Gemigliptin | LC15-0444 | CAS#911637-19-9 | DPP-4 inhibitor

MedKoo Cat#: 319789 | Name: Gemigliptin

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Description:

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

Gemigliptin, also known as LC15-0444, is a potent dipeptidyl peptidase-4 (DPP-4) inhibitor was approved in South Korea as an oral anti-hyperglycemic agent (anti-diabetic drug). Gemigliptin dose-dependently inhibited methylglyoxal-modified AGE-bovine serum albumin (BSA) formation (IC50=11.69 mM). AGE-collagen cross-linking assays showed that gemigliptin had a potent inhibitory effect (IC50=1.39 mM) on AGE-BSA cross-links to rat tail tendon collagen, and its activity was stronger than aminoguanidine (IC50=26.4 mM).

Chemical Structure

Gemigliptin

CAS#911637-19-9 (free base)

Theoretical Analysis

MedKoo Cat#: 319789

Name: Gemigliptin

CAS#: 911637-19-9 (free base)

Chemical Formula: C18H19F8N5O2

Exact Mass: 489.1411

Molecular Weight: 489.37

Elemental Analysis: C, 44.18; H, 3.91; F, 31.06; N, 14.31; O, 6.54

Price and Availability

Size	Price	Availability	Quantity
100mg	USD 750.00	2 Weeks
250mg	USD 1,450.00	2 Weeks

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Related CAS #

911637-19-9 (free base) 1375415-82-9 (tartrate 1.5 hydrate) 1374639-74-3 (tartrate)

Synonym

LC15-0444; LC 15-0444; LC-15-0444; LC150444; LC-150444; LC 150444; Gemigliptin; Gemigliptina; Gemigliptine; Gemigliptinum

IUPAC/Chemical Name

(S)-1-(2-amino-4-(2,4-bis(trifluoromethyl)-5,8-dihydropyrido[3,4-d]pyrimidin-7(6H)-yl)-4-oxobutyl)-5,5-difluoropiperidin-2-one

InChi Key

ZWPRRQZNBDYKLH-VIFPVBQESA-N

InChi Code

InChI=1S/C18H19F8N5O2/c19-16(20)3-1-12(32)31(8-16)6-9(27)5-13(33)30-4-2-10-11(7-30)28-15(18(24,25)26)29-14(10)17(21,22)23/h9H,1-8,27H2/t9-/m0/s1

SMILES Code

O=C1N(C[C@@H](N)CC(N2CCC3=C(C(F)(F)F)N=C(C(F)(F)F)N=C3C2)=O)CC(F)(F)CC1

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

Instruction

View handling instruction

Biological target:

Gemigliptin (LC15-0444) is a highly selective, reversible and competitive dipeptidyl peptidase-4 (DPP-4) inhibitor, with an IC50 of 10.3 nM for human recombinant DPP-4.

In vitro activity:

Gemigliptin-treated cells showed a significant reduction in the phosphorylation of Smad1/5/9, Smad2, and Smad3 induced by IL-1β. Densitometric analyses of band intensities showed that gemigliptin partially increased endogenous Smad1/5/9 in contrast to Smad2 and 3 (Fig. 3). These results indicate that gemigliptin blocks IL-1β-induced EndMT in part by inhibiting the BMP/Smad signaling pathway. Reference: Endocrinol Metab (Seoul). 2020 Jun;35(2):384-395. https://pubmed.ncbi.nlm.nih.gov/32615723/

In vivo activity:

High blood glucose levels were not altered by gemigliptin (Fig. 1D), but reduced saliva secretion was significantly recovered following gemigliptin administration (Fig. 1E). In the saliva analysis, amylase concentrations were decreased in DM rats and significantly increased in the DM-Ge100 group (Fig. 1F). Similarly, total secreted proteins were reduced in the DM group and were elevated by gemigliptin (Fig. 1G). Reference: Biomed Pharmacother. 2021 May;137:111297. https://pubmed.ncbi.nlm.nih.gov/33493968/

	Solvent	mg/mL	mM
Solubility
	DMSO	74.0	151.21
	Ethanol	7.0	14.30
	Water	12.0	24.52

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 489.37 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:

