PPACK

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C21H31ClN6O3
Molecular Weight	450.962
Optical Activity	UNSPECIFIED
Defined Stereocenters	3 / 3
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

N[C@H](CC1=CC=CC=C1)C(=O)N2CCC[C@H]2C(=O)N[C@@H](CCCNC(N)=N)C(=O)CCl

InChI

InChIKey=KWPACVJPAFGBEQ-IKGGRYGDSA-N

InChI=1S/C21H31ClN6O3/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)/t15-,16+,17+/m1/s1

HIDE SMILES / InChI

Description
Sources: https://www.caymanchem.com/product/15160 | https://www.ncbi.nlm.nih.gov/pubmed/3362867 | https://www.ncbi.nlm.nih.gov/pubmed/11703951

PPACK is a synthetic peptide that irreversibly inhibits thrombin-mediated platelet activation by binding to the active site of thrombin with a Ki = 0.24 nM. PPACK competes with alpha-thrombin at the high-affinity site and is an antagonist of alpha-thrombin induced activation. PPACK is used as a tool for assessment of Platelet function.

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Prothrombin 4 Target ID: P00734\|\|\|Q9UCA1 Gene ID: 2147.0 Gene Symbol: F2 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/1448784 \| https://www.ncbi.nlm.nih.gov/pubmed/19530705	Inhibitor 8297		24.0 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Blood clotting 6 Sources: https://www.ncbi.nlm.nih.gov/pubmed/3362867	Primary		Preclinical	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Activation of platelets by alpha-thrombin is a receptor-mediated event. D-phenylalanyl-L-prolyl-L-arginine chloromethyl ketone-thrombin, but not N alpha-tosyl-L-lysine chloromethyl ketone-thrombin, binds to the high affinity thrombin receptor.	1986 Dec 5	3023333
Interruption of acute platelet-dependent thrombosis by the synthetic antithrombin D-phenylalanyl-L-prolyl-L-arginyl chloromethyl ketone.	1988 May	3362867
Proton bridging in the interactions of thrombin with small inhibitors.	2009 Aug 4	19530705

Patents

Sample Use Guides

In Vivo Use Guide

Vascular graft-bearing baboons (Papio anubis) were administered PPACK (100 nmol/kg per min) by continuous intravenous infusion. The treatment abolished platelet deposition, vascular graft occlusion, thrombus associated release of platelet-specific proteins and fibrino-peptides, platelet hemostatic plug formation, platelet aggregation and thrombin-induced blood clotting. The effects of PPACK disappeared within 15 min after the infusion was discontinued.

Route of Administration: Intravenous

In Vitro Use Guide

Platelet-rich plasma was incubated with 10 uM PPACK and the drug completely inhibited thrombin-induced platelet aggregation. The effect of PPACK on platelet deposition at the site of balloon injury was measured with 10 uM of the drug. Platelet deposition at the site of balloon injury was reduced by 47%.

Name

Type

Language

PPACK

Common Name

English

L-PROLINAMIDE, D-PHENYLALANYL-N-((1S)-4-((AMINOIMINOMETHYL)AMINO)-1-(2-CHLOROACETYL)BUTYL)-

Systematic Name

English

FPRMECL

Common Name

English

PPACK [MI]

Common Name

English

D-PHENYLALANYL-PROLYL-ARGININE CHLOROMETHYL KETONE

Systematic Name

English

D-PHE-PRO-ARG-CHLOROMETHYL KETONE

Common Name

English

Code System Code Type Description

FDA UNII

N62UL02WW4