1. Xenotox, Inc.
1.1
New York Corporation (Incorporated 08/25/2005). New York S Corporation (since 2013). Tax ID: 203535033. Xenotox Inc.pdf
A framework of the Xenotox, Inc. [Introductory Section 1] is based on studies of xenobiotics affecting human health and disease, which are displayed semi-chronologically in Xenobiochemistry [Section 2], Dioxin Research [Section 3], and Xenovirology [Section 4].
The Xenotox, Inc. personnel is currently focusing on two subjects originated from previous research findings:
1. Implementation of Xenovirology, an Interdisciplinary Field Linked to Inflammatory and Neurodegenerative Diseases in Humans. (for more details, see sections 3 and 4). The most recent publication* on the subject:
- "Rising level of pulmonary dioxin might trigger CMV and HSV-1 reactivation via bHLH/PAS/AhR:ARNT transcription pathway in lungs of immunocompetent COVID-19 patients with ARDS". By Ilya Tsyrlov et al., Journal of Biological Chemistry, 299 (3):S50 (2023). DOI:10.1016/j.jbc.2023.103163 (in full see section 4.6)
2. Development of Long-Acting Drug Delivery Formulations for Analgesics, Synthetic Opioids and Antimalarials using Site-Specific Isopropylation of Parent Molecules. (the content of the subject is truncated due to patenting process requirements; for some data, see section 2). The most recent publications on the subject:
- "Re. Artemisinins ameliorate polycystic ovarian syndrome by mediating LONP1-CYP11A1 interaction". By Yang Liu et al., Science, Vol 384, Issue 6701 (14 Jun 2024). _eLetter to Science Editor_ on July 1, 2024. By Ilya Tsyrlov & Irina Shur. DOI:10.1126/science.adk5382 (in full see section 2.3.4)
- "Except for women from more vulnerable to malaria groups, a remedy hope for PCOS might be not Coartem® but rather long-acting formulations of oral Artemisinin". By Ilya Tsyrlov and Irina Shur.. Commentary article on July 12, 2024. Science, Vol 384, Issue 6701. DOI:10.1126/science.adk5382 (in full see section 2.3.4)
On August 25th, 2024 we celebrated the company 19th business anniversary. We are really excited and eagerly to provide consulting services to the academia and biotechnology industry dealing with human health-centered areas. Individuals and research organizations are welcome to become collaborative partners in scaling up implementation of appeared below Contributions to Basic Biomedical Research and Contributions to Applied Clinical Research.
1.2.1
• Contributions to Basic Biomedical Research:
• Discovery that "Phenobarbital-Type" Induction of Microsomal Monooxygenases Is Driven by a Parent Molecule of Inducer (details in section 2.3.2.).
Tsyrlov, I.B., Zakharova, N.E., Gromova, O.A., Lyakhovich, V.V. (January 1976). “Possible mechanism of induction of liver microsomal monooxygenase by phenobarbital”. _Biochimica et Biophysica Acta _**421**:44-56. **DOI: 10.1016/0304-4165(76)90168-9**
Tsyrlov, I.B., Polyakova, N.E., Gromova, O.A. Rivkind, N.B., Lyakhovich, V.V. (March 1979). “Cholestasis as an in vivo model for analysis of the induction of liver microsomal monooxygenases by sodium phenobarbital and 3-methylcholanthrene”. _Biochemical Pharmacology_ **28**:1473-1478. **DOI: 10.1016/0006-2952(79)90460-X**
Lyakhovich, V.V., Tsyrlov, I.B. (February 1981). “Индукция Ферментов Метаболизма Ксенобиотиков” (in Russian). “_Induction of Xenobiotic Metabolizing Enzymes_”. 239 pp. Ed. Academician A. Yasaitis. Novosibirsk, Nauka Publishing House. **ISBN: MH-05082**• Development of "Mutual Depletion Inhibition System” in Order to Quantitate the CYP' Catalytic Parameters in Relation to Subsequent Conjugation Reactions (details in section 2.4.1.)
Tsyrlov, I.B., Lyakhovich, V.V. (September 1978). "Genetic variations in cytochrome P-450 (P-448) catalytic center activities in relation to subsequent conjugation reactions". In: _Conjugation Reactions in Drug Biotransformation_, Ed. A. Aitio, Elsevier/North-Holland Biomedical Press, Amsterdam-New York, Oxford. pp.135-145. **ISBN:0-444-80090-5**
Lyakhovich, V.V., Tsyrlov, I.B. (February 1981). “Индукция Ферментов Метаболизма Ксенобиотиков” (in Russian)._ “Induction of Xenobiotic Metabolizing Enzymes_”. 239 pp. Ed. Academician A. Yasaitis. Novosibirsk, Nauka Publishing House. **ISBN: MH-05082**• Сomparison of Enzyme Kinetics Among cDNA-Expressed, Microsomal, and Isolated CYP1A1 and CYP1A2 (details in sections 2.4.1.; 2.4.2. & 3.1.2.).
