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 1447		0.41 µM [EC50]

Conditions

Condition	Modality	Highest Phase	Product
Solid tumors 147 Sources: https://clinicaltrials.gov/ct2/show/NCT02355535 http://adisinsight.springer.com/drugs/800042023	Primary	Phase I 438	Unknown Approved Use Unknown
Glioblastoma multiforme 30 Sources: http://adisinsight.springer.com/drugs/800042023	Primary	Phase I 438	Unknown Approved Use Unknown
Anaplastic astrocytoma 6 Sources: http://adisinsight.springer.com/drugs/800042023	Primary	Phase I 438	Unknown Approved Use Unknown
Lymphoma 60 Sources: https://clinicaltrials.gov/ct2/show/NCT02355535	Primary	Phase I 438	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
3800 ng/mL CLINICAL TRIAL https://www.nature.com/articles/s41416-022-02089-7	750 mg 1 times / day multiple, oral dose: 750 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PAC-1 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2600 ng/mL CLINICAL TRIAL https://www.nature.com/articles/s41416-022-02089-7	750 mg single, oral dose: 750 mg route of administration: Oral experiment type: SINGLE co-administered:	PAC-1 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
3250 ng/mL CLINICAL TRIAL https://www.nature.com/articles/s41416-022-02089-7	625 mg 1 times / day multiple, oral dose: 625 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PAC-1 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2800 ng/mL CLINICAL TRIAL https://www.nature.com/articles/s41416-022-02089-7	450 mg 1 times / day multiple, oral dose: 450 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PAC-1 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1900 ng/mL CLINICAL TRIAL https://www.nature.com/articles/s41416-022-02089-7	375 mg 1 times / day multiple, oral dose: 375 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PAC-1 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1600 ng/mL CLINICAL TRIAL https://www.nature.com/articles/s41416-022-02089-7	250 mg 1 times / day multiple, oral dose: 250 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PAC-1 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
375 ng/mL CLINICAL TRIAL https://www.nature.com/articles/s41416-022-02089-7	150 mg 1 times / day multiple, oral dose: 150 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PAC-1 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
480 ng/mL CLINICAL TRIAL https://www.nature.com/articles/s41416-022-02089-7	75 mg 1 times / day multiple, oral dose: 75 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PAC-1 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2500 ng/mL CLINICAL TRIAL https://www.nature.com/articles/s41416-022-02089-7	675 mg single, oral dose: 675 mg route of administration: Oral experiment type: SINGLE co-administered:	PAC-1 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1350 ng/mL CLINICAL TRIAL https://www.nature.com/articles/s41416-022-02089-7	450 mg single, oral dose: 450 mg route of administration: Oral experiment type: SINGLE co-administered:	PAC-1 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1750 ng/mL CLINICAL TRIAL https://www.nature.com/articles/s41416-022-02089-7	375 mg single, oral dose: 375 mg route of administration: Oral experiment type: SINGLE co-administered:	PAC-1 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1000 ng/mL CLINICAL TRIAL https://www.nature.com/articles/s41416-022-02089-7	250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered:	PAC-1 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
350 ng/mL CLINICAL TRIAL https://www.nature.com/articles/s41416-022-02089-7	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:	PAC-1 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
500 ng/mL CLINICAL TRIAL https://www.nature.com/articles/s41416-022-02089-7	75 mg single, oral dose: 75 mg route of administration: Oral experiment type: SINGLE co-administered:	PAC-1 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
28.5 h CLINICAL TRIAL https://www.nature.com/articles/s41416-022-02089-7	750 mg 1 times / day multiple, oral dose: 750 mg route of administration: Oral experiment type: MULTIPLE co-administered:		PAC-1 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
4% EXPERIMENT https://www.sciencedirect.com/science/article/abs/pii/S002228360900268X	0.5 μmol single, unknown dose: 0.5 μmol route of administration: UNKNOWN experiment type: SINGLE co-administered:		PAC-1 unknown	Homo sapiens population: HEALTHY age: ADULT sex: food status:

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer

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
eMolecules	1035009	https://orderbb.emolecules.com/search/#?query=1035009
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

PubMed

Title	Date	PubMed
Derivatives of Procaspase-Activating Compound 1 (PAC-1) and their Anticancer Activities.	2016	26630918
Small-molecule activation of procaspase-3 to caspase-3 as a personalized anticancer strategy.	2006-10	16936720

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 `Mon Mar 31 19:22:26 GMT 2025` Edited by `admin` on `Mon Mar 31 19:22:26 GMT 2025`
Record UNII	9LIS8N0B2C
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

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

Preferred Name

English

PAC-1

Code

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