PJ34 | CAS#344458-15-7 | 344458-19-1 | PARP inhibitor

MedKoo Cat#: 406128 | Name: PJ-34 HCl

Description:

WARNING: This product is for research use only, not for human or veterinary use.

PJ-34 is a novel and potent PARP-1 inhibitor with potential anticancer activity. PJ34 has a high affinity for PARP-1 (IC(50) = 20 nM). PJ-34 inhibits PARP-1 expression and ERK phosphorylation in glioma-conditioned brain microvascular endothelial cells. PJ-34 reduces mesenteric vascular injury induced by experimental cardiopulmonary bypass with cardiac arrest. PJ-34 reduce cell inflammation and damage that follow PARP-1 overexpression. PJ-34 negatively modulate proinflammatory commitment of human glioblastoma cells.

Chemical Structure

PJ-34 HCl

CAS#344458-15-7 (HCl)

Theoretical Analysis

MedKoo Cat#: 406128

Name: PJ-34 HCl

CAS#: 344458-15-7 (HCl)

Chemical Formula: C17H18ClN3O2

Exact Mass: 0.0000

Molecular Weight: 331.80

Elemental Analysis: C, 61.54; H, 5.47; Cl, 10.68; N, 12.66; O, 9.64

Price and Availability

Size	Price	Availability
200mg	USD 850.00	2 Weeks
500mg	USD 1,650.00	2 Weeks
1g	USD 2,850.00	2 Weeks
2g	USD 4,250.00	2 Weeks
5g	USD 6,950.00	2 Weeks

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Related CAS #

344458-15-7 (HCl) 344458-19-1 (free base)

Synonym

PJ34; PJ-34; PJ 34; PJ-34 HCl; PJ-34 hydrochloride.

IUPAC/Chemical Name

2-(dimethylamino)-N-(6-oxo-5,6-dihydrophenanthridin-2-yl)acetamide hydrochloride

InChi Key

RURAZZMDMNRXMI-UHFFFAOYSA-N

InChi Code

InChI=1S/C17H17N3O2.ClH/c1-20(2)10-16(21)18-11-7-8-15-14(9-11)12-5-3-4-6-13(12)17(22)19-15;/h3-9H,10H2,1-2H3,(H,18,21)(H,19,22);1H

SMILES Code

O=C(NC(C=C1C2=C3C=CC=C2)=CC=C1NC3=O)CN(C)C.[H]Cl

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

soluble in DMSO, soluble in dilute HCl, soluble in water.

Shelf Life

>5 years if stored properly

Drug Formulation

This drug may be formulated in DMSO or water

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Instruction

View handling instruction

Biological target:

PJ34 hydrochloride is an inhibitor of PARP1/2 with IC50 of 110 nM and 86 nM, respectively.

In vitro activity:

This study found that a small molecule inhibitor of poly (ADP-ribose) polymerase (PARP), PJ-34, is very effective in activating S/G2M cell cycle checkpoints, resulting in permanent cell cycle arrest and reactivation of p53 transcription functions and caspase-3-dependent apoptosis of HTLV-I-transformed and patient-derived ATLL tumor cells. This study also found that HTLV-I-transformed MT-2 cells are resistant to PJ-34 therapy associated with reduced cleaved caspase-3 activation and increased expression of RelA/p65. Reference: J Hematol Oncol. 2015 Oct 23;8:117. https://pubmed.ncbi.nlm.nih.gov/26497583/

In vivo activity:

Ischemia was induced by intravascular occlusion of the left middle cerebral artery for 1 h in male Swiss mice anaesthetized with ketamine and xylazine. The PARP inhibitor PJ34 (1.25-25 mg kg(-1)) was administered intraperitoneally 15 min before and 4 hours after, the onset of ischemia. Ischemia increased TNF-alpha protein in cerebral tissue at 6 and 24 h after ischemia. All doses of PJ34 blocked the increase in TNF-alpha at 6 h and 25 mg kg(-1) PJ34 had a sustained effect for up to 24 h. Quantitative real time polymerase chain reaction showed that PJ34 (25 mg kg(-1)) reduced the increase in TNF-alpha mRNA by 70% at 6 h. PJ34 also prevented the increase in mRNAs encoding IL-6 (-41%), E-selectin (-81%) and ICAM-1 (-54%). PJ34 (25 mg kg(-1)) reduced the infarct volume (-26%) and improved neurological deficit, 24 h after ischemia. Reference: Br J Pharmacol. 2006 Sep;149(1):23-30. https://pubmed.ncbi.nlm.nih.gov/16865091/

	Solvent	mg/mL	mM
Solubility
	DMF	10.0	30.14
	DMSO	28.2	84.90
	PBS (pH 7.2)	10.0	30.14
	Water	49.6	149.46

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 331.80 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Bai XT, Moles R, Chaib-Mezrag H, Nicot C. Small PARP inhibitor PJ-34 induces cell cycle arrest and apoptosis of adult T-cell leukemia cells. J Hematol Oncol. 2015 Oct 23;8:117. doi: 10.1186/s13045-015-0217-2. PMID: 26497583; PMCID: PMC4619390. 2. Motta C, D'Angeli F, Scalia M, Satriano C, Barbagallo D, Naletova I, Anfuso CD, Lupo G, Spina-Purrello V. PJ-34 inhibits PARP-1 expression and ERK phosphorylation in glioma-conditioned brain microvascular endothelial cells. Eur J Pharmacol. 2015 Aug 15;761:55-64. doi: 10.1016/j.ejphar.2015.04.026. Epub 2015 Apr 28. PMID: 25934569. 1. Bai XT, Moles R, Chaib-Mezrag H, Nicot C. Small PARP inhibitor PJ-34 induces cell cycle arrest and apoptosis of adult T-cell leukemia cells. J Hematol Oncol. 2015 Oct 23;8:117. doi: 10.1186/s13045-015-0217-2. PMID: 26497583; PMCID: PMC4619390. 2. Motta C, D'Angeli F, Scalia M, Satriano C, Barbagallo D, Naletova I, Anfuso CD, Lupo G, Spina-Purrello V. PJ-34 inhibits PARP-1 expression and ERK phosphorylation in glioma-conditioned brain microvascular endothelial cells. Eur J Pharmacol. 2015 Aug 15;761:55-64. doi: 10.1016/j.ejphar.2015.04.026. Epub 2015 Apr 28. PMID: 25934569. 3. Haddad M, Rhinn H, Bloquel C, Coqueran B, Szabó C, Plotkine M, Scherman D, Margaill I. Anti-inflammatory effects of PJ34, a poly(ADP-ribose) polymerase inhibitor, in transient focal cerebral ischemia in mice. Br J Pharmacol. 2006 Sep;149(1):23-30. doi: 10.1038/sj.bjp.0706837. Epub 2006 Jul 24. PMID: 16865091; PMCID: PMC1629400. 4. Scott GS, Kean RB, Mikheeva T, Fabis MJ, Mabley JG, Szabó C, Hooper DC. The therapeutic effects of PJ34 [N-(6-oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide.HCl], a selective inhibitor of poly(ADP-ribose) polymerase, in experimental allergic encephalomyelitis are associated with immunomodulation. J Pharmacol Exp Ther. 2004 Sep;310(3):1053-61. doi: 10.1124/jpet.103.063214. Epub 2004 May 24. PMID: 15159442.

In vitro protocol:

In vivo protocol:

1. Haddad M, Rhinn H, Bloquel C, Coqueran B, Szabó C, Plotkine M, Scherman D, Margaill I. Anti-inflammatory effects of PJ34, a poly(ADP-ribose) polymerase inhibitor, in transient focal cerebral ischemia in mice. Br J Pharmacol. 2006 Sep;149(1):23-30. doi: 10.1038/sj.bjp.0706837. Epub 2006 Jul 24. PMID: 16865091; PMCID: PMC1629400. 2. Scott GS, Kean RB, Mikheeva T, Fabis MJ, Mabley JG, Szabó C, Hooper DC. The therapeutic effects of PJ34 [N-(6-oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide.HCl], a selective inhibitor of poly(ADP-ribose) polymerase, in experimental allergic encephalomyelitis are associated with immunomodulation. J Pharmacol Exp Ther. 2004 Sep;310(3):1053-61. doi: 10.1124/jpet.103.063214. Epub 2004 May 24. PMID: 15159442.

1: Luo JM, Lin HB, Weng YQ, Lin YH, Lai LY, Li J, Li FX, Xu SY, Zhang HF, Zhao W. Inhibition of PARP1 improves cardiac function after myocardial infarction via up-regulated NLRC5. Chem Biol Interact. 2024 May 25;395:111010. doi: 10.1016/j.cbi.2024.111010. Epub 2024 Apr 26. PMID: 38679114. 2: Luo J, Cai Y, Wei D, Cao L, He Q, Wu Y. Formononetin alleviates cerebral ischemia-reperfusion injury in rats by targeting the PARP-1/PARG/Iduna signaling pathway. Brain Res. 2024 Apr 15;1829:148845. doi: 10.1016/j.brainres.2024.148845. Epub 2024 Mar 5. PMID: 38452845. 3: Vitali R, Mancuso AB, Palone F, Pioli C, Cesi V, Negroni A, Cucchiara S, Oliva S, Carissimi C, Laudadio I, Stronati L. PARP1 Activation Induces HMGB1 Secretion Promoting Intestinal Inflammation in Mice and Human Intestinal Organoids. Int J Mol Sci. 2023 Apr 12;24(8):7096. doi: 10.3390/ijms24087096. PMID: 37108260; PMCID: PMC10138503. 4: Dong L, Wang S, Wang X, Wang Z, Liu D, You H. Investigating the adverse outcome pathways (AOP) of neurotoxicity induced by DBDPE with a combination of in vitro and in silico approaches. J Hazard Mater. 2023 May 5;449:131021. doi: 10.1016/j.jhazmat.2023.131021. Epub 2023 Feb 17. PMID: 36821895. 5: Wen JJ, Dejesus JE, Radhakrishnan GL, Radhakrishnan RS. PARP1 Inhibition and Effect on Burn Injury-Induced Inflammatory Response and Cardiac Function. J Am Coll Surg. 2023 Apr 1;236(4):783-802. doi: 10.1097/XCS.0000000000000546. Epub 2023 Jan 12. PMID: 36728307. 6: Haque S, Kumar P, Mathkor DM, Bantun F, Jalal NA, Mufti AH, Prakash A, Kumar V. In silico evaluation of the inhibitory potential of nucleocapsid inhibitors of SARS-CoV-2: a binding and energetic perspective. J Biomol Struct Dyn. 2023 Nov;41(19):9797-9807. doi: 10.1080/07391102.2022.2146752. Epub 2022 Nov 15. PMID: 36379684. 7: Araki T, Hamada K, Myat AB, Ogino H, Hayashi K, Maeda M, Tong Y, Murakami Y, Nakao K, Masutani M. Enhanced Cytotoxicity on Cancer Cells by Combinational Treatment of PARP Inhibitor and 5-Azadeoxycytidine Accompanying Distinct Transcriptional Profiles. Cancers (Basel). 2022 Aug 28;14(17):4171. doi: 10.3390/cancers14174171. PMID: 36077707; PMCID: PMC9454563. 8: Wang X, Zhang W, Ge P, Yu M, Meng H. Parthanatos participates in glutamate- mediated HT22 cell injury and hippocampal neuronal death in kainic acid-induced status epilepticus rats. CNS Neurosci Ther. 2022 Dec;28(12):2032-2043. doi: 10.1111/cns.13934. Epub 2022 Jul 31. PMID: 35909335; PMCID: PMC9627358. 9: Çınar R, Nazıroğlu M. TRPM2 Channel Inhibition Attenuates Amyloid β42-Induced Apoptosis and Oxidative Stress in the Hippocampus of Mice. Cell Mol Neurobiol. 2023 Apr;43(3):1335-1353. doi: 10.1007/s10571-022-01253-0. Epub 2022 Jul 15. PMID: 35840808. 10: Santos SS, Brunialti MKC, Rodrigues LOCP, Liberatore AMA, Koh IHJ, Martins V, Soriano FG, Szabo C, Salomão R. Effects of the PARP Inhibitor Olaparib on the Response of Human Peripheral Blood Leukocytes to Bacterial Challenge or Oxidative Stress. Biomolecules. 