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16.09.2024 | Original Paper

Azamollugin, a mollugin derivative, has inhibitory activity on MyD88- and TRIF-dependent pathways

verfasst von: Yuki Nakajima, Hitomi Nishino, Kazunori Takahashi, Alfarius Eko Nugroho, Yusuke Hirasawa, Toshio Kaneda, Hiroshi Morita

Erschienen in: Journal of Natural Medicines | Ausgabe 1/2025

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Abstract

Previously, we reported that azamollugin, an aza-derivative of mollugin, exhibited potent inhibitory activity on NO production in LPS-stimulated RAW 264.7 cells. Further investigations in this study revealed that azamollugin not only suppressed iNOS gene expression regulated by NF-κB, but also inhibited LPS-induced IFN-β expression, which is known to be regulated by IRF3. Azamollugin exhibited an inhibitory activity on LPS-induced IRAK1 activation, suggesting inhibitory effect on the MyD88-dependent pathway. Furthermore, azamollugin inhibited LPS-induced phosphorylation of IRF3 and its upstream factor, TBK1/IKKε, suggesting an inhibitory effect on the TRIF-dependent pathway via TLR4. In addition, azamollugin also suppressed poly(I:C)-induced phosphorylation of TBK1 and IRF3, suggesting an inhibitory effect on the TRIF-dependent pathway via TLR3. These results suggest that azamollugin has inhibitory activity against both the MyD88-dependent and TRIF-dependent pathways, respectively.

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Literatur
1.
Zurück zum Zitat Itokawa H, Qiao Y, Takeya K (1989) Anthraquinones and naphthohydroquinones from Rubia cordifolia. Phytochemistry 28:3465–3468CrossRef Itokawa H, Qiao Y, Takeya K (1989) Anthraquinones and naphthohydroquinones from Rubia cordifolia. Phytochemistry 28:3465–3468CrossRef
2.
Zurück zum Zitat Itokawa H, Mihara K, Takeya K (1983) Studies on a novel anthraquinone and its glycosides isolated from Rubia cordifolia and R. akane. Chem Pharm Bull 31:2353–2358CrossRef Itokawa H, Mihara K, Takeya K (1983) Studies on a novel anthraquinone and its glycosides isolated from Rubia cordifolia and R. akane. Chem Pharm Bull 31:2353–2358CrossRef
3.
Zurück zum Zitat Kawasaki Y, Goda Y, Yoshihira K (1992) The mutagenic constituents of Rubia tinctorum. Chem Pharm Bull 40:1504–1509CrossRef Kawasaki Y, Goda Y, Yoshihira K (1992) The mutagenic constituents of Rubia tinctorum. Chem Pharm Bull 40:1504–1509CrossRef
4.
Zurück zum Zitat Dosseh C, Tessier AM, Delaveau P (1981) Rubia cordifolia roots. II: New quinones. Planta Med 43:141–147PubMedCrossRef Dosseh C, Tessier AM, Delaveau P (1981) Rubia cordifolia roots. II: New quinones. Planta Med 43:141–147PubMedCrossRef
5.
Zurück zum Zitat Wang SX, Hua HM, Wu LJ, Li X, Zhu TR (1992) Studies on anthraquinones from the roots of Rubia cordifolia L. Acta Pharm Sin 27:743–747 Wang SX, Hua HM, Wu LJ, Li X, Zhu TR (1992) Studies on anthraquinones from the roots of Rubia cordifolia L. Acta Pharm Sin 27:743–747
6.
Zurück zum Zitat Lee JE, Hitotsuyanagi Y, Kim IH, Hasuda T, Takeya K (2008) A novel bicyclic hexapeptide, RA-XVIII, from Rubia cordifolia: Structure, semisynthesis, and cytotoxicity. Bioorg Med Chem Lett 18:808–811PubMedCrossRef Lee JE, Hitotsuyanagi Y, Kim IH, Hasuda T, Takeya K (2008) A novel bicyclic hexapeptide, RA-XVIII, from Rubia cordifolia: Structure, semisynthesis, and cytotoxicity. Bioorg Med Chem Lett 18:808–811PubMedCrossRef
7.
