phorbol esters


Summary: Tumor-promoting compounds obtained from CROTON OIL (Croton tiglium). Some of these are used in cell biological experiments as activators of protein kinase C.

Top Publications

  1. Rullas J, Bermejo M, Garcia Perez J, Beltán M, González N, Hezareh M, et al. Prostratin induces HIV activation and downregulates HIV receptors in peripheral blood lymphocytes. Antivir Ther. 2004;9:545-54 pubmed
    ..These data support the potential use of prostratin to activate HIV from latency and purge viral reservoirs. ..
  2. Katz R, Jack Scott E, Narezkina A, Palagin I, Boimel P, Kulkosky J, et al. High-frequency epigenetic repression and silencing of retroviruses can be antagonized by histone deacetylase inhibitors and transcriptional activators, but uniform reactivation in cell clones is restricted by additional mechanisms. J Virol. 2007;81:2592-604 pubmed
    ..We conclude that HDACs can act rapidly to initiate and maintain promoter-independent retroviral epigenetic repression and silencing but that reactivation can be restricted by additional mechanisms. ..
  3. Perfetti A, Oriente F, Iovino S, Alberobello A, Barbagallo A, Esposito I, et al. Phorbol esters induce intracellular accumulation of the anti-apoptotic protein PED/PEA-15 by preventing ubiquitinylation and proteasomal degradation. J Biol Chem. 2007;282:8648-57 pubmed
    ..Exposure of untransfected C5N keratinocytes and transfected HEK293 cells to phorbol esters (12-O-tetradecanoylphorbol-13-acetate (TPA)) increased PED/PEA-15 cellular content and enhanced its ..
  4. Roach J, Devappa R, Makkar H, Becker K. Isolation, stability and bioactivity of Jatropha curcas phorbol esters. Fitoterapia. 2012;83:586-92 pubmed publisher
    ..curcas seed oil, which can be utilized for biodiesel production upon transesterification, is also rich in phorbol esters (PEs). In this study, PEs from J...
  5. Hezareh M. Prostratin as a new therapeutic agent targeting HIV viral reservoirs. Drug News Perspect. 2005;18:496-500 pubmed
    ..Prostratin represents a distinct subclass of protein kinase C activators, since unlike other phorbol esters it does not induce tumor formation...
  6. Boone M, Kortenoeven M, Robben J, Tamma G, Deen P. Counteracting vasopressin-mediated water reabsorption by ATP, dopamine, and phorbol esters: mechanisms of action. Am J Physiol Renal Physiol. 2011;300:F761-71 pubmed publisher
    ..Interestingly, phorbol esters only reduced AQP2 through the first pathway...
  7. Choi S, Czifra G, Kedei N, Lewin N, Lazar J, Pu Y, et al. Characterization of the interaction of phorbol esters with the C1 domain of MRCK (myotonic dystrophy kinase-related Cdc42 binding kinase) alpha/beta. J Biol Chem. 2008;283:10543-9 pubmed publisher
    C1 domains mediate the recognition and subsequent signaling response to diacylglycerol and phorbol esters by protein kinase C (PKC) and by several other families of signal-transducing proteins such as the chimerins or RasGRP...
  8. Wender P, Kee J, Warrington J. Practical synthesis of prostratin, DPP, and their analogs, adjuvant leads against latent HIV. Science. 2008;320:649-52 pubmed publisher
    ..This synthesis reliably supplies gram quantities of the therapeutically promising natural products, hitherto available only in low and variable amounts from natural sources, and opens access to a variety of new analogs. ..
  9. Li C, Devappa R, Liu J, Lv J, Makkar H, Becker K. Toxicity of Jatropha curcas phorbol esters in mice. Food Chem Toxicol. 2010;48:620-5 pubmed publisher
    b>Phorbol esters are the main toxins in Jatropha curcas seed and oil. The aim of this study was to assess the acute toxicity of phorbol esters given by intragastric administration and to determine the LD50 for Swiss Hauschka mice...

More Information


  1. Sharlow E, Giridhar K, LaValle C, Chen J, Leimgruber S, Barrett R, et al. Potent and selective disruption of protein kinase D functionality by a benzoxoloazepinolone. J Biol Chem. 2008;283:33516-26 pubmed publisher
    ..In summary, our findings indicate that CID755673 is a potent and selective PKD1 inhibitor with valuable pharmacological and cell biological potential. ..
