| Size | Price | Stock | Qty |
|---|---|---|---|
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| 500mg |
|
||
| Other Sizes |
Purity: ≥98%
Ertugliflozin L-pyroglutamic acid(formerly known as also known as PF-04971729; trade name: Steglatro), the L-pyroglutamic acid of ertugliflozin, is a potent, orally bioavailable and selective inhibitor of the sodium-dependent glucose cotransporter 2 (SGLT2)approved in 2017 by FDA for treating type 2 diabetes mellitus.
| Targets |
In vitro, ertugliflozin L-pyroglutamic acid (PF-04971729 L-pyroglutamic acid) shows a >2000-fold pivoting of SGLT2 inhibition in comparison to SGLT1 [3].
|
|---|---|
| ln Vitro |
In vitro, ertugliflozin L-pyroglutamic acid (PF-04971729 L-pyroglutamic acid) shows a >2000-fold pivoting of SGLT2 inhibition in comparison to SGLT1 [3].
Ertugliflozin demonstrates potent and selective inhibition of human SGLT2 in a functional assay using CHO cells expressing the SGLT transporter, with an IC₅₀ of 0.927 nM. The compound shows >60000-fold selectivity over facilitative glucose transporters (GLUT 1–4). [1] In human hepatocyte (HHEP) incubations, the apparent intrinsic clearance (CLint app) is 4.5 μL/min/million cells, indicating low phase 2 metabolic liability. [1] The compound tests negative in the in vitro micronucleus assay, indicating no clastogenic or aneugenic potential. [1] |
| ln Vivo |
Following shelf release, ertugliflozin L-pyroglutamic acid (PF-04971729 L-pyroglutamic acid) displays concentration-dependent glycosuria [3].
In Sprague–Dawley rats, oral administration of ertugliflozin induces a dose-responsive increase in urinary glucose excretion (UGE) over 24 hours, with maximal UGE of 2554 ± 141.1 mg/200 g body weight at 30 mg/kg. The free in vivo IC₅₀ is 1.8 nM (95% CI = 1.0–2.6 nM). [1] The compound shows robust pharmacodynamic effects in rats, with good agreement between in vitro and in vivo IC₅₀ values for SGLT2 inhibition. [1] |
| Enzyme Assay |
The potency at human SGLT (h-SGLT) was evaluated using a functional assay designed to detect the inhibition of methyl α-D-glucopyranoside (AMG) uptake via the SGLT transporter expressed in Chinese hamster ovary (CHO) cells. The assay measures the inhibition of AMG uptake as a surrogate for glucose transport inhibition. [1]
|
| Cell Assay |
The in vitro transport assay for organic anion/cation transporters used human embryonic kidney 293 cells (HEK293) transfected with appropriate transporters (hOAT1, hOAT3, hOCT2). Ertugliflozin showed no uptake by hOAT1, hOAT3, or hOCT2 transporters, indicating low potential for transporter-mediated drug–drug interactions. [1]
|
| Animal Protocol |
Male Sprague–Dawley rats (n=5 per group) were randomized to receive one of six doses of ertugliflozin (0.1, 1, 3, 10, 30, and 60 mg/kg) by oral gavage. The formulation used was 20% (v/v) PEG400/24% (v/v) HPBCD. Urine was collected over 24 hours for measurement of UGE. Satellite animals (n=2 per group) were used for drug exposure assessment. [1]
For rat intravenous PK studies, male Sprague–Dawley rats (n=2 per group) were administered 2 mg/kg of compound intravenously. The IV formulation for ertugliflozin was DMSO/PEG400/30% SBECD (10/30/60, v/v/v). [1] |
| ADME/Pharmacokinetics |