Zurück zum Zitat Hitotsuyanagi Y, Hasuda T, Aihara T, Ishikawa H, Yamaguchi K, Itokawa H, Takeya K (2004) Synthesis of [Gly-1]RA-VII, [Gly-2]RA-VII, and [Gly-4]RA-VII. Glycine-containing analogues of RA-VII, an antitumor bicyclic hexapeptide from Rubia plants. J Org Chem 69:1481–1486PubMedCrossRef Hitotsuyanagi Y, Hasuda T, Aihara T, Ishikawa H, Yamaguchi K, Itokawa H, Takeya K (2004) Synthesis of [Gly-1]RA-VII, [Gly-2]RA-VII, and [Gly-4]RA-VII. Glycine-containing analogues of RA-VII, an antitumor bicyclic hexapeptide from Rubia plants. J Org Chem 69:1481–1486PubMedCrossRef
8.
Zurück zum Zitat Hitotsuyanagi Y, Hirai M, Odagiri M, Komine M, Hasuda T, Fukaya H, Takeya K (2019) RA-XXV and RA-XXVI, bicyclic hexapeptides from Rubia cordifolia L.: Structure, synthesis, and conformation. Chem Asian J 14:205–215PubMedCrossRef Hitotsuyanagi Y, Hirai M, Odagiri M, Komine M, Hasuda T, Fukaya H, Takeya K (2019) RA-XXV and RA-XXVI, bicyclic hexapeptides from Rubia cordifolia L.: Structure, synthesis, and conformation. Chem Asian J 14:205–215PubMedCrossRef
9.
Zurück zum Zitat Hitotsuyanagi Y, Odagiri M, Kato S, Kusano J, Hasuda T, Fukaya H, Takeya K (2012) Isolation, structure determination, and synthesis of allo-RA-V and neo-RAV, RA-series bicyclic peptides from Rubia cordifolia L. Chemistry 18:2839–2846PubMedCrossRef Hitotsuyanagi Y, Odagiri M, Kato S, Kusano J, Hasuda T, Fukaya H, Takeya K (2012) Isolation, structure determination, and synthesis of allo-RA-V and neo-RAV, RA-series bicyclic peptides from Rubia cordifolia L. Chemistry 18:2839–2846PubMedCrossRef
10.
Zurück zum Zitat Ho LK, Don MJ, Chen HC, Yeh SF, Chen JM (1996) Inhibition of Hepatitis B surface antigen secretion on human hepatoma cells. components from Rubia cordifolia. J Nat Prod 59:330–333PubMedCrossRef Ho LK, Don MJ, Chen HC, Yeh SF, Chen JM (1996) Inhibition of Hepatitis B surface antigen secretion on human hepatoma cells. components from Rubia cordifolia. J Nat Prod 59:330–333PubMedCrossRef
11.
Zurück zum Zitat Itokawa H, Ibraheim Z, Qiao Y, Takeya K (1993) Anthraquinones, naphthohydroquinones and naphthohydroquinone dimers from Rubia cordifolia and their cytotoxic activity. Chem Pharm Bull 41:1869–1872CrossRef Itokawa H, Ibraheim Z, Qiao Y, Takeya K (1993) Anthraquinones, naphthohydroquinones and naphthohydroquinone dimers from Rubia cordifolia and their cytotoxic activity. Chem Pharm Bull 41:1869–1872CrossRef
12.
Zurück zum Zitat Son JK, Jung SJ, Jung JH, Fang Z, Lee CS, Seo CS, Moon DC, Min BS, Kim MR, Woo MH (2008) Anticancer constituents from the roots of Rubia cordifolia L. Chem Pharm Bull 56:213–216CrossRef Son JK, Jung SJ, Jung JH, Fang Z, Lee CS, Seo CS, Moon DC, Min BS, Kim MR, Woo MH (2008) Anticancer constituents from the roots of Rubia cordifolia L. Chem Pharm Bull 56:213–216CrossRef
13.
Zurück zum Zitat Kim KJ, Lee JS, Kwak MK, Choi HG, Yong CS, Kim JA, Lee YR, Lyoo WS, Park Y-J (2009) Anti-inflammatory action of mollugin and its synthetic derivatives in HT-29 human colonic epithelial cells is mediated through inhibition of NF-κB activation. Eur J Pharmacol 622:52–57PubMedCrossRef Kim KJ, Lee JS, Kwak MK, Choi HG, Yong CS, Kim JA, Lee YR, Lyoo WS, Park Y-J (2009) Anti-inflammatory action of mollugin and its synthetic derivatives in HT-29 human colonic epithelial cells is mediated through inhibition of NF-κB activation. Eur J Pharmacol 622:52–57PubMedCrossRef
14.