  2. Lauth M, Bergstrom A, Toftgard R. Phorbol esters inhibit the Hedgehog signalling pathway downstream of Suppressor of Fused, but upstream of Gli. Oncogene. 2007;26:5163-8 pubmed
  3. Goel G, Makkar H, Francis G, Becker K. Phorbol esters: structure, biological activity, and toxicity in animals. Int J Toxicol. 2007;26:279-88 pubmed
    b>Phorbol esters are the tetracyclic diterpenoids generally known for their tumor promoting activity...
  4. Marquez N, Calzado M, Sanchez Duffhues G, Perez M, Minassi A, Pagani A, et al. Differential effects of phorbol-13-monoesters on human immunodeficiency virus reactivation. Biochem Pharmacol. 2008;75:1370-80 pubmed publisher
    ..Nevertheless, this compound induces a translocation pattern of the PKC isotypes alpha and delta to cellular compartments distinctly different from that elicited by prostratin and PMA. ..
  5. Keck G, Poudel Y, Welch D, Kraft M, Truong A, Stephens J, et al. Substitution on the A-ring confers to bryopyran analogues the unique biological activity characteristic of bryostatins and distinct from that of the phorbol esters. Org Lett. 2009;11:593-6 pubmed publisher
    ..Biological assays reveal a crucial role for substitution in the bryostatin 1 A-ring in conferring those responses which are characteristic of bryostatin 1 and distinct from those observed with PMA. ..
  6. Zhang X, Wang L, Li F, Yu K, Wang M. Cytotoxic phorbol esters of Croton tiglium. J Nat Prod. 2013;76:858-64 pubmed publisher
    ..The cytotoxic activities of the phorbol diesters were evaluated against the SNU387 hepatic tumor cell line, and compound 3 exhibited the most potent activity (IC50 1.2 ?M)...
  7. Zhu J, Gaiha G, John S, Pertel T, Chin C, Gao G, et al. Reactivation of latent HIV-1 by inhibition of BRD4. Cell Rep. 2012;2:807-16 pubmed publisher
  8. Oskoueian E, Abdullah N, Ahmad S. Phorbol esters from Jatropha meal triggered apoptosis, activated PKC-?, caspase-3 proteins and down-regulated the proto-oncogenes in MCF-7 and HeLa cancer cell lines. Molecules. 2012;17:10816-30 pubmed publisher
    Jatropha meal produced from the kernel of Jatropha curcas Linn. grown in Malaysia contains phorbol esters (PEs). The potential benefits of PEs present in the meal as anticancer agent are still not well understood...
  9. Devappa R, Makkar H, Becker K. Biodegradation of Jatropha curcas phorbol esters in soil. J Sci Food Agric. 2010;90:2090-7 pubmed publisher
    Jatropha curcas seed cake is generated as a by-product during biodiesel production. Seed cake containing toxic phorbol esters (PEs) is currently used as a fertiliser and thus it is of eco-toxicological concern...
  10. He W, King A, Khan M, Cuevas J, Ramiaramanana D, Graham I. Analysis of seed phorbol-ester and curcin content together with genetic diversity in multiple provenances of Jatropha curcas L. from Madagascar and Mexico. Plant Physiol Biochem. 2011;49:1183-90 pubmed publisher
    ..Toxins present in the seeds of J. curcas include phorbol esters and a type-I ribosome inactivating protein (curcin). Although the edible seeds of J...
  11. Chen J, Deng F, Li J, Wang Q. Selective binding of phorbol esters and diacylglycerol by individual C1 domains of the PKD family. Biochem J. 2008;411:333-42 pubmed
    ..The twin C1 domains of PKD, designated C1a and C1b, have been shown to bind DAG or phorbol esters. However, their ligand-binding activities and selectivities have not been fully characterized...
  12. Sung T, Rice A. Effects of prostratin on Cyclin T1/P-TEFb function and the gene expression profile in primary resting CD4+ T cells. Retrovirology. 2006;3:66 pubmed
    ..Additionally, genes regulated by prostratin were identified that have the potential to regulate HIV-1 replication both positively and negatively. ..
  13. Warrilow D, Gardner J, Darnell G, Suhrbier A, Harrich D. HIV type 1 inhibition by protein kinase C modulatory compounds. AIDS Res Hum Retroviruses. 2006;22:854-64 pubmed
    ..This result hints at the possibility of inhibition by a PKC modulatory compound of an early pathway of viral entry in PBMC. ..
