PIK-75 HCl | CAS#372196-77-5 | PI3K inhibitor

MedKoo Cat#: 408028 | Name: PIK-75 HCl

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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 HCl

CAS#372196-77-5 (HCl)

Theoretical Analysis

MedKoo Cat#: 408028

Name: PIK-75 HCl

CAS#: 372196-77-5 (HCl)

Chemical Formula: C16H15BrClN5O4S

Exact Mass: 0.0000

Molecular Weight: 488.74

Elemental Analysis: C, 39.32; H, 3.09; Br, 16.35; Cl, 7.25; N, 14.33; O, 13.09; S, 6.56

Price and Availability

Size	Price	Availability
25mg	USD 350.00	2 weeks
50mg	USD 570.00	2 weeks
100mg	USD 880.00	2 Weeks

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Related CAS #

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

Synonym

PIK-75 HCl; PIK 75 HCl; PIK75 HCl; PIK-75 hydrochloride

IUPAC/Chemical Name

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

InChi Key

VOUDEIAYNKZQKM-MYHMWQFYSA-N

InChi Code

InChI=1S/C16H14BrN5O4S.ClH/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;1H/b19-9+;

SMILES Code

O=S(C1=CC([N+]([O-])=O)=CC=C1C)(N(C)/N=C/C2=CN=C3C=CC(Br)=CN32)=O.[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

Shelf Life

>3 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

Instruction

View handling instruction

Biological target:

PIK-75 hydrochloride 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.

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 tBHQ-activated 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-75-treated 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
Solubility
	DMF	0.5	1.02
	DMSO	5.6	11.51
	Ethanol	9.0	18.41

