475110-96-4

Usage

Uses

Used in Anticancer Applications:
ZSTK474 is used as a potent PI3K inhibitor for its strong antitumor activity against human cancer xenografts in mice. It modulates several oncological signaling pathways, making it a promising pharmaceutical candidate for various cancer treatments. The efficacy of ZSTK474 against certain cancer cells and tumors can be enhanced by combination therapy.
Used in Anti-inflammatory Applications:
ZSTK474 is used as an anti-inflammatory agent for its ability to modulate human CD14+ monocyte-derived dendritic cell functions and suppress experimental autoimmune encephalomyelitis. It also ameliorates the progression of adjuvant-induced arthritis in a rat model.
Used in Pharmaceutical Research:
ZSTK474 is used as a research tool for studying the role of PI3K in various cellular processes and diseases. Its high selectivity and potency make it a valuable compound for investigating the therapeutic potential of PI3K inhibition in different applications.
Used in Drug Development:
ZSTK474 is used in the development of novel drug delivery systems to enhance its applications and efficacy against cancer cells. Various organic and metallic nanoparticles have been employed as carriers for ZSTK474 delivery, aiming to improve its delivery, bioavailability, and therapeutic outcomes.

References

1) Kong and Yamori et al. (2007), ZSTK474 is an ATP-competitive inhibitor of class I phosphatidylinositol 3 kinase isoforms; Cancer Sci., 98 1638 2) Yaguchi et al. (2006), Antitumor activity of ZST474, a new phosphatidylinositol 3-kinase inhibitor; J. Natl. Cancer Inst., 98 545 3) Xue et al. (2014), ZSTK474, a novel PI3K inhibitor, modulates human CD14+ monocyte-derived dendritic cell functions and suppresses experimental autoimmune encephalomyelitis; J. Mol. Med. (Berl.), 92 1057 4) Haruta et al. (2012), Inhibitory effects of ZST474, a phosphatidylinositol 3-kinase inhibitor, on adjuvant-induced arthritis in rats; Inflamm. Res., 61 551

InChI:InChI=1/C19H21F2N7O2/c20-15(21)16-22-13-3-1-2-4-14(13)28(16)19-24-17(26-5-9-29-10-6-26)23-18(25-19)27-7-11-30-12-8-27/h1-4,15H,5-12H2

Upstream product

• 110-91-8 morpholine 
• 475111-38-7 4-(4-chloro-6-(2-(difluoromethyl)-1H-benzo[d]imidazole -1-yl)-1,3,5-triazin-2-yl)morpholine 
• 95-54-5 1,2-diamino-benzene 
• 7597-22-0 2-chloro-4,6-di-morpholin-4-yl-[1,3,5]triazine 
• 705-09-9 2-(difluoromethyl)-1H-benzo[d]imidazole 

Relevant academic research and scientific papers

Discovery of 2-ureidophenyltriazines bearing bridged morpholines as potent and selective ATP-competitive mTOR inhibitors

Incorporation of bridged morpholines in monocyclic triazine PI3K/mTOR inhibitors gave compounds with increased mTOR selectivity relative to the corresponding morpholine analogs. Compounds with ureidophenyl groups gave highly potent and selective mTOR inhi

Synthesis of new heteroaryl substituted morpholine tagged triazines and evaluation of their cytotoxic activity

Background: In the present study, new triazine derivatives 3, 4, 5, 6, 8 and 10 were synthesized starting from readily available cyanuric chloride 1 via nucleophilic displacement with morpholine followed by Suzuki or Stille coupling reactions and then the

PIPERAZINOTRIAZINES AS PI3K INHIBITORS FOR USE IN THE TREATMENT ANTIPROLIFERATIVE DISORDERS

The invention relates to compounds of formula (I) R1 is methyl, n-hexyl, aminoethyl, methylaminoethyl, ethylaminoethyl, dimethylaminoethyl, acryloylaminoethyl, methacryloylaminoethyl, methoxyethyl, ethoxyethyl, d-C4-alkyl-sulfonyl, acryloyl, or methacryloyl; or R1 is aminoethyl, acryloyl or acryloylaminoethyl carrying a linker and a tag, and R2 and R3, independently of each other, are hydrogen or CrC4-alkyl, or R2 and R3 together form a methylene or an ethylene bridge; and tautomers, solvates and pharmaceutically acceptable salts thereof. These compounds are effective in preventing or treating a disease or disorder modulated by PI3 kinases and/or mTOR, in particular treating a hyperproliferative disorder.

