Exploration of Drug Science

Table 1. Some drugs are FDA-approved and some active s-triazine biologically active species.

Compound/Code	Clinical status	Cancer type/target	Key features	References
Altretamine (Hexalen^®)	1990; FDA-approved	Recurrent ovarian cancer	Alkylating agent; induces DNA damage leading to apoptosis	[23]
Tretamine (Persistol)	Not FDA-approved	Anti-neoplastic	Alkylating agent induces cross-linking of DNA, thus inhibiting DNA, RNA, and protein synthesis	[29, 30]
Azacitidine (Vidaza)	2004; FDA-approved	Anti-neoplastic agent	Hypomethylation of cytosine residues in newly synthesised DNA by inhibiting DNA methyltransferase	[31]
Almitrine (Duxil)	Not FDA-approved	Respiratory stimulant	Acting as an agonist of peripheral chemoreceptors located on the carotid bodies	[32]
Enasidenib (Idhifa)	2017; FDA-approved	Refractory acute myeloid leukemia (AML), anti-leukemia	Isocitrate dehydrogenase-2 (IDH2) inhibitor	[26]
Gedatolisib	Not FDA-approved	Anti-breast cancer	PI3K/mTOR inhibitor by blocking the PI3K/Akt/mTOR (PAM) pathway	[19]
Bimiralisib	Not FDA-approved	Anti-breast cancer	Dual inhibitor of the PI3K and mTOR signaling pathways	[18]
ZSTK474	Not FDA-approved	Anti-cancer	PI3K inhibitor that targets signal transduction pathways	[27, 33]
Zandelisib	Not FDA-approved	Indolent B-cell non-Hodgkin lymphoma (iB-NHL)	Inhibitor of the PI3K delta pathway	[34]
Melarsoprol (Arsobal)	Not FDA-approved	Anti-trypanosomiasis	Inhibits parasitic glycolysis	[35]
Tretazicar (Prolarix) (CB1954 prodrug activator)	Not FDA-approved	Anticancer prodrug, anti-Leishmanial	s-Triazine derivative used as an enzyme-activated prodrug system, inhibits DNA replication after activation	[36]
Bendamustine-triazine hybrids (Treanda)	2008; FDA-approved	Leukemia, lymphoma	Combines alkylating function with triazine core for enhanced cytotoxicity	[37, 38]

Return to article view

PI3K: phosphoinositide 3-kinases; mTOR: mammalian target of rapamycin.

Declarations

Acknowledgments

The author Ihab Shawish would like to acknowledge Prince Sultan University for the support.

Author contributions

AEF, FA, and BGT: Conceptualization, Investigation, Validation, Supervision, Writing—original draft, Writing—review & editing. AS: Conceptualization, Investigation, Writing—original draft, Writing—review & editing. IS and AK: Writing—original draft, Writing—review & editing. All authors read and approved the submitted version.

Conflicts of interest

Fernando Albericio, who is the Editor-in-Chief and Guest Editor of Exploration of Drug Science; Beatriz G. de la Torre, who is the Associate Editor of Exploration of Drug Science; Ayman El-Faham, who is the Associate Editor and Guest Editor of Exploration of Drug Science, had no involvement in the decision-making or the review process of this manuscript. The other authors declare no conflicts of interest. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

Not applicable.

Copyright

Publisher’s note

Open Exploration maintains a neutral stance on jurisdictional claims in published institutional affiliations and maps. All opinions expressed in this article are the personal views of the author(s) and do not represent the stance of the editorial team or the publisher.