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 488.74 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: 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 May 22. doi: 10.1002/1878-0261.12506. [Epub ahead of print] PubMed PMID: 31115969. 2: 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. PubMed PMID: 30935856. 3: 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. PubMed PMID: 30606984. 4: 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. PubMed PMID: 29873877. 5: 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. PubMed PMID: 29793021. 6: Posfai D, Eubanks AL, Keim AI, Lu KY, Wang GZ, Hughes PF, Kato N, Haystead TA, Derbyshire ER. Identification of Hsp90 Inhibitors with Anti-Plasmodium Activity. Antimicrob Agents Chemother. 2018 Mar 27;62(4). pii: e01799-17. doi: 10.1128/AAC.01799-17. Print 2018 Apr. PubMed PMID: 29339390; PubMed Central PMCID: PMC5913967. 7: Meng C, Song L, Wang J, Li D, Liu Y, Cui X. Propofol induces proliferation partially via downregulation of p53 protein and promotes migration via activation of the Nrf2 pathway in human breast cancer cell line MDA-MB-231. Oncol Rep. 2017 Feb;37(2):841-848. doi: 10.3892/or.2016.5332. Epub 2016 Dec 23. PubMed PMID: 28035403. 8: Jan WC, Kao MC, Yang CH, Chang YY, Huang CJ. Phosphoinositide 3-Kinase Is Involved in Mediating the Anti-inflammation Effects of Vasopressin. Inflammation. 2017 Apr;40(2):435-441. doi: 10.1007/s10753-016-0489-x. PubMed PMID: 27943011. 9: Phillipson LJ, Segal DH, Nero TL, Parker MW, Wan SS, de Silva M, Guthridge MA, Wei AH, Burns CJ. Discovery and SAR of novel pyrazolo[1,5-a]pyrimidines as inhibitors of CDK9. Bioorg Med Chem. 2015 Oct 1;23(19):6280-96. doi: 10.1016/j.bmc.2015.08.035. Epub 2015 Aug 28. PubMed PMID: 26349627. 10: Perwitasari O, Yan X, O'Donnell J, Johnson S, Tripp RA. Repurposing Kinase Inhibitors as Antiviral Agents to Control Influenza A Virus Replication. Assay Drug Dev Technol. 2015 Dec;13(10):638-49. doi: 10.1089/adt.2015.0003.drrr. Epub 2015 Jul 20. PubMed PMID: 26192013; PubMed Central PMCID: PMC4692129. 11: Horiguchi M, Oiso Y, Sakai H, Motomura T, Yamashita C. Pulmonary administration of phosphoinositide 3-kinase inhibitor is a curative treatment for chronic obstructive pulmonary disease by alveolar regeneration. J Control Release. 2015 Sep 10;213:112-119. doi: 10.1016/j.jconrel.2015.07.004. Epub 2015 Jul 6. PubMed PMID: 26160307. 12: Cage TA, Chanthery Y, Chesler L, Grimmer M, Knight Z, Shokat K, Weiss WA, Gustafson WC. Downregulation of MYCN through PI3K Inhibition in Mouse Models of Pediatric Neural Cancer. Front Oncol. 2015 May 12;5:111. doi: 10.3389/fonc.2015.00111. eCollection 2015. PubMed PMID: 26029667; PubMed Central PMCID: PMC4429235. 13: Lee PY, Yang CH, Kao MC, Su NY, Tsai PS, Huang CJ. Phosphoinositide 3-kinase β, phosphoinositide 3-kinase δ, and phosphoinositide 3-kinase γ mediate the anti-inflammatory effects of magnesium sulfate. J Surg Res. 2015 Aug;197(2):390-7. doi: 10.1016/j.jss.2015.04.051. Epub 2015 Apr 18. PubMed PMID: 25972311. 14: Vantler M, Jesus J, Leppänen O, Scherner M, Berghausen EM, Mustafov L, Chen X, Kramer T, Zierden M, Gerhardt M, Ten Freyhaus H, Blaschke F, Sterner-Kock A, Baldus S, Zhao JJ, Rosenkranz S. Class IA Phosphatidylinositol 3-Kinase Isoform p110α Mediates Vascular Remodeling. Arterioscler Thromb Vasc Biol. 2015 Jun;35(6):1434-44. doi: 10.1161/ATVBAHA.114.304887. Epub 2015 Apr 23. PubMed PMID: 25908763. 15: Corrigendum. Int J Immunopathol Pharmacol. 2015 Mar;28(1):146. doi: 10.1177/0394632015572738. PubMed PMID: 25816420. 16: Martin KJ, Muessel MJ, Pullar CE, Willars GB, Wardlaw AJ. The role of phosphoinositide 3-kinases in neutrophil migration in 3D collagen gels. PLoS One. 2015 Feb 6;10(2):e0116250. doi: 10.1371/journal.pone.0116250. eCollection 2015. Erratum in: PLoS One. 2015;10(7):e0134924. PubMed PMID: 25659107; PubMed Central PMCID: PMC4320071. 17: Jeong JY, Lee YJ, Han JH, Park SY, Hwang KW, Sohn UD. The inhibitory effect of PIK-75 on inflammatory mediator response induced by hydrogen peroxide in feline esophageal epithelial cells. Mediators Inflamm. 2014;2014:178049. doi: 10.1155/2014/178049. Epub 2014 Sep 7. PubMed PMID: 25276052; PubMed Central PMCID: PMC4170708. 18: Höland K, Boller D, Hagel C, Dolski S, Treszl A, Pardo OE, Cwiek P, Salm F, Leni Z, Shepherd PR, Styp-Rekowska B, Djonov V, von Bueren AO, Frei K, Arcaro A. Targeting class IA PI3K isoforms selectively impairs cell growth, survival, and migration in glioblastoma. PLoS One. 2014 Apr 9;9(4):e94132. doi: 10.1371/journal.pone.0094132. eCollection 2014. PubMed PMID: 24718026; PubMed Central PMCID: PMC3981776. 19: 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. Erratum in: Int J Immunopathol Pharmacol. 2015 Mar;28(1):146. PubMed PMID: 24674679. 20: 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. PubMed PMID: 24366069; PubMed Central PMCID: PMC3928470.