PK11195 | CAS#85532-75-8 | MDM2, TSPO dual inhibitor

MedKoo Cat#: 407328 | Name: PK11195

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Description:

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

PK11195 is a 2‑Phenylindolylglyoxylyldipeptide Murine Double Minute (MDM)2/Translocator Protein (TSPO) Dual Inhibitor, and is potentially useful for the Treatment of Gliomas. PK-11195 binds selectively to the peripheral benzodiazepine receptor (PBR) (also known as the mitochondrial 18 kDa translocator protein or TSPO). It is one of the most commonly used PBR ligands due to its high affinity for the PBR in all species. [11C](R)-PK11195 has been used in positron emission tomography (PET) scanning to visualize brain inflammation in patients with neuronal damage. .

Chemical Structure

PK11195

CAS#85532-75-8

Theoretical Analysis

MedKoo Cat#: 407328

Name: PK11195

CAS#: 85532-75-8

Chemical Formula: C21H21ClN2O

Exact Mass: 352.1342

Molecular Weight: 352.86

Elemental Analysis: C, 71.48; H, 6.00; Cl, 10.05; N, 7.94; O, 4.53

Price and Availability

Size	Price	Availability	Quantity
10mg	USD 450.00	2 Weeks
50mg	USD 775.00	2 Weeks

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Synonym

PK11195; PK-11195; PK 11195.

IUPAC/Chemical Name

N-(sec-butyl)-1-(2-chlorophenyl)-N-methylisoquinoline-3-carboxamide

InChi Key

RAVIZVQZGXBOQO-UHFFFAOYSA-N

InChi Code

InChI=1S/C21H21ClN2O/c1-4-14(2)24(3)21(25)19-13-15-9-5-6-10-16(15)20(23-19)17-11-7-8-12-18(17)22/h5-14H,4H2,1-3H3

SMILES Code

O=C(C1=CC2=C(C(C3=CC=CC=C3Cl)=N1)C=CC=C2)N(C)C(C)CC

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, not in water

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

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

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Product Data

Product Data

Instruction

View handling instruction

Biological target:

PK 11195 (RP 52028) is a ligand of translocator protein (TSPO), which targets Leishmania chemotherapy, with IC50s of 14.2 μM, 8.2 μM, 3.5 μM for L. amazonensis, L. major and L. braziliensis, respectively.

In vitro activity:

The present study evaluated PK11195, a ligand of this protein, as an anti-leishmanial agent. The viability of axenic L. amazonensis, Leishmania major, and Leishmania braziliensis promastigotes was assessed after 48 h treatment with PK11195 (0.2-400 µM). Median IC50 values for PK11195 were 14.2 µM for L. amazonensis, 8.2 µM for L. major, and 3.5 µM for L. braziliensis. PK11195 causes the killing of amastigotes in vitro by mechanisms independent of inflammatory mediators and causes morphological alterations within Leishmania parasites, suggestive of autophagy, at doses that are non-toxic to macrophages. Reference: Mem Inst Oswaldo Cruz. 2018 Feb 5;113(4):e170345. https://pubmed.ncbi.nlm.nih.gov/29412342/

In vivo activity:

This study evaluated the protective effect of PK11195 on the learning and memory of rats. This study found that PK11195 ameliorated LPS-induced learning and memory impairment, as indicated by decreased escape latencies, swimming distances and increased target quadrant platform crossing times and swimming times during MWM tests. TSPO, ATG7, ATG5, LC3B and p62 protein and mRNA expression increased in the hippocampus of PND model rats. The hippocampal microglia of PND model rats also have severe mitochondrial damage, and a large number of autophagosomes and phagocytic vesicles can be seen. PK11195 pretreatment significantly decreased the expression of TSPO, ATG7, ATG5, LC3B and p62 protein and mRNA, as well as mitochondrial damage. Reference: Front Pharmacol. 2021 Jan 29;11:615543. https://pubmed.ncbi.nlm.nih.gov/33708121/

	Solvent	mg/mL	mM
Solubility
	Acetonitrile	10.0	28.34
	Chloroform	33.0	93.71
	DMSO	25.0	70.85
	Methanol	16.0	45.34

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 352.86 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. Guedes CES, Dias BRS, Petersen ALOA, Cruz KP, Almeida NJ, Andrade DR, Menezes JPB, Borges VM, Veras PST. In vitro evaluation of the anti-leishmanial activity and toxicity of PK11195. Mem Inst Oswaldo Cruz. 2018 Feb 5;113(4):e170345. doi: 10.1590/0074-02760170345. PMID: 29412342; PMCID: PMC5851033. 2. Li L, Chen T, Stanton JD, Sueyoshi T, Negishi M, Wang H. The peripheral benzodiazepine receptor ligand 1-(2-chlorophenyl-methylpropyl)-3-isoquinoline-carboxamide is a novel antagonist of human constitutive androstane receptor. Mol Pharmacol. 2008 Aug;74(2):443-53. doi: 10.1124/mol.108.046656. Epub 2008 May 20. PMID: 18492798; PMCID: PMC2562670. 3. Lan N, Liu Y, Juan Z, Zhang R, Ma B, Xie K, Sun L, Feng H, Sun M, Liu J. The TSPO-specific Ligand PK11195 Protects Against LPS-Induced Cognitive Dysfunction by Inhibiting Cellular Autophagy. Front Pharmacol. 2021 Jan 29;11:615543. doi: 10.3389/fphar.2020.615543. PMID: 33708121; PMCID: PMC7941270. 4. Ye C, Lin L, Zhang P, Chen Y, Huang J, Lin X. The protective effect of PK11195 on D-galactose-induced amnestic mild cognitive impairment in rats. Ann Transl Med. 2020 Sep;8(18):1190. doi: 10.21037/atm-20-6157. PMID: 33241039; PMCID: PMC7576013.

In vitro protocol:

In vivo protocol:

1. Lan N, Liu Y, Juan Z, Zhang R, Ma B, Xie K, Sun L, Feng H, Sun M, Liu J. The TSPO-specific Ligand PK11195 Protects Against LPS-Induced Cognitive Dysfunction by Inhibiting Cellular Autophagy. Front Pharmacol. 2021 Jan 29;11:615543. doi: 10.3389/fphar.2020.615543. PMID: 33708121; PMCID: PMC7941270. 2. Ye C, Lin L, Zhang P, Chen Y, Huang J, Lin X. The protective effect of PK11195 on D-galactose-induced amnestic mild cognitive impairment in rats. Ann Transl Med. 2020 Sep;8(18):1190. doi: 10.21037/atm-20-6157. PMID: 33241039; PMCID: PMC7576013.

1: Yokokura M, Terada T, Bunai T, Nakaizumi K, Takebayashi K, Iwata Y, Yoshikawa E, Futatsubashi M, Suzuki K, Mori N, Ouchi Y. Depiction of microglial activation in aging and dementia: Positron emission tomography with [11C]DPA713 versus [11C](R)PK11195. J Cereb Blood Flow Metab. 2016 Apr 26. pii: 0271678X16646788. [Epub ahead of print] PubMed PMID: 27117856. 2: Afzelius P, Nielsen OL, Alstrup AK, Bender D, Leifsson PS, Jensen SB, Schønheyder HC. Biodistribution of the radionuclides (18)F-FDG, (11)C-methionine, (11)C-PK11195, and (68)Ga-citrate in domestic juvenile female pigs and morphological and molecular imaging of the tracers in hematogenously disseminated Staphylococcus aureus lesions. Am J Nucl Med Mol Imaging. 2016 Jan 28;6(1):42-58. eCollection 2016. PubMed PMID: 27069765; PubMed Central PMCID: PMC4749504. 3: Xu JN, Shen D, Mao WD, Lin QF, Lin F, Lu C. The effects of PK11195 on the MCF-7 and T47D were associated with the allopregnanolone biosynthesis, which was mediated by Translocator Protein 18 KDa. Cancer Biomark. 2016 Apr 1. [Epub ahead of print] PubMed PMID: 27062569. 4: Wu Y, Shamoto-Nagai M, Maruyama W, Osawa T, Naoi M. Rasagiline prevents cyclosporine A-sensitive superoxide flashes induced by PK11195, the initial signal of mitochondrial membrane permeabilization and apoptosis. J Neural Transm (Vienna). 2016 May;123(5):491-4. doi: 10.1007/s00702-016-1531-8. Epub 2016 Mar 2. PubMed PMID: 26931622. 5: Ma L, Zhang H, Liu N, Wang PQ, Guo WZ, Fu Q, Jiao LB, Ma YQ, Mi WD. TSPO ligand PK11195 alleviates neuroinflammation and beta-amyloid generation induced by systemic LPS administration. Brain Res Bull. 2016 Mar;121:192-200. doi: 10.1016/j.brainresbull.2016.02.001. Epub 2016 Feb 2. PubMed PMID: 26851069. 6: Gao ZW, Huang JB, Lin Q, Qin Q, Liang YJ, Zhou L, Luo M. The effects of PK11195 on meningioma was associated with allopregnanolone biosynthesis, which was mediated by translocator protein 18 KDa. Cancer Biomark. 2016 Jan 18;16(1):65-9. doi: 10.3233/CBM-150541. PubMed PMID: 26835706. 7: Parente A, Kopschina Feltes P, Vállez Garcia D, Sijbesma JW, Moriguchi Jeckel CM, Dierckx R Ajo, de Vries EF, Doorduin J. Pharmacokinetic analysis of 11C-PBR28 in the rat model of herpes encephalitis (HSE): comparison with (R)-11C-PK11195. J Nucl Med. 2016 Jan 28. pii: jnumed.115.165019. [Epub ahead of print] PubMed PMID: 26823567. 8: Vállez García D, Otte A, Dierckx RA, Doorduin J. Three Month Follow-Up of Rat Mild Traumatic Brain Injury: A Combined [(18)F]FDG and [(11)C]PK11195 Positron Emission Study. J Neurotrauma. 2016 Mar 18. [Epub ahead of print] PubMed PMID: 26756169. 9: Kim YK, Zhang M, Lu JJ, Xu F, Chen BA, Xing L, Jiang HL. PK11195-chitosan-graft-polyethylenimine-modified SPION as a mitochondria-targeting gene carrier. J Drug Target. 2016 Jun;24(5):457-67. doi: 10.3109/1061186X.2015.1087527. Epub 2015 Sep 22. PubMed PMID: 26390926. 10: Retraction Note: A translocator protein ligand PK11195 shows antigrowth activity in human choriocarcinoma cells. Tumour Biol. 2015 Sep;36(9):7293. doi: 10.1007/s13277-015-3646-1. PubMed PMID: 26141040. 11: Nielsen OL, Afzelius P, Bender D, Schønheyder HC, Leifsson PS, Nielsen KM, Larsen JO, Jensen SB, Alstrup AK. Comparison of autologous (111)In-leukocytes, (18)F-FDG, (11)C-methionine, (11)C-PK11195 and (68)Ga-citrate for diagnostic nuclear imaging in a juvenile porcine haematogenous staphylococcus aureus osteomyelitis model. Am J Nucl Med Mol Imaging. 