PIK-75 | CAS#372196-67-3 | 372196-77-5 | PI3K inhibitor

MedKoo Cat#: 202238 | Name: PIK-75

Description:

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

PIK-75 was developed as part of a PI 3-kinase drug discovery program. PIK75 attenuates insulin stimulation of Akt/PKB in a range of cell types at 100 nM. The compound has been reported to block growth of a range of cell lines with an IC50 value in the region of 50 nM. In vivo studies have shown that PIK-75, administered at 50 mg/kg, inhibited the growth of HeLa cell xenografts in mice models.

Chemical Structure

PIK-75

CAS#372196-67-3 (free base)

Theoretical Analysis

MedKoo Cat#: 202238

Name: PIK-75

CAS#: 372196-67-3 (free base)

Chemical Formula: C16H14BrN5O4S

Exact Mass: 450.9950

Molecular Weight: 452.28

Elemental Analysis: C, 42.49; H, 3.12; Br, 17.67; N, 15.48; O, 14.15; S, 7.09

Price and Availability

Size	Price	Availability
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 1,550.00	Ready to ship
1g	USD 2,650.00	Ready to ship
2g	USD 4,850.00	Ready to ship

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Related CAS #

372196-67-3 (free base) 372196-77-5 (HCl)

Synonym

PIK75; PIK-75; PIK 75.

IUPAC/Chemical Name

(E)-N'-((6-bromoimidazo[1,2-a]pyridin-3-yl)methylene)-N,2-dimethyl-5-nitrobenzenesulfonohydrazide

InChi Key

QTHCAAFKVUWAFI-DJKKODMXSA-N

InChi Code

InChI=1S/C16H14BrN5O4S/c1-11-3-5-13(22(23)24)7-15(11)27(25,26)20(2)19-9-14-8-18-16-6-4-12(17)10-21(14)16/h3-10H,1-2H3/b19-9+

SMILES Code

O=S(C1=CC([N+]([O-])=O)=CC=C1C)(N(C)/N=C/C2=CN=C3N2C=C(C=C3)Br)=O

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 soluble in water.

Shelf Life

>5 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

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#C9R09B06

QC Data

View QC data: current batch, Lot#C9R09B06

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

PIK-75 is a reversible DNA-PK and p110α-selective inhibitor, which inhibits DNA-PK, p110α and p110γ with IC50s of 2, 5.8 and 76 nM, respectively

In vitro activity:

The effect of PIK-75 on the mRNA expression of NRF2 and its target gene was assessed by qRT-PCR in the cDNAs from AsPC-1 cells transfected with FLAG-NRF2 and treated with PIK-75. As expected, overexpression of FLAG-NRF2 (Fig. 2D) markedly increased the mRNA expression of NRF2 target gene HO-1 (Fig. 2E) and MRP5 (Fig. 2F). Under these conditions, PIK-75 reduced the NRF2-mediated expression of HO-1 and MRP5 mRNA (Fig. 2E and F). On the contrary, the effect of PIK-75 on the NRF2 mRNA was limited (Fig. 2D) and the NRF2 mRNA was slightly reduced at 1 μM concentration of PIK-75 (data not shown). The effect of PIK-75 on the endogenous NRF2 was also further determined by tBHQ activation model. Two pancreatic cancer cells, MIA PaCa-2 and AsPC-1 were activated by tBHQ for 1 h followed by PIK-75 treatment for 8 h. Again, PIK-75 reduced the levels of tBHQactivated NRF2 and its downstream targets, HO-1 as early as 8 h post-treatment in both cells (Fig. 2I). Taken together, PIK-75 represses NRF2-target gene expression through downregulation of the NRF2 protein. Reference: Int J Oncol. 2014 Mar; 44(3): 959–969. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3928470/

In vivo activity:

It was sought to determine the effect of PIK75 in a model of EAE that is dependent on CD4+ T cells. Oral administration of PIK-75 had a significant effect on most clinical parameters considered, including the average score, the average maximal disease score, or the average disease index (Fig. 7b-d). The average day of disease onset was\ not significantly changed, as expected from the late beginning of PIK-75 administration (Fig. 7a). The lymph node cells from the PIK-75-treated mice still showed reduced proliferation (Fig. 7e). The analysis of cytokines involved in the pathogenesis of encephalomyelitis showed that IL-17A was reduced in the PIK-75treated group. PIK-75 was developed as a potent P13-K pl lOn inhibitor that suppressed growth of tumor cells in vitro or in human xenograft models in vivo. Reference: Int J Immunopathol Pharmacol. Jan-Mar 2014;27(1):53-67. https://pubmed.ncbi.nlm.nih.gov/24674679/