Tsyrlov, I.B., Duzchak, T.G. (November 1990). “Interspecies features of hepatic cytochromes P450 IA1 and P450 IA2 in rodents”. _Xenobiotica _**20**(11):1163-1170. **DOI:10.3109/00498259009046836**
Tsyrlov, I.B., Goldfarb, I.S., Gelboin, H.V. (December 1993). “Enzyme-kinetic and immunochemical characteristics of mouse cDNA-expressed, microsomal, and purified CYP1A1 and CYP1A2”._ Archives of Biochemistry and Biophysics_ **307**:259-266. **DOI:10.1006/abbi.1993.1588**
Goldman, R., Tsyrlov, I.B., Grogan, J., Kagan, V.E. (March 1997). “Reaction of phenoxyl radicals with NADPH-cytochrome P-450 oxidoreductase and NADPH: reduction of the radicals and inhibition of the enzyme”. _Biochemistry _**36**:3186-3192. **DOI: 10.1021/bi9621728**
Sinclair, P.R., Gorman, N., Tsyrlov, I.B., Fuhr, U., Walton, H.S., Sinclair, J.F (October 1998). “Uroporphyrinogen oxidation catalyzed by human cytochromes P450”. _Drug Metabolism and Disposition_ **26**:1019-1025. **Print ISSN: 0090-9556. PubMed: 9763408A**
Tsyrlov, I.B. (December 2021). Comparative enzyme kinetics analysis of the cDNA-expressed, microsomal and purified mammalian P450 monooxygenases. _Journal of Metabolic Syndrome_ (an open access journal) **10 **(4):2-7. **ISSN:2167-0943**• Lipophilic Protonophore as the Probe Disclosing Hydrophobic Zones in Microsomal Membrane Specific to Substrate-Binding and Electron-Accepting CYP Moieties (details in section 2.2.2.].
Tsyrlov, I.B., Gromova, O.A., Lyakhovich, V.V. (October 1976). “Mechanism of inhibition by carbonyl cyanide m- chlorophenylhydrozone and sodium deoxycholate of cytochrome P-450-catalyzed hepatic microsomal drug metabolism”. _ The Biochemical Journal._ **160**(1):75-83. **DOI:10.1042/bj1600075 **
Tsyrlov, I.B., Gromova, O.A., Lyakhovich, V.V. (June 1975) "Mechanism of the Inhibition by Carbonyl Cyanide m- Chlorophenylhydrazone of Cytochrome P-450-Catalyzed Drug Metabolism in Rat Liver Microsomal Fraction". _London' Biochemical Society Transactions._ **3**(6):1020-1023. **https://doi.org/10.1042/bst0031020**• Bonding Chemistry of Monooxygenase Inducer Imprints Enzyme Specificity Towards Substrates with Similar Bonds (details in section 2.3.2.).
Anshitz, A.G., Sokolovsky, V.D., Burilin, S.Yu., Lyakhovich, V.V., Tsyrlov, I.B. (January 1979). “Influence of inducer structure on catalytic activities of microsomal enzymes”. _Kinetics and Catalysis _(Science Press) **20**(4):865-869. **UDK: 577.15.02:577.158**
Tsyrlov, I.B., Gerasimov, K.G. (June 1991). “Aminopyrine-N-demethylase I. Directed modification of substrates' structure as a way of production of inducer of the monooxygenase isoform P-450b”. _European Journal of Drug Metabolism and Pharmacokinetics _**16**(3):207-212. **DOI:10.1007/BF03189961**
Tsyrlov, I.B., Woo, C.S.T., Martin, V.P., Shur, I.N. (April 2014). “Modification of CYP2B6-mediated site of metabolism on Artemisinin molecule as a way to prolong its maximal antimalarial efficacy”. _International Journal of Infectious diseases_ **21** (S1):174-177. **DOI:10.1016/j.ijid.2014.03.784**• Geometry of the Ah Receptor Ligand Binding Site Studied with Idiotypic and Anti-Idiotypic Monoclonal Antibodies to 2,3,7,8-TCDD
Tsyrlov, I.B., Roschke, V. (July 1994). "Development of monoclonal antibodies to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)". _Proceedings of 4th European ISSX Meeting_, Bologna, Italy,**1**:77-78
Tsyrlov, I.B. (June 2015). "IDIOTYPIC AND ANTI-IDIOTYPIC MONOCLONAL ANTIBODIES TO TCDD AS APPROACH TO STUDY GEOMETRY OF Ah RECEPTOR BINDING SITE". In _Proceedings of 13th European ISSX Meeting_, Glasgow, Scotland,**1**:303-306
Tsyrlov. I.B. (March 2022). "Geometry of of Ah receptor' ligand binding site studied with idiotypic and anti-idiotypic monoclonal antibodies to 2,3,7,8-TCDD". _Journal of Metabolic Syndrome _(an open access journal)** 11** (2):44-7. **ISSN:2167-0943**• 2,3,7,8-TCDD at the Single Nanomolar Range is Potent to trans-Activate HIV-1, HBV, and NS1BP Genes Expression in Corresponding Target Cells (details in sections 3.4.1.-3.4.3. & 3.5.)
Pokrovsky, A.G., Chernykh, A.I., Yastrebova, O.N., Tsyrlov, I.B. (August 1991). “2,3,7,8-tetrachlorodibenzo-p-dioxin as a possible activator of HIV infection”. _Biochemical and Biophysical Research Communications_ **179**:46-51. **ISSN: 0006-291X**
Tsyrlov, I.B., Pokrovsky, A.G. (September 1993), “Stimulatory effect of the CYP1A1 inducer 2,3,7,8-tetrachlorodibenzo-p-dioxin on the reproduction of HIV-1 in human lymphoid cell culture”. _Xenobiotica _**23**:457-467. **DOI: 10.3109/00498259309057034**
Tsyrlov, I.B. (July 2006). “The role of body burden 2,3,7,8-TCDD in triggering malignancy-associated human viruses: from early data to mechanistic concept”. _Organohalogen Compounds_ **68**:552-555. **ISSN:1026-4892**
Tsyrlov, I.B., Shur, I.N. (August 2008). "Mechanistic Insight into Activation by Dioxin-Type Xenobiotics of Cancer-Linked Common Human Viruses and HIV-1 Virus". _The Lancet Infectious Diseases_ **8**:P496-9. **DOI:https://doi.org/10.1016/S1473-3099(08)70172-5**
Tsyrlov, I.B., Pokrovsky, A.G., Wu, J., Shur, I.N. (September 2015). “Multidisciplinary approach to the trans-activation of human Hepatitis B Virus by body burden dioxin or dioxin-like polychlorinated biphenyls”. _Journal of Viral Hepatitis_ **22** (S3-P40):27-28. Online **ISSN:1365-2893**• Multiple Dioxin Response Elements Locate in Promoter Regions of Human Genes Encoding Cytosolic Ah Receptor Complex Components (details in section 3.2.).
