Canagliflozin hemihydrate
(Synonyms: 卡格列净半水合物,JNJ 28431754 hemihydrate) 目录号 : GC35603
An inhibitor of SGLT2
Cas No.:928672-86-0
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Canagliflozin is an inhibitor of sodium-glucose cotransporter 2 (SGLT2; IC50 = 2.2 nM) that less potently blocks SGLT1 (IC50 = 910 nM).1 Canagliflozin is orally bioavailable and lowers plasma glucose by lowering the renal threshold for glucose and increasing urinary glucose excretion in animals.1,2 Formulations containing SGLT2 inhibitors, including canagliflozin, are used to treat type 2 diabetes mellitus.3
1.Nomura, S., Sakamaki, S., Hongu, M., et al.Discovery of canagliflozin, a novel C-glucoside with thiophene ring, as sodium-dependent glucose cotransporter 2 inhibitor for the treatment of type 2 diabetes mellitusJ. Med. Chem.53(17)6355-6360(2010) 2.Sha, S., Devineni, D., Ghosh, A., et al.Canagliflozin, a novel inhibitor of sodium glucose co-transporter 2, dose dependently reduces calculated renal threshold for glucose excretion and increases urinary glucose excretion in healthy subjectsDiabetes Obes. Metab.13(7)669-672(2011) 3.Reed, J.W.Impact of sodium-glucose cotransporter 2 inhibitors on blood pressureVasc. Health Risk Manag.12393-405(2016)
| Cas No. | 928672-86-0 | SDF | |
| 别名 | 卡格列净半水合物,JNJ 28431754 hemihydrate | ||
| Canonical SMILES | CC1=CC=C([C@H]2[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O2)C=C1CC3=CC=C(C4=CC=C(F)C=C4)S3.[0.5H2O] | ||
| 分子式 | C24H26FO5.5S | 分子量 | 453.52 |
| 溶解度 | DMSO: ≥ 100 mg/mL (220.50 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.205 mL | 11.0249 mL | 22.0497 mL |
| 5 mM | 0.441 mL | 2.205 mL | 4.4099 mL |
| 10 mM | 0.2205 mL | 1.1025 mL | 2.205 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes
N Engl J Med 2017 Aug 17;377(7):644-657.PMID:28605608DOI:10.1056/NEJMoa1611925.
Background Canagliflozin is a sodium-glucose cotransporter 2 inhibitor that reduces glycemia as well as blood pressure, body weight, and albuminuria in people with diabetes. We report the effects of treatment with Canagliflozin on cardiovascular, renal, and safety outcomes. Methods The CANVAS Program integrated data from two trials involving a total of 10,142 participants with type 2 diabetes and high cardiovascular risk. Participants in each trial were randomly assigned to receive Canagliflozin or placebo and were followed for a mean of 188.2 weeks. The primary outcome was a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. Results The mean age of the participants was 63.3 years, 35.8% were women, the mean duration of diabetes was 13.5 years, and 65.6% had a history of cardiovascular disease. The rate of the primary outcome was lower with Canagliflozin than with placebo (occurring in 26.9 vs. 31.5 participants per 1000 patient-years; hazard ratio, 0.86; 95% confidence interval [CI], 0.75 to 0.97; P<0.001 for noninferiority; P=0.02 for superiority). Although on the basis of the prespecified hypothesis testing sequence the renal outcomes are not viewed as statistically significant, the results showed a possible benefit of Canagliflozin with respect to the progression of albuminuria (hazard ratio, 0.73; 95% CI, 0.67 to 0.79) and the composite outcome of a sustained 40% reduction in the estimated glomerular filtration rate, the need for renal-replacement therapy, or death from renal causes (hazard ratio, 0.60; 95% CI, 0.47 to 0.77). Adverse reactions were consistent with the previously reported risks associated with Canagliflozin except for an increased risk of amputation (6.3 vs. 3.4 participants per 1000 patient-years; hazard ratio, 1.97; 95% CI, 1.41 to 2.75); amputations were primarily at the level of the toe or metatarsal. Conclusions In two trials involving patients with type 2 diabetes and an elevated risk of cardiovascular disease, patients treated with Canagliflozin had a lower risk of cardiovascular events than those who received placebo but a greater risk of amputation, primarily at the level of the toe or metatarsal. (Funded by Janssen Research and Development; CANVAS and CANVAS-R ClinicalTrials.gov numbers, NCT01032629 and NCT01989754 , respectively.).
Canagliflozin, dapagliflozin and empagliflozin monotherapy for treating type 2 diabetes: systematic review and economic evaluation
Health Technol Assess 2017 Jan;21(2):1-218.PMID:28105986DOI:10.3310/hta21020.