	Solvent	mg/mL	mM	comments
Solubility
	DMSO	0.0	0.00

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 452.28 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. Acosta YY, Montes-Casado M, Aragoneses-Fenoll L, Dianzani U, Portoles P, Rojo JM. Suppression of CD4+ T lymphocyte activation in vitro and experimental encephalomyelitis in vivo by the phosphatidyl inositol 3-kinase inhibitor PIK-75. Int J Immunopathol Pharmacol. 2014 Jan-Mar;27(1):53-67. doi: 10.1177/039463201402700108. Erratum in: Int J Immunopathol Pharmacol. 2015 Mar;28(1):146. PMID: 24674679. 2. Duong HQ, Yi YW, Kang HJ, Hong YB, Tang W, Wang A, Seong YS, Bae I. Inhibition of NRF2 by PIK-75 augments sensitivity of pancreatic cancer cells to gemcitabine. Int J Oncol. 2014 Mar;44(3):959-69. doi: 10.3892/ijo.2013.2229. Epub 2013 Dec 23. PMID: 24366069; PMCID: PMC3928470.

In vitro protocol:

In vivo protocol:

1: Piper AK, Penney C, Holliday J, Tincknell G, Ma Y, Napaki S, Pantel K, Brungs D, Ranson M. EGFR and PI3K Signalling Pathways as Promising Targets on Circulating Tumour Cells from Patients with Metastatic Gastric Adenocarcinoma. Int J Mol Sci. 2024 May 20;25(10):5565. doi: 10.3390/ijms25105565. PMID: 38791602; PMCID: PMC11122469. 2: Cai T, Feng T, Li G, Wang J, Jin S, Ye D, Zhu Y. Deciphering the prognostic features of bladder cancer through gemcitabine resistance and immune-related gene analysis and identifying potential small molecular drug PIK-75. Cancer Cell Int. 2024 Apr 3;24(1):125. doi: 10.1186/s12935-024-03258-9. PMID: 38570787; PMCID: PMC10993528. 3: Perry JR, Genenger B, Thind AS, Ashford B, Ranson M. PIK Your Poison: The Effects of Combining PI3K and CDK Inhibitors against Metastatic Cutaneous Squamous Cell Carcinoma In Vitro. Cancers (Basel). 2024 Jan 15;16(2):370. doi: 10.3390/cancers16020370. PMID: 38254859; PMCID: PMC10814950. 4: Oktem EK, Yazar M. Drug Repositioning Identifies Six Drug Candidates for Systemic Autoimmune Diseases by Integrative Analyses of Transcriptomes from Scleroderma, Systemic Lupus Erythematosus, and Sjogren's Syndrome. OMICS. 2022 Dec;26(12):683-693. doi: 10.1089/omi.2022.0138. Epub 2022 Nov 15. PMID: 36378860. 5: Lim FQ, Chan AS, Yokomori R, Huang XZ, Theardy MS, Yeoh AEJ, Tan SH, Sanda T. Targeting dual oncogenic machineries driven by TAL1 and PI3K-AKT pathways in T-cell acute lymphoblastic leukemia. Haematologica. 2023 Feb 1;108(2):367-381. doi: 10.3324/haematol.2022.280761. PMID: 36073513; PMCID: PMC9890034. 6: Huang YS, Wu CC, Chang CC, Huang SF, Kuo HY, Shih HM. Reciprocal regulation of Daxx and PIK3CA promotes colorectal cancer cell growth. Cell Mol Life Sci. 2022 Jun 19;79(7):367. doi: 10.1007/s00018-022-04399-8. PMID: 35718818; PMCID: PMC11072676. 7: Huang S, Liu Y, Chen Z, Wang M, Jiang VC. PIK-75 overcomes venetoclax resistance via blocking PI3K-AKT signaling and MCL-1 expression in mantle cell lymphoma. Am J Cancer Res. 2022 Mar 15;12(3):1102-1115. PMID: 35411248; PMCID: PMC8984906. 8: Narci K, Kahraman DC, Koyas A, Ersahin T, Tuncbag N, Atalay RC. Context dependent isoform specific PI3K inhibition confers drug resistance in hepatocellular carcinoma cells. BMC Cancer. 2022 Mar 24;22(1):320. doi: 10.1186/s12885-022-09357-y. PMID: 35331184; PMCID: PMC8953069. 