Home GPCR & G Protein SGLT inhibitor Canagliflozin (JNJ-28431754)

연구용

Canagliflozin (JNJ-28431754) SGLT2 Inhibitor

제품 번호: S2760

Canagliflozin (TA 7284, JNJ 28431754) is a highly potent and selective SGLT2 inhibitor for hSGLT2 with IC50 of 2.2 nM in a cell-free assay, exhibits 413-fold selectivity over hSGLT1.
Canagliflozin (JNJ-28431754) SGLT inhibitor Chemical Structure

화학 구조

분자량: 444.52

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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
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 = 0.0022 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 = 0.265 μM. 28447791
CHO-K1 Function assay Inhibition of human SGLT2 expressed in CHO-K1 cells by [14C]AMG uptake assay, IC50 = 0.0067 μM. 22652255
CHO-K1 Function assay Inhibition of human SGLT1 expressed in CHO-K1 cells by [14C]AMG uptake assay, IC50 = 1.9 μM. 22652255
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화학 정보, 보관 및 안정성 (Chemical Information, Storage & Stability)

분자량 444.52 화학식

C24H25FO5S

 보관 (수령일로부터)
CAS 번호 842133-18-0 SDF 다운로드 원액 보관

동의어 TA 7284 Smiles CC1=C(C=C(C=C1)C2C(C(C(C(O2)CO)O)O)O)CC3=CC=C(S3)C4=CC=C(C=C4)F

용해도 (Solubility)

In vitro
배치:

DMSO : 89 mg/mL (200.21 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
mSGLT2
(Cell-free assay)
2 nM
rSGLT2
(Cell-free assay)
3.7 nM
hSGLT2
(Cell-free assay)
4.4 nM
시험관 내(In vitro)
Canagliflozin (JNJ 28431754) is a novel C-glucoside with thiophene ring. It inhibits Na+-dependent 14C-AMG uptake in a concentration-dependent fashion. This compound inhibits 14C-AMG uptake in CHO-hSGLT1 and mSGLT1 cells with IC50 of 0.7 μM and >1 μM, respectively. It inhibits the facilitative (non-Na+-linked) GLUT-mediated 2H-2-DG uptake in L6 myoblasts by less than 50%. In sham-injected oocytes, Canagliflozin (10 μM) or phlorizin (3 mM) alone in the presence of 50 μM DNJ does not affect currents. In SGLT3-injected oocytes, DMSO and Canagliflozin 10 μM inhibits DNJ-induced currents by 15.6% and 23.4%, respectively.
생체 내(In vivo)
Canagliflozin (JNJ 28431754) shows pronounced anti-hyperglycemic effects in high-fat diet fed KK (HF-KK) mice. Oral administration at 30 mg/kg of this compound to male SD rats induces glucose excretion over 24 hours by 3,696 mg per 200 g body weight. Pharmacokinetic studies reveals a much higher exposure following oral administration. Following intravenous and oral doses of 3 and 10 mg/kg, respectively, to male SD rats, AUC0−inf, po, t1/2 and oral bioavailability are determined to be 35,980 ng·h/mL, 5.2 hours, and 85%, respectively. Thus, inhibition of SGLT2 in renal tubules after oral dosing is likely to continuously suppress reabsorption of glucose. The extensive UGE would reflect excellent pharmacokinetic properties in vivo as well as high potency of SGLT2 inhibition. Since most of the filtered glucose is reabsorbed by SGLT2 in the renal tubules, the novel compound would be useful for an anti-diabetic agent. Single oral administration at 3 mg/kg remarkably reduced blood glucose levels without influencing food intake in hyperglycemic high-fat diet fed KK (HF-KK) mice. There is a 48% reduction in blood glucose level versus vehicle at 6 hours. In contrast, it only slightly affects blood glucose levels in normoglycemic mice. Therefore, Canagliflozin would control hyperglycemia in the therapy of T2DM with low risk of hypoglycemia.
참조

적용 분야 (Applications)

방법 바이오마커 이미지 PMID
Western blot p-β-catenin / β-catenin / Cyclin D1 pACC / ACC / p-AMPKα / AMPKα / p-S6K / S6K / p-S6 / S6
S2760-WB1
31142735

임상시험 정보 (Clinical Trial Information)

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

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