References

Sharma A, Sheyi R, de la Torre BG, El-Faham A, Albericio F. s-Triazine: A Privileged Structure for Drug Discovery and Bioconjugation. Molecules. 2021;26:864. [DOI] [PubMed] [PMC]

Davidson MW, Boykin DW Jr. Synthesis of as-triazines as potential antiviral agents. J Pharm Sci. 1978;67:737–9. [DOI] [PubMed]

Tang X, Su S, Chen M, He J, Xia R, Guo T, et al. Novel chalcone derivatives containing a 1,2,4-triazine moiety: design, synthesis, antibacterial and antiviral activities. RSC Adv. 2019;9:6011–20. [DOI] [PubMed] [PMC]

Xing J, Yao C, Xu Y, Yang G, Shi L. Synthesis, characterization, and antiviral activity of 1,3,5-triazine derivatives as potential PIKfyve inhibitor. J Saudi Chem Soc. 2025;29:15. [DOI]

Shah DR, Modh RP, Chikhalia KH. Privileged s-triazines: structure and pharmacological applications. Future Med Chem. 2014;6:463–77. [DOI] [PubMed]

Ali MI, Naseer MM. Recent biological applications of heterocyclic hybrids containing s-triazine scaffold. RSC Adv. 2023;13:30462–90. [DOI] [PubMed] [PMC]

Blotny G. Recent applications of 2,4,6-trichloro-1,3,5-triazine and its derivatives in organic synthesis. Tetrahedron. 2006;62:9507–22. [DOI]

Sethiya A, Jangid DK, Pradhan J, Agarwal S. Role of cyanuric chloride in organic synthesis: A concise overview. J Heterocycl Chem. 2023;60:1495–516. [DOI]

Banerjee B, Priya A, Kaur J, Kaur M, Singh A, Sharma A. Cyanuric chloride promoted various organic transformations. Synth Commun. 2023;53:855–82. [DOI]

10.

Sharma A, Sheyi R, Kumar A, El-Faham A, de la Torre BG, Albericio F. Investigating Triorthogonal Chemoselectivity. Effect of Azide Substitution on the Triazine Core. Org Lett. 2019;21:7888–92. [DOI] [PubMed]

11.

Sheyi R, Sharma A, El-Faham A, de la Torre BG, Albericio F. Phenol as a Modulator in the Chemical Reactivity of TCT: Rules of the Game II. Aust J Chem. 2020;73:352–6. [DOI]

12.

Sheyi R, Sharma A, Kumar A, El-Faham A, de la Torre BG, Albericio F. 1, 3, 5-Triazine as core for the preparation of dendrons. Arkivoc. 2020;iii:64–73. [DOI]

13.

Shukla A, Devine MD. Chapter 9 - Basis of Crop Selectivity and Weed Resistance to Triazine Herbicides. In: LeBaron HM, McFarland JE, Burnside OC, editors. The Triazine Herbicides. San Diego: Elsevier; 2008. pp. 111–8. [DOI]

14.

Liu X, Zheng C, Xiao J, Ye J, Liu C, Wang S, et al. Novel bipolar host materials based on 1,3,5-triazine derivatives for highly efficient phosphorescent OLEDs with extremely low efficiency roll-off. Phys Chem Chem Phys. 2012;14:14255–61. [DOI]

15.

Zassowski P, Ledwon P, Kurowska A, Herman AP, Lapkowski M, Cherpak V, et al. 1,3,5-Triazine and carbazole derivatives for OLED applications. Dyes Pigments. 2018;149:804–11. [DOI]

16.

Dash MK, Das S, Giri S, Chandra De G, Roymahapatra G. Comprehensive in silico study on lithiated Triazine isomers and its H₂storage efficiency. J Indian Chem Soc. 2021;98:100134. [DOI]

17.

Bag A, Chandra De G, Bhattacharyya S, Bepari B, Das HS, Bandaru S, et al. Ag(I) decorated isomeric triazine complexes as efficient hydrogen storage materials - A theoretical investigation. Chem Inorg Mater. 2025;5:100093. [DOI]

18.

Dai Q, Sun Q, Ouyang X, Liu J, Jin L, Liu A, et al. Antitumor Activity of s-Triazine Derivatives: A Systematic Review. Molecules. 2023;28:4278. [DOI] [PubMed] [PMC]

19.