Nedosekina, E.A., Oshchepkov, D.Yu., Mordvinov, V.A., Katokhin, A.V., Kuznetsova, T.N., Shamanina, M., Tsyrlov, I.B. (August 2007). “Detection of new potentially active DRE sites in the regulatory region of human genes encoding components of Ah receptor cytosolic complex”. _Organohalogen Compounds_ **69**(2):1890-1894.** ISSN:1026-4892**
Tsyrlov, I.B., Shur, I.N., Oshchepkov, D.Yu., Pokrovsky, A.G. (June 2012). "Xenobiotical virology: novel mechanistic concept of hazardous human viruses upregulation by body burden level of dioxins via AhR-mediated transcriptional pathway". _International Journal of Infectious Diseases_. **16**(Suppl. 1):e115-119. **DOI:org/10.1016/j.ijid.2012.05.258.e112**
Wu, J., Shur, I.N., Tsyrlov, I.B. (July 2008). “Current human body burden of dioxins might upregulate DRE-containing cytomegalovirus (CMV) linked to inflammation and malignancy pathways”. _Organohalogen Compounds_ **70**: 1471-1474 (2008). **ISSN:1026-4892**
Tsyrlov, I.B., Shur, I.N., Wu, J., Furman, D.N., Oshchepkov, D.Yu. (August 2014). A proposed mechanism of transactivation by body burden dioxin of Herpes Simplex Virus genes might be responsible for weakening the host antiviral defense”. _Organohalogen Compounds_ **76**:289-292. **ISSN:1026-4892**• Inception and Development of Xenovirology, an Interdisciplinary Field Linked to Inflammatory and Neurodegenerative Diseases in Humans (details in sections 4.2.1.-4.2.3.; 4.3.1.; 4.5.1-4.5.3.].
Tsyrlov, I.B., Shur, I.N., Oshchepkov, D.Yu., Pokrovsky, A.G. (June 2012). "Xenobiotical Virology: novel mechanistic concept of hazardous human viruses up-regulation by body burden level of dioxins via AhR-mediated transcriptional pathway". I_nternational Journal of Infectious Diseases._ **16**(S1):e115-119. DOI:org/10.1016/j.ijid.2012.05.258.e112
Tsyrlov, I.B., Shur, I.N., Wu, J., Furman, D.N., Oshchepkov, D.Yu. (August 2014). A proposed mechanism of transactivation by body burden dioxin of Herpes Simplex Virus genes might be responsible for weakening the host antiviral defense”. _Organohalogen Compounds_ **76**:289-292. ISSN:1026-4892
Tsyrlov, I.B., Wu, J., Shur, I.N., Oshchepkov, D.Yu. (July 2016). “Alzheimer’s disease causative viruses HSV-1 and CMV are highly susceptible targets for bHLH/PAS dioxin receptor-Arnt transcription pathway in glial cells”. _Alzheimer's and Dementia. The Journal of the Alzheimer Association_ **12(**7):P632-635. DOI:10.1016/j.jalz.2017.06.2252
Tsyrlov, I.B., Shur, I.N., Appelbaum, J., Wu, J. (June 2017). “AhR-ARNT signaling pathway mediates transcriptional activation of HSV-1 in glial cells: a pathogenic factor that might affect AD development”. _Alzheimer's and Dementia. The Journal of the Alzheimer Association_ **13**(7):P1438-P1439. **DOI: 10.1016/j.jalz.2017.06.2252**
Tsyrlov, I.B., Shur, I.N. (Jan 2023) "Rising level of pulmonary dioxin might trigger CMV and HSV-1 reactivation via bHLH/PAS/AhR:ARNT transcription pathway in lungs of immunocompetent COVID-19 patients with ARDS". _Journal of Biological Chemistry_ **299**(3):S50 (2023). DOI: 10.1016/j.jbc.2023.1031631.2.2
• Contributions to Applied Clinical Research:
• Authentic Model of Human Laennec’ Type Cirrhosis of the Liver (details in section 2.2.1.).
Tsyrlov, I.B., Mishin, V.M., Lyakhovich, V.V. (November 1972). “Resistance of microsomes from CCl4-cirrhotic rat liver to lipoperoxidation activity”. _Life Sciences_ **11**(21):1045-1054. **DOI: 10.1016/0024-3205(72)90206-8**
Mishin, V., Tsyrlov, I., Gromova, O., Lyakhovich, V. (May 1974). “Phospholipids as cinchocaine action site during inhibition of lipoperoxidative reactions in rat liver microsomes”. Hoppe-Seyler’s Zeitschrift fur Physiologische Chemie 355:626-632. ISSN: 0372-9672; Biological Chemistry. **https://doi.org/10.1515/bchm2.1974.355.1.626 **
Tsyrlov, I.B., Lyakhovich, V.V. (May 1975). “Rate-limiting steps in drug metabolism by microsomes from CCl4-cirrhotic rat liver”. _Chemico-Biological Interactions_ **10**:77-89. **DOI: 10.1016/0009-2797(75)90102-7**.• Comparison Between Primary and Secondary Bile Acids' Effects on Hepatic Drug Metabolism in Vitro and in the Course of Cholestasis (details in section 2.2.3.).