Zurück zum Zitat Jeong GS, Lee DS, Kim DC, Jahng Y, Son JK, Lee SH, Kim YC (2011) Neuroprotective and anti-inflammatory effects of mollugin via up-regulation of heme oxygenase-1 in mouse hippocampal and microglial cells. Eur J Pharmacol 654:226–234PubMedCrossRef Jeong GS, Lee DS, Kim DC, Jahng Y, Son JK, Lee SH, Kim YC (2011) Neuroprotective and anti-inflammatory effects of mollugin via up-regulation of heme oxygenase-1 in mouse hippocampal and microglial cells. Eur J Pharmacol 654:226–234PubMedCrossRef
15.
Zurück zum Zitat Zhu ZG, Jin H, Yu PJ, Tian YX, Zhang JJ, Wu SG (2013) Mollugin inhibits the inflammatory response in lipopolysaccharide-stimulated RAW264.7 macrophages by blocking the janus kinase-signal transducers and activators of transcription signaling pathway. Biol Pharm Bull 36:399–406PubMedCrossRef Zhu ZG, Jin H, Yu PJ, Tian YX, Zhang JJ, Wu SG (2013) Mollugin inhibits the inflammatory response in lipopolysaccharide-stimulated RAW264.7 macrophages by blocking the janus kinase-signal transducers and activators of transcription signaling pathway. Biol Pharm Bull 36:399–406PubMedCrossRef
16.
Zurück zum Zitat Do MT, Hwang YP, Kim HG, Na M, Jeong HG (2013) Mollugin inhibits proliferation and induces apoptosis by suppressing fatty acid synthase in HER2-overexpressing cancer cells. J Cell Physio 228:1087–1097CrossRef Do MT, Hwang YP, Kim HG, Na M, Jeong HG (2013) Mollugin inhibits proliferation and induces apoptosis by suppressing fatty acid synthase in HER2-overexpressing cancer cells. J Cell Physio 228:1087–1097CrossRef
17.
Zurück zum Zitat Zhang L, Wang H, Zhu J, Xu J, Ding K (2014) Mollugin induces tumor cell apoptosis and autophagy via the PI3K/AKT/mTOR/p70S6 K and ERK signaling pathways. Biochem Biophys Res Commun 450:247–254PubMedCrossRef Zhang L, Wang H, Zhu J, Xu J, Ding K (2014) Mollugin induces tumor cell apoptosis and autophagy via the PI3K/AKT/mTOR/p70S6 K and ERK signaling pathways. Biochem Biophys Res Commun 450:247–254PubMedCrossRef
18.
Zurück zum Zitat Baek JM, Kim JY, Jung Y, Moon SH, Choi MK, Kim SH, Lee MS, Kim I, Oh J (2015) Mollugin from Rubea cordifolia suppresses receptor activator of nuclear factor-κB ligand-induced osteoclastogenesis and bone resorbing activity in vitro and prevents lipopolysaccharide-induced bone loss in vivo. Phytomedicine 22:27–35PubMedCrossRef Baek JM, Kim JY, Jung Y, Moon SH, Choi MK, Kim SH, Lee MS, Kim I, Oh J (2015) Mollugin from Rubea cordifolia suppresses receptor activator of nuclear factor-κB ligand-induced osteoclastogenesis and bone resorbing activity in vitro and prevents lipopolysaccharide-induced bone loss in vivo. Phytomedicine 22:27–35PubMedCrossRef
19.
Zurück zum Zitat Han L, Yong FL, Hong Z, Jiang MH, Hong ML, Shou JL (2021) synthesis and antitumor activity of 1-substituted 1,2,3-Triazole-Mollugin derivatives. Molecules 26:3249CrossRef Han L, Yong FL, Hong Z, Jiang MH, Hong ML, Shou JL (2021) synthesis and antitumor activity of 1-substituted 1,2,3-Triazole-Mollugin derivatives. Molecules 26:3249CrossRef
20.
Zurück zum Zitat Zhang LH, Li MY, Wang DY, Jin XJ, Chen FE, Piao HR (2022) synthesis and evaluation of NF-κB inhibitory activity of Mollugin derivatives. Molecules 27:7925PubMedPubMedCentralCrossRef Zhang LH, Li MY, Wang DY, Jin XJ, Chen FE, Piao HR (2022) synthesis and evaluation of NF-κB inhibitory activity of Mollugin derivatives. Molecules 27:7925PubMedPubMedCentralCrossRef
21.