  14. Griner E, Kazanietz M. Protein kinase C and other diacylglycerol effectors in cancer. Nat Rev Cancer. 2007;7:281-94 pubmed
  15. Bond J, Gescher A, Verschoyle R, Lemoine N, Errington R, Wiltshire M, et al. Cytotoxic action of phorbol esters on human pancreatic cancer cells. Int J Cancer. 2007;121:1445-54 pubmed
    We previously showed that phorbol esters are cytotoxic to human thyroid epithelial cells expressing a mutant RAS oncogene...
  16. Kedei N, Lubart E, Lewin N, Telek A, Lim L, Mannan P, et al. Some phorbol esters might partially resemble bryostatin 1 in their actions on LNCaP prostate cancer cells and U937 leukemia cells. Chembiochem. 2011;12:1242-51 pubmed publisher
    ..Since phorbol ester lipophilicity influences PKCδ localization, we have examined in LNCaP cells a series of phorbol esters and related derivatives spanning some eight logs in lipophilicity (logP) to see if any behave like bryostatin ..
  17. Klausen T, Pagani A, Minassi A, Ech Chahad A, Prenen J, Owsianik G, et al. Modulation of the transient receptor potential vanilloid channel TRPV4 by 4alpha-phorbol esters: a structure-activity study. J Med Chem. 2009;52:2933-9 pubmed publisher
    The mechanism of activation of the transient receptor potential vanilloid 4 (TRPV4) channel by 4alpha-phorbol esters was investigated by combining information from chemical modification of 4alpha-phorbol-didecanoate (4alpha-PDD, 2a), site-..
  18. Makkar H, Becker K. Are Jatropha curcas phorbol esters degraded by rumen microbes?. J Sci Food Agric. 2010;90:1562-5 pubmed publisher
    ..However, the presence of highly toxic phorbol esters limits its use. Degradation of J...
  19. Lou X, Korogod N, Brose N, Schneggenburger R. Phorbol esters modulate spontaneous and Ca2+-evoked transmitter release via acting on both Munc13 and protein kinase C. J Neurosci. 2008;28:8257-67 pubmed publisher
    Diacylglycerol (DAG) and phorbol esters strongly potentiate transmitter release at synapses by activating protein kinase C (PKC) and members of the Munc13 family of presynaptic vesicle priming proteins...
  20. JOHNSON H, Banack S, Cox P. Variability in content of the anti-AIDS drug candidate prostratin in Samoan populations of Homalanthus nutans. J Nat Prod. 2008;71:2041-4 pubmed publisher
    ..The reversed-phase HPLC assay will allow plants to be selected for agricultural development and genetic analysis by identifying those individuals above and below a 95% confidence interval for the median concentration. ..
  21. Reuse S, Calao M, Kabeya K, Guiguen A, Gatot J, Quivy V, et al. Synergistic activation of HIV-1 expression by deacetylase inhibitors and prostratin: implications for treatment of latent infection. PLoS ONE. 2009;4:e6093 pubmed publisher
    ..Our results suggest that combinations of different kinds of proviral activators may have important implications for reducing the size of latent HIV-1 reservoirs in HAART-treated patients. ..
  22. Fonseca B, Lee V, Proud C. The binding of PRAS40 to 14-3-3 proteins is not required for activation of mTORC1 signalling by phorbol esters/ERK. Biochem J. 2008;411:141-9 pubmed publisher
    ..In a similar manner to insulin, phorbol esters also activate mTORC1 signalling, in this case via PKC (protein kinase C) and ERK (extracellular-signal-..
  23. Joshi C, Mathur P, Khare S. Degradation of phorbol esters by Pseudomonas aeruginosa PseA during solid-state fermentation of deoiled Jatropha curcas seed cake. Bioresour Technol. 2011;102:4815-9 pubmed publisher
    ..Presence of toxic phorbol esters restricts its utilization as livestock feed...
  24. Brose N, Rosenmund C. Move over protein kinase C, you've got company: alternative cellular effectors of diacylglycerol and phorbol esters. J Cell Sci. 2002;115:4399-411 pubmed
    ..The most prominent intracellular targets of diacylglycerol and of the functionally analogous phorbol esters belong to the protein kinase C (PKC) family...
