Ertugliflozin | CAS#1210344-57-2 | SGLT2 inhibitor

MedKoo Cat#: 326661 | Name: Ertugliflozin

Description:

WARNING: This product is for research use only, not for human or veterinary use.

Ertugliflozin, also known as also known as PF-04971729, is is an inhibitor of sodium-glucose cotransporter 2 (SGLT2; IC50 = 0.927 nM for the human enzyme). clinical study showed that Ertugliflozin (1-25 mg/day) improved glycaemic control, body weight and blood pressure in patients with T2DM suboptimally controlled on metformin, and was well tolerated.

Chemical Structure

Ertugliflozin

CAS#1210344-57-2 (free base)

Theoretical Analysis

MedKoo Cat#: 326661

Name: Ertugliflozin

CAS#: 1210344-57-2 (free base)

Chemical Formula: C22H25ClO7

Exact Mass: 436.1289

Molecular Weight: 436.89

Elemental Analysis: C, 60.48; H, 5.77; Cl, 8.11; O, 25.63

Price and Availability

Size	Price	Availability
25mg	USD 150.00	Ready to ship
50mg	USD 250.00	Ready to ship
100mg	USD 450.00	Ready to ship
200mg	USD 750.00	Ready to ship
500mg	USD 1,650.00	Ready to ship
1g	USD 2,950.00	Ready to ship
2g	USD 5,250.00	Ready to ship

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Related CAS #

1210344-83-4 (pidolate) 1210344-57-2 (free base)

Synonym

PF-04971729; PF 04971729; PF04971729; PF-4971729; PF 4971729; PF4971729; PF-04971729-00; PF 04971729-00; PF04971729-00; Ertugliflozin; Steglatro.

IUPAC/Chemical Name

(1S,2S,3S,4R,5S)-5-(4-Chloro-3-(4-ethoxybenzyl)phenyl)-1-hydroxymethyl-6,8-dioxabicyclo(3.2.1)octane-2,3,4-triol

InChi Key

MCIACXAZCBVDEE-CUUWFGFTSA-N

InChi Code

InChI=1S/C22H25ClO7/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/h3-8,10,18-20,24-27H,2,9,11-12H2,1H3/t18-,19-,20+,21-,22-/m0/s1

SMILES Code

O[C@@H]1[C@](O2)(CO)CO[C@]2(C3=CC=C(Cl)C(CC4=CC=C(C=C4)OCC)=C3)[C@H](O)[C@H]1O

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO, not in water

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#A8T06K25

QC Data

View QC data: current batch, Lot#A8T06K25

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Ertugliflozin (MK-8835, PF-04971729) is a potent and selective sodium-dependent glucose cotransporter 2 inhibitor with IC50 values of 0.877 nM for h-SGLT2 and 1000-fold higher for h-SGLT1.

In vitro activity:

The extent of in vitro binding of PF-04971729 to plasma proteins was evaluated by equilibrium dialysis in rat, dog, and human plasma. The mean percentages ± S.D. of plasma protein binding of PF-04971729 at concentrations of 2.3 and 23 μM were 96.0 ± 0.4 and 96.4 ± 0.5% (rat), 96.8 ± 0.02 and 96.8 ± 0.1% (dog), and 93.6 ± 0.1 and 94.7 ± 0.3% (human). These results show that PF-04971729 is highly bound to plasma proteins among the species examined, and binding is independent of concentration. PF-04971729 was stable in rat, dog, and human plasma for >6 h at 37°C at the concentrations used in the plasma free fraction determination. Figure 4 depicts the extracted ion chromatograms of incubation mixtures of PF-04971729 in NADPH-supplemented liver microsomes from rat, dog, and human. PF-04971729 was the major peak in all microsomal incubations, and there were no human-unique metabolites. Four metabolites (labeled M1, M2, M3, and M4) of PF-04971729 were detected in liver microsomes from rat, dog, and human at the retention times (tR) noted in Table 2. M7 was a rat-specific metabolite. M1 to M4 and M7 were not detected when NADPH was omitted from the microsomal incubations, suggesting that P450 isozymes catalyzed the rate-limiting step in their formation. PF-04971729 exhibited an ammonium adduct [M + NH4]+, which possessed an exact mass of 454.1632 (Table 2; Fig. 5). Theoretical exact masses for the proposed fragment ion structures for m/z 329, 273, 207, and 135 in the CID spectrum of PF-04971729 (Fig. 5) were consistent with the observed accurate masses (<2 ppm difference). Reference: Drug Metab Dispos. 2011 Sep;39(9):1609-19. http://dmd.aspetjournals.org/cgi/pmidlookup?view=long&pmid=21690265

In vivo activity:

In the acute setting, empagliflozin in combination with 1.5 IU insulin induced a similar glucose-lowering effect as 6 IU insulin. Both interventions were more efficacious than monotherapy with 1.5 IU insulin. In the subchronic study, 12-h blood glucose profile on day 28 in the combination group was lower than with one implant, and similar to two implants. Plasma HbA(1c) was improved in the combination group and in animals with two implants. Reference: Diabetes Obes Metab. 2012 Jul;14(7):601-7. https://doi.org/10.1111/j.1463-1326.2012.01569.x

	Solvent	mg/mL	mM
Solubility
	DMSO	46.0	105.29
	Ethanol	87.0	199.14
	Water	10.8	24.72

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 436.89 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

In vitro protocol:

1. Kalgutkar AS, Tugnait M, Zhu T, Kimoto E, Miao Z, Mascitti V, Yang X, Tan B, Walsky RL, Chupka J, Feng B, Robinson RP. Preclinical species and human disposition of PF-04971729, a selective inhibitor of the sodium-dependent glucose cotransporter 2 and clinical candidate for the treatment of type 2 diabetes mellitus. Drug Metab Dispos. 2011 Sep;39(9):1609-19. doi: 10.1124/dmd.111.040675. Epub 2011 Jun 20. PMID: 21690265.

In vivo protocol:

1: Liu J, Patel S, Cater NB, Wu L, Huyck S, Terra SG, Hickman A, Darekar A, Pong A, Gantz I. Efficacy and safety of ertugliflozin in East/Southeast Asian patients with type 2 diabetes mellitus. Diabetes Obes Metab. 2019 Dec 3. doi: 10.1111/dom.13931. [Epub ahead of print] PubMed PMID: 31797522. 2: Erratum: Ertugliflozin for type 2 diabetes [Correction]. Aust Prescr. 2019 Jun;42(3):115. doi: 10.18773/austprescr.2019.036. Epub 2019 Apr 26. PubMed PMID: 31363318; PubMed Central PMCID: PMC6594852. 3: Fediuk DJ, Matschke K, Liang Y, Pelletier KB, Wei H, Shi H, Bass A, Hickman A, Terra SG, Zhou S, Krishna R, Sahasrabudhe V. Bioequivalence of Ertugliflozin/Sitagliptin Fixed-Dose Combination Tablets and Coadministration of Respective Strengths of Individual Components. Clin Pharmacol Drug Dev. 2019 Oct;8(7):884-894. doi: 10.1002/cpdd.722. Epub 2019 Jun 20. PubMed PMID: 31219248; PubMed Central PMCID: PMC6851892. 4: Common Drug Review New Combination Product: Ertugliflozin/Metformin Fixed-Dose Combination (Segluromet): Merck Canada Inc. Indication: Type 2 Diabetes Mellitus [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2019 Feb. Available from http://www.ncbi.nlm.nih.gov/books/NBK542579/ PubMed PMID: 31211542. 5: Pharmacoeconomic Review Report: Ertugliflozin (Steglatro): (Merck Canada Inc.): Indication: Type 2 Diabetes Mellitus [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2019 Feb. Available from http://www.ncbi.nlm.nih.gov/books/NBK542500/ PubMed PMID: 31211532. 6: CADTH Canadian Drug Expert Committee Recommendation: Ertugliflozin (Steglatro — Merck Canada Inc.): Indication: Diabetes mellitus, type 2 [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2019 Jan 25. No abstract available. Available from http://www.ncbi.nlm.nih.gov/books/NBK542402/ PubMed PMID: 31206291. 7: CADTH Canadian Drug Expert Committee Recommendation: Ertugliflozin/Metformin (Segluromet — Merck Canada Inc.): Indication: Diabetes mellitus, type 2 [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2019 Jan 25. No abstract available. Available from http://www.ncbi.nlm.nih.gov/books/NBK542401/ PubMed PMID: 31206287. 8: Clinical Review Report: Ertugliflozin (Steglatro): (Merck Canada Inc.): Indication: Type 2 Diabetes Mellitus [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2019 Feb. Available from http://www.ncbi.nlm.nih.gov/books/NBK542486/ PubMed PMID: 31206284. 9: Dawra VK, Liang Y, Wei H, Pelletier K, Shi H, Hickman A, Bass A, Terra SG, Zhou S, Krishna R, Sahasrabudhe V. Bioequivalence of Ertugliflozin/Metformin Fixed-Dose Combination Tablets and Coadministration of Respective Strengths of Individual Components. Clin Pharmacol Drug Dev. 2019 Jun 17. doi: 10.1002/cpdd.703. [Epub ahead of print] PubMed PMID: 31207178. 10: Han DG, Yun H, Yoon IS. A novel high-performance liquid chromatographic method combined with fluorescence detection for determination of ertugliflozin in rat plasma: Assessment of pharmacokinetic drug interaction potential of ertugliflozin with mefenamic acid and ketoconazole. J Chromatogr B Analyt Technol Biomed Life Sci. 2019 Aug 1;1122-1123:49-57. doi: 10.1016/j.jchromb.2019.05.023. Epub 2019 May 25. PubMed PMID: 31153131. 11: Liu J, Tarasenko L, Terra SG, Huyck S, Wu L, Pong A, Calle RA, Gallo S, Darekar A, Mancuso JP. Efficacy of ertugliflozin in monotherapy or combination therapy in patients with type 2 diabetes: A pooled analysis of placebo-controlled studies. Diab Vasc Dis Res. 2019 Sep;16(5):415-423. doi: 10.1177/1479164119842513. Epub 2019 May 13. PubMed PMID: 31081371. 12: Liu J, Pong A, Gallo S, Darekar A, Terra SG. Effect of ertugliflozin on blood pressure in patients with type 2 diabetes mellitus: a post hoc pooled analysis of randomized controlled trials. Cardiovasc Diabetol. 2019 May 7;18(1):59. doi: 10.1186/s12933-019-0856-7. PubMed PMID: 31064361; PubMed Central PMCID: PMC6503446. 13: Nguyen VK, White JR Jr. Overview of Ertugliflozin. Clin Diabetes. 2019 Apr;37(2):176-178. doi: 10.2337/cd18-0097. PubMed PMID: 31057225; PubMed Central PMCID: PMC6468829. 14: Ertugliflozin for type 2 diabetes. Aust Prescr. 2019 Apr;42(2):70-72. doi: 10.18773/austprescr.2019.018. Epub 2019 Feb 28. Review. Erratum in: Aust Prescr. 2019 Jun;42(3):115. PubMed PMID: 31048942; PubMed Central PMCID: PMC6478963. 15: Wang W, Gan N, Sun Q, Wu D, Gan R, Zhang M, Tang P, Li H. Study on the interaction of ertugliflozin with human serum albumin in vitro by multispectroscopic methods, molecular docking, and molecular dynamics simulation. Spectrochim Acta A Mol Biomol Spectrosc. 2019 Aug 5;219:83-90. doi: 10.1016/j.saa.2019.04.047. Epub 2019 Apr 18. PubMed PMID: 31030051. 16: Sharma R, Razdan K, Kuhad A, Kuhad A. Ertugliflozin for the treatment of type 2 diabetes. Drugs Today (Barc). 2019 Mar;55(3):167-175. doi: 10.1358/dot.2019.55.3.2904972. Review. PubMed PMID: 30938372. 17: Li Y, Mu Y, Shi H, Liang Y, Liu Z, Matschke K, Hickman A, Krishna R, Sahasrabudhe V. Pharmacokinetic Properties of Single and Multiple Doses of Ertugliflozin, a Selective Inhibitor of SGLT2, in Healthy Chinese Subjects. Clin Pharmacol Drug Dev. 2019 Apr 1. doi: 10.1002/cpdd.686. [Epub ahead of print] PubMed PMID: 30934166. 18: Ji L, Liu Y, Miao H, Xie Y, Yang M, Wang W, Mu Y, Yan P, Pan S, Lauring B, Liu S, Huyck S, Qiu Y, Terra SG. Safety and efficacy of ertugliflozin in Asian patients with type 2 diabetes mellitus inadequately controlled with metformin monotherapy: VERTIS Asia. Diabetes Obes Metab. 2019 Jun;21(6):1474-1482. doi: 10.1111/dom.13681. Epub 2019 Apr 5. PubMed PMID: 30830724. 19: Dawra VK, Liang Y, Shi H, Bass A, Hickman A, Terra SG, Zhou S, Cutler D, Sahasrabudhe V. A PK/PD study comparing twice-daily to once-daily dosing regimens of ertugliflozin in healthy subjects. Int J Clin Pharmacol Ther. 2019 Apr;57(4):207-216. doi: 10.5414/CP203343. PubMed PMID: 30802200; PubMed Central PMCID: PMC6528385. 20: Hollander P, Hill J, Johnson J, Wei Jiang Z, Golm G, Huyck S, Terra SG, Mancuso JP, Engel SS, Lauring B, Liu J. Results of VERTIS SU extension study: safety and efficacy of ertugliflozin treatment over 104 weeks compared to glimepiride in patients with type 2 diabetes mellitus inadequately controlled on metformin. Curr Med Res Opin. 2019 Aug;35(8):1335-1343. doi: 10.1080/03007995.2019.1583450. Epub 2019 Mar 25. PubMed PMID: 30760125.