Zurück zum Zitat Morita H, Nishino H, Nakajima Y, Kakubari Y, Nakata A, Deguchi J, Alfarius EN, Hirasawa Y, Kaneda T, Kawasaki Y, Goda Y (2015) Oxomollugin, a potential inhibitor of lipopolysaccharide-induced nitric oxide production including nuclear factor kappa B signals. J Nat Med 69:608–611PubMedCrossRef Morita H, Nishino H, Nakajima Y, Kakubari Y, Nakata A, Deguchi J, Alfarius EN, Hirasawa Y, Kaneda T, Kawasaki Y, Goda Y (2015) Oxomollugin, a potential inhibitor of lipopolysaccharide-induced nitric oxide production including nuclear factor kappa B signals. J Nat Med 69:608–611PubMedCrossRef
22.
Zurück zum Zitat Nakajima Y, Tsuboi N, Katori K, Waili M, Nugroho AE, Takahashi K, Nishino H, Hirasawa Y, Kawasaki Y, Goda Y, Kaneda T, Morita H (2024) Oxomollugin, an oxidized substance in mollugin, inhibited LPS-induced NF-κB activation via the suppressive effects on essential activation factors of TLR4 signaling. J Nat Med 78:568–575PubMedCrossRef Nakajima Y, Tsuboi N, Katori K, Waili M, Nugroho AE, Takahashi K, Nishino H, Hirasawa Y, Kawasaki Y, Goda Y, Kaneda T, Morita H (2024) Oxomollugin, an oxidized substance in mollugin, inhibited LPS-induced NF-κB activation via the suppressive effects on essential activation factors of TLR4 signaling. J Nat Med 78:568–575PubMedCrossRef
23.
Zurück zum Zitat Kawai T, Akira S (2010) The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol 11:373–384PubMedCrossRef Kawai T, Akira S (2010) The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol 11:373–384PubMedCrossRef
24.
Zurück zum Zitat Tanimura N, Saitoh S, Matsumoto F, Akashi-Takamura S, Miyake K (2008) Roles for LPS-dependent interaction and relocation of TLR4 and TRAM in TRIF-signaling. Brioche Biophys Res Commun 368:94–99CrossRef Tanimura N, Saitoh S, Matsumoto F, Akashi-Takamura S, Miyake K (2008) Roles for LPS-dependent interaction and relocation of TLR4 and TRAM in TRIF-signaling. Brioche Biophys Res Commun 368:94–99CrossRef
25.
Zurück zum Zitat Nishino H, Nakajima Y, Kakubari Y, Asami N, Deguchi J, Nugroho AE, Hirasawa Y, Kaneda T, Kawasaki Y, Goda Y, Morita H (2016) Syntheses and anti-inflammatory activity of azamollugin derivatives. Bioorg Med Chem Lett 26:524–525PubMedCrossRef Nishino H, Nakajima Y, Kakubari Y, Asami N, Deguchi J, Nugroho AE, Hirasawa Y, Kaneda T, Kawasaki Y, Goda Y, Morita H (2016) Syntheses and anti-inflammatory activity of azamollugin derivatives. Bioorg Med Chem Lett 26:524–525PubMedCrossRef
26.
Zurück zum Zitat Kinoshita E, Kinoshita-Kikuta E, Takiyama K, Koike T (2006) Phosphate-binding tag, a new tool to visualize phosphorylated proteins. Mol Cell Proteomics 5:749–757PubMedCrossRef Kinoshita E, Kinoshita-Kikuta E, Takiyama K, Koike T (2006) Phosphate-binding tag, a new tool to visualize phosphorylated proteins. Mol Cell Proteomics 5:749–757PubMedCrossRef
27.
Zurück zum Zitat Hatti I, Sreenivasulu R, Jadav S, Jayaprakash V, Kumar CG, Raju R (2015) Synthesis, cytotoxic activity and docking studies of new 4-aza-podophyllotoxin derivatives. Med Chem Res 24:3305–3313CrossRef Hatti I, Sreenivasulu R, Jadav S, Jayaprakash V, Kumar CG, Raju R (2015) Synthesis, cytotoxic activity and docking studies of new 4-aza-podophyllotoxin derivatives. Med Chem Res 24:3305–3313CrossRef
28.