  25. Chumkaew P, Karalai C, Ponglimanont C, Chantrapromma K. Antimycobacterial activity of phorbol esters from the fruits of Sapium indicum. J Nat Prod. 2003;66:540-3 pubmed
    Three new phorbol esters, 12-(2-N-methylaminobenzoyl)-4beta,5,20-trideoxyphorbol-13-acetate (1), 12-(2-N-methylaminobenzoyl)-4alpha,5,20-trideoxyphorbol-13-acetate (2), and 12-(2-N-methylaminobenzoyl)-4alpha, 20-dideoxy-5-hydroxyphorbol-..
  26. Kulkosky J, Sullivan J, Xu Y, Souder E, Hamer D, Pomerantz R. Expression of latent HAART-persistent HIV type 1 induced by novel cellular activating agents. AIDS Res Hum Retroviruses. 2004;20:497-505 pubmed
  27. Vriens J, Watanabe H, Janssens A, Droogmans G, Voets T, Nilius B. Cell swelling, heat, and chemical agonists use distinct pathways for the activation of the cation channel TRPV4. Proc Natl Acad Sci U S A. 2004;101:396-401 pubmed
    ..b>Phorbol esters and heat operate by means of a distinct, PLA(2)- and cytochrome p450 epoxygenase-independent pathway, which ..
  28. Hezareh M, Moukil M, Szanto I, Pondarzewski M, Mouche S, Cherix N, et al. Mechanisms of HIV receptor and co-receptor down-regulation by prostratin: role of conventional and novel PKC isoforms. Antivir Chem Chemother. 2004;15:207-22 pubmed
  29. Silinsky E, Searl T. Phorbol esters and neurotransmitter release: more than just protein kinase C?. Br J Pharmacol. 2003;138:1191-201 pubmed
    This review focuses on the effects of phorbol esters and the role of phorbol ester receptors in the secretion of neurotransmitter substances...
  30. Gardner A, Olah M. Distinct protein kinase C isoforms mediate regulation of vascular endothelial growth factor expression by A2A adenosine receptor activation and phorbol esters in pheochromocytoma PC12 cells. J Biol Chem. 2003;278:15421-8 pubmed
    ..Together, the findings suggest that phorbol ester-induced down-regulation of VEGF mRNA occurs as a result of a reduction of PKCepsilon activity, whereas that mediated by the A(2A)AR occurs following deactivation of PKCzeta. ..
  31. Roberts D, Anderson A, Hidaka M, Swetenburg R, Patterson C, Stanford W, et al. A vascular gene trap screen defines RasGRP3 as an angiogenesis-regulated gene required for the endothelial response to phorbol esters. Mol Cell Biol. 2004;24:10515-28 pubmed
    ..b>Phorbol esters mimic the second messenger diacylglycerol (DAG) in activating both protein kinase C (PKC) and non-PKC phorbol ..
  32. Wada R, Suto Y, Kanai M, Shibasaki M. Dramatic switching of protein kinase C agonist/antagonist activity by modifying the 12-ester side chain of phorbol esters. J Am Chem Soc. 2002;124:10658-9 pubmed
    ..The approach of controlling the agonist/antagonist activity of phorbol esters by the nature (i.e., hydrophilicity, charge, and rigidity, etc...
  33. Trushin S, Bren G, Asin S, Pennington K, Paya C, Badley A. Human immunodeficiency virus reactivation by phorbol esters or T-cell receptor ligation requires both PKCalpha and PKCtheta. J Virol. 2005;79:9821-30 pubmed
    ..Antigens, T-cell receptor (TCR) ligation, and phorbol esters can reactivate HIV from latency in a protein kinase C (PKC)-dependent manner; however, it is unknown which ..
  34. Searl T, Silinsky E. Phorbol esters and adenosine affect the readily releasable neurotransmitter pool by different mechanisms at amphibian motor nerve endings. J Physiol. 2003;553:445-56 pubmed
    b>Phorbol esters and adenosine have been proposed to interact at common sites downstream of calcium entry at amphibian motor nerve endings...
  35. Brooks D, Hamer D, Arlen P, Gao L, Bristol G, Kitchen C, et al. Molecular characterization, reactivation, and depletion of latent HIV. Immunity. 2003;19:413-23 pubmed
    ..We demonstrate that activation of latent virus is required for targeting by antiviral agents and provide the basis for future therapeutic strategies to eradicate the latent reservoir. ..