1. Hong OK, Lee SS, Yoo SJ, Lee MK, Kim MK, Baek KH, Song KH, Kwon HS. Gemigliptin Inhibits Interleukin-1β-Induced Endothelial-Mesenchymal Transition via Canonical-Bone Morphogenetic Protein Pathway. Endocrinol Metab (Seoul). 2020 Jun;35(2):384-395. doi: 10.3803/EnM.2020.35.2.384. Epub 2020 Jun 24. PMID: 32615723; PMCID: PMC7386109. 2. Seo JB, Choi YK, Woo HI, Jung YA, Lee S, Lee S, Park M, Lee IK, Jung GS, Park KG. Gemigliptin Attenuates Renal Fibrosis Through Down-Regulation of the NLRP3 Inflammasome. Diabetes Metab J. 2019 Dec;43(6):830-839. doi: 10.4093/dmj.2018.0181. Epub 2019 Mar 5. PMID: 30877711; PMCID: PMC6943262. 3. Kang WS, Jung WK, Park SB, Kim HR, Kim J. Gemigliptin suppresses salivary dysfunction in streptozotocin-induced diabetic rats. Biomed Pharmacother. 2021 May;137:111297. doi: 10.1016/j.biopha.2021.111297. Epub 2021 Jan 22. PMID: 33493968. 4. Nam DH, Park J, Park SH, Kim KS, Baek EB. Effect of gemigliptin on cardiac ischemia/reperfusion and spontaneous hypertensive rat models. Korean J Physiol Pharmacol. 2019 Sep;23(5):329-334. doi: 10.4196/kjpp.2019.23.5.329. Epub 2019 Aug 26. PMID: 31496870; PMCID: PMC6717789.

In vitro protocol:

In vivo protocol:

1. Kang WS, Jung WK, Park SB, Kim HR, Kim J. Gemigliptin suppresses salivary dysfunction in streptozotocin-induced diabetic rats. Biomed Pharmacother. 2021 May;137:111297. doi: 10.1016/j.biopha.2021.111297. Epub 2021 Jan 22. PMID: 33493968. 2. Nam DH, Park J, Park SH, Kim KS, Baek EB. Effect of gemigliptin on cardiac ischemia/reperfusion and spontaneous hypertensive rat models. Korean J Physiol Pharmacol. 2019 Sep;23(5):329-334. doi: 10.4196/kjpp.2019.23.5.329. Epub 2019 Aug 26. PMID: 31496870; PMCID: PMC6717789.

