PD-166793 | CAS#199850-67-4 | MMP inhibitor

MedKoo Cat#: 598116 | Name: PD-166793

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Description:

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

PD-166793 is a cell-permeable biphenylsulfonylvaline compound that acts as a potent inhibitor against MMP-2, -3, and -13 (IC50 = 47, 12, and 8 nM, respectively) and a weaker inhibitor against AMP deaminase (20% inhibition at 0.1 µM), MMP-1, -7, -9, and -14 (IC50 = 6.1, 7.2, 7.9, and 0.24 µM, respectively). Shown to offer therapeutic benefits in vivo in various animal models of heart failure and diabetes.

Chemical Structure

PD-166793

CAS#199850-67-4

Theoretical Analysis

MedKoo Cat#: 598116

Name: PD-166793

CAS#: 199850-67-4

Chemical Formula: C17H18BrNO4S

Exact Mass: 411.0140

Molecular Weight: 412.30

Elemental Analysis: C, 49.52; H, 4.40; Br, 19.38; N, 3.40; O, 15.52; S, 7.78

Price and Availability

Size	Price	Availability
25mg	USD 250.00	2 Weeks
50mg	USD 450.00	2 Weeks
100mg	USD 750.00	2 Weeks
200mg	USD 1,250.00	2 Weeks
500mg	USD 2,650.00	2 Weeks
1g	USD 4,250.00	2 Weeks
2g	USD 6,450.00	2 Weeks

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Synonym

PD-166793; PD 166793; PD166793; PD-166793-0000;

IUPAC/Chemical Name

((4'-bromo-[1,1'-biphenyl]-4-yl)sulfonyl)-L-valine

InChi Key

GJOCABIDMCKCEG-INIZCTEOSA-N

InChi Code

InChI=1S/C17H18BrNO4S/c1-11(2)16(17(20)21)19-24(22,23)15-9-5-13(6-10-15)12-3-7-14(18)8-4-12/h3-11,16,19H,1-2H3,(H,20,21)/t16-/m0/s1

SMILES Code

CC(C)[C@@H](C(O)=O)NS(=O)(C1=CC=C(C2=CC=C(Br)C=C2)C=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

>3 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

2934.99.03.00

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Product Data

Product Data

Instruction

View handling instruction

Biological target:

PD-166793 is a potent, selective, orally active and wide‐broad spectrum inhibitor of MMP, exhibiting nanomolar potency against MMP-2, MMP-3 and MMP-13 (IC50=4, 7, and 8 nM, respectively) and micromolar potency vs MMP-1, -7 and -9 (IC50=6.0, 7.2, and 7.9 μM, respectively).

In vitro activity:

This study found that NE induced endogenous MMP-2 activation, and 10−4 M PD166793, which is a specific inhibitor of MMP activity that blocks zinc-binding sites, inhibited the increased endogenous MMP-2 activity induced by NE. This study investigated whether endogenously induced MMP-2 stimulates FAK phosphorylation and collagen-I synthesis in cardiac fibroblasts by incubating cells with NE and/or PD166793. Although NE significantly enhanced FAK (Tyr397) phosphorylation and collagen-I expression, levels were significantly attenuated by simultaneous treatment with PD166793 (Fig. 5, A and B). Reference: Am J Physiol Cell Physiol. 2012 Nov 1;303(9):C947-53. https://pubmed.ncbi.nlm.nih.gov/22914642/

In vivo activity:

This study studied cardiac remodeling in mice after experimental MI under treatment with citalopram, a selective serotonin reuptake inhibitor widely used as antidepressant. There was a significant increase of MMP13 in citalopram treated animals after MI. Pretreatment with the MMP inhibitor PD 166793 prevented left ventricular ruptures and demonstrated a tendency to improved survival after citalopram treatment. Reference: J Mol Cell Cardiol. 2016 Sep;98:28-36. https://pubmed.ncbi.nlm.nih.gov/27397875/