  36. Bocklandt S, Blumberg P, Hamer D. Activation of latent HIV-1 expression by the potent anti-tumor promoter 12-deoxyphorbol 13-phenylacetate. Antiviral Res. 2003;59:89-98 pubmed
    ..The combination of high potency and anti-tumor promoting activity make DPP an attractive candidate for the adjunctive therapy of persistent HIV-1 infection. ..
  37. Shindo M, Irie K, Masuda A, Ohigashi H, Shirai Y, Miyasaka K, et al. Synthesis and phorbol ester binding of the cysteine-rich domains of diacylglycerol kinase (DGK) isozymes. DGKgamma and DGKbeta are new targets of tumor-promoting phorbol esters. J Biol Chem. 2003;278:18448-54 pubmed
    ..Although most PKC C1 domains strongly bind phorbol esters, there has been no direct evidence that DGK C1 domains bind phorbol esters...
  38. Geiger M, Wrulich O, Jenny M, Schwaiger W, Grunicke H, Uberall F. Defining the human targets of phorbol ester and diacylglycerol. Curr Opin Mol Ther. 2003;5:631-41 pubmed
    b>Phorbol esters (PEs) and their derivatives are potent tumor-promoting agents...
  39. Williams S, Chen L, Kwon H, Fenard D, Bisgrove D, Verdin E, et al. Prostratin antagonizes HIV latency by activating NF-kappaB. J Biol Chem. 2004;279:42008-17 pubmed
    ..These findings provide new insights into the molecular pathway through which prostratin antagonizes HIV latency highlighting a central role for the action of NF-kappaB. ..
  40. Witvrouw M, Pannecouque C, Fikkert V, Hantson A, Van Remoortel B, Hezareh M, et al. Potent and selective inhibition of HIV and SIV by prostratin interacting with viral entry. Antivir Chem Chemother. 2003;14:321-8 pubmed
    ..We concluded that prostratin inhibits the entry step of the replication cycle of HIV by interacting with a cellular target necessary for viral entry. ..
  41. Jayanthi L, Samuvel D, Ramamoorthy S. Regulated internalization and phosphorylation of the native norepinephrine transporter in response to phorbol esters. Evidence for localization in lipid rafts and lipid raft-mediated internalization. J Biol Chem. 2004;279:19315-26 pubmed
  42. Wright D, Geiger P, Rheinheimer M, Han D, Holloszy J. Phorbol esters affect skeletal muscle glucose transport in a fiber type-specific manner. Am J Physiol Endocrinol Metab. 2004;287:E305-9 pubmed
    ..However, earlier studies demonstrated that phorbol esters increase glucose transport in skeletal muscle...
  43. Schomerus C, Laedtke E, Korf H. Activation of arylalkylamine N-acetyltransferase by phorbol esters in bovine pinealocytes suggests a novel regulatory pathway in melatonin synthesis. J Neuroendocrinol. 2004;16:741-9 pubmed
    ..Other compounds which are known to influence the melatonin-generating system are phorbol esters. The effect of phorbol esters on regulation of melatonin synthesis has been mainly investigated in rat ..
  44. Biancotto A, Grivel J, Gondois Rey F, Bettendroffer L, Vigne R, Brown S, et al. Dual role of prostratin in inhibition of infection and reactivation of human immunodeficiency virus from latency in primary blood lymphocytes and lymphoid tissue. J Virol. 2004;78:10507-15 pubmed
  45. Chen H, Roper S. PKA and PKC enhance excitatory synaptic transmission in human dentate gyrus. J Neurophysiol. 2003;89:2482-8 pubmed
    ..In addition, the occlusion experiments suggest that the two kinases may share a common signal pathway. ..
  46. Arniges M, Vazquez E, Fernández Fernández J, Valverde M. Swelling-activated Ca2+ entry via TRPV4 channel is defective in cystic fibrosis airway epithelia. J Biol Chem. 2004;279:54062-8 pubmed
    ..Together, these results suggest that defective RVD in CF airway epithelia might be caused by the absence of a TRPV4-mediated Ca(2+) signal and the subsequent activation of Ca(2+)-dependent K(+) channels. ..