1: Jung E, Kim J, Kim CS, Kim SH, Cho MH. Gemigliptin, a dipeptidyl peptidase-4 inhibitor, inhibits retinal pericyte injury in db/db mice and retinal neovascularization in mice with ischemic retinopathy. Biochim Biophys Acta. 2015 Dec;1852(12):2618-29. doi: 10.1016/j.bbadis.2015.09.010. Epub 2015 Sep 21. PubMed PMID: 26391252. 2: Choi SH, Park S, Oh CJ, Leem J, Park KG, Lee IK. Dipeptidyl peptidase-4 inhibition by gemigliptin prevents abnormal vascular remodeling via NF-E2-related factor 2 activation. Vascul Pharmacol. 2015 Oct;73:11-9. doi: 10.1016/j.vph.2015.07.005. Epub 2015 Jul 15. PubMed PMID: 26187356. 3: Jung E, Kim J, Ho Kim S, Kim S, Cho MH. Gemigliptin improves renal function and attenuates podocyte injury in mice with diabetic nephropathy. Eur J Pharmacol. 2015 Aug 15;761:116-24. doi: 10.1016/j.ejphar.2015.04.055. Epub 2015 May 11. PubMed PMID: 25977232. 4: Park SI, Lee H, Oh J, Lim KS, Jang IJ, Kim JA, Jung JH, Yu KS. A fixed-dose combination tablet of gemigliptin and metformin sustained release has comparable pharmacodynamic, pharmacokinetic, and tolerability profiles to separate tablets in healthy subjects. Drug Des Devel Ther. 2015 Feb 4;9:729-36. doi: 10.2147/DDDT.S75980. eCollection 2015. PubMed PMID: 25678778; PubMed Central PMCID: PMC4324327. 5: Jung E, Kim J, Kim SH, Kim S, Cho MH. Gemigliptin, a novel dipeptidyl peptidase-4 inhibitor, exhibits potent anti-glycation properties in vitro and in vivo. Eur J Pharmacol. 2014 Dec 5;744:98-102. doi: 10.1016/j.ejphar.2014.10.008. Epub 2014 Oct 18. PubMed PMID: 25448307. 6: Choi HY, Lim HS, Kim YH, Jeon HS, Kim MJ, Lee SH, Jung JH, Lee YK, Kim HJ, Bae KS. Evaluation of the pharmacokinetics of the DPP-4 inhibitor gemigliptin when coadministered with rosuvastatin or irbesartan to healthy subjects. Curr Med Res Opin. 2015 Feb;31(2):229-41. doi: 10.1185/03007995.2014.980886. Epub 2014 Nov 6. PubMed PMID: 25350224. 7: Choi HY, Kim YH, Kim MJ, Lee SH, Bang K, Han S, Lim HS, Bae KS. Evaluation of pharmacokinetic drug interactions between gemigliptin (dipeptidylpeptidase-4 inhibitor) and glimepiride (sulfonylurea) in healthy volunteers. Drugs R D. 2014 Sep;14(3):165-76. doi: 10.1007/s40268-014-0054-8. PubMed PMID: 24962635; PubMed Central PMCID: PMC4153964. 8: Hwang HJ, Jung TW, Ryu JY, Hong HC, Choi HY, Seo JA, Kim SG, Kim NH, Choi KM, Choi DS, Baik SH, Yoo HJ. Dipeptidyl petidase-IV inhibitor (gemigliptin) inhibits tunicamycin-induced endoplasmic reticulum stress, apoptosis and inflammation in H9c2 cardiomyocytes. Mol Cell Endocrinol. 2014 Jul 5;392(1-2):1-7. doi: 10.1016/j.mce.2014.04.017. Epub 2014 May 9. PubMed PMID: 24813659. 9: Kim Y, Kim U, Kim IS, Lee SH, Lee J, Kim DH, Yoo HH. Absorption, distribution, metabolism and excretion of gemigliptin, a novel dipeptidyl peptidase IV inhibitor, in rats. Xenobiotica. 2014 Jul;44(7):627-34. doi: 10.3109/00498254.2013.873156. Epub 2014 Apr 16. PubMed PMID: 24738939. 10: Shon JH, Kim N, Park SJ, Oh MK, Kim EY, Lee SH, Kim YH, Shin JG. Effect of renal impairment and haemodialysis on the pharmacokinetics of gemigliptin (LC15-0444). Diabetes Obes Metab. 2014 Oct;16(10):1028-31. doi: 10.1111/dom.12292. Epub 2014 Apr 16. PubMed PMID: 24641348. 11: Shin D, Cho YM, Lee S, Lim KS, Kim JA, Ahn JY, Cho JY, Lee H, Jang IJ, Yu KS. Pharmacokinetic and pharmacodynamic interaction between gemigliptin and metformin in healthy subjects. Clin Drug Investig. 2014 Jun;34(6):383-93. doi: 10.1007/s40261-014-0184-3. PubMed PMID: 24627290. 12: Choi HY, Noh YH, Kim YH, Kim MJ, Lee SH, Kim JA, Kim B, Lim HS, Bae KS. Effects of food on the pharmacokinetics of gemigliptin/metformin sustained-release 50/1,000 mg (25/500 mg x 2 tablets) fixeddose combination tablet in healthy male volunteers. Int J Clin Pharmacol Ther. 2014 May;52(5):381-91. doi: 10.5414/CP202038. PubMed PMID: 24495314. 13: Kim N, Patrick L, Mair S, Stevens L, Ford G, Birks V, Lee SH. Absorption, metabolism and excretion of [14C]gemigliptin, a novel dipeptidyl peptidase 4 inhibitor, in humans. Xenobiotica. 2014 Jun;44(6):522-30. doi: 10.3109/00498254.2013.865856. Epub 2013 Dec 4. PubMed PMID: 24304170. 14: Kim SH, Lee SH, Yim HJ. Gemigliptin, a novel dipeptidyl peptidase 4 inhibitor: first new anti-diabetic drug in the history of Korean pharmaceutical industry. Arch Pharm Res. 2013 Oct;36(10):1185-8. doi: 10.1007/s12272-013-0171-x. Epub 2013 Jun 15. PubMed PMID: 23771499. 15: Rhee EJ, Lee WY, Min KW, Shivane VK, Sosale AR, Jang HC, Chung CH, Nam-Goong IS, Kim JA, Kim SW; Gemigliptin Study 006 Group. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor gemigliptin compared with sitagliptin added to ongoing metformin therapy in patients with type 2 diabetes inadequately controlled with metformin alone. Diabetes Obes Metab. 2013 Jun;15(6):523-30. doi: 10.1111/dom.12060. Epub 2013 Jan 30. PubMed PMID: 23320436. 16: Yang SJ, Min KW, Gupta SK, Park JY, Shivane VK, Pitale SU, Agarwal PK, Sosale A, Gandhi P, Dharmalingam M, Mohan V, Mahesh U, Kim DM, Kim YS, Kim JA, Kim PK, Baik SH. A multicentre, multinational, randomized, placebo-controlled, double-blind, phase 3 trial to evaluate the efficacy and safety of gemigliptin (LC15-0444) in patients with type 2 diabetes. Diabetes Obes Metab. 2013 May;15(5):410-6. doi: 10.1111/dom.12042. Epub 2012 Dec 17. PubMed PMID: 23170990. 17: Noh YH, Lim HS, Jin SJ, Kim MJ, Kim YH, Sung HR, Choi HY, Bae KS. Effects of ketoconazole and rifampicin on the pharmacokinetics of gemigliptin, a dipeptidyl peptidase-IV inhibitor: a crossover drug-drug interaction study in healthy male Korean volunteers. Clin Ther. 2012 May;34(5):1182-94. doi: 10.1016/j.clinthera.2012.04.001. Epub 2012 Apr 24. PubMed PMID: 22534255.