Tsyrlov, I.B., Zakharova-Polyakova, N.E., Gromova, O.A., Pospelova, L.N., Lyakhovich, V.V. (October 1978). “An in vivo – in vitro comparison of the effects of bile acids on the structural organization and functional activity of liver microsomal monooxygenases”. _Experimental and Molecular Pathology_ **20**:131-143. **DOI:10.1016/0014-4800(78)90033-3**
Lyakhovich, V.V., Tsyrlov, I.B. ”_Structural Aspects of Monooxygenases Biochemistry_” (“Структурные Аспекты Биохимии Монооксигеназ») (July 1978). Novosibirsk, Nauka Publishing House. Ed. Acad. Rudolf Salganik. 242 pp. **ISBN:21003-743/686-78** Tsyrlov, I.B., Polyakova, N.E., Gromova, O.A. Rivkind, N.B., Lyakhochovih, V.V. (March 1979). “Cholestasis as an in vivo model for analysis of the induction of liver microsomal monooxygenases by sodium phenobarbital and 3-methylcholanthrene”. _Biochemical Pharmacology_ **28**:1473-1478. **DOI: 10.1016/0006-2952(79)90460-X ** • Extrahepatic Tumors Followed by First-Pass Metabolism of Dietary Benzo[a]pyrene in Rodents with Low-Affinity Form of Ah Receptor (details in section 3.2.1.).
Tsyrlov, I.B., Duzchak, T.G. (November 1990). “Interspecies features of hepatic cytochromes P450 IA1 and P450 IA2 in rodents”. _Xenobiotica_ **20**(11):1163-1170. **DOI:10.3109/00498259009046836**
Tsyrlov, I.B., Lyakhovich, V.V. (April 1979). “A comparison of the activities of aryl hydrocarbon monooxygenase in liver microsomes from mice of different strains during prolong 3,4-benzo(a)pyrene administration”. _Biochimica et Biophysica Acta_ **584**:11-20. **ISSN: 0304-4165**
Lyakhovich, V.V., Tsyrlov, I.B. (February 1981). “Индукция Ферментов Метаболизма Ксенобиотиков” (in Russian). _“Induction of Xenobiotic Metabolizing Enzymes_”. 239 pp. Ed. Academician A. Yasaitis. Novosibirsk, Nauka Publishing House. **ISBN: MH-05082**
Goldman, R., Tsyrlov, I.B., Grogan, J., Kagan, V.E. (March 1997). “Reaction of phenoxyl radicals with NADPH-cytochrome P-450 oxidoreductase and NADPH: reduction of the radicals and inhibition of the enzyme”. _Biochemistry_ **36**:3186-3192. DOI: 10.1021/bi9621728 • Human Liver CYP1A2 Rather Than CYP2E1 Represents the Major Monooxygenase Isoform of Microsomal Ethanol-Oxidizing System (MEOS) (details in section 2.4.3.).
Salmela, K.S., Kessova, I.G, Tsyrlov, I.B., Lieber, C.S. (December 1998). “Respective roles of human cytochrome P4502E1, 1A2 and 3A4 in the hepatic microsomal ethanol oxidizing system”. _Alcoholism: Clinical and Experimental Research_ **22**:2125-2132. **DOI: 10.1111/j.1530-0277.1998.tb05926.x**
Chaloupka, K., Santostefano, M., Goldfarb, I.S., Liu, G., Myers, M.J., Tsyrlov, I.B., Gelboin, H.V., Krishnan, V., Safe, S. (December 1994). “Aryl hydrocarbon (Ah) receptor-independent induction of Cyp1a2 gene expression by acenaphthylene and related compounds in B6C3F1 mice”. _Carcinogenesis _**15**:2835-2840. **DOI:10.1093/carcin/15.12.2835**
Tsyrlov. I.B.. Salmela, K.S. (November 1996). "Inhibitory effect of 3-methylcholanthrene on hepatic microsomal ethanol inducible cytochrome CYP2E1 in rats". Mount Sinai Journal of Medicine. _A Journal of Translational and Personalized Medicine_ **64**(1):30-33. **ISSN:0027-2507**• 30 Years of Discovery of Inhibitory/Stimulatory Effects of Bioflavonoids on Human CYP1s and CYP2s (details in section 2.4.2.).
Lyakhovich, V.V., Chasovnikova, O.B., Tsyrlov, I.B (December 1989). "Effect of TCDD and comparable inducers upon synthesis of monooxygenase forms P-450c and P-450d in rats". _Chemosphere_ **18**:715-722. **DOI: 10.1016/0045-6535(89)90187-2**
Tsyrlov, I.B., Mikhailenko, V.M., Gelboin, H.V. (March 1994). “Isozyme- and species-specific susceptibility of cDNA-expressed CYP1A P-450s to different flavonoids”. _Biochimica et Biophysica Acta_ **1205**:325-335. **DOI: 10.1016/0167-4838(94)90252-6**
Tsyrlov, I.B. (October 1998). "Bioflavonoids are Isozyme-Specific Modulators of cDNA-Expressed and Microsomal CYP1s: Structure-Activity Study". _5th International ISSX Meeting_, Cairns, Australia. Volume **1**:17-18• Influenza A Virus NS1BP in Avian Cells Was a Centrepiece of 2005-2007 H5N1 Influenza A Virus Outbreaks in Southeast Asia Regions Contaminated with Dioxin-Like Compounds (details in section 4.5.1.-4.5.3.).