  47. Auer A, von Blume J, Sturany S, von Wichert G, Van Lint J, Vandenheede J, et al. Role of the regulatory domain of protein kinase D2 in phorbol ester binding, catalytic activity, and nucleocytoplasmic shuttling. Mol Biol Cell. 2005;16:4375-85 pubmed
    Protein kinase D2 (PKD2) belongs to the PKD family of serine/threonine kinases that is activated by phorbol esters and G protein-coupled receptors (GPCRs)...
  48. Brown H, McBride W, Zack J, Sun R. Prostratin and bortezomib are novel inducers of latent Kaposi's sarcoma-associated herpesvirus. Antivir Ther. 2005;10:745-51 pubmed
  49. Makkar H, Siddhuraju P, Becker K. Plant secondary metabolites. Methods Mol Biol. 2007;393:1-122 pubmed
  50. Muiwo P, Pandey P, Ahmad H, Ramachandran S, Bhattacharya A. IsomiR processing during differentiation of myelogenous leukemic cell line K562 by phorbol ester PMA. Gene. 2018;641:172-179 pubmed publisher
    Chronic myelocytic leukemia cell line K562 undergoes differentiation by phorbol esters to megakaryocytes and we have used this system to understand miRNA processing leading to isomiR generation...
  51. Kempson S, Edwards J, Sturek M. Inhibition of the renal betaine transporter by calcium ions. Am J Physiol Renal Physiol. 2006;291:F305-13 pubmed
    ..Amino acid transport system A, assayed as a control, was not inhibited. Brief treatment with phorbol esters reproduced the specific inhibition of Na(+)-GABA cotransport, and the inhibition was blocked by staurosporine...
  52. d Aldebert E, Cenac N, Rousset P, Martin L, Rolland C, Chapman K, et al. Transient receptor potential vanilloid 4 activated inflammatory signals by intestinal epithelial cells and colitis in mice. Gastroenterology. 2011;140:275-85 pubmed publisher
    ..TRPV4 is expressed and functional in intestinal epithelial cells; its activation in the gastrointestinal tract causes increases in intracellular calcium concentrations, chemokine release, and colitis. ..
  53. Kamiya T, Goto A, Kurokawa E, Hara H, Adachi T. Cross Talk Mechanism among EMT, ROS, and Histone Acetylation in Phorbol Ester-Treated Human Breast Cancer MCF-7 Cells. Oxid Med Cell Longev. 2016;2016:1284372 pubmed publisher
    ..We herein determined the cross talk mechanism among EMT, ROS, and histone acetylation, and our results provide an insight into the progression of cancer metastasis. ..
  54. Loukin S, Su Z, Zhou X, Kung C. Forward genetic analysis reveals multiple gating mechanisms of TRPV4. J Biol Chem. 2010;285:19884-90 pubmed publisher
    ..We conclude that TRPV4 contains an additional voltage-dependent gating mechanism in series with the main intracellular gate. ..
  55. Carraway R, Hassan S, Dobner P. Protein kinase C inhibitors alter neurotensin receptor binding and function in prostate cancer PC3 cells. Regul Pept. 2008;147:96-109 pubmed publisher
    ..Since NT can activate PKC upon binding to its receptor, it is possible that NT receptor is also subject to homologous regulation by PKC. ..
  56. D hoedt D, Owsianik G, Prenen J, Cuajungco M, Grimm C, Heller S, et al. Stimulus-specific modulation of the cation channel TRPV4 by PACSIN 3. J Biol Chem. 2008;283:6272-80 pubmed publisher
    ..a variety of stimuli, including cell swelling, moderate heat, and chemical compounds such as synthetic 4alpha-phorbol esters. TRPV4 displays a widespread expression in various cells and tissues and has been implicated in diverse ..
  57. Szamałek M, Baer Dubowska W. [RasGRP proteins--Ras-activating factors]. Postepy Biochem. 2007;53:112-20 pubmed
    ..C1 domain, allows them to bind diacylglycerol as well as DAG-analogs like phorbol esters. Binding of the ligand leads to activation of RasGRPs and in consequence to the activation of Ras and Rap ..
  58. Stuhlmeier K, Pollaschek C. Quinacrine but not chloroquine inhibits PMA induced upregulation of matrix metalloproteinases in leukocytes: quinacrine acts at the transcriptional level through a PLA2-independent mechanism. J Rheumatol. 2006;33:472-80 pubmed
    ..Inhibition of MMP by quinacrine might, in part, account for its reported immunosuppressive action. Synthesizing more potent derivatives of quinacrine may be a means of suppressing undesired MMP activation. ..