	Solvent	mg/mL	mM
Solubility
	DMF	50.0	121.27
	DMSO	63.7	154.61
	DMSO:PBS (pH 7.2) (1:1)	0.5	1.21
	Ethanol	25.6	62.13

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 412.30 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. Hori Y, Kashimoto T, Yonezawa T, Sano N, Saitoh R, Igarashi S, Chikazawa S, Kanai K, Hoshi F, Itoh N, Higuchi S. Matrix metalloproteinase-2 stimulates collagen-I expression through phosphorylation of focal adhesion kinase in rat cardiac fibroblasts. Am J Physiol Cell Physiol. 2012 Nov 1;303(9):C947-53. doi: 10.1152/ajpcell.00401.2011. Epub 2012 Aug 22. PMID: 22914642. 2. Mendes O, Kim HT, Stoica G. Expression of MMP2, MMP9 and MMP3 in breast cancer brain metastasis in a rat model. Clin Exp Metastasis. 2005;22(3):237-46. doi: 10.1007/s10585-005-8115-6. PMID: 16158251. 3. Frey A, Saxon VM, Popp S, Lehmann M, Mathes D, Pachel C, Hofmann U, Ertl G, Lesch KP, Frantz S. Early citalopram treatment increases mortality due to left ventricular rupture in mice after myocardial infarction. J Mol Cell Cardiol. 2016 Sep;98:28-36. doi: 10.1016/j.yjmcc.2016.07.002. Epub 2016 Jul 7. PMID: 27397875. 4. Ulasova E, Gladden JD, Chen Y, Zheng J, Pat B, Bradley W, Powell P, Zmijewski JW, Zelickson BR, Ballinger SW, Darley-Usmar V, Dell'italia LJ. Loss of interstitial collagen causes structural and functional alterations of cardiomyocyte subsarcolemmal mitochondria in acute volume overload. J Mol Cell Cardiol. 2011 Jan;50(1):147-56. doi: 10.1016/j.yjmcc.2010.10.034. Epub 2010 Nov 6. PMID: 21059354; PMCID: PMC3092361.

In vitro protocol:

In vivo protocol:

1. Frey A, Saxon VM, Popp S, Lehmann M, Mathes D, Pachel C, Hofmann U, Ertl G, Lesch KP, Frantz S. Early citalopram treatment increases mortality due to left ventricular rupture in mice after myocardial infarction. J Mol Cell Cardiol. 2016 Sep;98:28-36. doi: 10.1016/j.yjmcc.2016.07.002. Epub 2016 Jul 7. PMID: 27397875. 2. Ulasova E, Gladden JD, Chen Y, Zheng J, Pat B, Bradley W, Powell P, Zmijewski JW, Zelickson BR, Ballinger SW, Darley-Usmar V, Dell'italia LJ. Loss of interstitial collagen causes structural and functional alterations of cardiomyocyte subsarcolemmal mitochondria in acute volume overload. J Mol Cell Cardiol. 2011 Jan;50(1):147-56. doi: 10.1016/j.yjmcc.2010.10.034. Epub 2010 Nov 6. PMID: 21059354; PMCID: PMC3092361.