Zurück zum Zitat Hitotsuyanagi Y, Fukuyo M, Tsuda K, Kobayashi M, Ozeki A, Itokawa H, Takeya K (2000) 4-Aza-2,3-dehydro-4-deoxypodophyllotoxins: simple aza-podophyllotoxin analogues possessing potent cytotoxicity. Bioorg Med Chem Lett 10:315–317PubMedCrossRef Hitotsuyanagi Y, Fukuyo M, Tsuda K, Kobayashi M, Ozeki A, Itokawa H, Takeya K (2000) 4-Aza-2,3-dehydro-4-deoxypodophyllotoxins: simple aza-podophyllotoxin analogues possessing potent cytotoxicity. Bioorg Med Chem Lett 10:315–317PubMedCrossRef
29.
Zurück zum Zitat Le Nguyen T, De Borggraeve WM, Grellier P, Pham VC, Dehaen W, Nguyen VH (2014) Synthesis of 11-aza-artemisinin derivatives using the Ugi reaction and an evaluation of their antimalarial activity. Tetrahedron Lett 55:4892–4894CrossRef Le Nguyen T, De Borggraeve WM, Grellier P, Pham VC, Dehaen W, Nguyen VH (2014) Synthesis of 11-aza-artemisinin derivatives using the Ugi reaction and an evaluation of their antimalarial activity. Tetrahedron Lett 55:4892–4894CrossRef
30.
Zurück zum Zitat Fujita Y, Islam R, Sakai K, Kaneda H, Kudo K, Tamura D, Aomatsu K, Nagai T, Kimura H, Matsumoto K, de Velasco M, Arao T, Okawara T, Nishio K (2012) Aza-derivatives of resveratrol are potent macrophage migration inhibitory factor inhibitors. Invest New Drugs 30:1878–1886PubMedCrossRef Fujita Y, Islam R, Sakai K, Kaneda H, Kudo K, Tamura D, Aomatsu K, Nagai T, Kimura H, Matsumoto K, de Velasco M, Arao T, Okawara T, Nishio K (2012) Aza-derivatives of resveratrol are potent macrophage migration inhibitory factor inhibitors. Invest New Drugs 30:1878–1886PubMedCrossRef
31.
Zurück zum Zitat Kawaii S, Endo K, Tokiwano T, Yoshizawa Y (2012) Relationship between structure and antiproliferative activity of 1-azaflavanones. Anticancer Res 32:2819–2825PubMed Kawaii S, Endo K, Tokiwano T, Yoshizawa Y (2012) Relationship between structure and antiproliferative activity of 1-azaflavanones. Anticancer Res 32:2819–2825PubMed
32.
Zurück zum Zitat Kleinert H, Pautz A, Linker K, Schwarz PM (2004) Regulation of the expression of inducible nitric oxide synthase. Eur J Pharmacol 500:255–266PubMedCrossRef Kleinert H, Pautz A, Linker K, Schwarz PM (2004) Regulation of the expression of inducible nitric oxide synthase. Eur J Pharmacol 500:255–266PubMedCrossRef
33.
35.
Zurück zum Zitat Li S, Strelow A, Fontana EJ, Wesche H (2002) IRAK-4: a novel member of the IRAK family with the properties of an IRAK-kinase. Proc Natl Acad Sci USA 99:5567–5572PubMedPubMedCentralCrossRef Li S, Strelow A, Fontana EJ, Wesche H (2002) IRAK-4: a novel member of the IRAK family with the properties of an IRAK-kinase. Proc Natl Acad Sci USA 99:5567–5572PubMedPubMedCentralCrossRef
36.
Zurück zum Zitat Kollewe C, Mackensen AC, Neumann D, Knop J, Cao P, Li S, Wesche H, Martin MU (2004) Sequential autophosphorylation steps in the interleukin-1 receptor-associated kinase-1 regulate its availability as an adapter in interleukin-1 signaling. J Biol Chem 279:5227–5236PubMedCrossRef Kollewe C, Mackensen AC, Neumann D, Knop J, Cao P, Li S, Wesche H, Martin MU (2004) Sequential autophosphorylation steps in the interleukin-1 receptor-associated kinase-1 regulate its availability as an adapter in interleukin-1 signaling. J Biol Chem 279:5227–5236PubMedCrossRef
37.
