Linagliptin | BI1356 | CAS#668270-12-0 | DPP-4 inhibitor

MedKoo Cat#: 300125 | Name: Linagliptin

Description:

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

Linagliptin, also known as BI-1356, is a DPP-4 inhibitor developed by Boehringer Ingelheim for treatment of type II diabetes. Linagliptin (once-daily) was approved by the US FDA on 2 May 2011 for treatment of type II diabetes. It is being marketed by Boehringer Ingelheim and Lilly.

Chemical Structure

Linagliptin

CAS#668270-12-0

Theoretical Analysis

MedKoo Cat#: 300125

Name: Linagliptin

CAS#: 668270-12-0

Chemical Formula: C25H28N8O2

Exact Mass: 472.2335

Molecular Weight: 472.54

Elemental Analysis: C, 63.54; H, 5.97; N, 23.71; O, 6.77

Price and Availability

Size	Price	Availability
500mg	USD 90.00	Ready to ship
1g	USD 150.00	Ready to ship
2g	USD 250.00	Ready to ship
5g	USD 450.00	Ready to ship
10g	USD 850.00	Ready to ship
20g	USD 1,250.00	Ready to ship
50g	USD 2,150.00	Ready to ship

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Synonym

BI1356; BI 1356; BI-1356; Linagliptin. trade names Tradjenta and Trajenta

IUPAC/Chemical Name

8-[(3R)-3-aminopiperidin-1-yl]-7-(but-2-yn-1-yl)-3- methyl-1-[(4-methylquinazolin-2-yl)methyl]-3,7-dihydro-1H-purine-2,6-dione

InChi Key

LTXREWYXXSTFRX-QGZVFWFLSA-N

InChi Code

InChI=1S/C25H28N8O2/c1-4-5-13-32-21-22(29-24(32)31-12-8-9-17(26)14-31)30(3)25(35)33(23(21)34)15-20-27-16(2)18-10-6-7-11-19(18)28-20/h6-7,10-11,17H,8-9,12-15,26H2,1-3H3/t17-/m1/s1

SMILES Code

O=C(N1CC2=NC(C)=C3C=CC=CC3=N2)N(C)C4=C(N(CC#CC)C(N5C[C@H](N)CCC5)=N4)C1=O

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.

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#C8R12B11

QC Data

View QC data: current batch, Lot#C8R12B11

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Linagliptin (BI-1356) is a highly potent, selective DPP-4 inhibitor with IC50 of 1 nM and exhibits a 10,000-fold higher selectivity for DPP-4 than for other dipeptidyl peptidases such as DPP-2, DPP-8, and DPP-9.

In vitro activity:

Treatment with LNG did not cause statistically significant decreases of cell viability at lower concentrations than 100 mg/L as compared to untreated cultures. However, LNG exhibited cytotoxic action at 250 and 500 mg/L. Also, IC20 and IC50 values of LNG were determined as 8.827 and 70.307 mg/L, respectively. In addition, the oxidative analysis revealed that LNG supported antioxidant capacity at concentrations of 2.5, 5, 10, 25, 50 and 100 mg/L without generating oxidative stress. Besides, the results of CA and 8-oxo-dG assays showed in vitro non-genotoxic feature of LNG. As a conclusion, these findings clearly revealed that LNG had no cytotoxic and genotoxic actions, but exhibited antioxidative activity. In conclusion, therefore it is suggested that LNG use in diabetic patients is safe and provides protection against diabetic vascular and oxidative complications. Reference: Acta Endocrinol (Buchar). 2019 Jan-Mar;-5(1):9-15. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/31149054/

In vivo activity:

DPP-4 activity was inhibited by oral administration of linagliptin during healing. Wound tissue was analyzed by using histological, molecular, and biochemical techniques. In healthy mice, DPP-4 was constitutively expressed in the keratinocytes of nonwounded skin. After skin injury, DPP-4 expression declined and was lowest during the most active phase of tissue reassembly. In contrast, in ob/ob mice, we observed increasing levels of DPP-4 at late time points, when delayed tissue repair still occurs. Oral administration of the DPP-4 inhibitor linagliptin strongly reduced DPP-4 activity, stabilized active GLP-1 in chronic wounds, and improved healing in ob/ob mice. At day 10 postwounding, linagliptin-treated ob/ob mice showed largely epithelialized wounds characterized by the absence of neutrophils. In addition, DPP-4 inhibition reduced the expression of the proinflammatory markers cyclooxygenase-2 and macrophage inflammatory protein-2, but enhanced the formation of myofibroblasts in healing wounds from ob/ob mice. Reference: J Pharmacol Exp Ther. 2012 Jul;342(1):71-80. https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=22493041