Shor RE, Dai J, Lee SY, Pisarsky L, Matei I, Lucotti S, et al. The PI3K/mTOR inhibitor Gedatolisib eliminates dormant breast cancer cells in organotypic culture, but fails to prevent metastasis in preclinical settings. Mol Oncol. 2022;16:130–47. [DOI] [PubMed] [PMC]

20.

Dong G, Jiang Y, Zhang F, Zhu F, Liu J, Xu Z. Recent updates on 1,2,3-, 1,2,4-, and 1,3,5-triazine hybrids (2017-present): The anticancer activity, structure-activity relationships, and mechanisms of action. Arch Pharm (Weinheim). 2023;356:e2200479. [DOI] [PubMed]

21.

Ashadul Sk M, K H, Matada GSP, Pal R, B V M, Mounika S, et al. Current developments in PI3K-based anticancer agents: Designing strategies, biological activity, selectivity, structure-activity correlation, and docking insight. Bioorg Chem. 2025;154:108011. [DOI] [PubMed]

22.

Canh Pham E, Thi Le BN, Ngo AM, Vong LB, Truong TN. Symmetrical di-substituted phenylamino-s-triazine derivatives as anticancer agents: in vitro and in silico approach. RSC Adv. 2025;15:9968–84. [DOI] [PubMed] [PMC]

23.

Hansen LA, Hughes TE. Altretamine. DICP. 1991;25:146–52. [DOI] [PubMed]

24.

Damia G, D’Incalci M. Clinical pharmacokinetics of altretamine. Clin Pharmacokinet. 1995;28:439–48. [DOI] [PubMed]

25.

Kim ES. Enasidenib: First Global Approval. Drugs. 2017;77:1705–11. [DOI] [PubMed]

26.

Del Principe MI, Paterno G, Palmieri R, Maurillo L, Buccisano F, Venditti A. An evaluation of enasidenib for the treatment of acute myeloid leukemia. Expert Opin Pharmacother. 2019;20:1935–42. [DOI] [PubMed]

27.

Vanhaesebroeck B, Perry MWD, Brown JR, André F, Okkenhaug K. PI3K inhibitors are finally coming of age. Nat Rev Drug Discov. 2021;20:741–69. [DOI] [PubMed] [PMC]

28.

Junaid A, Lim FPL, Tiekink ERT, Dolzhenko AV. New One-Pot Synthesis of 1,3,5-Triazines: Three-Component Condensation, Dimroth Rearrangement, and Dehydrogenative Aromatization. ACS Comb Sci. 2019;21:548–55. [DOI] [PubMed]

29.

Todd I. Drug therapy of cancer. Br J Cancer. 1973;28:102. [DOI]

30.

Chabner BA, Amrein PC, Druker BJ, Michaelson MD, Mitsiades CS, Goss PE. Antineoplastic agents. In: Brunton LL, Lazo JS, Parker KL, editors. Goodman and Gilman’s the pharmacological basis of therapeutics. 11th ed. New York: McGraw-Hill; 2006. pp. 1352–4.

31.

Siddiqui MA, Scott LJ. Azacitidine: in myelodysplastic syndromes. Drugs. 2005;65:1781–9; discussion 1790. [DOI] [PubMed]

32.

Golder FJ, Hewitt MM, McLeod JF. Respiratory stimulant drugs in the post-operative setting. Respir Physiol Neurobiol. 2013;189:395–402. [DOI] [PubMed]

33.

Kong DX, Yamori T. ZSTK474, a novel phosphatidylinositol 3-kinase inhibitor identified using the JFCR39 drug discovery system. Acta Pharmacol Sin. 2010;31:1189–97. [DOI] [PubMed] [PMC]

34.