Zurück zum Zitat Yamin TT, Miller DK (1997) The interleukin-1 receptor-associated kinase is degraded by proteasomes following its phosphorylation. J Biol Chem 272:21540–21547PubMedCrossRef Yamin TT, Miller DK (1997) The interleukin-1 receptor-associated kinase is degraded by proteasomes following its phosphorylation. J Biol Chem 272:21540–21547PubMedCrossRef
38.
Zurück zum Zitat Fitzgerald KA, McWhirter SM, Faia KL, Rowe DC, Latz E, Golenbock DT, Coyle AJ, Liao SM, Maniatis T (2003) IKKepsilon and TBK1 are essential components of the IRF3 signaling pathway. Nat Immunol 4:491–496PubMedCrossRef Fitzgerald KA, McWhirter SM, Faia KL, Rowe DC, Latz E, Golenbock DT, Coyle AJ, Liao SM, Maniatis T (2003) IKKepsilon and TBK1 are essential components of the IRF3 signaling pathway. Nat Immunol 4:491–496PubMedCrossRef
39.
Zurück zum Zitat Zhou J, Sun T, Jin S, Guo Z, Cui J (2020) Dual Feedforward Loops Modulate Type I Interferon Responses and Induce Selective Gene Expression during TLR4 Activation. Iscience 23:100881PubMedPubMedCentralCrossRef Zhou J, Sun T, Jin S, Guo Z, Cui J (2020) Dual Feedforward Loops Modulate Type I Interferon Responses and Induce Selective Gene Expression during TLR4 Activation. Iscience 23:100881PubMedPubMedCentralCrossRef
40.
Zurück zum Zitat Shimada T, Kawai T, Takeda K, Matsumoto M, Inoue J, Tatsumi Y, Kanamaru A, Akira S (1999) IKK-i, a novel lipopolysaccharideinducible kinase that is related to IkB kinases. Int Immunol 11:1357–1362PubMedCrossRef Shimada T, Kawai T, Takeda K, Matsumoto M, Inoue J, Tatsumi Y, Kanamaru A, Akira S (1999) IKK-i, a novel lipopolysaccharideinducible kinase that is related to IkB kinases. Int Immunol 11:1357–1362PubMedCrossRef
41.
Zurück zum Zitat Clark K, Plater L, Peggie M, Cohen P (2009) Use of the pharmacological inhibitor BX795 to study the regulation and physiological roles of TBK1 and IkappaB kinase epsilon: a distinct upstream kinase mediates Ser-172 phosphorylation and activation. J Biol Chem 284:14136–14146PubMedPubMedCentralCrossRef Clark K, Plater L, Peggie M, Cohen P (2009) Use of the pharmacological inhibitor BX795 to study the regulation and physiological roles of TBK1 and IkappaB kinase epsilon: a distinct upstream kinase mediates Ser-172 phosphorylation and activation. J Biol Chem 284:14136–14146PubMedPubMedCentralCrossRef
42.
Zurück zum Zitat Aminin D, Polonik S (2020) 1,4-Naphthoquinones: some biological properties and application. Chem Pharm Bull 68:46–57CrossRef Aminin D, Polonik S (2020) 1,4-Naphthoquinones: some biological properties and application. Chem Pharm Bull 68:46–57CrossRef
43.
Zurück zum Zitat Mahmoud IS, Hatmal MM, Abuarqoub D, Esawi E, Zalloum H, Wehaibi S, Nsairat H, Alshaer W (2021) 1,4-Naphthoquinone Is a potent Inhibitor of IRAK1 kinases and the production of inflammatory cytokines in THP-1 differentiated macrophages. ACS Omega 6:25299–25310PubMedPubMedCentralCrossRef Mahmoud IS, Hatmal MM, Abuarqoub D, Esawi E, Zalloum H, Wehaibi S, Nsairat H, Alshaer W (2021) 1,4-Naphthoquinone Is a potent Inhibitor of IRAK1 kinases and the production of inflammatory cytokines in THP-1 differentiated macrophages. ACS Omega 6:25299–25310PubMedPubMedCentralCrossRef
44.