	Solvent	mg/mL	mM
Solubility
	DMSO	17.0	35.98
	Ethanol	1.0	2.12

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 472.54 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. Çadirci K, Türkez H, Özdemir Ö. THE IN VITRO CYTOTOXICITY, GENOTOXICITY AND OXIDATIVE DAMAGE POTENTIAL OF THE ORAL DIPEPTIDYL PEPTIDASE-4 INHIBITOR, LINAGLIPTIN, ON CULTURED HUMAN MONONUCLEAR BLOOD CELLS. Acta Endocrinol (Buchar). 2019 Jan-Mar;-5(1):9-15. doi: 10.4183/aeb.2019.9. PMID: 31149054; PMCID: PMC6535332. 2. Thomas L, Eckhardt M, Langkopf E, Tadayyon M, Himmelsbach F, Mark M. (R)-8-(3-amino-piperidin-1-yl)-7-but-2-ynyl-3-methyl-1-(4-methyl-quinazolin-2-ylmethyl)-3,7-dihydro-purine-2,6-dione (BI 1356), a novel xanthine-based dipeptidyl peptidase 4 inhibitor, has a superior potency and longer duration of action compared with other dipeptidyl peptidase-4 inhibitors. J Pharmacol Exp Ther. 2008 Apr;325(1):175-82. doi: 10.1124/jpet.107.135723. Epub 2008 Jan 25. PMID: 18223196.

In vivo protocol:

1. Schürmann C, Linke A, Engelmann-Pilger K, Steinmetz C, Mark M, Pfeilschifter J, Klein T, Frank S. The dipeptidyl peptidase-4 inhibitor linagliptin attenuates inflammation and accelerates epithelialization in wounds of diabetic ob/ob mice. J Pharmacol Exp Ther. 2012 Jul;342(1):71-80. doi: 10.1124/jpet.111.191098. Epub 2012 Apr 4. PMID: 22493041. 2. Eckhardt M, Langkopf E, Mark M, Tadayyon M, Thomas L, Nar H, Pfrengle W, Guth B, Lotz R, Sieger P, Fuchs H, Himmelsbach F. 8-(3-(R)-aminopiperidin-1-yl)-7-but-2-ynyl-3-methyl-1-(4-methyl-quinazolin-2-ylmethyl)-3,7-dihydropurine-2,6-dione (BI 1356), a highly potent, selective, long-acting, and orally bioavailable DPP-4 inhibitor for the treatment of type 2 diabetes. J Med Chem. 2007 Dec 27;50(26):6450-3. doi: 10.1021/jm701280z. Epub 2007 Dec 1. PMID: 18052023.

1: Linagliptin. Avoid gliptins! Prescrire Int. 2013 Feb;22(135):36-7. Review. PubMed PMID: 23444496. 2: Brown DX, Choudhury M, Evans M. Linagliptin as add-on therapy for type 2 diabetes - an overview. Drugs Today (Barc). 2012 Oct;48(10):645-54. doi: 10.1358/dot.2012.48.10.1860771. Review. PubMed PMID: 23110260. 3: Deeks ED. Linagliptin: a review of its use in the management of type 2 diabetes mellitus. Drugs. 2012 Sep 10;72(13):1793-824. doi: 10.2165/11209570-000000000-00000. Review. Erratum in: Drugs. 2013 Jan;73(1):99. PubMed PMID: 22913735. 4: Graefe-Mody U, Retlich S, Friedrich C. Clinical pharmacokinetics and pharmacodynamics of linagliptin. Clin Pharmacokinet. 2012 Jul 1;51(7):411-27. doi: 10.2165/11630900-000000000-00000. Review. PubMed PMID: 22568694. 5: Ohmura T, Hayashi N, Encinas J. [Pharmacological and clinical profiles of the DPP-4 inhibitor linagliptin (Trazenta)]. Nihon Yakurigaku Zasshi. 2012 Apr;139(4):174-83. Review. Japanese. PubMed PMID: 22498683. 6: Neumiller JJ, Setter SM. Review of linagliptin for the treatment of type 2 diabetes mellitus. Clin Ther. 2012 May;34(5):993-1005. doi: 10.1016/j.clinthera.2012.02.029. Epub 2012 Mar 21. Review. PubMed PMID: 22440191. 7: Agrawal R, Jain P, Dikshit SN. Linagliptin: a novel methylxanthin based approved dipeptidyl peptidase-4 inhibitor. Curr Drug Targets. 2012 Jun;13(7):970-83. Review. PubMed PMID: 22420306. 8: Singh-Franco D, McLaughlin-Middlekauff J, Elrod S, Harrington C. The effect of linagliptin on glycaemic control and tolerability in patients with type 2 diabetes mellitus: a systematic review and meta-analysis. Diabetes Obes Metab. 2012 Aug;14(8):694-708. doi: 10.1111/j.1463-1326.2012.01586.x. Epub 2012 Mar 20. Review. PubMed PMID: 22340363. 9: Neumiller JJ. Pharmacology, efficacy, and safety of linagliptin for the treatment of type 2 diabetes mellitus. Ann Pharmacother. 2012 Mar;46(3):358-67. doi: 10.1345/aph.1Q522. Epub 2012 Feb 7. Review. PubMed PMID: 22318932. 10: Forst T, PfÃ¼tzner A. Linagliptin, a dipeptidyl peptidase-4 inhibitor with a unique pharmacological profile, and efficacy in a broad range of patients with type 2 diabetes. Expert Opin Pharmacother. 2012 Jan;13(1):101-10. doi: 10.1517/14656566.2012.642863. Review. PubMed PMID: 22149370.