Pagel JM, Soumerai JD, Reddy N, Jagadeesh D, Stathis A, Asch A, et al. Zandelisib with continuous or intermittent dosing as monotherapy or in combination with rituximab in patients with relapsed or refractory B-cell malignancy: a multicentre, first-in-patient, dose-escalation and dose-expansion, phase 1b trial. Lancet Oncol. 2022;23:1021–30. [DOI]

35.

Nok AJ. Arsenicals (melarsoprol), pentamidine and suramin in the treatment of human African trypanosomiasis. Parasitol Res. 2003;90:71–9. [DOI] [PubMed]

36.

Sarker D, Anderson D, Spanswick VJ, Davies S, Agarwal R, Aitken G, et al. Preliminary results of a Cancer Research UK phase I trial combining the dinitrobenzamide prodrug CB1954 (tretazicar) and the NQO2 substrate EP-0152R (caricotamide) intravenously (IV) every 3 weeks. J Clin Oncol. 2008;26:2505. [DOI]

37.

Balfour JA, Goa KL. Bendamustine. Drugs. 2001;61:631–8; discussion 639. [DOI] [PubMed]

38.

Cheson BD, Rummel MJ. Bendamustine: rebirth of an old drug. J Clin Oncol. 2009;27:1492–501. [DOI] [PubMed]

39.

Oudir S, Rigo B, Hénichart J-P, Gautret P. A Convenient Method for the Conversion of a Carboxy Group into a 4,6-Dimethoxy-1,3,5-triazine Group: Application to N-Benzylpyroglutamic Acids. Synthesis. 2006;2006:2845–8. [DOI]

40.

Pinner A. Ueber diphenyloxykyanidin. Ber Dtsch Chem Ges. 1890;23:2919–22. [DOI]

41.

Shie JJ, Fang JM. Microwave-assisted one-pot tandem reactions for direct conversion of primary alcohols and aldehydes to triazines and tetrazoles in aqueous media. J Org Chem. 2007;72:3141–4. [DOI] [PubMed]

42.

Simons JK, Saxton MR. Benzoguanamine: s-Triazine, 2, 4-diamino-6-phenyl-. In: Organic Syntheses. John Wiley & Sons, Inc.; 2003. p. 13. [DOI]

43.

Łażewska D, Więcek M, Ner J, Kamińska K, Kottke T, Schwed JS, et al. Aryl-1,3,5-triazine derivatives as histamine H4 receptor ligands. Eur J Med Chem. 2014;83:534–46. [DOI] [PubMed]

44.

Kuo GH, Deangelis A, Emanuel S, Wang A, Zhang Y, Connolly PJ, et al. Synthesis and identification of [1,3,5]triazine-pyridine biheteroaryl as a novel series of potent cyclin-dependent kinase inhibitors. J Med Chem. 2005;48:4535–46. [DOI] [PubMed]

45.

Hodous BL, Geuns-Meyer SD, Hughes PE, Albrecht BK, Bellon S, Caenepeel S, et al. Synthesis, structural analysis, and SAR studies of triazine derivatives as potent, selective Tie-2 inhibitors. Bioorg Med Chem Lett. 2007;17:2886–9. [DOI] [PubMed]

46.

Hodous BL, inventor; Blueprint Medicines Corp, assignee. Compositions useful for treating disorders related to kit. United States patent US 9944651B2. 2018 Apr 17.

47.

Scholz A, inventor; Bayer Pharma AG, assignee. Use of 4-(4-fluoro-2-methoxyphenyl)-n-{3-[(s-methylsulfonimidoyl)methyl]phenyl}-1,3,5-triazin-2-amine for treating multiple myeloma. United States patent US 20180078560A1. 2018 Mar 22.

48.

Lücking U, inventor; Bayer Intellectual Property GmbH, assignee. 4-aryl-N-phenyl-1,3,5-triazin-2-amines containing a sulfoximine group. United States patent US 9669034B2. 2017 Jun 6.

49.