Zurück zum Zitat Ackerman L, Acloque G, Bacchelli S, Schwartz H, Feinstein BJ, La Stella P, Alavi A, Gollerkeri A, Davis J, Campbell V, McDonald A, Agarwal S, Karnik R, Shi K, Mishkin A, Culbertson J, Klaus C, Enerson B, Massa V, Kuhn E, Sharma K, Keaney E, Barnes R, Chen D, Zheng X, Rong H, Sabesan V, Ho C, Mainolfi N, Slavin A, Gollob JA (2023) IRAK4 degrader in hidradenitis suppurativa and atopic dermatitis: a phase 1 trial. Nat Med 29:3127–3136PubMedPubMedCentralCrossRef Ackerman L, Acloque G, Bacchelli S, Schwartz H, Feinstein BJ, La Stella P, Alavi A, Gollerkeri A, Davis J, Campbell V, McDonald A, Agarwal S, Karnik R, Shi K, Mishkin A, Culbertson J, Klaus C, Enerson B, Massa V, Kuhn E, Sharma K, Keaney E, Barnes R, Chen D, Zheng X, Rong H, Sabesan V, Ho C, Mainolfi N, Slavin A, Gollob JA (2023) IRAK4 degrader in hidradenitis suppurativa and atopic dermatitis: a phase 1 trial. Nat Med 29:3127–3136PubMedPubMedCentralCrossRef
45.
Zurück zum Zitat Guillermo GM, Lewis RS, Lucy Y (2024) Phase 1b Trial of Irak 1/4 inhibition for low-risk myelodysplastic syndrome refractory/resistant to prior therapies: a trial in progress. Blood 142:3247–3248 Guillermo GM, Lewis RS, Lucy Y (2024) Phase 1b Trial of Irak 1/4 inhibition for low-risk myelodysplastic syndrome refractory/resistant to prior therapies: a trial in progress. Blood 142:3247–3248
46.
Zurück zum Zitat Sun Y, Revach OY, Anderson S, Kessler EA, Wolfe CH, Jenney A, Mills CE, Robitschek EJ, Davis TGR, Kim S, Fu A, Ma X, Gwee J, Tiwari P, Du PP, Sindurakar P, Tian J, Mehta A, Schneider AM, Yizhak K, Sade-Feldman M, LaSalle T, Sharova T, Xie H, Liu S, Michaud WA, Saad-Beretta R, Yates KB, Iracheta-Vellve A, Spetz JKE, Qin X, Sarosiek KA, Zhang G, Kim JW, Su MY, Cicerchia AM, Rasmussen MQ, Klempner SJ, Juric D, Pai SI, Miller DM, Giobbie-Hurder A, Chen JH, Pelka K, Frederick DT, Stinson S, Ivanova E, Aref AR, Paweletz CP, Barbie DA, Sen DR, Fisher DE, Corcoran RB, Hacohen N, Sorger PK, Flaherty KT, Boland GM, Manguso RT, Jenkins RW (2023) Targeting TBK1 to overcome resistance to cancer immunotherapy. Nature 615:158–167PubMedPubMedCentralCrossRef Sun Y, Revach OY, Anderson S, Kessler EA, Wolfe CH, Jenney A, Mills CE, Robitschek EJ, Davis TGR, Kim S, Fu A, Ma X, Gwee J, Tiwari P, Du PP, Sindurakar P, Tian J, Mehta A, Schneider AM, Yizhak K, Sade-Feldman M, LaSalle T, Sharova T, Xie H, Liu S, Michaud WA, Saad-Beretta R, Yates KB, Iracheta-Vellve A, Spetz JKE, Qin X, Sarosiek KA, Zhang G, Kim JW, Su MY, Cicerchia AM, Rasmussen MQ, Klempner SJ, Juric D, Pai SI, Miller DM, Giobbie-Hurder A, Chen JH, Pelka K, Frederick DT, Stinson S, Ivanova E, Aref AR, Paweletz CP, Barbie DA, Sen DR, Fisher DE, Corcoran RB, Hacohen N, Sorger PK, Flaherty KT, Boland GM, Manguso RT, Jenkins RW (2023) Targeting TBK1 to overcome resistance to cancer immunotherapy. Nature 615:158–167PubMedPubMedCentralCrossRef
Metadaten
Titel
Azamollugin, a mollugin derivative, has inhibitory activity on MyD88- and TRIF-dependent pathways
verfasst von
Yuki Nakajima
Hitomi Nishino
Kazunori Takahashi
Alfarius Eko Nugroho
Yusuke Hirasawa
Toshio Kaneda
Hiroshi Morita
Publikationsdatum
16.09.2024
Verlag
Springer Nature Singapore
Erschienen in
Journal of Natural Medicines / Ausgabe 1/2025
Print ISSN: 1340-3443
Elektronische ISSN: 1861-0293
DOI
https://doi.org/10.1007/s11418-024-01842-x