2022 Jun 4;12(6):788. doi: 10.3390/biom12060788. PMID: 35740913; PMCID: PMC9221060. 11: Vaidya B, Kaur H, Thapak P, Sharma SS, Singh JN. Pharmacological Modulation of TRPM2 Channels via PARP Pathway Leads to Neuroprotection in MPTP-induced Parkinson's Disease in Sprague Dawley Rats. Mol Neurobiol. 2022 Mar;59(3):1528-1542. doi: 10.1007/s12035-021-02711-4. Epub 2022 Jan 8. PMID: 34997907. 12: Wang X, Dong C, Zhou Q, Duan H, Zou D, Gong Y, Ma B, Li Z, Shi W. Poly(ADP- ribose) polymerase inhibitor PJ34 protects against UVA-induced oxidative damage in corneal endothelium. Apoptosis. 2021 Dec;26(11-12):600-611. doi: 10.1007/s10495-021-01690-0. Epub 2021 Sep 28. PMID: 34581992. 13: Jiao Y, Li G. PARP inhibitor PJ34 ameliorates cognitive impairments induced by transient cerebral ischemia/reperfusion through its anti-inflammatory effects in a rat model. Neurosci Lett. 2021 Nov 1;764:136202. doi: 10.1016/j.neulet.2021.136202. Epub 2021 Aug 31. PMID: 34478817. 14: Yazğan Y, Nazıroğlu M. Involvement of TRPM2 in the Neurobiology of Experimental Migraine: Focus on Oxidative Stress and Apoptosis. Mol Neurobiol. 2021 Nov;58(11):5581-5601. doi: 10.1007/s12035-021-02503-w. Epub 2021 Aug 9. PMID: 34370177. 15: Bonnin P, Vitalis T, Schwendimann L, Boutigny A, Mohamedi N, Besson VC, Charriaut-Marlangue C. Poly(ADP-Ribose) Polymerase Inhibitor PJ34 Reduces Brain Damage after Stroke in the Neonatal Mouse Brain. Curr Issues Mol Biol. 2021 Jun 7;43(1):301-312. doi: 10.3390/cimb43010025. PMID: 34200155; PMCID: PMC8929080. 16: Sinha A, Katyal S, Kauppinen TM. PARP-DNA trapping ability of PARP inhibitors jeopardizes astrocyte viability: Implications for CNS disease therapeutics. Neuropharmacology. 2021 Apr 1;187:108502. doi: 10.1016/j.neuropharm.2021.108502. Epub 2021 Feb 22. PMID: 33631119. 17: Gao F, Li Z, Kang Z, Liu D, Li P, Ou Q, Xu JY, Li W, Tian H, Jin C, Wang J, Zhang J, Zhang J, Lu L, Xu GT. Inhibition of PARP activity improves therapeutic effect of ARPE-19 transplantation in RCS rats through decreasing photoreceptor death. Exp Eye Res. 2021 Mar;204:108448. doi: 10.1016/j.exer.2021.108448. Epub 2021 Jan 20. PMID: 33484702. 18: Chen X, Huang Y, Wang D, Dong N, Du X. PJ34, a PARP1 inhibitor, attenuates acute allograft rejection after murine heart transplantation via regulating the CD4+ T lymphocyte response. Transpl Int. 2021 Mar;34(3):561-571. doi: 10.1111/tri.13809. Epub 2021 Feb 26. PMID: 33368686. 19: Sharma C, Yang W, Steen H, Freeman MR, Hemler ME. Antioxidant functions of DHHC3 suppress anti-cancer drug activities. Cell Mol Life Sci. 2021 Mar;78(5):2341-2353. doi: 10.1007/s00018-020-03635-3. Epub 2020 Sep 28. PMID: 32986127; PMCID: PMC8751980. 20: Bonnin P, Charriaut-Marlangue C, Pansiot J, Boutigny A, Launay JM, Besson VC. Cerebral Vasodilator Property of Poly(ADP-Ribose) Polymerase Inhibitor (PJ34) in the Neonatal and Adult Mouse Is Mediated by the Nitric Oxide Pathway. Int J Mol Sci. 2020 Sep 8;21(18):6569. doi: 10.3390/ijms21186569. PMID: 32911782; PMCID: PMC7555622.