/ [3] https://pubmed.ncbi.nlm.nih.gov/19996149/ [4] https://pubmed.ncbi.nlm.nih.gov/20880347/ [5] https://pubmed.ncbi.nlm.nih.gov/34836340/

Applicazioni

Metodi	Biomarcatori	PMID
Western blot	p-elf2α / t-elf2α / tubulin-α HIF-1α / PHD2 / tubulin DDR1 HIF-1α / p-AMPK / AMPK / p-ERK / ERK / β-actin Bax / Bcl2 / PARP / β-actin	31285506
Growth inhibition assay	Tumor volume	28763435
IHC	HE staining / SGLT2 mice kidney sections TUNEL-positive cells HIF1 TUNEL-positive cells	28763435
Immunofluorescence	podocytes PECAM-1 / α-SMA EdU F-actin Metabolic switch in diabetic kidneys	30089717

Informazioni sullo studio clinico

(dati da https://clinicaltrials.gov, aggiornato il 2024-05-22)

Numero NCT	Reclutamento	Condizioni	Sponsor/Collaboratori	Data di inizio	Fasi
NCT06012266	Not yet recruiting	Heart Failure	Centre Hospitalier Universitaire Vaudois\|Great Ormond Street Hospital for Children NHS Foundation Trust\|University College London	August 2024	Phase 2
NCT06336330	Recruiting	Heart Diseases\|Cardiovascular Diseases\|Heart Failure	AstraZeneca	April 25 2024	--
NCT04887935	Not yet recruiting	Prostate Cancer\|Cancer of Prostate	Washington University School of Medicine\|The Foundation for Barnes-Jewish Hospital	April 30 2024	Phase 1
NCT06398977	Recruiting	Peritoneal Dialysis Complication\|Renal Function Aggravated\|Sodium-glucose Co-transporter-2 Inhibitors	Sichuan Academy of Medical Sciences	March 11 2024	Not Applicable

Supporto tecnico

Istruzioni per la manipolazione

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C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):

Dapagliflozin (BMS-512148) inibitore di SGLT2

Struttura chimica

Peso molecolare: 408.87