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MedKoo Cat#: 597813 | Name: PPACK HCl
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Description:

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

PPACK is a synthetic peptide derivative that irreversibly and specifically inhibits thrombin-mediated platelet activation by binding with high affinity to the active site of thrombin (Ki = 0.24 nM). It has been used as an anticoagulant (100 μM) and to study thrombin-mediated fibrin deposition, angiogenesis, and proinflammatory processes. PPACK is a serine protease inhibitor.

Chemical Structure

PPACK HCl
PPACK HCl
CAS#82188-90-7 (HCl)

Theoretical Analysis

MedKoo Cat#: 597813

Name: PPACK HCl

CAS#: 82188-90-7 (HCl)

Chemical Formula: C21H33Cl3N6O3

Exact Mass: 0.0000

Molecular Weight: 523.88

Elemental Analysis: C, 48.15; H, 6.35; Cl, 20.30; N, 16.04; O, 9.16

Price and Availability

Size Price Availability Quantity
5mg USD 550.00 2 Weeks
10mg USD 950.00 2 Weeks
25mg USD 1,650.00 2 Weeks
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Related CAS #
82188-90-7 (HCl) 71142-71-7 (free base)
Synonym
PPACK; D-Phe-pro-arg CH2Cl;
IUPAC/Chemical Name
D-phenylalanyl-N-[(1S)-4-[(aminoiminomethyl)amino]-1-(chloroacetyl)butyl]-L-prolinamide, dihydrochloride
InChi Key
XKDCRQWZLPWLFG-LKLBIAKRSA-N
InChi Code
InChI=1S/C21H31ClN6O3.2ClH/c22-13-18(29)16(8-4-10-26-21(24)25)27-19(30)17-9-5-11-28(17)20(31)15(23)12-14-6-2-1-3-7-14;;/h1-3,6-7,15-17H,4-5,8-13,23H2,(H,27,30)(H4,24,25,26);2*1H/t15-,16+,17+;;/m1../s1
SMILES Code
O=C(N[C@H](C(CCl)=O)CCCNC(N)=N)[C@H]1N(C([C@@H](CC2=CC=CC=C2)N)=O)CCC1.[H]Cl.[H]Cl
Appearance
Solid powder
Purity
>95% (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
More Info
Product Data
Product Data
Instruction
View handling instruction
Biological target:
PPACK is a synthetic peptide derivative that irreversibly and specifically inhibits thrombin-mediated platelet activation by binding with high affinity to the active site of thrombin (Ki = 0.24 nM).
In vitro activity:
Large increases in Tm indicated that calcium led to protein stabilization (0 vs. 2 mM Ca2+) for fibrinogen (54.0 vs. 62.3 °C) and fibrin (62.3 vs. 72.2 °C). Additionally, active site inhibition with PPACK dramatically increased the Tm of thrombin (58.3 vs. 78.3 °C). Treatment of fibrinogen with fibrin polymerization inhibitor GPRP increased fibrinogen stability by ΔTm = 9.3 °C, similar to the ΔTm when fibrinogen was converted to fibrin monomer (ΔTm = 8.8 °C) or to fibrin (ΔTm = 10.4 °C). Reference: Biochim Biophys Acta Gen Subj. 2021 Feb;1865(2):129805. https://pubmed.ncbi.nlm.nih.gov/33276061/
In vivo activity:
Each PFC NP (perfluorocarbon nanoparticle) was complexed with ~13,650 copies of the direct thrombin inhibitor, PPACK (proline-phenylalanine-arginine-chloromethyl-ketone). Mice treated after the onset of AKI with PPACK PFC NP exhibited downregulated VCAM-1, ICAM-1, PGD2 prostanoid, M-CSF, IL-6, and mast cell infiltrates. Microvascular architecture, tubular basement membranes, and brush border components were better preserved. Non-reperfusion was reduced as indicated by reduced red blood cell trapping and non-heme iron. Kidney function and tubular necrosis improved at 24 hours versus the untreated control group, suggesting a benefit for dual inhibition of thrombosis and inflammation by PPACK PFC NP. Reference: Nanomedicine. 2021 Nov;38:102449. https://pubmed.ncbi.nlm.nih.gov/34303838/

Preparing Stock Solutions

The following data is based on the product molecular weight 523.88 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:
1. Crossen J, Diamond SL. Thermal shift assay to probe melting of thrombin, fibrinogen, fibrin monomer, and fibrin: Gly-Pro-Arg-Pro induces a fibrin monomer-like state in fibrinogen. Biochim Biophys Acta Gen Subj. 2021 Feb;1865(2):129805. doi: 10.1016/j.bbagen.2020.129805. Epub 2020 Dec 1. PMID: 33276061; PMCID: PMC7752828. 2. Trigani KT, Diamond SL. Intrathrombus Fibrin Attenuates Spatial Sorting of Phosphatidylserine Exposing Platelets during Clotting Under Flow. Thromb Haemost. 2021 Jan;121(1):46-57. doi: 10.1055/s-0040-1715648. Epub 2020 Sep 22. PMID: 32961573. 3. Vargas I, Stephenson DJ, Baldwin M, Gaut JP, Chalfant CE, Pan H, Wickline SA. Sustained local inhibition of thrombin preserves renal microarchitecture and function after onset of acute kidney injury. Nanomedicine. 2021 Nov;38:102449. doi: 10.1016/j.nano.2021.102449. Epub 2021 Jul 23. PMID: 34303838; PMCID: PMC8541929. 4. Palekar RU, Jallouk AP, Myerson JW, Pan H, Wickline SA. Inhibition of Thrombin With PPACK-Nanoparticles Restores Disrupted Endothelial Barriers and Attenuates Thrombotic Risk in Experimental Atherosclerosis. Arterioscler Thromb Vasc Biol. 2016 Mar;36(3):446-55. doi: 10.1161/ATVBAHA.115.306697. Epub 2016 Jan 14. PMID: 26769047; PMCID: PMC4767676.
In vitro protocol:
1. Crossen J, Diamond SL. Thermal shift assay to probe melting of thrombin, fibrinogen, fibrin monomer, and fibrin: Gly-Pro-Arg-Pro induces a fibrin monomer-like state in fibrinogen. Biochim Biophys Acta Gen Subj. 2021 Feb;1865(2):129805. doi: 10.1016/j.bbagen.2020.129805. Epub 2020 Dec 1. PMID: 33276061; PMCID: PMC7752828. 2. Trigani KT, Diamond SL. Intrathrombus Fibrin Attenuates Spatial Sorting of Phosphatidylserine Exposing Platelets during Clotting Under Flow. Thromb Haemost. 2021 Jan;121(1):46-57. doi: 10.1055/s-0040-1715648. Epub 2020 Sep 22. PMID: 32961573.
In vivo protocol:
1. Vargas I, Stephenson DJ, Baldwin M, Gaut JP, Chalfant CE, Pan H, Wickline SA. Sustained local inhibition of thrombin preserves renal microarchitecture and function after onset of acute kidney injury. Nanomedicine. 2021 Nov;38:102449. doi: 10.1016/j.nano.2021.102449. Epub 2021 Jul 23. PMID: 34303838; PMCID: PMC8541929. 2. Palekar RU, Jallouk AP, Myerson JW, Pan H, Wickline SA. Inhibition of Thrombin With PPACK-Nanoparticles Restores Disrupted Endothelial Barriers and Attenuates Thrombotic Risk in Experimental Atherosclerosis. Arterioscler Thromb Vasc Biol. 2016 Mar;36(3):446-55. doi: 10.1161/ATVBAHA.115.306697. Epub 2016 Jan 14. PMID: 26769047; PMCID: PMC4767676.
