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MedKoo Cat#: 530450 | Name: MDK00245
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Description:

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

MDK00245, also known as TGR5 Receptor Agonist. MDK00245 has the CAS# 1197300-24-5. The last 5 digits of CAS# is used in it's name. MDK00245 is a synthetic small molecule activator of the bile acid receptor (pEC50 = 6.8-7.5) which is reported to improve glucagon-like peptide-1 (GLP-1) secretion by increasing intracellular cAMP levels via TGR5.

Chemical Structure

MDK00245
MDK00245
CAS#1197300-24-5

Theoretical Analysis

MedKoo Cat#: 530450

Name: MDK00245

CAS#: 1197300-24-5

Chemical Formula: C18H14Cl2N2O2

Exact Mass: 360.0432

Molecular Weight: 361.22

Elemental Analysis: C, 59.85; H, 3.91; Cl, 19.63; N, 7.76; O, 8.86

Price and Availability

Size Price Availability Quantity
50mg USD 450.00 2 Weeks
100mg USD 750.00 2 Weeks
250mg USD 1,250.00 2 Weeks
500mg USD 2,650.00 2 Weeks
1g USD 4,250.00 2 Weeks
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Synonym
TGR5 Receptor Agonist; MDK00245; MDK-00245; MDK 00245
IUPAC/Chemical Name
3-(2-chlorophenyl)-N-(4-chlorophenyl)-N,5-dimethyl-4-isoxazolecarboxamide
InChi Key
IGRCWJPBLWGNPX-UHFFFAOYSA-N
InChi Code
InChI=1S/C18H14Cl2N2O2/c1-11-16(17(21-24-11)14-5-3-4-6-15(14)20)18(23)22(2)13-9-7-12(19)8-10-13/h3-10H,1-2H3
SMILES Code
O=C(C1=C(C)ON=C1C2=CC=CC=C2Cl)N(C3=CC=C(Cl)C=C3)C
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
Instruction
View handling instruction
Biological target:
MDK00245, also known as TGR5 Receptor Agonist.
In vitro activity:
A series of 3-aryl-4-isoxazolecarboxamides identified from a high-throughput screening campaign as novel, potent small molecule agonists of the human TGR5 G-protein coupled receptor is described. Subsequent optimization resulted in the rapid identification of potent exemplars 6 and 7 which demonstrated improved GLP-1 secretion in vivo via an intracolonic dose coadministered with glucose challenge in a canine model. These novel TGR5 receptor agonists are potentially useful therapeutics for metabolic disorders such as type II diabetes and its associated complications. Reference: J Med Chem. 2009 Dec 24;52(24):7962-5. https://pubmed.ncbi.nlm.nih.gov/19902954/
In vivo activity:
A series of 3-aryl-4-isoxazolecarboxamides identified from a high-throughput screening campaign as novel, potent small molecule agonists of the human TGR5 G-protein coupled receptor is described. Subsequent optimization resulted in the rapid identification of potent exemplars 6 and 7 which demonstrated improved GLP-1 secretion in vivo via an intracolonic dose coadministered with glucose challenge in a canine model. These novel TGR5 receptor agonists are potentially useful therapeutics for metabolic disorders such as type II diabetes and its associated complications. Reference: J Med Chem. 2009 Dec 24;52(24):7962-5. https://pubmed.ncbi.nlm.nih.gov/19902954/
Solvent mg/mL mM
Solubility
DMF 50.0 138.42
DMSO 64.7 179.02
DMSO:PBS (pH 7.2) (1:4) 0.2 0.55
Ethanol 21.0 58.14
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 361.22 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.

