PAC-1

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C23H28N4O2
Molecular Weight	392.494
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC1=C(CC=C)C=CC=C1\C=N\NC(=O)CN2CCN(CC3=CC=CC=C3)CC2

InChI

InChIKey=YQNRVGJCPCNMKT-LFVJCYFKSA-N

InChI=1S/C23H28N4O2/c1-2-7-20-10-6-11-21(23(20)29)16-24-25-22(28)18-27-14-12-26(13-15-27)17-19-8-4-3-5-9-19/h2-6,8-11,16,29H,1,7,12-15,17-18H2,(H,25,28)/b24-16+

HIDE SMILES / InChI

Molecular Formula	C23H28N4O2
Molecular Weight	392.494
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	1
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/16936720 | https://www.ncbi.nlm.nih.gov/pubmed/26630918 | https://www.ncbi.nlm.nih.gov/pubmed/20638399 | https://news.illinois.edu/view/6367/365713

Procaspase-activating compound 1, PAC-1, has been introduced as a direct activator of procaspase-3 and has been suggested as a therapeutic agent against cancer. Its activation of procaspase-3 is dependent on the chelation of zinc. In 2015, a phase I clinical trial of PAC-1 opened for enrollment of cancer patients, and in 2016, it was announced that PAC-1 had been granted Orphan Drug Designation for treatment of glioblastoma by the FDA.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Caspase-3 21 Target ID: CHEMBL2334 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19281821 \| https://www.ncbi.nlm.nih.gov/pubmed/25053517	Activator 1430		0.41 µM [EC50]

Conditions

Condition	Modality	Highest Phase	Product
Solid tumors 145 Sources: https://clinicaltrials.gov/ct2/show/NCT02355535 http://adisinsight.springer.com/drugs/800042023	Primary	Phase I 428	Unknown Approved Use Unknown
Glioblastoma multiforme 30 Sources: http://adisinsight.springer.com/drugs/800042023	Primary	Phase I 428	Unknown Approved Use Unknown
Anaplastic astrocytoma 6 Sources: http://adisinsight.springer.com/drugs/800042023	Primary	Phase I 428	Unknown Approved Use Unknown
Lymphoma 58 Sources: https://clinicaltrials.gov/ct2/show/NCT02355535	Primary	Phase I 428	Unknown Approved Use Unknown

Sourcing

Vendor/Aggregator	ID	URL
A2Z Synthesis	A2Z00034699
ChemBridge	5851625	http://www.hit2lead.com/screening-compounds/5851625
ChemDiv	3254-2341	http://chemistryondemand.com:8080/eShop/search_results.jsp?idnumber=3254-2341
Lab Network	LN01986203	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01986203
MolPort	MolPort-000-445-407	https://www.molport.com/shop/molecule-link/MolPort-000-445-407
Otava	7210801533	https://search.otavachemicals.com/#!/search?query=7210801533&type=code
TimTec	ST022713	http://www.echemstore.com/catalogsearch/result/?q=ST022713
eMolecules	1035009	https://orderbb.emolecules.com/search/#?query=1035009

PubMed

Title	Date	PubMed

Patents

Sample Use Guides

In Vivo Use Guide

Using a dose-escalation design, PAC-1 is administered orally on days 1-21, at the assigned dose, of a 28-day cycle.

Route of Administration: Oral

In Vitro Use Guide

Next, the ability of PAC-1 to activate procaspase-3 and caspase-3 in a dose-dependent manner was assessed in the presence and absence of zinc. For these experiments, concentrations of PAC-1 from 0.025 uM to 100 uM were evaluated. In the presence of zinc and very low concentrations of PAC-1, the procaspase-3/caspase-3 enzymes are powerfully inhibited. However, as PAC-1 concentration is increased, the activity of the enzymes in the buffer containing zinc is increased to 40-60% of the maximal rate.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 18:50:51 UTC 2023` Edited by `admin` on `Fri Dec 15 18:50:51 UTC 2023`
Record UNII	9LIS8N0B2C
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

PAC-1

Code

English

1-PIPERAZINEACETIC ACID, 4-(PHENYLMETHYL)-, ((2-HYDROXY-3-(2-PROPENYL)PHENYL)METHYLENE)HYDRAZIDE

Common Name

English

2-(4-BENZYLPIPERAZIN-1-YL)-N-((2-HYDROXY-3-PROP-2-ENYL-PHENYL)METHYLIDENEAMINO)ACETAMIDE

Systematic Name

English

PROCASPASE-ACTIVATING COMPOUND 1

Common Name

English

1-PIPERAZINEACETIC ACID, 4-(PHENYLMETHYL)-, 2-((2-HYDROXY-3-(2-PROPEN-1-YL)PHENYL)METHYLENE)HYDRAZIDE

Common Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

486615