Background: Most people with type 2 diabetes are overweight, so initial treatment is aimed at reducing weight and increasing physical activity. Even modest weight loss can improve control of blood glucose. If drug treatment is necessary, the drug of first choice is metformin. However, some people cannot tolerate metformin, which causes diarrhoea in about 10%, and it cannot be used in people with renal impairment. This review appraises three of the newest class of drugs for monotherapy when metformin cannot be used, the sodium-glucose co-transporter 2 (SGLT2) inhibitors. Objective: To review the clinical effectiveness and cost-effectiveness of dapagliflozin (Farxiga, Bristol-Myers Squibb, Luton, UK), Canagliflozin (Invokana, Janssen, High Wycombe, UK) and empagliflozin (Jardiance, Merck & Co., Darmstadt, Germany), in monotherapy in people who cannot take metformin. Sources: MEDLINE (1946 to February 2015) and EMBASE (1974 to February 2015) for randomised controlled trials lasting 24 weeks or more. For adverse events, a wider range of studies was used. Three manufacturers provided submissions. Methods: Systematic review and economic evaluation. A network meta-analysis was carried out involving the three SGLT2 inhibitors and key comparators. Critical appraisal of submissions from three manufacturers. Results: We included three trials of dapagliflozin and two each for Canagliflozin and empagliflozin. The trials were of good quality. The Canagliflozin and dapagliflozin trials compared them with placebo, but the two empagliflozin trials included active comparators. All three drugs were shown to be effective in improving glycaemic control, promoting weight loss and lowering blood pressure (BP). Limitations: There were no head-to-head trials of the different flozins, and no long-term data on cardiovascular outcomes in this group of patients. Most trials were against placebo. The trials were done in patient groups that were not always comparable, for example in baseline glycated haemoglobin or body mass index. Data on elderly patients were lacking. Conclusions: Dapagliflozin, Canagliflozin and empagliflozin are effective in improving glycaemic control, with added benefits of some reductions in BP and weight. Adverse effects are urinary and genital tract infections in a small proportion of users. In monotherapy, the three drugs do not appear cost-effective compared with gliclazide or pioglitazone, but may be competitive against sitagliptin (Januvia, Boehringer Ingelheim, Bracknell, UK). Funding: The National Institute for Health Research Health Technology Assessment programme.
The SGLT2 inhibitor Canagliflozin in heart failure: the CHIEF-HF remote, patient-centered randomized trial
Nat Med 2022 Apr;28(4):809-813.PMID:35228753DOI:10.1038/s41591-022-01703-8.
Large traditional clinical trials suggest that sodium-glucose co-transporter 2 inhibitors improve symptoms in patients with heart failure and reduced ejection fraction (HFrEF) and in patients with heart failure and preserved ejection fraction (HFpEF). In the midst of the Coronavirus Disease 2019 pandemic, we sought to confirm these benefits in a new type of trial that was patient centered and conducted in a completely remote fashion. In the CHIEF-HF trial ( NCT04252287 ), 476 participants with HF, regardless of EF or diabetes status, were randomized to 100 mg of Canagliflozin or placebo. Enrollment was stopped early due to shifting sponsor priorities, without unblinding. The primary outcome was change in the Kansas City Cardiomyopathy Questionnaire Total Symptom Score (KCCQ TSS) at 12 weeks. The 12-week change in KCCQ TSS was 4.3 points (95% confidence interval, 0.8-7.8; P = 0.016) higher with Canagliflozin than with placebo, meeting the primary endpoint. Similar effects were observed in participants with HFpEF and in those with HFrEF and in participants with and without diabetes, demonstrating that Canagliflozin significantly improves symptom burden in HF, regardless of EF or diabetes status. This randomized, double-blind trial, conducted without in-person interactions between doctor and patient, can serve as a model for future all-virtual clinical trials.
Canagliflozin and renal outcomes in type 2 diabetes: results from the CANVAS Program randomised clinical trials
Lancet Diabetes Endocrinol 2018 Sep;6(9):691-704.PMID:29937267DOI:10.1016/S2213-8587(18)30141-4.