In Sprague-Dawley rats, after intravenous injection (2 mg/kg), the total plasma clearance (CLplasma) was 4.04 mL/min/kg, the steady-state volume of distribution (Vss) was 1.13 L/kg, and the half-life (t₁/₂) was 4.1 h. [1]
After oral administration of L-pyroglutamic acid cocrystal (5 mg/kg) to rats, the maximum systemic exposure (Cmax) was 1.94 ± 0.185 μg/mL, the time to peak concentration was 1.0 h, and the oral bioavailability (F) was 69%. [1] Human pharmacokinetic parameters predicted by allometric scaling: CLplasma = 1.7 mL/min/kg, Vss = 1.8 L/kg, t₁/₂ = 12 h, and the oral bioavailability was estimated to be 65%. [1] In vitro stability in human liver microsomes (HLM) showed that the CLIt app was 12 μL/min/mg. [1] |
| Toxicity/Toxicokinetics |
In vitro mammalian cell micronucleus assays showed that Ertugliflozin was negative, indicating no genotoxicity under the test conditions. [1]
The compound exhibits very weak uptake by rat organic cation transporter 2 (rOct2) and organic anion transporter 3 (rOat3), and is not uptaken by human OAT1, OAT3, or OCT2 transporters, suggesting a low risk of transporter-mediated toxicity. [1] |
| References |
|
| Additional Infomation |
See also: Apagliflozin (containing the active moiety); Apagliflozin pyridine carboxylate; Metformin hydrochloride (component). Apagliflozin belongs to a novel class of SGLT2 inhibitors with a structure comprising a dioxabicyclo[3.2.1]octane (bridged ketal) ring system, which imparts rigidity to the compound and may enhance its potency and selectivity. [1] This compound is currently undergoing a Phase II clinical trial for the treatment of type 2 diabetes. [1] A pharmacokinetic-pharmacodynamic (PKPD) model has been developed to predict human dose and efficacy, and this model reliably predicts the results of a Phase I clinical trial. [1]
|
| Molecular Formula |
C27H32CLNO10
|
|
|---|---|---|
| Molecular Weight |
566.0
|
|
| Exact Mass |
565.171
|
|
| CAS # |
1210344-83-4
|
|
| Related CAS # |
Ertugliflozin;1210344-57-2
|
|
| PubChem CID |
57339449
|
|
| Appearance |
White to off-white solid powder
|
|
| Hydrogen Bond Donor Count |
6
|
|
| Hydrogen Bond Acceptor Count |
10
|
|
| Rotatable Bond Count |
7
|
|
| Heavy Atom Count |
39
|
|
| Complexity |
740
|
|
| Defined Atom Stereocenter Count |
6
|
|
| SMILES |
CCOC1=CC=C(C=C1)CC2=C(C=CC(=C2)[C@@]34[C@@H]([C@H]([C@@H]([C@@](O3)(CO4)CO)O)O)O)Cl.C1CC(=O)N[C@@H]1C(=O)O
|
|
| InChi Key |
YHIUPZFKHZTLSH-LXYIGGQGSA-N
|
|
| InChi Code |
InChI=1S/C22H25ClO7.C5H7NO3/c1-2-28-16-6-3-13(4-7-16)9-14-10-15(5-8-17(14)23)22-20(27)18(25)19(26)21(11-24,30-22)12-29-22;7-4-2-1-3(6-4)5(8)9/h3-8,10,18-20,24-27H,2,9,11-12H2,1H3;3H,1-2H2,(H,6,7)(H,8,9)/t18-,19-,20+,21-,22-;3-/m00/s1
|
|
| Chemical Name |
|
|
| Synonyms |
|
|
| HS Tariff Code |
2934.99.9001
|
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
|
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
|
|||
|---|---|---|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (3.67 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (3.67 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (3.67 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7668 mL | 8.8339 mL | 17.6678 mL | |
| 5 mM | 0.3534 mL | 1.7668 mL | 3.5336 mL | |
| 10 mM | 0.1767 mL | 0.8834 mL | 1.7668 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
 J Med Chem.2011 Apr 28;54(8):2952-60 |
|---|
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA