PS-1145 | CAS#431898-65-6 | 1049743-58-9 | IKK inhibitor

MedKoo Cat#: 407262 | Name: PS-1145

Description:

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

PS-1145 is a selective IκB kinase (IKK) inhibitor (IC50 = 100 nM). PS1145 efficiently inhibited both basal and induced NF-kappaB activity in PC cells. PS1145 induced caspase 3/7-dependent apoptosis in PC cells and significantly sensitized PC cells to apoptosis induced by tumor necrosis factor alpha. PS1145 inhibited PC cell proliferation. PS1145 enhances apoptosis in DMBA-induced tumor in male Wistar rats. PS1145 can overcome imatinib resistance.

Chemical Structure

PS-1145

CAS#431898-65-6 (free base)

Theoretical Analysis

MedKoo Cat#: 407262

Name: PS-1145

CAS#: 431898-65-6 (free base)

Chemical Formula: C17H11ClN4O

Exact Mass: 322.0621

Molecular Weight: 322.75

Elemental Analysis: C, 63.26; H, 3.44; Cl, 10.98; N, 17.36; O, 4.96

Price and Availability

Size	Price	Availability
10mg	USD 90.00	Ready to ship
25mg	USD 150.00	Ready to ship
50mg	USD 250.00	Ready to ship
100mg	USD 450.00	Ready to ship
200mg	USD 750.00	Ready to ship
500mg	USD 1,650.00	2 Weeks
1g	USD 2,950.00	2 Weeks
2g	USD 5,250.00	2 Weeks

Bulk Inquiry

Buy Now

Add to Cart

Related CAS #

431898-65-6 (free base) 1049743-58-9 (2HCl)

Synonym

PS-1145; PS 1145; PS1145.

IUPAC/Chemical Name

N-(6-chloro-9H-pyrido[3,4-b]indol-8-yl)nicotinamide

InChi Key

JZRMBDHPALEPDM-UHFFFAOYSA-N

InChi Code

InChI=1S/C17H11ClN4O/c18-11-6-13-12-3-5-20-9-15(12)21-16(13)14(7-11)22-17(23)10-2-1-4-19-8-10/h1-9,21H,(H,22,23)

SMILES Code

O=C(C1=CC=CN=C1)NC2=CC(Cl)=CC3=C2NC4=C3C=CN=C4

Appearance

Yellow 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

More Info

CAS# 431898-65-6 (free base); 1049743-58-9 (dihydrchloride salt)

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#TZC60329

QC Data

View QC data: current batch, Lot#TZC60329

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

PS-1145 is an IκB kinase (IKK) inhibitor with an IC50 of 88 nM.

In vitro activity:

As shown in Figure 1 panel a, PS1145 was able to reduce the NF-κB binding activity in K562 and KCL by 92 and 87%, respectively, when compared to controls. Similar results were obtained in resistant cells K562r and KCLr showing an inhibition of NF-κB activity of 93 and 82%, respectively. Imatinib incubation followed by TNF stimulation resulted in a modest effect on NF-κB activity with a 20 and 16% inhibition in K562 and KCL cells, respectively. Similar results were obtained in BM cells from CML patients (Figure 1 panel b). PS1145 reduced NF-κB activity by 67±11% (mean value±s.d.; range 52–85%) in BM cells from sensitive (patients 1–8 of Figure 1) and resistant CML patients (patients from 9 to 15 of Figure 1). Reference: Leukemia. 2006 Jan;20(1):61-7. https://pubmed.ncbi.nlm.nih.gov/16270044/

In vivo activity:

The mice in the treatment group for both HONE1 and C666 fared better than the control group, with significantly smaller tumor burdens with a low dose of PS1145 (3 mg/kg) (Fig. 2). Overall, C666 was more responsive to the inhibitory effects of PS1145 than the HONE1, as shown by an earlier suppression of tumor growth, and a significantly smaller average tumor size throughout the study (Fig. 2). Importantly, from the gross appearance and body weight of the animal, there was no apparent adverse effect for mice treated with PS1145 (Fig. 2). Reference: Sci Rep. 2019; 9: 12064. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6700134/