1: Pintus G, Giordo R, Wang Y, Zhu W, Kim SH, Zhang L, Ni L, Zhang J, Telljohann R, McGraw KR, Monticone RE, Ferris C, Liu L, Wang M, Lakatta EG. Reduced vasorin enhances angiotensin II signaling within the aging arterial wall. Oncotarget. 2018 Jun 5;9(43):27117-27132. doi: 10.18632/oncotarget.25499. PMID: 29930755; PMCID: PMC6007470. 2: Frey A, Saxon VM, Popp S, Lehmann M, Mathes D, Pachel C, Hofmann U, Ertl G, Lesch KP, Frantz S. Early citalopram treatment increases mortality due to left ventricular rupture in mice after myocardial infarction. J Mol Cell Cardiol. 2016 Sep;98:28-36. doi: 10.1016/j.yjmcc.2016.07.002. Epub 2016 Jul 7. PMID: 27397875. 3: Hori Y, Kashimoto T, Yonezawa T, Sano N, Saitoh R, Igarashi S, Chikazawa S, Kanai K, Hoshi F, Itoh N, Higuchi S. Matrix metalloproteinase-2 stimulates collagen-I expression through phosphorylation of focal adhesion kinase in rat cardiac fibroblasts. Am J Physiol Cell Physiol. 2012 Nov 1;303(9):C947-53. doi: 10.1152/ajpcell.00401.2011. Epub 2012 Aug 22. PMID: 22914642. 4: Wang M, Zhang J, Telljohann R, Jiang L, Wu J, Monticone RE, Kapoor K, Talan M, Lakatta EG. Chronic matrix metalloproteinase inhibition retards age- associated arterial proinflammation and increase in blood pressure. Hypertension. 2012 Aug;60(2):459-66. doi: 10.1161/HYPERTENSIONAHA.112.191270. Epub 2012 Jun 11. PMID: 22689745; PMCID: PMC3537179. 5: Kandalam V, Basu R, Abraham T, Wang X, Awad A, Wang W, Lopaschuk GD, Maeda N, Oudit GY, Kassiri Z. Early activation of matrix metalloproteinases underlies the exacerbated systolic and diastolic dysfunction in mice lacking TIMP3 following myocardial infarction. Am J Physiol Heart Circ Physiol. 2010 Oct;299(4):H1012-23. doi: 10.1152/ajpheart.00246.2010. Epub 2010 Jul 30. PMID: 20675565; PMCID: PMC4116393. 6: Romero-Perez D, Agrawal A, Jacobsen J, Yan Y, Thomas R, Cohen S, Villarreal F. Effects of novel semiselective matrix metalloproteinase inhibitors on ex vivo cardiac structure-function. J Cardiovasc Pharmacol. 2009 Jun;53(6):452-61. doi: 10.1097/FJC.0b013e3181a6aa83. PMID: 19365278; PMCID: PMC2835692. 7: Kaludercic N, Lindsey ML, Tavazzi B, Lazzarino G, Paolocci N. Inhibiting metalloproteases with PD 166793 in heart failure: impact on cardiac remodeling and beyond. Cardiovasc Ther. 2008 Spring;26(1):24-37. doi: 10.1111/j.1527-3466.2007.00034.x. PMID: 18466418. 8: León H, Baczkó I, Sawicki G, Light PE, Schulz R. Inhibition of matrix metalloproteinases prevents peroxynitrite-induced contractile dysfunction in the isolated cardiac myocyte. Br J Pharmacol. 2008 Feb;153(4):676-83. doi: 10.1038/sj.bjp.0707621. Epub 2007 Dec 10. PMID: 18071296; PMCID: PMC2259199. 9: Sung MM, Schulz CG, Wang W, Sawicki G, Bautista-López NL, Schulz R. Matrix metalloproteinase-2 degrades the cytoskeletal protein alpha-actinin in peroxynitrite mediated myocardial injury. J Mol Cell Cardiol. 2007 Oct;43(4):429-36. doi: 10.1016/j.yjmcc.2007.07.055. Epub 2007 Jul 31. PMID: 17854826. 