PKCι

PKCι (PRKCI) is an atypical serine/threonine protein kinase that supports epithelial cell polarity, proliferation, survival, and stem/progenitor-cell control^[1]^[2]. Mechanistically, PRKCI links polarity signaling to Notch-dependent stem/progenitor expansion, and loss of Prkci increased multiple stem/progenitor populations through NUMB inactivation and NOTCH1 activation^[2]. In cancer models, PKCι supports Ras-mediated transformation and colon carcinogenesis through a Ras-PKCι-Rac1 axis^[3]. In lung squamous cell carcinoma, PRKCI and SOX2 are coamplified, and PKCι phosphorylates SOX2 to activate HHAT/Hedgehog signaling and maintain a stem-like phenotype^[4]. Compared with the related atypical isoform PKCζ, PKCι shows distinct, non-overlapping cancer functions; in NSCLC cells, PKCι is highly expressed whereas PKCζ is undetectable^[5]^[6]. For experimental applications, aurothiomalate and related gold compounds disrupt PKCι-Par6 PB1-domain interactions, block PKCι-dependent Rac1 signaling, and inhibit transformed growth in NSCLC models^[7]^[8]. Fragment-based discovery has also produced potent PKCι inhibitors, supporting chemical-probe development for isoform-focused pathway studies^[9].

References:

[1]. Reina-Campos M, et al. The Dual Roles of the Atypical Protein Kinase Cs in Cancer. Cancer Cell. 2019 Sep 16;36(3):218-235.

[2]. Mah IK, et al. Atypical PKC-iota Controls Stem Cell Expansion via Regulation of the Notch Pathway. Stem Cell Reports. 2015 Nov 10;5(5):866-880.

[3]. Murray NR, et al. Protein kinase Ciota is required for Ras transformation and colon carcinogenesis in vivo. J Cell Biol. 2004 Mar 15;164(6):797-802.

[4]. Justilien V, et al. The PRKCI and SOX2 oncogenes are coamplified and cooperate to activate Hedgehog signaling in lung squamous cell carcinoma. Cancer Cell. 2014 Feb 10;25(2):139-51.

[5]. Regala RP, et al. Atypical protein kinase Ciota plays a critical role in human lung cancer cell growth and tumorigenicity. J Biol Chem. 2005 Sep 2;280(35):31109-15. [Content Brief]

[6]. Fields AP, et al. Protein kinase C iota: human oncogene, prognostic marker and therapeutic target. Pharmacol Res. 2007 Jun;55(6):487-97.

[7]. Ali SR, et al. Nerve Density and Neuronal Biomarkers in Cancer. Cancers (Basel). 2022 Oct 1;14(19):4817.

[8]. Erdogan E, et al. Aurothiomalate inhibits transformed growth by targeting the PB1 domain of protein kinase Ciota. J Biol Chem. 2006 Sep 22;281(38):28450-9.

[9]. Kwiatkowski J, et al. Fragment-Based Drug Discovery of Potent Protein Kinase C Iota Inhibitors. J Med Chem. 2018 May 24;61(10):4386-4396. [Content Brief]

PKCι Inhibitors (6)

PKCι Related Products (6):

By Type:	Selective (6)

Cat. No.	Product Name	Effect	Purity

HY-106381

Aurothiomalate sodium	Inhibitor	98.0%
Aurothiomalate sodium is the tetrameric form of Aurothiomalate sodium (HY-106381). Aurothiomalate sodium acts as an inhibitor of PKCI and TrxR1. Aurothiomalate sodium disrupts the PKCI-Par6-Rac1 signaling pathway, and also inhibits TrxR1 activity, TNFα-induced NF-κB activation, and the expression of pro-inflammatory genes. Aurothiomalate sodium blocks Kras-mediated BASC expansion and lung tumor growth, inhibits anchorage-independent growth and tumorigenicity of lung cancer cells, and suppresses neutrophil chemotaxis, phagocytosis, and leukocyte extravasation. Aurothiomalate sodium can be used in research related to rheumatoid arthritis and non-small cell lung cancer.

HY-117366

PS432	Inhibitor	99.9%
PS432 is a PKC inhibitor with IC₅₀s of 16.9 μM (PKC_ι) and 18.5 μM (PKC_ζ), respectively. PS432 effectively inhibits the proliferation of non-small cell lung cancer cells (NSCLCs) and tumor growth in mouse xenograft models.

HY-106381A

Aurothiomalate tetramer sodium	Inhibitor	98.0%
Aurothiomalate tetramer sodium is the tetrameric form of Aurothiomalate sodium (HY-106381). Aurothiomalate tetramer sodium acts as an inhibitor of PKCI and TrxR1. Aurothiomalate tetramer sodium disrupts the PKCI-Par6-Rac1 signaling pathway, and also inhibits TrxR1 activity, TNFα-induced NF-κB activation, and the expression of pro-inflammatory genes. Aurothiomalate tetramer sodium blocks Kras-mediated BASC expansion and lung tumor growth, inhibits anchorage-independent growth and tumorigenicity of lung cancer cells, and suppresses neutrophil chemotaxis, phagocytosis, and leukocyte extravasation. Aurothiomalate tetramer sodium can be used in research related to rheumatoid arthritis and non-small cell lung cancer.

HY-122858A

PKCiota-IN-2 formic	Inhibitor	99.04%
PKCiota-IN-2 formic is a potent PKCiota (PKC-ι) inhibitor with an IC₅₀ of 2.8 nM. PKCiota-IN-2 formic also inhibits PKC-α and PKC-ε with IC₅₀s of 71 nM and 350 nM, respectively.

HY-122858

PKCiota-IN-2	Inhibitor
PKCiota-IN-2 (Compound 49) is a potent PKCiota (PKC-ι) inhibitor with an IC₅₀ of 2.8 nM. PKCiota-IN-2 also inhibits PKC-α and PKC-ε with IC₅₀s of 71 nM and 350 nM, respectively.

HY-122857

PKCiota-IN-1	Inhibitor
PKCiota-IN-1 (compound 51) is a potent PKCiota (PKC-ι) inhibitor with an IC₅₀ of 2.7 nM. PKCiota-IN-1 also inhibits PKC-α and PKC-ε with IC₅₀s of 45 nM and 450 nM, respectively.

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