Hu Z, Ma T, Chen Z, Ye Z, Zhang G, Lou Y, et al. Solid-phase synthesis and antitumor evaluation of 2,4-diamino-6-aryl-1,3,5-triazines. J Comb Chem. 2009;11:267–73. [DOI] [PubMed]

50.

El-Faham A, Soliman SM, Ghabbour HA, Elnakady YA, Mohaya TA, Siddiqui MRH, et al. Ultrasonic promoted synthesis of novel s-triazine-Schiff base derivatives; molecular structure, spectroscopic studies and their preliminary anti-proliferative activities. J Mol Struct. 2016;1125:121–35. [DOI]

51.

Sharma A, Ghabbour H, Khan ST, de la Torre BG, Albericio F, El-Faham A. Novel pyrazolyl-s-triazine derivatives, molecular structure and antimicrobial activity. J Mol Struct. 2017;1145:244–53. [DOI]

52.

Al Rasheed H, Dahlous K, Sharma A, Sholkamy E, El-Faham A, de la Torre BG, et al. Barbiturate- and Thiobarbituarte-Based s-Triazine Hydrazone Derivatives with Promising Antiproliferative Activities. ACS Omega. 2020;5:15805–11. [DOI] [PubMed] [PMC]

53.

Al-Rasheed HH, Al-Khamis SA, Barakat A, Masoud AA, Sobhy AA, Ghareeb DA, et al. Design and synthesis of s-triazine-Isatin hybrids with potent anticancer activity, targeting A549 lung adenocarcinoma via EGF inhibition. Tetrahedron. 2025;171:134424. [DOI]

54.

Shawish I, Nafie MS, Barakat A, Aldalbahi A, Al-Rasheed HH, Ali M, et al. Pyrazolyl-s-triazine with indole motif as a novel of epidermal growth factor receptor/cyclin-dependent kinase 2 dual inhibitors. Front Chem. 2022;10:1078163. [DOI] [PubMed] [PMC]

55.

Lee T, Seo YH. Targeting the hydrophobic region of Hsp90’s ATP binding pocket with novel 1,3,5-triazines. Bioorg Med Chem Lett. 2013;23:6427–31. [DOI] [PubMed]

56.

Miura T, Fukami TA, Hasegawa K, Ono N, Suda A, Shindo H, et al. Lead generation of heat shock protein 90 inhibitors by a combination of fragment-based approach, virtual screening, and structure-based drug design. Bioorg Med Chem Lett. 2011;21:5778–83. [DOI] [PubMed]

57.

Wang Y, Tang X, Yi L. Design and Discovery of Novel 1,3,5-Triazines as Dipeptidyl Peptidase-4 Inhibitor against Diabetes. Pharmacology. 2019;103:273–81. [DOI] [PubMed]

58.

Farooq M, Sharma A, Almarhoon Z, Al-Dhfyan A, El-Faham A, Taha NA, et al. Design and synthesis of mono-and di-pyrazolyl-s-triazine derivatives, their anticancer profile in human cancer cell lines, and in vivo toxicity in zebrafish embryos. Bioorg Chem. 2019;87:457–64. [DOI] [PubMed]

59.

Shawish I, Barakat A, Aldalbahi A, Malebari AM, Nafie MS, Bekhit AA, et al. Synthesis and Antiproliferative Activity of a New Series of Mono- and Bis(dimethylpyrazolyl)-s-triazine Derivatives Targeting EGFR/PI3K/AKT/mTOR Signaling Cascades. ACS Omega. 2022;7:24858–70. [DOI] [PubMed] [PMC]

60.

Suda A, Koyano H, Hayase T, Hada K, Kawasaki K, Komiyama S, et al. Design and synthesis of novel macrocyclic 2-amino-6-arylpyrimidine Hsp90 inhibitors. Bioorg Med Chem Lett. 2012;22:1136–41. [DOI] [PubMed]

61.