1: Allison M, Davie RL, Mogg AJ, Hampton SL, Emsley J, Stocks MJ. Discovery of α-Amidobenzylboronates as Highly Potent Covalent Inhibitors of Plasma Kallikrein. ACS Med Chem Lett. 2024 Mar 28;15(4):501-509. doi: 10.1021/acsmedchemlett.3c00572. PMID: 38628785; PMCID: PMC11017388. 2: Marcos-Contreras OA, Myerson JW, Nong J, Brenner JS, Muzykantov VR, Glassman PM. Effective Prevention of Arterial Thrombosis with Albumin-Thrombin Inhibitor Conjugates. Mol Pharm. 2023 Nov 6;20(11):5476-5485. doi: 10.1021/acs.molpharmaceut.3c00325. Epub 2023 Oct 12. PMID: 37823223. 3: Curry BJ, Rikken AOFS, Gibson CM, Granger CB, van 't Hof AWJ, Ten Berg JM, Jennings LK. Comparison of the effects of the GPIIb-IIIa antagonist Zalunfiban and the P2Y12 antagonist Selatogrel on Platelet Aggregation. J Thromb Thrombolysis. 2023 Nov;56(4):499-510. doi: 10.1007/s11239-023-02867-x. Epub 2023 Aug 10. PMID: 37563502; PMCID: PMC10550877. 4: Vargas I, Grabau RP, Chen J, Weinheimer C, Kovacs A, Dominguez-Viqueira W, Mitchell A, Wickline SA, Pan H. Simultaneous Inhibition of Thrombosis and Inflammation Is Beneficial in Treating Acute Myocardial Infarction. Int J Mol Sci. 2023 Apr 15;24(8):7333. doi: 10.3390/ijms24087333. PMID: 37108494; PMCID: PMC10138953. 5: Crossen J, Shankar KN, Diamond SL. Investigating thrombin-loaded fibrin in whole blood clot microfluidic assay via fluorogenic peptide. Biophys J. 2023 Feb 21;122(4):697-712. doi: 10.1016/j.bpj.2023.01.008. Epub 2023 Jan 12. PMID: 36635963; PMCID: PMC9989883. 6: Trigani KT, DeCortin ME, Diamond SL. ADP and Thromboxane Inhibitors Both Reduce Global Contraction of Clot Length, While Thromboxane Inhibition Attenuates Internal Aggregate Contraction. TH Open. 2022 Jun 13;6(2):e135-e143. doi: 10.1055/a-1832-9293. PMID: 35707619; PMCID: PMC9192180. 7: Yang CC, Hsiao LD, Shih YF, Hsu CK, Hu CY, Yang CM. Thrombin Induces COX-2 and PGE2 Expression via PAR1/PKCalpha/MAPK-Dependent NF-kappaB Activation in Human Tracheal Smooth Muscle Cells. Mediators Inflamm. 2022 Apr 19;2022:4600029. doi: 10.1155/2022/4600029. PMID: 35497094; PMCID: PMC9042634. 8: Bentur OS, Li J, Jiang CS, Martin LH, Kereiakes DJ, Coller BS. Application of Auxiliary VerifyNow Point-of-Care Assays to Assess the Pharmacodynamics of RUC-4, a Novel αIIbβ3 Receptor Antagonist. TH Open. 2021 Sep 28;5(3):e449-e460. doi: 10.1055/s-0041-1732343. PMID: 34604694; PMCID: PMC8478527. 9: Vargas I, Stephenson DJ, Baldwin M, Gaut JP, Chalfant CE, Pan H, Wickline SA. Sustained local inhibition of thrombin preserves renal microarchitecture and function after onset of acute kidney injury. Nanomedicine. 2021 Nov;38:102449. doi: 10.1016/j.nano.2021.102449. Epub 2021 Jul 23. PMID: 34303838; PMCID: PMC8541929. 10: Crossen J, Diamond SL. Thermal shift assay to probe melting of thrombin, fibrinogen, fibrin monomer, and fibrin: Gly-Pro-Arg-Pro induces a fibrin monomer-like state in fibrinogen. Biochim Biophys Acta Gen Subj. 2021 Feb;1865(2):129805. doi: 10.1016/j.bbagen.2020.129805. Epub 2020 Dec 1. PMID: 33276061; PMCID: PMC7752828. 