9: Wong RLY, Wong MRE, Kuick CH, Saffari SE, Wong MK, Tan SH, Merchant K, Chang KTE, Thangavelu M, Periyasamy G, Chen ZX, Iyer P, Tan EEK, Soh SY, Iyer NG, Fan Q, Loh AHP. Integrated Genomic Profiling and Drug Screening of Patient-Derived Cultures Identifies Individualized Copy Number-Dependent Susceptibilities Involving PI3K Pathway and 17q Genes in Neuroblastoma. Front Oncol. 2021 Oct 14;11:709525. doi: 10.3389/fonc.2021.709525. PMID: 34722256; PMCID: PMC8551924. 10: Bourdakou MM, Spyrou GM, Kolios G. Colon Cancer Progression Is Reflected to Monotonic Differentiation in Gene Expression and Pathway Deregulation Facilitating Stage-specific Drug Repurposing. Cancer Genomics Proteomics. 2021 Nov-Dec;18(6):757-769. doi: 10.21873/cgp.20295. PMID: 34697067; PMCID: PMC8569813. 11: Beattie SR, Krysan DJ. A Unique Dual-Readout High-Throughput Screening Assay To Identify Antifungal Compounds with Aspergillus fumigatus. mSphere. 2021 Aug 25;6(4):e0053921. doi: 10.1128/mSphere.00539-21. Epub 2021 Aug 18. PMID: 34406854; PMCID: PMC8386399. 12: Zahra R, Furqan M, Ullah R, Mithani A, Saleem RSZ, Faisal A. A cell-based high-throughput screen identifies inhibitors that overcome P-glycoprotein (Pgp)-mediated multidrug resistance. PLoS One. 2020 Jun 2;15(6):e0233993. doi: 10.1371/journal.pone.0233993. PMID: 32484843; PMCID: PMC7266297. 13: Chen F, Zheng A, Li F, Wen S, Chen S, Tao Z. In vivo and in vitro investigation of KIN-193 anti-tumor effects on nasopharyngeal carcinoma. Transl Cancer Res. 2020 Jan;9(1):49-57. doi: 10.21037/tcr.2019.11.03. PMID: 35117157; PMCID: PMC8799205. 14: Gündüz D, Troidl C, Tanislav C, Rohrbach S, Hamm C, Aslam M. Role of PI3K/Akt and MEK/ERK Signalling in cAMP/Epac-Mediated Endothelial Barrier Stabilisation. Front Physiol. 2019 Nov 7;10:1387. doi: 10.3389/fphys.2019.01387. PMID: 31787905; PMCID: PMC6855264. 15: Benzler M, Benzler J, Stoehr S, Hempp C, Rizwan MZ, Heyward P, Tups A. "Insulin-like" effects of palmitate compromise insulin signalling in hypothalamic neurons. J Comp Physiol B. 2019 Aug;189(3-4):413-424. doi: 10.1007/s00360-019-01220-0. Epub 2019 May 23. PMID: 31123821. 16: Pedini F, De Luca G, Felicetti F, Puglisi R, Boe A, Arasi MB, Fratini F, Mattia G, Spada M, Caporali S, Biffoni M, Giuliani A, Carè A, Felli N. Joint action of miR-126 and MAPK/PI3K inhibitors against metastatic melanoma. Mol Oncol. 2019 Sep;13(9):1836-1854. doi: 10.1002/1878-0261.12506. Epub 2019 Aug 6. PMID: 31115969; PMCID: PMC6717748. 17: Li G, Zhang X, Ou H, Wang H, Liu D, Yang H, Wu Z. PIK-75 promotes homology- directed DNA repair. J Genet Genomics. 2019 Mar 20;46(3):141-144. doi: 10.1016/j.jgg.2019.03.002. Epub 2019 Mar 15. PMID: 30935856. 18: Hamada K, Maeda Y, Mizutani A, Okada S. The Phosphatidylinositol 3-Kinase p110α/PTEN Signaling Pathway Is Crucial for HIV-1 Entry. Biol Pharm Bull. 2019;42(1):130-138. doi: 10.1248/bpb.b18-00801. PMID: 30606984. 19: Tesch R, Becker C, Müller MP, Beck ME, Quambusch L, Getlik M, Lategahn J, Uhlenbrock N, Costa FN, Polêto MD, Pinheiro PSM, Rodrigues DA, Sant'Anna CMR, Ferreira FF, Verli H, Fraga CAM, Rauh D. An Unusual Intramolecular Halogen Bond Guides Conformational Selection. Angew Chem Int Ed Engl. 2018 Jul 26;57(31):9970-9975. doi: 10.1002/anie.201804917. Epub 2018 Jul 9. PMID: 29873877. 20: Blair TA, Moore SF, Walsh TG, Hutchinson JL, Durrant TN, Anderson KE, Poole AW, Hers I. Phosphoinositide 3-kinase p110α negatively regulates thrombopoietin- mediated platelet activation and thrombus formation. Cell Signal. 2018 Oct;50:111-120. doi: 10.1016/j.cellsig.2018.05.005. Epub 2018 May 21. PMID: 29793021.