Background: In the Canagliflozin Cardiovascular Assessment Study (CANVAS) Program, Canagliflozin reduced the rates of major adverse cardiovascular events and the results suggested a renal benefit in patients with type 2 diabetes who were at high risk for cardiovascular events, compared with those treated with placebo. Here we report the results of a prespecified exploratory analysis of the long-term effects of Canagliflozin on a range of sustained and adjudicated renal outcomes. Methods: The CANVAS Program consists of two double-blind, randomised trials that assessed Canagliflozin versus placebo in participants with type 2 diabetes who were at high risk of cardiovascular events, done at 667 centres in 30 countries. People with type 2 diabetes and an HbA1c of 7·0-10·5% (53-91 mmol/mol) who were aged at least 30 years and had a history of symptomatic atherosclerotic vascular disease, or who were aged at least 50 years and had at least two cardiovascular risk factors were eligible to participate. Participants in CANVAS were randomly assigned (1:1:1) to receive 300 mg Canagliflozin, 100 mg Canagliflozin, or matching placebo once daily. Participants in CANVAS-R were randomly assigned (1:1) to receive Canagliflozin or matching placebo, at an initial dose of 100 mg daily, with optional uptitration to 300 mg from week 13 or matching placebo. Participants and all study staff were masked to treatment allocations until study completion. Prespecified outcomes reported here include a composite of sustained and adjudicated doubling in serum creatinine, end-stage kidney disease, or death from renal causes; the individual components of this composite outcome; annual reductions in estimated glomerular filtration rate (eGFR); and changes in urinary albumin-to-creatinine ratio (UACR). The trials are registered with ClinicalTrials.gov, numbers NCT01032629 (CANVAS) and NCT01989754 (CANVAS-R). Findings: Between Nov 17, 2009, and March 7, 2011 (CANVAS), and Jan 17, 2014, and May 29, 2015 (CANVAS-R), 15 494 people were screened, of whom 10 142 participants (with a baseline mean eGFR 76·5 mL/min per 1·73 m2, median UACR 12·3 mg/g, and 80% of whom were receiving renin-angiotensin system blockade) were randomly allocated to receive either Canagliflozin or placebo. The composite outcome of sustained doubling of serum creatinine, end-stage kidney disease, and death from renal causes occurred less frequently in the Canagliflozin group compared with the placebo group (1·5 per 1000 patient-years in the Canagliflozin group vs 2·8 per 1000 patient-years in the placebo group; hazard ratio 0·53, 95% CI 0·33-0·84), with consistent findings across prespecified patient subgroups. Annual eGFR decline was slower (slope difference between groups 1·2 mL/min per 1·73 m2 per year, 95% CI 1·0-1·4) and mean UACR was 18% lower (95% CI 16-20) in participants treated with Canagliflozin than in those treated with placebo. Total serious renal-related adverse events were similar between the Canagliflozin and placebo groups (2·5 vs 3·3 per 1000 patient-years; HR 0·76, 95% CI 0·49-1·19). Interpretation: In a prespecified exploratory analysis, Canagliflozin treatment was associated with a reduced risk of sustained loss of kidney function, attenuated eGFR decline, and a reduction in albuminuria, which supports a possible renoprotective effect of this drug in people with type 2 diabetes. Funding: Janssen Research & Development.
Canagliflozin and Heart Failure in Type 2 Diabetes Mellitus: Results From the CANVAS Program
Circulation 2018 Jul 31;138(5):458-468.PMID:29526832DOI:10.1161/CIRCULATIONAHA.118.034222.
Background: Canagliflozin is a sodium glucose cotransporter 2 inhibitor that reduces the risk of cardiovascular events. We report the effects on heart failure (HF) and cardiovascular death overall, in those with and without a baseline history of HF, and in other participant subgroups. Methods: The CANVAS Program (Canagliflozin Cardiovascular Assessment Study) enrolled 10 142 participants with type 2 diabetes mellitus and high cardiovascular risk. Participants were randomly assigned to Canagliflozin or placebo and followed for a mean of 188 weeks. The primary end point for these analyses was adjudicated cardiovascular death or hospitalized HF. Results: Participants with a history of HF at baseline (14.4%) were more frequently women, white, and hypertensive and had a history of prior cardiovascular disease (all P<0.001). Greater proportions of these patients were using therapies such as blockers of the renin angiotensin aldosterone system, diuretics, and β-blockers at baseline (all P<0.001). Overall, cardiovascular death or hospitalized HF was reduced in those treated with Canagliflozin compared with placebo (16.3 versus 20.8 per 1000 patient-years; hazard ratio [HR], 0.78; 95% confidence interval [CI], 0.67-0.91), as was fatal or hospitalized HF (HR, 0.70; 95% CI, 0.55-0.89) and hospitalized HF alone (HR, 0.67; 95% CI, 0.52-0.87). The benefit on cardiovascular death or hospitalized HF may be greater in patients with a prior history of HF (HR, 0.61; 95% CI, 0.46-0.80) compared with those without HF at baseline (HR, 0.87; 95% CI, 0.72-1.06; P interaction =0.021). The effects of Canagliflozin compared with placebo on other cardiovascular outcomes and key safety outcomes were similar in participants with and without HF at baseline (all interaction P values >0.130), except for a possibly reduced absolute rate of events attributable to osmotic diuresis among those with a prior history of HF ( P=0.03). Conclusions: In patients with type 2 diabetes mellitus and an elevated risk of cardiovascular disease, Canagliflozin reduced the risk of cardiovascular death or hospitalized HF across a broad range of different patient subgroups. Benefits may be greater in those with a history of HF at baseline. Clinical trial registration: URL: https://www.clinicaltrials.gov . Unique identifiers: NCT01032629 and NCT01989754.