Synthesis and biological evaluation of novel analogues of the pan class i phosphatidylinositol 3-kinase (PI3K) inhibitor 2-(Difluoromethyl)-1-[4,6-di(4- morpholinyl)-1,3,5-triazin-2-yl]-1 H -benzimidazole (ZSTK474)

A structure-activity relationship (SAR) study of the pan class I PI 3-kinase inhibitor 2-(difluoromethyl)-1-[4,6-di(4-morpholinyl)-1,3,5-triazin-2- yl]-1H-benzimidazole (ZSTK474) identified substitution at the 4 and 6 positions of the benzimidazole ring as having significant effects on the potency of substituted derivatives. The 6-amino-4-methoxy analogue displayed a greater than 1000-fold potency enhancement over the corresponding 6-aza-4-methoxy analogue against all three class Ia PI 3-kinase enzymes (p110α, p110β, and p110δ) and also displayed significant potency against two mutant forms of the p110α isoform (H1047R and E545K). This compound was also evaluated in vivo against a U87MG human glioblastoma tumor xenograft model in Rag1 -/- mice, and at a dose of 50 mg/kg given by ip injection at a qd ?- 10 dosing schedule it dramatically reduced cancer growth by 81% compared to untreated controls.

PIPERAZINOTRIAZINES AS PI3K INHIBITORS FOR USE IN THE TREATMENT ANTIPROLIFERATIVE DISORDERS

The invention relates to compounds of formula (I) R1 is methyl, n-hexyl, aminoethyl, methylaminoethyl, ethylaminoethyl, dimethylaminoethyl, acryloylaminoethyl, methacryloylaminoethyl, methoxyethyl, ethoxyethyl, d-C4-alkyl- sulfonyl, acryloyl, or methacryloyl; or R1 is aminoethyl, acryloyl or acryloylaminoethyl carrying a linker and a tag, and R2 and R3, independently of each other, are hydrogen or CrC4-alkyl, or R2 and R3 together form a methylene or an ethylene bridge; and tautomers, solvates and pharmaceutically acceptable salts thereof. These compounds are effective in preventing or treating a disease or disorder modulated by PI3 kinases and/or mTOR, in particular treating a hyperproliferative disorder.

Treatment of prostate cancer, melanoma or hepatic cancer

The present application describes a method of treating prostate cancer, melanoma or hepatic cancer in a subject in need thereof, the method comprising administering to said subject a therapeutically effective amount of the heterocyclic compound represented by Formula I or its pharmaceutically acceptable salt:

IMMUNOSUPPRESSIVE AGENT AND ANTI-TUMOR AGENT COMPRISING HETEROCYCLIC COMPOUND AS ACTIVE INGREDIENT

A novel immunosuppressive agent, more specifically an immunosuppressive agent comprising, as an active ingredient, a heterocyclic compound represented by the general formula (I) (wherein X or other variables are as defined in the specification) or a pharmaceutically acceptable salt thereof; a novel heterocyclic compound represented by the general formula (II) (wherein X or other variables are as defined in the specification) or a pharmaceutically acceptable salt thereof; and use of the compound or salt as an antitumor agent.

HETEROCYCLIC COMPOUND AND ANTITUMOR AGENT CONTAINING THE SAME AS ACTIVE INGREDIENT

The present invention relates to heterocyclic compounds represented by the formula I or pharmaceutically acceptable salts thereof and antitumor agents containing the heterocyclic compounds as effective components: wherein X represents nitrogen atom or CH; R1 represents CHnF3-n (wherein n is 1 or 2), hydroxy C1-C6 alkyl, NHR6 [wherein R6 represents hydrogen atom or COR (wherein R represents hydrogen atom, C1-C6 alkyl or C1-C6 alkoxy)]; R2 represents morpholino (which may be substituted with one to four C1-C6 alkyl), thiomorpholino, piperidino, pyrrolidinyl (which may be substituted with hydroxy C1-C6 alkyl), oxazolidinyl (which may be substituted with one or two C1-C6 alkyl) or tetrahydro-1,4-thiazin-1-oxo-4-yl; R3 and R4 each represent hydrogen atom or C1-C6 alkyl; and R5 represents hydrogen atom, amino or hydroxyl.