Suda A, Kawasaki K, Komiyama S, Isshiki Y, Yoon DO, Kim SJ, et al. Design and synthesis of 2-amino-6-(1H,3H-benzo[de]isochromen-6-yl)-1,3,5-triazines as novel Hsp90 inhibitors. Bioorg Med Chem. 2014;22:892–905. [DOI] [PubMed]

62.

Baindur N, Chadha N, Brandt BM, Asgari D, Patch RJ, Schalk-Hihi C, et al. 2-Hydroxy-4,6-diamino-[1,3,5]triazines: a novel class of VEGF-R2 (KDR) tyrosine kinase inhibitors. J Med Chem. 2005;48:1717–20. [DOI] [PubMed]

63.

Saczewski F, Bułakowska A. Synthesis, structure and anticancer activity of novel alkenyl-1,3,5-triazine derivatives. Eur J Med Chem. 2006;41:611–5. [DOI] [PubMed]

64.

Saczewski F, Bułakowska A, Bednarski P, Grunert R. Synthesis, structure and anticancer activity of novel 2,4-diamino-1,3,5-triazine derivatives. Eur J Med Chem. 2006;41:219–25. [DOI] [PubMed]

65.

Ciuffreda L, Di Sanza C, Incani UC, Milella M. The mTOR pathway: a new target in cancer therapy. Curr Cancer Drug Targets. 2010;10:484–95. [DOI] [PubMed]

66.

Peterson EA, Andrews PS, Be X, Boezio AA, Bush TL, Cheng AC, et al. Discovery of triazine-benzimidazoles as selective inhibitors of mTOR. Bioorg Med Chem Lett. 2011;21:2064–70. [DOI] [PubMed]

67.

Fresno Vara JA, Casado E, de Castro J, Cejas P, Belda-Iniesta C, González-Barón M. PI3K/Akt signalling pathway and cancer. Cancer Treat Rev. 2004;30:193–204. [DOI] [PubMed]

68.

Smith AL, D’Angelo ND, Bo YY, Booker SK, Cee VJ, Herberich B, et al. Structure-Based Design of a Novel Series of Potent, Selective Inhibitors of the Class I Phosphatidylinositol 3-Kinases. J Med Chem. 2012;55:5188–219. [DOI]

69.

Wurz RP, Liu L, Yang K, Nishimura N, Bo Y, Pettus LH, et al. Synthesis and structure-activity relationships of dual PI3K/mTOR inhibitors based on a 4-amino-6-methyl-1,3,5-triazine sulfonamide scaffold. Bioorg Med Chem Lett. 2012;22:5714–20. [DOI] [PubMed]

70.

Norman MH, Andrews KL, Bo YY, Booker SK, Caenepeel S, Cee VJ, et al. Selective class I phosphoinositide 3-kinase inhibitors: optimization of a series of pyridyltriazines leading to the identification of a clinical candidate, AMG 511. J Med Chem. 2012;55:7796–816. [DOI] [PubMed]

71.

Yaguchi S, Fukui Y, Koshimizu I, Yoshimi H, Matsuno T, Gouda H, et al. Antitumor activity of ZSTK474, a new phosphatidylinositol 3-kinase inhibitor. J Natl Cancer Inst. 2006;98:545–56. [DOI] [PubMed]

72.

Kong D, Yamori T. ZSTK474 is an ATP-competitive inhibitor of class I phosphatidylinositol 3 kinase isoforms. Cancer Sci. 2007;98:1638–42. [DOI] [PubMed] [PMC]

73.

Dan S, Okamura M, Mukai Y, Yoshimi H, Inoue Y, Hanyu A, et al. ZSTK474, a specific phosphatidylinositol 3-kinase inhibitor, induces G1 arrest of the cell cycle in vivo. Eur J Cancer. 2012;48:936–43. [DOI] [PubMed]

74.

