WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H407262
CAS#: 431898-65-6 (free base)
Description: 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.
Hodoodo Cat#: H407262
Name: PS-1145
CAS#: 431898-65-6 (free base)
Chemical Formula: C17H11ClN4O
Exact Mass: 322.06
Molecular Weight: 322.750
Elemental Analysis: C, 63.26; H, 3.44; Cl, 10.98; N, 17.36; O, 4.96
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)
| 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 | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 20.8 | 64.40 |
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: | 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. |
| In vivo 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. 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. |
1: Shukla S, Kanwal R, Shankar E, Datt M, Chance MR, Fu P, MacLennan GT, Gupta S. Apigenin blocks IKKα activation and suppresses prostate cancer progression. Oncotarget. 2015 Oct 13;6(31):31216-32. doi: 10.18632/oncotarget.5157. PubMed PMID: 26435478.
2: 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. PubMed PMID: 26148342.
3: Muto M, Baghdadi M, Maekawa R, Wada H, Seino K. Myeloid molecular characteristics of human γδ T cells support their acquisition of tumor antigen-presenting capacity. Cancer Immunol Immunother. 2015 Aug;64(8):941-9. doi: 10.1007/s00262-015-1700-x. Epub 2015 Apr 24. PubMed PMID: 25904200.
4: Rider CF, Shah S, Miller-Larsson A, Giembycz MA, Newton R. Cytokine-induced loss of glucocorticoid function: effect of kinase inhibitors, long-acting β(2)-adrenoceptor [corrected] agonist and glucocorticoid receptor ligands. PLoS One. 2015 Jan 27;10(1):e0116773. doi: 10.1371/journal.pone.0116773. eCollection 2015. Erratum in: PLoS One. 2015;10(5):e0128728. PubMed PMID: 25625944; PubMed Central PMCID: PMC4308083.
5: Ottina E, Sochalska M, Sgonc R, Villunger A. The BH3-only protein Bad is dispensable for TNF-mediated cell death. Cell Death Dis. 2015 Jan 22;6:e1611. doi: 10.1038/cddis.2014.575. PubMed PMID: 25611386; PubMed Central PMCID: PMC4669773.
6: Dong X, Tong F, Qian C, Zhang R, Dong J, Wu G, Hu Y. NEMO modulates radiation-induced endothelial senescence of human umbilical veins through NF-κB signal pathway. Radiat Res. 2015 Jan;183(1):82-93. doi: 10.1667/RR13682.1. Epub 2014 Dec 23. PubMed PMID: 25536232.
7: Yang L, Zhou Y, Li Y, Zhou J, Wu Y, Cui Y, Yang G, Hong Y. Mutations of p53 and KRAS activate NF-κB to promote chemoresistance and tumorigenesis via dysregulation of cell cycle and suppression of apoptosis in lung cancer cells. Cancer Lett. 2015 Feb 28;357(2):520-6. doi: 10.1016/j.canlet.2014.12.003. Epub 2014 Dec 8. PubMed PMID: 25499080.
8: Campa VM, Baltziskueta E, Bengoa-Vergniory N, Gorroño-Etxebarria I, Wesołowski R, Waxman J, Kypta RM. A screen for transcription factor targets of glycogen synthase kinase-3 highlights an inverse correlation of NFκB and androgen receptor signaling in prostate cancer. Oncotarget. 2014 Sep 30;5(18):8173-87. PubMed PMID: 25327559; PubMed Central PMCID: PMC4226675.
9: Wellhauser L, Belsham DD. Activation of the omega-3 fatty acid receptor GPR120 mediates anti-inflammatory actions in immortalized hypothalamic neurons. J Neuroinflammation. 2014 Mar 27;11:60. doi: 10.1186/1742-2094-11-60. PubMed PMID: 24674717; PubMed Central PMCID: PMC3986641.
10: Jayasooriya RG, Dilshara MG, Park SR, Choi YH, Hyun JW, Chang WY, Kim GY. 18β-Glycyrrhetinic acid suppresses TNF-α induced matrix metalloproteinase-9 and vascular endothelial growth factor by suppressing the Akt-dependent NF-κB pathway. Toxicol In Vitro. 2014 Aug;28(5):751-8. doi: 10.1016/j.tiv.2014.02.015. Epub 2014 Mar 12. PubMed PMID: 24613819.