Wu, J., Pokrovsky, A.G., Rumak, V.S., Tsyrlov, I.B. (July 2007). “Regulation of human gene of Influenza A virus-associated NS1-binding protein by 2,3,7,8-TCDD: mechanistic data and epidemiological findings”. _Organohalogen Compounds_ **69**(2):1885-1889. **ISSN:1026-4892**
Tsyrlov, I.B., Shur, I.N., Roumak, V.S. (August 2017). “The NS1A binding protein in alveolar epithelial cells as centerpiece of Influenza virus A lung injury mechanism mediated via AhR/Arnt signaling pathway”. _European Respiratory Journal _**50**:PA352. **DOI:10.1183/1393003.congress-2017.PA352** • Human Herpes Viruses Linked to Inflammatory and Neurodegenerative Pathways Might be trans-Activated by Dioxin in the Low Picomolar Range (details in section 4.5.1.-4.5.3.).
Tsyrlov, I.B., Shur, I.N., Oshchepkov, D.Yu., Pokrovsky, A.G. (June 2012). "Xenobiotical Virology: novel mechanistic concept of hazardous human viruses upregulation by body burden level of dioxins via AhR-mediated transcriptional pathway". _International Journal of Infectious Diseases_. **16**(S1):e115-119. **DOI:org/10.1016/j.ijid.2012.05.258.e112**
Wu, J., Shur, I.N., Tsyrlov, I.B. (July 2008). “Current human body burden of dioxins might upregulate DRE-containing cytomegalovirus (CMV) linked to inflammation and malignancy pathways”. _Organohalogen Compounds_ **70**: 1471-1474 (2008). **ISSN:1026-4892**
Tsyrlov, I.B., Shur, I.N., Wu, J., Furman, D.N., Oshchepkov, D.Yu. (August 2014). "A proposed mechanism of transactivation by body burden dioxin of Herpes Simplex Virus genes might be responsible for weakening the host antiviral defense". _Organohalogen Compounds _**76**:289-292. **ISSN:1026-4892**
Tsyrlov, I., Wu, J., Oshchepkov, D. (June 2017). "Transactivation by Body Burden Dioxin of Herpes Simplex Virus Genes and Cytokines Genes can Weaken the Host Antiviral Defense". _MOJ Cell Science & Report_ **4**(3):1-5. **DOI: 10.15406/mojcsr.2017.04.00089** • Development of Prolonged Release Forms of First-Line Analgesics, Synthetic Opioids, and Antimalarials by Means of Direct Modification of Drug Molecule N-Demethylation Site (details in section 2.3.3.).
Tsyrlov, I.B., Gerasimov, K.G. (May 1986). “New Approach to Production of Prolong Acting Medicines Facilitating Hepatic Drug Detoxification System“. Patent SU/EP: 1457593 A1 4 G 01 N 33/48
Tsyrlov, I.B., Gerasimov, K.G. (June 1991). “Aminopyrine-N-demethylase I. Directed modification of substrates' structure as a way of production of inducer of the monooxygenase isoform P-450b”. _European Journal of Drug Metabolism and Pharmacokinetics_ **16**(3):207-212. **DOI:10.1007/BF03189961**
Tsyrlov, I.B., Woo, C.S.T., Martin, V.P., Shur, I.N. (April 2014). “Modification of CYP2B6-mediated site of metabolism on Artemisinin molecule as a way to prolong its maximal antimalarial efficacy”. _International Journal of Infectious diseases_ **21**(S1):174-177. **DOI:10.1016/j.ijid.2014.03.784**
Tsyrlov, I.B., Shur, I.N. (March 2024) "Site-specific isopropylation of parent molecule as a way to develop artemisinin long-acting antimalarial and anti-cytomegalovirus formulation. _J. Biol. Chem.,_ **300**, S21:1260. (2024). doi.org/10.1016/j.jbc.2024.105825
Tsyrlov, I.B., Shur, I.N. eLetter to _Science_ Editor (July 1, 2024) Title: "Re. Artemisinins ameliorate polycystic ovarian syndrome by mediating LONP1-CYP11A1 interaction". By Yang Liu et al., _Science_, Vol **384**, Issue 6701 (14 JUN 2024). DOI: 10.1126/science.adk5382
Tsyrlov, I., Shur, I. (July 12 2024) Except for women from more vulnerable to malaria groups, a remedy hope for PCOS might be not Coartem® but rather long-acting formulations of oral Artemisinin". By Ilya Tsyrlov and Irina Shur.. Commentary article on July 12, 2024. Science, Vol 384, Issue 6701. DOI:10.1126/science.adk5382 Original Murine Model of Human Clonal Hematopoiesis of Indeterminate Potential (CHIP) (details in section 3.1.3.).
Tsyrlova, I.G., Kozlov, V.A., Tsyrlov, I.B. (April 1986). “A new experimental model for studying bone marrow cells participation in antibody genesis”. _Cytology_ **28**:102-106. **UDC:57.083.3:612.419**1.3
Professional career of Dr. Tsyrlov - in context of studies at Laboratory of Xenobiochemistry; NCI/NIH; MSSM, and current research at Xenotox, Inc.
Education and Scientific Occupation
Tsyrlov attended Novosibirsk Medical University, Russian Federation, graduating with M.D. degree (with distinction) in Internal Medicine, Diploma No. P467542 (1970).
In 1973, Tsyrlov got a Ph.D. degree in Biochemistry (Ph.D. of Вiological Sciences), Thesis: "Structural and Functional Changes of Biological Oxidation Systems During Liver Cirrhosis Development". Scientific Supervisor: Prof. Vyacheslav Lyakhovich. Official Opponents: Prof. Rudolf Salganik, Prof. Yu. Izyumov. Diploma # MBL-01811.
First-time Plenary speaker at International Conference in Turku, Finland (1978)
In 1983, Tsyrlov earned a higher doctorate D.Sci. degree (Doctor of Biological Sciences, Specialty: Biochemistry) from Institute of Experimental Medicine, Russian Academy of Sciences. Thesis: "Induction by Xenobiotics, and Functional Peculiarities of Membrane-Bound Monooxygenases". Official Opponents: Academician R. Salganik, Academician A. Archakov, Prof. V. Gaitzhoki. Diploma # BL 0011240.