Kong D, Okamura M, Yoshimi H, Yamori T. Antiangiogenic effect of ZSTK474, a novel phosphatidylinositol 3-kinase inhibitor. Eur J Cancer. 2009;45:857–65. [DOI] [PubMed]

75.

Rewcastle GW, Gamage SA, Flanagan JU, Frederick R, Denny WA, Baguley BC, et al. 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]-1H-benzimidazole (ZSTK474). J Med Chem. 2011;54:7105–26. [DOI] [PubMed]

76.

Richard DJ, Verheijen JC, Yu K, Zask A. Triazines incorporating (R)-3-methylmorpholine are potent inhibitors of the mammalian target of rapamycin (mTOR) with selectivity over PI3Kalpha. Bioorg Med Chem Lett. 2010;20:2654–7. [DOI] [PubMed]

77.

Verheijen JC, Richard DJ, Curran K, Kaplan J, Yu K, Zask A. 2-Arylureidophenyl-4-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)triazines as highly potent and selective ATP competitive mTOR inhibitors: optimization of human microsomal stability. Bioorg Med Chem Lett. 2010;20:2648–53. [DOI] [PubMed]

78.

Dehnhardt CM, Venkatesan AM, Chen Z, Delos-Santos E, Ayral-Kaloustian S, Brooijmans N, et al. Identification of 2-oxatriazines as highly potent pan-PI3K/mTOR dual inhibitors. Bioorg Med Chem Lett. 2011;21:4773–8. [DOI] [PubMed]

79.

Venkatesan AM, Dehnhardt CM, Delos Santos E, Chen Z, Dos Santos O, Ayral-Kaloustian S, et al. Bis(morpholino-1,3,5-triazine) derivatives: potent adenosine 5’-triphosphate competitive phosphatidylinositol-3-kinase/mammalian target of rapamycin inhibitors: discovery of compound 26 (PKI-587), a highly efficacious dual inhibitor. J Med Chem. 2010;53:2636–45. [DOI] [PubMed]

80.

Paquin I, Raeppel S, Leit S, Gaudette F, Zhou N, Moradei O, et al. Design and synthesis of 4-[(s-triazin-2-ylamino)methyl]-N-(2-aminophenyl)-benzamides and their analogues as a novel class of histone deacetylase inhibitors. Bioorg Med Chem Lett. 2008;18:1067–71. [DOI] [PubMed]

81.

Singla P, Luxami V, Paul K. Triazine-benzimidazole hybrids: anticancer activity, DNA interaction and dihydrofolate reductase inhibitors. Bioorg Med Chem. 2015;23:1691–700. [DOI] [PubMed]

82.

Zhu W, Liu Y, Zhao Y, Wang H, Tan L, Fan W, et al. Synthesis and biological evaluation of novel 6-hydrazinyl-2,4-bismorpholino pyrimidine and 1,3,5-triazine derivatives as potential antitumor agents. Arch Pharm (Weinheim). 2012;345:812–21. [DOI] [PubMed]

83.

Huang Q, Fu Q, Liu Y, Bai J, Wang Q, Liao H, et al. Design, synthesis and anticancer activity of novel 6-(aminophenyl)-2,4-bismorpholino-1,3,5-triazine derivatives bearing arylmethylene hydrazine moiety. Chem Res Chin Univ. 2014;30:257–65. [DOI]

84.

Zheng M, Xu C, Ma J, Sun Y, Du F, Liu H, et al. Synthesis and antitumor evaluation of a novel series of triaminotriazine derivatives. Bioorg Med Chem. 2007;15:1815–27. [DOI]

85.

Singla P, Luxami V, Paul K. Synthesis and in vitro evaluation of novel triazine analogues as anticancer agents and their interaction studies with bovine serum albumin. Eur J Med Chem. 2016;117:59–69. [DOI] [PubMed]

86.

Singla P, Luxami V, Paul K. Synthesis, in vitro antitumor activity, dihydrofolate reductase inhibition, DNA intercalation and structure-activity relationship studies of 1,3,5-triazine analogues. Bioorg Med Chem Lett. 2016;26:518–23. [DOI] [PubMed]

87.