11: Trigani KT, Diamond SL. Intrathrombus Fibrin Attenuates Spatial Sorting of Phosphatidylserine Exposing Platelets during Clotting Under Flow. Thromb Haemost. 2021 Jan;121(1):46-57. doi: 10.1055/s-0040-1715648. Epub 2020 Sep 22. PMID: 32961573. 12: Wilson AJ, Zhou Q, Vargas I, Palekar R, Grabau R, Pan H, Wickline SA. Formulation and Characterization of Antithrombin Perfluorocarbon Nanoparticles. Methods Mol Biol. 2020;2118:111-120. doi: 10.1007/978-1-0716-0319-2_8. PMID: 32152974. 13: Vootukuri S, Li J, Nedelman M, Thomas C, Jiang JK, Babayeva M, Coller BS. Preclinical Studies of RUC-4, a Novel Platelet αIIbβ3 Antagonist, in Non-Human Primates and With Human Platelets. J Clin Transl Sci. 2019 Jun;3(2-3):65-74. doi: 10.1017/cts.2019.382. Epub 2019 Jun 28. PMID: 31544007; PMCID: PMC6753935. 14: Pelc LA, Koester SK, Chen Z, Gistover NE, Di Cera E. Residues W215, E217 and E192 control the allosteric E*-E equilibrium of thrombin. Sci Rep. 2019 Aug 23;9(1):12304. doi: 10.1038/s41598-019-48839-1. PMID: 31444378; PMCID: PMC6707225. 15: Pathak M, Manna R, Li C, Kaira BG, Hamad BK, Belviso BD, Bonturi CR, Dreveny I, Fischer PM, Dekker LV, Oliva MLV, Emsley J. Crystal structures of the recombinant β-factor XIIa protease with bound Thr-Arg and Pro-Arg substrate mimetics. Acta Crystallogr D Struct Biol. 2019 Jun 1;75(Pt 6):578-591. doi: 10.1107/S2059798319006910. Epub 2019 Jun 4. PMID: 31205020. 16: Trabold K, Makhoul S, Gambaryan S, van Ryn J, Walter U, Jurk K. The Direct Thrombin Inhibitors Dabigatran and Lepirudin Inhibit GPIbα-Mediated Platelet Aggregation. Thromb Haemost. 2019 Jun;119(6):916-929. doi: 10.1055/s-0039-1685139. Epub 2019 Apr 20. PMID: 31005062. 17: Vemuri C, Upadhya GA, Arif B, Jia J, Lin Y, Gaut JP, Fazal J, Pan H, Wickline SA, Chapman WC. Antithrombin Perfluorocarbon Nanoparticles Improve Renal Allograft Function in a Murine Deceased Criteria Donor Model. Transplant Direct. 2018 Aug 21;4(9):e384. doi: 10.1097/TXD.0000000000000817. PMID: 30234153; PMCID: PMC6133403. 18: Chen J, Verni CC, Jouppila A, Lassila R, Diamond SL. Dual antiplatelet and anticoagulant (APAC) heparin proteoglycan mimetic with shear-dependent effects on platelet-collagen binding and thrombin generation. Thromb Res. 2018 Sep;169:143-151. doi: 10.1016/j.thromres.2018.07.026. Epub 2018 Jul 25. PMID: 30071479; PMCID: PMC6179373. 19: Zarà M, Canobbio I, Visconte C, Canino J, Torti M, Guidetti GF. Molecular mechanisms of platelet activation and aggregation induced by breast cancer cells. Cell Signal. 2018 Aug;48:45-53. doi: 10.1016/j.cellsig.2018.04.008. Epub 2018 Apr 26. PMID: 29705335. 20: Moore JK, Chen J, Pan H, Gaut JP, Jain S, Wickline SA. Quantification of vascular damage in acute kidney injury with fluorine magnetic resonance imaging and spectroscopy. Magn Reson Med. 2018 Jun;79(6):3144-3153. doi: 10.1002/mrm.26985. Epub 2017 Nov 16. PMID: 29148253; PMCID: PMC5897913.