11: Yu NY, Gdalevitch M, Murphy CM, Mikulec K, Peacock L, Fitzpatrick J, Cantrill LC, Ruys AJ, Cooper-White JJ, Little DG, Schindeler A. Spatial control of bone formation using a porous polymer scaffold co-delivering anabolic rhBMP-2 and anti-resorptive agents. Eur Cell Mater. 2014 Jan 31;27:98-109; discussion 109-111. PubMed PMID: 24488823.
12: Park DW, Jiang S, Tadie JM, Stigler WS, Gao Y, Deshane J, Abraham E, Zmijewski JW. Activation of AMPK enhances neutrophil chemotaxis and bacterial killing. Mol Med. 2013 Nov 8;19:387-98. doi: 10.2119/molmed.2013.00065. PubMed PMID: 24091934; PubMed Central PMCID: PMC3883969.
13: Wang CZ, Li B, Wen XD, Zhang Z, Yu C, Calway TD, He TC, Du W, Yuan CS. Paraptosis and NF-κB activation are associated with protopanaxadiol-induced cancer chemoprevention. BMC Complement Altern Med. 2013 Jan 3;13:2. doi: 10.1186/1472-6882-13-2. PubMed PMID: 23281928; PubMed Central PMCID: PMC3575249.
14: Roy S, Chakraborti T, Chowdhury A, Chakraborti S. Role of PKC-α in NF-κB-MT1-MMP-mediated activation of proMMP-2 by TNF-α in pulmonary artery smooth muscle cells. J Biochem. 2013 Mar;153(3):289-302. doi: 10.1093/jb/mvs150. Epub 2012 Dec 24. PubMed PMID: 23266860.
15: Gancz D, Lusthaus M, Fishelson Z. A role for the NF-κB pathway in cell protection from complement-dependent cytotoxicity. J Immunol. 2012 Jul 15;189(2):860-6. doi: 10.4049/jimmunol.1103451. Epub 2012 Jun 8. PubMed PMID: 22685314.
16: Lupino E, Ramondetti C, Piccinini M. IκB kinase β is required for activation of NF-κB and AP-1 in CD3/CD28-stimulated primary CD4(+) T cells. J Immunol. 2012 Mar 15;188(6):2545-55. doi: 10.4049/jimmunol.1102938. Epub 2012 Feb 13. PubMed PMID: 22331067.
17: Elkind E, Vaisid T, Kornspan JD, Barnoy S, Rottem S, Kosower NS. Calpastatin upregulation in Mycoplasma hyorhinis-infected cells is promoted by the mycoplasma lipoproteins via the NF-κB pathway. Cell Microbiol. 2012 Jun;14(6):840-51. doi: 10.1111/j.1462-5822.2012.01760.x. Epub 2012 Feb 24. PubMed PMID: 22288381.
18: Raskatov JA, Meier JL, Puckett JW, Yang F, Ramakrishnan P, Dervan PB. Modulation of NF-κB-dependent gene transcription using programmable DNA minor groove binders. Proc Natl Acad Sci U S A. 2012 Jan 24;109(4):1023-8. doi: 10.1073/pnas.1118506109. Epub 2011 Dec 27. PubMed PMID: 22203967; PubMed Central PMCID: PMC3268328.
19: Tanabe T, Kanoh S, Tsushima K, Yamazaki Y, Kubo K, Rubin BK. Clarithromycin inhibits interleukin-13-induced goblet cell hyperplasia in human airway cells. Am J Respir Cell Mol Biol. 2011 Nov;45(5):1075-83. doi: 10.1165/rcmb.2010-0327OC. Epub 2011 Jun 3. PubMed PMID: 21642590.
20: Chang Y, Al-Alwan L, Risse PA, Roussel L, Rousseau S, Halayko AJ, Martin JG, Hamid Q, Eidelman DH. TH17 cytokines induce human airway smooth muscle cell migration. J Allergy Clin Immunol. 2011 Apr;127(4):1046-53.e1-2. doi: 10.1016/j.jaci.2010.12.1117. Epub 2011 Feb 22. PubMed PMID: 21345484.