Klon AE, Héroux A, Ross LJ, Pathak V, Johnson CA, Piper JR, et al. Atomic structures of human dihydrofolate reductase complexed with NADPH and two lipophilic antifolates at 1.09 a and 1.05 a resolution. J Mol Biol. 2002;320:677–93. [DOI] [PubMed]

88.

Kumar GJ, Kumar SN, Thummuri D, Adari LBS, Naidu VGM, Srinivas K, et al. Synthesis and characterization of new s-triazine bearing benzimidazole and benzothiazole derivatives as anticancer agents. Med Chem Res. 2015;24:3991–4001. [DOI]

89.

Shen TL, Park AY, Alcaraz A, Peng X, Jang I, Koni P, et al. Conditional knockout of focal adhesion kinase in endothelial cells reveals its role in angiogenesis and vascular development in late embryogenesis. J Cell Biol. 2005;169:941–52. [DOI] [PubMed] [PMC]

90.

Infusino GA, Jacobson JR. Endothelial FAK as a therapeutic target in disease. Microvasc Res. 2012;83:89–96. [DOI] [PubMed] [PMC]

91.

Dao P, Jarray R, Le Coq J, Lietha D, Loukaci A, Lepelletier Y, et al. Synthesis of novel diarylamino-1,3,5-triazine derivatives as FAK inhibitors with anti-angiogenic activity. Bioorg Med Chem Lett. 2013;23:4552–6. [DOI] [PubMed]

92.

Aromokeye R, Ackerman-Berrier M, Araujo RDC, Lambousis M, Cardoza S, Chen LC, et al. Development of a high-throughput TR-FRET assay to identify inhibitors of the FAK-paxillin protein-protein interaction. SLAS Discov. 2025;34:100237. [DOI] [PubMed] [PMC]

93.

Neckers L, Mimnaugh E, Schulte TW. Hsp90 as an anti-cancer target. Drug Resist Updat. 1999;2:165–72. [DOI] [PubMed]

94.

Zhao Z, Zhu J, Quan H, Wang G, Li B, Zhu W, et al. X66, a novel N-terminal heat shock protein 90 inhibitor, exerts antitumor effects without induction of heat shock response. Oncotarget. 2016;7:29648–63. [DOI] [PubMed] [PMC]

95.

Chalermnon M, Cherdchom S, Sereemaspun A, Rojanathanes R, Khotavivattana T. Biguanide-Based Synthesis of 1,3,5-Triazine Derivatives with Anticancer Activity and 1,3,5-Triazine Incorporated Calcium Citrate Nanoparticles. Molecules. 2021;26:1028. [DOI] [PubMed] [PMC]

96.

Chalermnon M. Synthesis and encapsulation of 1,3,5-triazine derivatives as anticancer agent [dissertation]. Bangkok: Chulalongkorn University; 2020. [DOI]

97.

Moreno LM, Quiroga J, Abonia R, Lauria A, Martorana A, Insuasty H, et al. Synthesis, biological evaluation, and in silico studies of novel chalcone- and pyrazoline-based 1,3,5-triazines as potential anticancer agents. RSC Adv. 2020;10:34114–29. [DOI] [PubMed] [PMC]

98.

Arya K, Dandia A. Synthesis and cytotoxic activity of trisubstituted-1,3,5-triazines. Bioorg Med Chem Lett. 2007;17:3298–304. [DOI] [PubMed]

99.

Wróbel A, Kolesińska B, Frączyk J, Kamiński ZJ, Tankiewicz-Kwedlo A, Hermanowicz J, et al. Synthesis and cellular effects of novel 1,3,5-triazine derivatives in DLD and Ht-29 human colon cancer cell lines. Invest New Drugs. 2020;38:990–1002. [DOI] [PubMed] [PMC]