For 20 years Tsyrlov held progressively responsible positions of Research Team Leader (1972-79), and Head of Laboratory of Xenobiochemistry (1979-92), at Institute of Experimental and Clinical Medicine (since 1998 - Institute of Molecular Biology and Biophysics, Russian Academy of Sciences. http://www.imbb.soramn.ru/
Collaborating Scientists Through Ilya Tsyrlov' 20 years of Research in the Former Soviet Union:
The early-1970s. "D'Artagnan and Three Musketeers": V. Lyakhovich (late), A. Panov, V. Mishin, I. Tsyrlov.
The early-1980s: V. Lyakhovich (late), V. Mishin, A. Panov, V. Ostashevsky, O. Khatsenko, V. Solovjev (late), K. Gerasimov, D. Maletin.
The mid-1980s: A. Grishanova, V. Mishin, D. Mishina, V. Vavilin, L. Vavilina, O. Gromova (late), A. Panov, N. Gutkina, S. Makarova, A. Chasovnikov, L. Gulyaeva, O. Kondrashova-Chasovnikova, I. Balzovskaya.
The late-1980s: Yu. Levin, N. Gutkina, K. Gerasimov, N. Kozlovskaya, V. Ostashevsky, A. Grishanova.
The mid-1990s: N. Slinko, O. Chasovnikova, T. Subhankulova, I. Tsyrlov (visited from USA), S. Kovalenko, V. Vavilin, A. Grishanova, I. Kessova, N. Polyakova, A. Panov (visited from USA), unknown person, L. Gulyaeva.
The mid-2000s: I. Tsyrlov (visited from USA), L. Gulyaeva, V. Lyakhovich (late).
In 1990, the US National Institutes of Health (NIH) designated Tsyrlov an "internationally recognized scientist with a distinguished record of accomplishment", granting him the position of Senior Staff Fellow (Enzymology) in Laboratory of Molecular Carcinogenesis (headed by Harry V. Gelboin) at National Cancer Institute/NIH, where Tsyrlov worked till 1995. Thereafter, he consequently held positions of Research Associate Professor/Research Professor/Visiting Research Professor in the Department of Medicine and the Division of Occupational and Environmental Medicine, Mount Sinai School of Medicine (since 2012 - Icahn School of Medicine at Mount Sinai), New York, NY. In 2005, Tsyrlov founded the Xenotox, Inc., a life sciences consulting company certified with New York State, where he served a Chief Scientific Officer. In 2009, Dr. Tsyrlov became the company's President/CEO. A non-for-profit Xenotox, Inc. is implementing an earlier discovered site-directed synthesis of long-acting medications, and thoroughly studying the transactivation of the latent human herpesviruses by dioxin-like compounds situated inside target cells in the picomolar range.
1.4
Co-authors, Fellow Scientists and Advisors Collaborating with Laboratory of Xenobiochemistry and Xenotox, Inc.
1.5.1
Recognitions
In 1980, Russian Government Higher Attestation Commission and the Ministry of Education and Science awarded Dr. Tsyrlov the "Distinguished Senior Scientist” title (Certificate #CH 18029), the accolade bestowed on notable national researchers.
RAS Academician Abel G. Aganbegyan handed over a Doctor of Sciences Diploma (autumn of 1983).
In 1978-1980, Tsyrlov had participated in the organizing drug metabolism scientists from 45 countries into novel International Society for Study of Xenobiotics, ISSX (www.issx.org), which currently is one of the largest research societies worldwide. He has served a Contributing Editor of ISSX Newsletter (1981-91), a member of the International Scientific Affairs Committee (1992-99) and the Nominating Committee (1991-97). In 2015, the ISSX Council elected Ilya Tsyrlov its Honorable Emeritus Fellow. https://www.issx.org/page/Emeritus_List?&hhsearchterms file:///Users/ilyatsyrlov/Documents/DOCUMENTS/Ilya%20Documents/2016%20Ilya%20B.%20Tsyrlov%20-%20International%20Society%20for%20the%20Study%20of%20Xenobiotics.html
With ISSX co-founder Academician Ron W. Estabrook and Prof. Fred P. Guengerich at the Xenobiochemistry Congress in Bratislava (1980).
Editorship at the ISSX journal (back cover)
In 1989, Tsyrlov got a special invitation from the Rutgers' Robert Wood Johnson Medical School and Environmental and Occupational Health Sciences Institute, and delivered the Rutgers' "First Special Lecture of the International Program" titled "Biological & Medical Aspects of Polychlorinated Dioxins", for what an Academician Allan H. Conney bestowed on him the "Distinguished Achievement Award".
In 1992, Tsyrlov was granted by the US government an Alien of Extraordinary Ability (category EB-1A) reserved for distinguished foreign national professionals https://www.immi-usa.com/eb1-green-card/eb-1-extraordinary-ability/. The same year he became a Fellow of Fogarty International Center at National Cancer Institute (NIH).
In 1992-1993, Tsyrlov passed thru multi-step selection by the World Health Organization (WHO) Council to the final candidate for the post of Director of the International Agency for Research on Cancer (IARC).
In 2006, Tsyrlov was specially invited to deliver the US EPA's Distinguished Lecture on "The Role of Body Burden 2,3,7,8-TCDD in Triggering Malignancy-Associated Human Viruses: From Early Data to Mechanistic Concept".