2015 Jan 15;5(2):169-82. eCollection 2015. PubMed PMID: 25973338; PubMed Central PMCID: PMC4396013. 12: Wu Y, Kazumura K, Maruyama W, Osawa T, Naoi M. Rasagiline and selegiline suppress calcium efflux from mitochondria by PK11195-induced opening of mitochondrial permeability transition pore: a novel anti-apoptotic function for neuroprotection. J Neural Transm (Vienna). 2015 Oct;122(10):1399-407. doi: 10.1007/s00702-015-1398-0. Epub 2015 Apr 12. PubMed PMID: 25863936. 13: Hunter HJ, Hinz R, Gerhard A, Talbot PS, Su Z, Holland G, Hopkins SJ, Griffiths CE, Kleyn CE. Brain inflammation and psoriasis: a [11C]-(R)-PK11195 positron emission tomography study. Br J Dermatol. 2015 Mar 27. doi: 10.1111/bjd.13788. [Epub ahead of print] PubMed PMID: 25819441. 14: Su Z, Roncaroli F, Durrenberger PF, Coope DJ, Karabatsou K, Hinz R, Thompson G, Turkheimer FE, Janczar K, Du Plessis D, Brodbelt A, Jackson A, Gerhard A, Herholz K. The 18-kDa mitochondrial translocator protein in human gliomas: an 11C-(R)PK11195 PET imaging and neuropathology study. J Nucl Med. 2015 Apr;56(4):512-7. doi: 10.2967/jnumed.114.151621. Epub 2015 Feb 26. PubMed PMID: 25722450. 15: Hatano K, Sekimata K, Yamada T, Abe J, Ito K, Ogawa M, Magata Y, Toyohara J, Ishiwata K, Biggio G, Serra M, Laquintana V, Denora N, Latrofa A, Trapani G, Liso G, Suzuki H, Sawada M, Nomura M, Toyama H. Radiosynthesis and in vivo evaluation of two imidazopyridineacetamides, [(11)C]CB184 and [ (11)C]CB190, as a PET tracer for 18 kDa translocator protein: direct comparison with [ (11)C](R)-PK11195. Ann Nucl Med. 2015 May;29(4):325-35. doi: 10.1007/s12149-015-0948-8. Epub 2015 Jan 24. PubMed PMID: 25616581. 16: Tu LN, Zhao AH, Stocco DM, Selvaraj V. PK11195 effect on steroidogenesis is not mediated through the translocator protein (TSPO). Endocrinology. 2015 Mar;156(3):1033-9. doi: 10.1210/en.2014-1707. Epub 2014 Dec 23. PubMed PMID: 25535830; PubMed Central PMCID: PMC4330312. 17: Giannetti P, Politis M, Su P, Turkheimer FE, Malik O, Keihaninejad S, Wu K, Waldman A, Reynolds R, Nicholas R, Piccini P. Increased PK11195-PET binding in normal-appearing white matter in clinically isolated syndrome. Brain. 2015 Jan;138(Pt 1):110-9. doi: 10.1093/brain/awu331. Epub 2014 Nov 21. PubMed PMID: 25416179; PubMed Central PMCID: PMC4383265. 18: Boutin H, Murray K, Pradillo J, Maroy R, Smigova A, Gerhard A, Jones PA, Trigg W. 18F-GE-180: a novel TSPO radiotracer compared to 11C-R-PK11195 in a preclinical model of stroke. Eur J Nucl Med Mol Imaging. 2015 Mar;42(3):503-11. doi: 10.1007/s00259-014-2939-8. Epub 2014 Oct 29. PubMed PMID: 25351507. 19: Kumar A, Williams MT, Chugani HT. Evaluation of basal ganglia and thalamic inflammation in children with pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection and tourette syndrome: a positron emission tomographic (PET) study using 11C-[R]-PK11195. J Child Neurol. 2015 May;30(6):749-56. doi: 10.1177/0883073814543303. Epub 2014 Aug 12. PubMed PMID: 25117419. 20: Bogdanović RM, Syvänen S, Michler C, Russmann V, Eriksson J, Windhorst AD, Lammertsma AA, de Lange EC, Voskuyl RA, Potschka H. (R)-[11C]PK11195 brain uptake as a biomarker of inflammation and antiepileptic drug resistance: evaluation in a rat epilepsy model. Neuropharmacology. 2014 Oct;85:104-12. doi: 10.1016/j.neuropharm.2014.05.002. Epub 2014 May 28. PubMed PMID: 24880085.