Name: PAC-1
Brand: Selleck Chemicals
SKU: S2738
Availability: InStock
Rating: 5 (18 reviews)

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Quality Control

Batch: Purity: 99.99%

99.99

Related Targets	Bcl-2 PD-1/PD-L1 Ferroptosis p53 Apoptosis related Synthetic Lethality STAT TNF-alpha Ras KRas
Other Caspase Inhibitors	Z-VAD-FMK Z-DEVD-FMK Q-VD-Oph Emricasan (IDN-6556) Belnacasan (VX-765) Z-IETD-FMK Ac-DEVD-CHO Z-LEHD-FMK TFA Z-VAD(OH)-FMK Z-YVAD-FMK

Solubility

In vitro
Batch:

DMSO : 78 mg/mL (198.73 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Ethanol : 78 mg/mL

Water : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
Mass value Mass unit	Concentration value Concentration unit	Volume value Volume unit	Molecular weight (g/mol)

Dilution Calculator Molecular Weight Calculator

In vivo batch selection In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	30%PEG400 1 0.5%Tween80 2 5%propylene glycol Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	30.000mg/ml (76.44mM)	Taking the 1 mL working solution as an example, add 300 μL of 100 mg/ml clarified PEG400 stock solution to 5 μL of Tween80, mix evenly to clarify it; add 50 μL Propylene glycol to the above system, mix evenly to clarify it; then continue to add 645 μL ddH2O to adjust the volume. to 1 mL. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg

Average weight of animals: g

Dosing volume per animal: μL

Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO

%

% Tween 80

% ddH₂O

% DMSO

+

%

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Chemical Information, Storage & Stability

Molecular Weight	392.49	Formula	C₂₃H₂₈N₄O₂	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	315183-21-2	Download SDF		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	N/A			Smiles	C=CCC1=C(C(=CC=C1)C=NNC(=O)CN2CCN(CC2)CC3=CC=CC=C3)O

Mechanism of Action

Features	The first small molecule known to directly activate procaspase-3 to caspase-3.
Targets/IC₅₀/Ki	Procaspase-3 0.22 μM(EC50)
In vitro	PAC-1 activates procaspase-7 in a less efficient manner with EC50 of 4.5 μM. Elevated caspase 3 level in cancer cell lines allows this compound to selectively induce apoptosis in a manner proportional to procaspase-3 concentration with IC50 of 0.35 μM for NCI-H226 cells to ~3.5 μM for UACC-62 cells. It induces apoptosis in the primary cancerous cells with IC50 values of 3 nM to 1.41 μM, more potently than in the adjacent noncancerous cells with IC50 of 5.02 μM to 9.98 μM, which is also directly related to the distinct procaspase-3 concentration. This chemical activates procaspase-3 by chelating zinc ions, thus relieving the zinc-mediated inhibition and allowing procaspase-3 to auto-activate itself to caspase-3. It is capable to induce cell death in Bax/Bak double-knockout cells and Bcl-2 and Bcl-xL-overexpressing cells with the same efficacy as its wild-type counterpart in a delayed manner. This compound induces cytochrome c release in a caspase-3 independent manner, which subsequently triggers downstream caspase-3 activation and cell death. It can not induce cell death and caspase-3 activation in Apaf-1 knockout cells, suggesting that apoptosome formation is essential for caspase-3 activation by PAC-1-mediated cell death.
Kinase Assay	In vitro procaspase-3 activation
Kinase Assay	Procaspase-3 is expressed and purified in Escherichia coli. Various concentrations of PAC-1 are added to 90 μL of a 50 ng/mL of procaspase-3 in caspase assay buffer in a 96-well plate, The plate is incubated for 12 hours at 37 °C. A 10 μL volume of a 2 mM solution of caspase-3 peptidic substrate acetyl Asp-Glu-Val-Asp-p-nitroanilide (Ac-DEVD-pNa) in caspase assay buffer is then added to each well. The plate is read every 2 minutes at 405 nm for 2 hours in a Spectra Max Plus 384 well plate reader. The slope of the linear portion for each well is determined, and the relative increase in activation from untreated control wells is calculated.
In vivo	Administration of PAC-1 at 5 mg with low and steady releasing significantly inhibits the growth of ACHN renal cancer xenograft in mice. Oral administration of this compound (50 or 100 mg/kg) significantly retards tumor growth of NCI-H226 lung cancer xenograft in a dose-dependent manner, and markedly prevents the cancer cells from infiltrating the lung tissue. The in vivo anti-tumor effect of this chemical is ascribed to procaspase-3 activation and subsequently apoptosis induction consistent with the activity in vitro.
References	[1] https://pubmed.ncbi.nlm.nih.gov/16936720/ [2] https://pubmed.ncbi.nlm.nih.gov/19281821/ [3] https://pubmed.ncbi.nlm.nih.gov/21900958/

Applications

Methods	Biomarkers	Images	PMID
Western blot	Ero1-Lα / Calnexin / IRE-1α / p-eIF2α / eIF2α / CHOP		24357799
Immunofluorescence	Hif1α p-H2AX / Rad51		30287840

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT05967741	Recruiting	Platelet Aggregation Spontaneous\|Vascular Thrombosis	University of California Davis	July 20 2023	Not Applicable
NCT03927248	Withdrawn	Metastatic Renal Cell Carcinoma	HealthPartners Institute	September 2020	Phase 1\|Phase 2
NCT03441412	Completed	Healthy Volunteers	Vastra Gotaland Region\|Gothia Forum - Center for Clinical Trial\|Uppsala University	February 28 2018	Phase 1

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PAC-1 Caspase activator

Chemical Structure

Molecular Weight: 392.49