10: Paolocci N, Tavazzi B, Biondi R, Gluzband YA, Amorini AM, Tocchetti CG, Hejazi M, Caturegli PM, Kajstura J, Lazzarino G, Kass DA. Metalloproteinase inhibitor counters high-energy phosphate depletion and AMP deaminase activity enhancing ventricular diastolic compliance in subacute heart failure. J Pharmacol Exp Ther. 2006 May;317(2):506-13. doi: 10.1124/jpet.105.099168. Epub 2006 Jan 25. PMID: 16436497. 11: Mendes O, Kim HT, Stoica G. Expression of MMP2, MMP9 and MMP3 in breast cancer brain metastasis in a rat model. Clin Exp Metastasis. 2005;22(3):237-46. doi: 10.1007/s10585-005-8115-6. PMID: 16158251. 12: Zhou YP, Madjidi A, Wilson ME, Nothhelfer DA, Johnson JH, Palma JF, Schweitzer A, Burant C, Blume JE, Johnson JD. Matrix metalloproteinases contribute to insulin insufficiency in Zucker diabetic fatty rats. Diabetes. 2005 Sep;54(9):2612-9. doi: 10.2337/diabetes.54.9.2612. PMID: 16123349. 13: Ikonomidis JS, Hendrick JW, Parkhurst AM, Herron AR, Escobar PG, Dowdy KB, Stroud RE, Hapke E, Zile MR, Spinale FG. Accelerated LV remodeling after myocardial infarction in TIMP-1-deficient mice: effects of exogenous MMP inhibition. Am J Physiol Heart Circ Physiol. 2005 Jan;288(1):H149-58. doi: 10.1152/ajpheart.00370.2004. PMID: 15598866. 14: Chen H, Li D, Saldeen T, Mehta JL. TGF-beta 1 attenuates myocardial ischemia-reperfusion injury via inhibition of upregulation of MMP-1. Am J Physiol Heart Circ Physiol. 2003 May;284(5):H1612-7. doi: 10.1152/ajpheart.00992.2002. PMID: 12679326. 15: Yarbrough WM, Mukherjee R, Brinsa TA, Dowdy KB, Scott AA, Escobar GP, Joffs C, Lucas DG, Crawford FA Jr, Spinale FG. Matrix metalloproteinase inhibition modifies left ventricular remodeling after myocardial infarction in pigs. J Thorac Cardiovasc Surg. 2003 Mar;125(3):602-10. doi: 10.1067/mtc.2003.197. PMID: 12658202. 16: Mukherjee R, Brinsa TA, Dowdy KB, Scott AA, Baskin JM, Deschamps AM, Lowry AS, Escobar GP, Lucas DG, Yarbrough WM, Zile MR, Spinale FG. Myocardial infarct expansion and matrix metalloproteinase inhibition. Circulation. 2003 Feb 4;107(4):618-25. doi: 10.1161/01.cir.0000046449.36178.00. PMID: 12566376. 17: Chancey AL, Brower GL, Peterson JT, Janicki JS. Effects of matrix metalloproteinase inhibition on ventricular remodeling due to volume overload. Circulation. 2002 Apr 23;105(16):1983-8. doi: 10.1161/01.cir.0000014686.73212.da. PMID: 11997287. 18: Wang W, Sawicki G, Schulz R. Peroxynitrite-induced myocardial injury is mediated through matrix metalloproteinase-2. Cardiovasc Res. 2002 Jan;53(1):165-74. doi: 10.1016/s0008-6363(01)00445-x. PMID: 11744025. 19: Peterson JT, Hallak H, Johnson L, Li H, O'Brien PM, Sliskovic DR, Bocan TM, Coker ML, Etoh T, Spinale FG. Matrix metalloproteinase inhibition attenuates left ventricular remodeling and dysfunction in a rat model of progressive heart failure. Circulation. 2001 May 8;103(18):2303-9. doi: 10.1161/01.cir.103.18.2303. PMID: 11342481. 20: Parker MH, Ortwine DF, O'Brien PM, Lunney EA, Banotai CA, Mueller WT, McConnell P, Brouillette CG. Stereoselective binding of an enantiomeric pair of stromelysin-1 inhibitors caused by conformational entropy factors. Bioorg Med Chem Lett. 2000 Nov 6;10(21):2427-30. doi: 10.1016/s0960-894x(00)00495-9. PMID: 11078193.