	Solvent	mg/mL	mM
Solubility
	DMSO	20.8	64.40

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 322.75 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. Lung HL, Kan R, Chau WY, Man OY, Mak NK, Fong CH, Shuen WH, Tsao SW, Lung ML. The anti-tumor function of the IKK inhibitor PS1145 and high levels of p65 and KLF4 are associated with the drug resistance in nasopharyngeal carcinoma cells. Sci Rep. 2019 Aug 19;9(1):12064. doi: 10.1038/s41598-019-48590-7. PMID: 31427673; PMCID: PMC6700134. 2. Cilloni D, Messa F, Arruga F, Defilippi I, Morotti A, Messa E, Carturan S, Giugliano E, Pautasso M, Bracco E, Rosso V, Sen A, Martinelli G, Baccarani M, Saglio G. The NF-kappaB pathway blockade by the IKK inhibitor PS1145 can overcome imatinib resistance. Leukemia. 2006 Jan;20(1):61-7. doi: 10.1038/sj.leu.2403998. PMID: 16270044. 3. Rajmani RS, Gandham RK, Gupta SK, Sahoo AP, Singh PK, Saxena S, Kumar R, Chaturvedi U, Tiwari AK. Administration of IκB-kinase inhibitor PS1145 enhances apoptosis in DMBA-induced tumor in male Wistar rats. Cell Biol Int. 2015 Nov;39(11):1317-28. doi: 10.1002/cbin.10510. Epub 2015 Aug 3. PMID: 26148342.

In vitro protocol:

In vivo protocol:

1: Ho JY, Lu HY, Cheng HH, Kuo YC, Lee YA, Cheng CH. UBE2S activates NF-κB signaling by binding with IκBα and promotes metastasis of lung adenocarcinoma cells. Cell Oncol (Dordr). 2021 Dec;44(6):1325-1338. doi: 10.1007/s13402-021-00639-4. Epub 2021 Sep 28. PMID: 34582005. 2: Xia M, Meng G, Dong J. [Synergistic Effect of NF-κB Signaling Pathway Inhibitor and Oncolytic  Measles Virus Vaccine Strain against Lung Cancer and Underlying Mechanisms]. Zhongguo Fei Ai Za Zhi. 2021 Apr 20;24(4):245-253. Chinese. doi: 10.3779/j.issn.1009-3419.2021.102.14. Epub 2021 Mar 29. PMID: 33775041; PMCID: PMC8105609. 3: Kocbek V, Imboden S, Nirgianakis K, Mueller M, McKinnon B. Dual influence of TNFα on diverse in vitro models of ovarian cancer subtypes. Heliyon. 2021 Feb 10;7(2):e06099. doi: 10.1016/j.heliyon.2021.e06099. PMID: 33615005; PMCID: PMC7881225. 4: Kandasamy M. NF-κB signalling as a pharmacological target in COVID-19: potential roles for IKKβ inhibitors. Naunyn Schmiedebergs Arch Pharmacol. 2021 Mar;394(3):561-567. doi: 10.1007/s00210-020-02035-5. Epub 2021 Jan 4. PMID: 33394134; PMCID: PMC7780215. 5: Mao D, Tian XY, Mao D, Hung SW, Wang CC, Lau CBS, Lee HM, Wong CK, Chow E, Ming X, Cao H, Ma RC, Chan PKS, Kong APS, Li JJX, Rutter GA, Tam WH, Chan JCN. A polysaccharide extract from the medicinal plant Maidong inhibits the IKK-NF-κB pathway and IL-1β-induced islet inflammation and increases insulin secretion. J Biol Chem. 2020 Sep 4;295(36):12573-12587. doi: 10.1074/jbc.RA120.014357. Epub 2020 Jun 30. PMID: 32605924; PMCID: PMC7476719. 6: Im JH, Yeo IJ, Hwang CJ, Lee KS, Hong JT. PEGylated Erythropoietin Protects against Brain Injury in the MCAO-Induced Stroke Model by Blocking NF-κB Activation. Biomol Ther (Seoul). 2020 Mar 1;28(2):152-162. doi: 10.4062/biomolther.2019.147. PMID: 31813204; PMCID: PMC7059808. 7: Cernackova A, Mikova L, Horvathova L, Tillinger A, Mravec B. Cachexia induced by Yoshida ascites hepatoma in Wistar rats is not associated with inflammatory response in the spleen or brain. J Neuroimmunol. 2019 Dec 15;337:577068. doi: 10.1016/j.jneuroim.2019.577068. Epub 2019 Sep 12. PMID: 31606594. 8: Lung HL, Kan R, Chau WY, Man OY, Mak NK, Fong CH, Shuen WH, Tsao SW, Lung ML. The anti-tumor function of the IKK inhibitor PS1145 and high levels of p65 and KLF4 are associated with the drug resistance in nasopharyngeal carcinoma cells. Sci Rep. 2019 Aug 19;9(1):12064. doi: 10.1038/s41598-019-48590-7. PMID: 31427673; PMCID: PMC6700134. 9: Molagoda IMN, Lee S, Jayasooriya RGPT, Jin CY, Choi YH, Kim GY. Deoxynivalenol enhances IL-1ß expression in BV2 microglial cells through activation of the NF-?B pathway and the ASC/NLRP3 inflammasome. EXCLI J. 2019 Jun 11;18:356-369. doi: 10.17179/excli2018-1974. PMID: 31338007; PMCID: PMC6635726. 10: Song W, Zhang CL, Gou L, He L, Gong YY, Qu D, Zhao L, Jin N, Chan TF, Wang L, Tian XY, Luo JY, Huang Y. Endothelial TFEB (Transcription Factor EB) Restrains IKK (IκB Kinase)-p65 Pathway to Attenuate Vascular Inflammation in Diabetic db/db Mice. Arterioscler Thromb Vasc Biol. 2019 Apr;39(4):719-730. doi: 10.1161/ATVBAHA.119.312316. PMID: 30816805. 11: Clemenzi MN, Wellhauser L, Aljghami ME, Belsham DD. Tumour necrosis factor α induces neuroinflammation and insulin resistance in immortalised hypothalamic neurones through independent pathways. J Neuroendocrinol. 2019 Jan;31(1):e12678. doi: 10.1111/jne.12678. Epub 2019 Jan 20. PMID: 30582235. 12: Salehi A, Loganathan N, Belsham DD. Bisphenol A induces Pomc gene expression through neuroinflammatory and PPARγ nuclear receptor-mediated mechanisms in POMC-expressing hypothalamic neuronal models. Mol Cell Endocrinol. 2019 Jan 5;479:12-19. doi: 10.1016/j.mce.2018.08.009. Epub 2018 Aug 24. PMID: 30149043. 13: Verhoeven RJA, Tong S, Zong J, Chen Y, Tsao SW, Pan J, Chen H. NF-κB Signaling Regulates Epstein-Barr Virus BamHI-Q-Driven EBNA1 Expression. Cancers (Basel). 2018 Apr 16;10(4):119. doi: 10.3390/cancers10040119. PMID: 29659505; PMCID: PMC5923374. 14: Chorzalska A, Ahsan N, Rao RSP, Roder K, Yu X, Morgan J, Tepper A, Hines S, Zhang P, Treaba DO, Zhao TC, Olszewski AJ, Reagan JL, Liang O, Gruppuso PA, Dubielecka PM. Overexpression of Tpl2 is linked to imatinib resistance and activation of MEK-ERK and NF-κB pathways in a model of chronic myeloid leukemia. Mol Oncol. 2018 May;12(5):630-647. doi: 10.1002/1878-0261.12186. Epub 2018 Apr 6. PMID: 29485707; PMCID: PMC5928369. 15: Yun J, Park MH, Son DJ, Nam KT, Moon DB, Ju JH, Hwang OK, Choi JS, Kim TH, Jung YS, Hwang DY, Han SB, Yoon DY, Hong JT. IL-32 gamma reduces lung tumor development through upregulation of TIMP-3 overexpression and hypomethylation. Cell Death Dis. 2018 Feb 21;9(3):306. doi: 10.1038/s41419-018-0375-6. PMID: 29467412; PMCID: PMC5833366. 16: Maciejewski BA, Jamieson KC, Arnason JW, Kooi C, Wiehler S, Traves SL, Leigh R, Proud D. Rhinovirus-bacteria coexposure synergistically induces CCL20 production from human bronchial epithelial cells. Am J Physiol Lung Cell Mol Physiol. 2017 May 1;312(5):L731-L740. doi: 10.1152/ajplung.00362.2016. Epub 2017 Mar 10. PMID: 28283475. 17: Duan K, Chen Q, Cheng M, Zhao C, Lin Z, Tan S, Xi F, Gao T, Shi J, Shen J, Li W, Yu W, Li J, Li N. Hypothalamic activation is essential for endotoxemia- induced acute muscle wasting. Sci Rep. 2016 Dec 6;6:38544. doi: 10.1038/srep38544. PMID: 27922103; PMCID: PMC5138608. 18: Kocbek V, Grandi G, Blank F, Wotzkow C, Bersinger NA, Mueller MD, Kyo S, McKinnon BD. TNFα-induced IKKβ complex activation influences epithelial, but not stromal cell survival in endometriosis. Mol Hum Reprod. 2016 Nov;22(11):768-777. doi: 10.1093/molehr/gaw054. Epub 2016 Aug 19. PMID: 27542948. 19: Han C, Wu W, Ale A, Kim MS, Cai D. Central Leptin and Tumor Necrosis Factor-α (TNFα) in Diurnal Control of Blood Pressure and Hypertension. J Biol Chem. 2016 Jul 15;291(29):15131-42. doi: 10.1074/jbc.M116.730408. Epub 2016 May 13. PMID: 27226618; PMCID: PMC4946929. 20: Verhoeven RJ, Tong S, Zhang G, Zong J, Chen Y, Jin DY, Chen MR, Pan J, Chen H. NF-κB Signaling Regulates Expression of Epstein-Barr Virus BART MicroRNAs and Long Noncoding RNAs in Nasopharyngeal Carcinoma. J Virol. 2016 Jun 24;90(14):6475-88. doi: 10.1128/JVI.00613-16. PMID: 27147748; PMCID: PMC4936125.