US EPA Lecture July252006 (5).pdf
In 1980s-2010s, Tsyrlov has been invited to give lectures and seminars to the university academics and researchers in 14 countries, international research companies (Hoechst AG/Frankfurt; Merck Sharp/Rahway; Boehringer Ingelheim/Ridgefield; etc.) and governmental agencies in USA (NIH, EPA, DHHS, CDC) and UK (Imperial Cancer Fund). Tsyrlov has served a member of Organizing Committee of International meeting DIOXIN'1985, Germany; International ISSX Meeting'1995, USA; DIOXIN meeting'2006, Norway; Alzheimer's Association International Conference'2016, Canada; Influenza Congress'2017, UK; Infectious Diseases Congress'2018, Japan; etc. He was (together with Vyacheslav Lyakhovich) an Editor of “Cytochrome P450 and Environment” book (1987), and edited several congressional proceedings on drug metabolism and various aspects of hazard xenobiotics. He served a Session Chair/Plenary lecturer at eleven national/international meetings, and a Keynote Speaker at nine national/international congresses. Since the 1990s, Tsyrlov has been a senior reviewer of the International Human Frontier Science Program. Also, he served an officer/fellow of European Society of Biochemical Pharmacology, Liver Diseases and Hepatitis Program, ASBMB, American Cancer Society, Society of Environmental Toxicology and Chemistry, The Biochemical Society, AAAS, SOT, FAS.
An open-minded public speaker, Tsyrlov has exposed environmental issues of hazard xenobiotics that affect human health. He addressed environmental health problems that existed throughout the Soviet Union/Russia (“The Ailing Mother Russia”. ''Environmental Health Perspectives'' 102, Feb 1994 1994 paper in EHP .pdf. The same year Tsyrlov was invited as a distinguished member to US CDC and Citizen Ambassador Program' delegation to attend a conference with the Russian Ministry of Environmental Protection, held in Moscow. With the President of Fishkill Ridge Caretakers, Inc., P. Rostenberg, Tsyrlov petitioned on behalf of the Superfund Research Program to then Governor of New York State George Pataki to support clean up of the toxic polychlorinated biphenyls deposited over 30 years by the General Electric Corporation in the Hudson River (“GE wants to stick to own PCB control” and other articles in the ''Poughkeepsie Journal'' (2000-02).
In 2006, Tsyrlov was specially invited to the International Scientific Conference “Victims of Agent Orange/Dioxin in Vietnam – the Expectation” held in Hanoi, where he made two keynote scientific communications on damaging effects of dioxin-like compounds (DLC). Tsyrlov chaired meetings of American and Vietnamese scientists and widows of Vietnam War fallen warriors. For that the Vietnamese government bestowed him with Ly-Viet Hands antique. In 2005-07, Tsyrlov consulted the US government in international issues on dioxins toxicity and was awarded by then US Vice President Richard Cheney.
In 2017, Tsyrlov was elected a Member/Fellow of the ALZFORUM (Alzheimer Research Forum) https://www.alzforum.org/member-directory/ilya-b-tsyrlov
In 2021, an Article about Ilya B. Tsyrlov was editorially contributed to The English Wikipedia (https://en.wikipedia.org/wiki/Ilya_B._Tsyrlov), which by October 2024 accumulated 7,400+ page visits.
In 2022, Tsyrlov was selected to the New York CEO Club as a Founder/President of the Xenotox, Inc. (http://ifbusy.org/ceonewyork/).
In 2023, Tsyrlov was designated a National Member in the Smithsonian Institution.
In 2022-2023, Tsyrlov has been recommended by a Nobel Prize winner Dr. Harald zur Hausen, and a member of the National Academy of Science (NAS USA) Dr. Bettie Sue Masters to be elected into membership of the National Academy of Medicine (NAM USA).
In 2023, Tsyrlov was designated an Emeritus Member of the Metabolomics Society.
1.5.2
Author-level bibliometrics analysis
• Tsyrlov' Google Scholar h-index is 30; and Google Scholar Citation number is 3,614
https://scholar.google.com/citations?user=pwb2jxcAAAAJ&hl=en
• Tsyrlov' journal articles/lectures/seminars/discussions have been fully read/downloaded by 64,500+ scientists
https://www.researchgate.net/profile/Ilya_Tsyrlov
• The English Wikipedia article about Ilya B. Tsyrlov has been read by 7,400+ page visitors
https://en.wikipedia.org/wiki/Ilya_B._Tsyrlov
1.6
Publications
Dr. Tsyrlov has published 6 books,
16 reviews and book chapters, and 280+ peer-reviewed papers in world's academic research journals with the SNIP of 5.0 and higher, and Impact Factor of 7 and higher, namely: Science, Archives of Biochemistry and Biophysics; Biochemistry; The Biochemical Journal; The Journal of Biological Chemistry; Carcinogenesis; Chemosphere; Drug Metabolism and Disposition; Chemico-Biological Interactions; The FASEB Journal; FEBS Letters; Experimental and Molecular Pathology; Hoppe-Seyler's Zeitschrift für Physiologische Chemie; Journal of Viral hepatitis; Lancet Infectious Diseases; Alcoholism: Clinical and Experimental Research; Life Sciences; International Journal of Infectious Diseases; Environmental Health Perspectives; Alzheimer’s and Dementia (The Journal of the Alzheimer’s Association); Virology Research Journal; European Respiratory Journal; Drug Metabolism Reviews; Xenobiotica.
Books:
• Ilya Tsyrlov: "POLYCHLORINATED DIOXINS: BIOLOGICAL AND MEDICAL ASPECTS". The National Academy of Sciences, 1990, 239 pp. + illustrations edited by Academician V. Vlassov, 01/1990; NAUKA Publishing House, ISBN: BBK P 284.6 50300-887-1990
• Vyacheslav Lyakhovich and Ilya Tsyrlov (editors) "CYTOCHROME P-450 AND ENVIRONMENT". 1987, 411 pp. National Academy of Sciences Publishing House.