Recalculate based on batch purity %
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:
Evans KA, Budzik BW, Ross SA, Wisnoski DD, Jin J, Rivero RA, Vimal M, Szewczyk GR, Jayawickreme C, Moncol DL, Rimele TJ, Armour SL, Weaver SP, Griffin RJ, Tadepalli SM, Jeune MR, Shearer TW, Chen ZB, Chen L, Anderson DL, Becherer JD, De Los Frailes M, Colilla FJ. Discovery of 3-aryl-4-isoxazolecarboxamides as TGR5 receptor agonists. J Med Chem. 2009 Dec 24;52(24):7962-5. doi: 10.1021/jm901434t. PMID: 19902954.
In vitro protocol:
Evans KA, Budzik BW, Ross SA, Wisnoski DD, Jin J, Rivero RA, Vimal M, Szewczyk GR, Jayawickreme C, Moncol DL, Rimele TJ, Armour SL, Weaver SP, Griffin RJ, Tadepalli SM, Jeune MR, Shearer TW, Chen ZB, Chen L, Anderson DL, Becherer JD, De Los Frailes M, Colilla FJ. Discovery of 3-aryl-4-isoxazolecarboxamides as TGR5 receptor agonists. J Med Chem. 2009 Dec 24;52(24):7962-5. doi: 10.1021/jm901434t. PMID: 19902954.
In vivo protocol:
Evans KA, Budzik BW, Ross SA, Wisnoski DD, Jin J, Rivero RA, Vimal M, Szewczyk GR, Jayawickreme C, Moncol DL, Rimele TJ, Armour SL, Weaver SP, Griffin RJ, Tadepalli SM, Jeune MR, Shearer TW, Chen ZB, Chen L, Anderson DL, Becherer JD, De Los Frailes M, Colilla FJ. Discovery of 3-aryl-4-isoxazolecarboxamides as TGR5 receptor agonists. J Med Chem. 2009 Dec 24;52(24):7962-5. doi: 10.1021/jm901434t. PMID: 19902954.
1: Lo SH, Cheng KC, Li YX, Chang CH, Cheng JT, Lee KS. Development of betulinic acid as an agonist of TGR5 receptor using a new in vitro assay. Drug Des Devel Ther. 2016 Aug 22;10:2669-76. doi: 10.2147/DDDT.S113197. PubMed PMID: 27578964; PubMed Central PMCID: PMC5001664. 2: Duboc H, Tolstanova G, Yuan PQ, Wu VS, Kaji I, Biraud M, Akiba Y, Kaunitz JD, Million M, Tache Y, Larauche M. Reduction of epithelial secretion in male rat distal colonic mucosa by bile acid receptor TGR5 agonist, INT-777: role of submucosal neurons. Neurogastroenterol Motil. 2016 Nov;28(11):1663-1676. doi: 10.1111/nmo.12866. PubMed PMID: 27259385; PubMed Central PMCID: PMC5083223. 3: Yanguas-Casás N, Barreda-Manso MA, Nieto-Sampedro M, Romero-Ramírez L. TUDCA: An Agonist of the Bile Acid Receptor GPBAR1/TGR5 with Anti-Inflammatory Effects in Microglial Cells. J Cell Physiol. 2016 Dec 17. doi: 10.1002/jcp.25742. [Epub ahead of print] PubMed PMID: 27987324. 4: Agarwal S, Patil A, Aware U, Deshmukh P, Darji B, Sasane S, Sairam KV, Priyadarsiny P, Giri P, Patel H, Giri S, Jain M, Desai RC. Discovery of a Potent and Orally Efficacious TGR5 Receptor Agonist. ACS Med Chem Lett. 2015 Nov 20;7(1):51-5. doi: 10.1021/acsmedchemlett.5b00323. PubMed PMID: 26819665; PubMed Central PMCID: PMC4716599. 5: Yang Z, Li J, Xiong F, Huang J, Chen C, Liu P, Huang H. Berberine attenuates high glucose-induced fibrosis by activating the G protein-coupled bile acid receptor TGR5 and repressing the S1P2/MAPK signaling pathway in glomerular mesangial cells. Exp Cell Res. 2016 Aug 15;346(2):241-7. doi: 10.1016/j.yexcr.2016.06.005. PubMed PMID: 27292312. 6: Zambad SP, Tuli D, Mathur A, Ghalsasi SA, Chaudhary AR, Deshpande S, Gupta RC, Chauthaiwale V, Dutt C. TRC210258, a novel TGR5 agonist, reduces glycemic and dyslipidemic cardiovascular risk in animal models of diabesity. Diabetes Metab Syndr Obes. 2013 Dec 21;7:1-14. doi: 10.2147/DMSO.S50209. PubMed PMID: 24379686; PubMed Central PMCID: PMC3873233. 7: Sakanaka T, Inoue T, Yorifuji N, Iguchi M, Fujiwara K, Narabayashi K, Kakimoto K, Nouda S, Okada T, Kuramoto T, Ishida K, Abe Y, Takeuchi T, Umegaki E, Akiba Y, Kaunitz JD, Higuchi K. The effects of a TGR5 agonist and a dipeptidyl peptidase IV inhibitor on dextran sulfate sodium-induced colitis in mice. J Gastroenterol Hepatol. 2015 Mar;30 Suppl 1:60-5. doi: 10.1111/jgh.12740. PubMed PMID: 25827806; PubMed Central PMCID: PMC4874188. 8: Kumar DP, Asgharpour A, Mirshahi F, Park SH, Liu S, Imai Y, Nadler JL, Grider JR, Murthy KS, Sanyal AJ. Activation of Transmembrane Bile Acid Receptor TGR5 Modulates Pancreatic Islet α Cells to Promote Glucose Homeostasis. J Biol Chem. 2016 Mar 25;291(13):6626-40. doi: 10.1074/jbc.M115.699504. PubMed PMID: 26757816; PubMed Central PMCID: PMC4807250. 