PB 28 dihydrochloride

Modify Date: 2024-01-08 16:11:00

PB 28 dihydrochloride structure	Common Name	PB 28 dihydrochloride
	CAS Number	172906-90-0	Molecular Weight	443.49300
	Density	N/A	Boiling Point	N/A
	Molecular Formula	C₂₄H₃₈N₂O	Melting Point	N/A
	MSDS	USA	Flash Point	N/A
	Symbol	GHS07	Signal Word	Warning

Use of PB 28 dihydrochloride

PB28 is a cyclohexylpiperazine derivative and a high affinity and selective sigma 2 (σ2) receptor agonist with a Ki of 0.68 nM. PB28 is also a σ1 antagonist with a Ki of 0.38 nM. PB28 is less affinity for other receptors. PB28 inhibits electrically evoked twitch in guinea pig bladder and ileum with EC50 values of 2.62 μM and 3.96 μM, respectively. PB28 can modulate SARS-CoV-2-human protein-protein interaction. PB28 induces caspase-independent apoptosis and has antitumor activity[1][2][3][4][5].

Name	PB28 dihydrochloride
Synonym	More Synonyms

Description	PB28 is a cyclohexylpiperazine derivative and a high affinity and selective sigma 2 (σ2) receptor agonist with a Ki of 0.68 nM. PB28 is also a σ1 antagonist with a Ki of 0.38 nM. PB28 is less affinity for other receptors. PB28 inhibits electrically evoked twitch in guinea pig bladder and ileum with EC50 values of 2.62 μM and 3.96 μM, respectively. PB28 can modulate SARS-CoV-2-human protein-protein interaction. PB28 induces caspase-independent apoptosis and has antitumor activity[1][2][3][4][5].
Related Catalog	Signaling Pathways >> Apoptosis >> Apoptosis Research Areas >> Cancer Research Areas >> Infection Signaling Pathways >> Anti-infection >> SARS-CoV Signaling Pathways >> GPCR/G Protein >> Sigma Receptor
Target	Ki: 0.68 nM (σ2 receptor); 0.38 nM (σ1 receptor)[4]
In Vitro	PB28 (15-25 nM; 24-48 hours; MCF7 and MCF7 ADR cells) treatment shows an accumulation in the G0-G1 phase for MCF7 and MCF7 ADR cells that are time and concentration independent[1]. PB28 has a higher σ2 receptor affinity expressed as Ki (0.28 nM and 0.17 nM in MCF7 and MCF7 ADR cells, respectively) than σ1 receptor affinity (13.0 nMand 10.0 nM, respectively)[1]. PB28 inhibits cell growth of MCF7 and MCF7 ADR cells with IC50s of 25 nM and 15 nM, respectively after 2-day treatment[1]. PB28 induces apoptosis through a caspase-independent pathway[1]. PB28 also reduces P-gp expression in a concentration- and time-dependent manner (approximately 60% in MCF7 and 90% in MCF7 ADR)[1]. PB28 displays antiproliferative and cytotoxic effects in both C6 rat glioma and SK-N-SH human neuroblastoma cell lines[1]. Cell Cycle Analysis[1] Cell Line: MCF7 and MCF7 ADR cells Concentration: 25 nM and 15 nM Incubation Time: 24 hours, 48 hours Result: Showed an accumulation in the G0-G1 phase for MCF7 and MCF7 ADR cells that were time and concentration independent.
In Vivo	PB28 (10.7 mg/mL; intraperitoneal injection; daily; for two weeks; C57BL/6 female mice) treatment inhibits tumor growth in Panc02 tumor burden mice. PB28 also conferres a survival advantage for mice[2]. Animal Model: C57BL/6 female mice (10 weeks old) injected with Panc02 cells[2] Dosage: 10.7 mg/mL Administration: Intraperitoneal injection; daily; for two weeks Result: Inhibited tumor growth in Panc02 tumor burden mice.
References	[1]. Amalia Azzariti, et al. Cyclohexylpiperazine Derivative PB28, a sigma2 Agonist and sigma1 Antagonist Receptor, Inhibits Cell Growth, Modulates P-glycoprotein, and Synergizes With Anthracyclines in Breast Cancer. Mol Cancer Ther. 2006 Jul;5(7):1807-16. [2]. Maria Laura Pati, et al. Sigma-2 Receptor Agonist Derivatives of 1-Cyclohexyl-4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]piperazine (PB28) Induce Cell Death via Mitochondrial Superoxide Production and Caspase Activation in Pancreatic Cancer. BMC Cancer. 2017 Jan 13;17(1):51. [3]. Nicola A Colabufo, et al. A New Method for Evaluating sigma(2) Ligand Activity in the Isolated Guinea-Pig Bladder. Naunyn Schmiedebergs Arch Pharmacol. 2003 Aug;368(2):106-12. [4]. Francesco Berardi, et al. Exploring the Importance of Piperazine N-atoms for sigma(2) Receptor Affinity and Activity in a Series of Analogs of 1-cyclohexyl-4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]piperazine (PB28). J Med Chem. 2009 Dec 10;52(23):7817-28. [5]. David E Gordon, et al. A SARS-CoV-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug-Repurposing. bioRxiv. 2020 Mar 22;2020.03.22.002386.

Molecular Formula	C₂₄H₃₈N₂O
Molecular Weight	443.49300
Exact Mass	442.25200
PSA	15.71000
LogP	6.32540

Symbol	GHS07
Signal Word	Warning
Hazard Statements	H315-H319-H335
Precautionary Statements	P261-P305 + P351 + P338
Personal Protective Equipment	dust mask type N95 (US);Eyeshields;Gloves
Hazard Codes	Xi: Irritant;
Risk Phrases	R36/37/38
Safety Phrases	S26
RIDADR	NONH for all modes of transport

1-Cyclohexylpip...

CAS#:17766-28-8

(3-bromopropyl)...

CAS#:161923-64-4

~70%

PB 28 dihydroch...

CAS#:172906-90-0

Literature: Berardi; Colabufo; Giudice; Perrone; Tortorella; Govoni; Lucchi Journal of Medicinal Chemistry, 1996 , vol. 39, # 1 p. 176 - 182

4-(3-bromo-n-pr...

CAS#:153526-80-8

PB 28 dihydroch...

CAS#:172906-90-0

Literature: Berardi; Colabufo; Giudice; Perrone; Tortorella; Govoni; Lucchi Journal of Medicinal Chemistry, 1996 , vol. 39, # 1 p. 176 - 182

Precursor 3
CAS#:17766-28-8 1-Cyclohexylpip... CAS#:161923-64-4 (3-bromopropyl)... CAS#:153526-80-8 4-(3-bromo-n-pr...
DownStream 0

A new method for evaluating sigma(2) ligand activity in the isolated guinea-pig bladder.

Naunyn Schmiedebergs Arch. Pharmacol. 368 , 106-112, (2003)

We demonstrated the presence of sigma(2) receptors in the guinea-pig ileum by saturation analysis and extended our investigation to guinea-pig bladder and rat bladder. In functional assays of the isol...

1-cyclohexyl-4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]piperazine,dihydrochloride