9: Baghdasaryan A, Claudel T, Gumhold J, Silbert D, Adorini L, Roda A, Vecchiotti S, Gonzalez FJ, Schoonjans K, Strazzabosco M, Fickert P, Trauner M. Dual farnesoid X receptor/TGR5 agonist INT-767 reduces liver injury in the Mdr2-/- (Abcb4-/-) mouse cholangiopathy model by promoting biliary HCO⁻₃ output. Hepatology. 2011 Oct;54(4):1303-12. doi: 10.1002/hep.24537. PubMed PMID: 22006858; PubMed Central PMCID: PMC3744065. 10: Mobraten K, Haugbro T, Karlstrom E, Kleiveland CR, Lea T. Activation of the bile acid receptor TGR5 enhances LPS-induced inflammatory responses in a human monocytic cell line. J Recept Signal Transduct Res. 2015;35(5):402-9. doi: 10.3109/10799893.2014.986744. PubMed PMID: 25418122. 11: Rizzo G, Passeri D, De Franco F, Ciaccioli G, Donadio L, Rizzo G, Orlandi S, Sadeghpour B, Wang XX, Jiang T, Levi M, Pruzanski M, Adorini L. Functional characterization of the semisynthetic bile acid derivative INT-767, a dual farnesoid X receptor and TGR5 agonist. Mol Pharmacol. 2010 Oct;78(4):617-30. doi: 10.1124/mol.110.064501. PubMed PMID: 20631053; PubMed Central PMCID: PMC2981390. 12: Alemi F, Kwon E, Poole DP, Lieu T, Lyo V, Cattaruzza F, Cevikbas F, Steinhoff M, Nassini R, Materazzi S, Guerrero-Alba R, Valdez-Morales E, Cottrell GS, Schoonjans K, Geppetti P, Vanner SJ, Bunnett NW, Corvera CU. The TGR5 receptor mediates bile acid-induced itch and analgesia. J Clin Invest. 2013 Apr;123(4):1513-30. doi: 10.1172/JCI64551. PubMed PMID: 23524965; PubMed Central PMCID: PMC3613908. 13: Zhuang L, Fan Y, Lu L, Ding W, Ni C, Wang X, Zhang F, Rao J. Ischemic Preconditioning protects hepatocytes from ischemia-reperfusion injury via TGR5-mediated anti-apoptosis. Biochem Biophys Res Commun. 2016 May 13;473(4):966-72. doi: 10.1016/j.bbrc.2016.03.162. PubMed PMID: 27045083. 14: Alemi F, Poole DP, Chiu J, Schoonjans K, Cattaruzza F, Grider JR, Bunnett NW, Corvera CU. The receptor TGR5 mediates the prokinetic actions of intestinal bile acids and is required for normal defecation in mice. Gastroenterology. 2013 Jan;144(1):145-54. doi: 10.1053/j.gastro.2012.09.055. PubMed PMID: 23041323. 15: Wang XX, Edelstein MH, Gafter U, Qiu L, Luo Y, Dobrinskikh E, Lucia S, Adorini L, D'Agati VD, Levi J, Rosenberg A, Kopp JB, Gius DR, Saleem MA, Levi M. G Protein-Coupled Bile Acid Receptor TGR5 Activation Inhibits Kidney Disease in Obesity and Diabetes. J Am Soc Nephrol. 2016 May;27(5):1362-78. doi: 10.1681/ASN.2014121271. PubMed PMID: 26424786; PubMed Central PMCID: PMC4849814. 16: Wang YD, Chen WD, Yu D, Forman BM, Huang W. The G-protein-coupled bile acid receptor, Gpbar1 (TGR5), negatively regulates hepatic inflammatory response through antagonizing nuclear factor κ light-chain enhancer of activated B cells (NF-κB) in mice. Hepatology. 2011 Oct;54(4):1421-32. doi: 10.1002/hep.24525. PubMed PMID: 21735468; PubMed Central PMCID: PMC3184183. 17: Keitel V, Reich M, Häussinger D. TGR5: pathogenetic role and/or therapeutic target in fibrosing cholangitis? Clin Rev Allergy Immunol. 2015 Jun;48(2-3):218-25. doi: 10.1007/s12016-014-8443-x. Review. PubMed PMID: 25138774. 18: Li T, Holmstrom SR, Kir S, Umetani M, Schmidt DR, Kliewer SA, Mangelsdorf DJ. The G protein-coupled bile acid receptor, TGR5, stimulates gallbladder filling. Mol Endocrinol. 2011 Jun;25(6):1066-71. doi: 10.1210/me.2010-0460. PubMed PMID: 21454404; PubMed Central PMCID: PMC3100601. 19: Hodge RJ, Nunez DJ. Therapeutic potential of Takeda-G-protein-receptor-5 (TGR5) agonists. Hope or hype? Diabetes Obes Metab. 2016 May;18(5):439-43. doi: 10.1111/dom.12636. Review. PubMed PMID: 26818602. 20: Hodge RJ, Lin J, Vasist Johnson LS, Gould EP, Bowers GD, Nunez DJ; SB-756050 Project Team.. Safety, Pharmacokinetics, and Pharmacodynamic Effects of a Selective TGR5 Agonist, SB-756050, in Type 2 Diabetes. Clin Pharmacol Drug Dev. 2013 Jul;2(3):213-22. doi: 10.1002/cpdd.34. PubMed PMID: 27121782.

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