• Ilya Tsyrlov: Genetic Variations in Cytochrome P-450(P-448) Catalytic Centers Activities in Relation to Subsequent Conjugation Reactions. CONJUGATION REACTIONS IN DRUG BIOTRANSFORMATION, Amsterdam-New York-Oxford. Edited by A. Aitio, 01/1978: Elsevier/North-Holland Biomedical Press., ISBN: 0-444-80090-5
• Vyacheslav Lyakhovich and Ilya Tsyrlov: "INDUCTION OF XENOBIOTICS METABOLIZING ENZYMES". National Academy of Science, Edited by Academician A. Yasaitis, 1981; Science Press, 341 pp.., ISBN: 50300-737 18-14-1980
• Vyacheslav Lyakhovich and Ilya B. Tsyrlov: "STRUCTURAL ASPECTS OF MONOOXYGENASES BIOCHEMISTRY", Edited by Academician R. Salganik, 1978; 337 pp., "Science Press", ISBN: 21003-743 686-78
• Ilya Tsyrlov: Factors Controlling Induction of Different Forms of P-450 in the Liver. MOLECULAR MECHANISMS OF CELLULAR HOMEOSTASIS, National Academy of Science. Edited by Academician I. Gitelzon, 01/1987; NAUKA Publishing House., ISBN: 50303-747 18-14-1987Book Chapters (marked with •) & Reviews:
• Ilya Tsyrlov, Vladimir Ostashevsky, K. Gerasimov, V. Roumak: Characteristics of Hepatic and Lymphocyte Monooxygenases in South Vietnam' People with Chlorophenoxy Herbicides Exposure. IARC monographs on the evaluation of carcinogenic risks to humans. Volume 113., Supplement 06/2015; volume 113 06/2015; World Health Organization, International Agency for Research on Cancer, WHO.
• Ilya Tsyrlov, Vladimir Ostashevsky: 389:;<= <8>?@9@<=ABC@D@ @>89A;C8E >9;C@F8@:8>@G G A8<H@I8:=J \>?@G8 K8:;A;L .B;:C=<=, M@NG;?D=GO8J9E G@PN;L9:G8Q N8@>98C@G. «0*123*45 – 36789123*0:4;5 21-<& "82:», Russian National Academy of Science, Institute of Animal Evolution; Edited by G. Sofronov & V. Roumak, 09/2006: chapter 3, pages 77-95; NAUKA/Elsevier Interperiodica.
• Ilya Tsyrlov: DIOXIN-LIKE CHLOROPHENOXY HERBICIDES MIGHT AUGMENT HUMAN COMMON VIRUSES ASSOCIATED WITH CELL MALIGNIZATION. "Victims of the Agent Orange/Dioxin in Vietnam", March 2006. Edited by Ngueng Thi Bing, 03/2006: pages 149-155; FFRP Publishing House, Hanoi, Vietnam.
• Ilya Tsyrlov: The Membrane Aspects of the Regulation of Monooxygenases. Industrial and Environmental Xenobiotics, Edited by J. Fouts, I. Gut, 01/1978: pages 87-99; Springer, Amsterdam.
• Ilya Tsyrlov, Nikolay Rivkind, V. Lyakhovich: Metabolism of Polycyclic Hydrocarbons in the Liver of Different Murine Strains in the Course of Chemical Carcinogenesis. Industrial and Environmental Xenobiotics, Edited by Editors: J. Fouts, I. Gut, 01/1978: pages volume 2, pp. 164-184; Springer, Amsterdam.
• Vyacheslav Lyakhovich, Ilya Tsyrlov, V. Mishin, O. Gromova: Reconstitution of the Microsomal System of Xenobiotic Metabolism. Industrial and Environmental Xenobiotics, Publisher:, Edited by Editors: J. Fouts, I. Gut, 01/1978: pages 1: 99-108; Springer, Amsterdam.
• Ilya Tsyrlov, Olga Gromova, V. Lyakhovich: Different Phospholipid-Dependent Hydrophobic Zones in Microsomal Membrane Surrounding Cytochrome P-450. Physico-Chemical Basics of Function of Supermolecular Cellular Structures (dedicated to the late Academician A. Belozersky), Edited by A. Belozersky, V. Skulachev, 01/1974: pages volume 2, pp. 120-133; Moscow University Academic Press.
• Olga Gromova, Ilya Tsyrlov, V. Mishin, N. Zakharova, V. Lyakhovich: Cytochromes P-450 and P-448 Have Different Resistance to the Factors Destabilizing Microsomal Membrane. Physico-Chemical Basics of Function of Supermolecular Cellular Structures (dedicated to the late Academician A. Belozersky),, Edited by Edited by A. Belozersky, V. Skulachev, pages volume, 01/1974: pages vol. 1:61-67; Moscow University Academic Press.
Tsyrlov I.B., Shur I.N., Wu J.S., Roumak V.S. 2005-2007 Global Spread of H5N1: Causative Role of Body Burden Dioxin in Up-Regulating Gene of Influenza Virus NS1 Protein in Chicken and Humans in Southeast Asia. Lecture at Global Congress on Bacteriology and Infectious Diseases, Amsterdam, Netherlands, Jun 2018.
Tsyrlov I.B., Wu J.S., Shur I.N., Oshchepkov D.Yu. Human Herpes Viruses as a Novel Target for bHLH/PAS Dioxin Receptor-Arnt Transcription Factor: Basic Findings & Clinical Implications. Lecture at Global Experts Meeting on Infectious Diseases, Tokyo, Japan, Sept 2018.
Ilya B. Tsyrlov. Irina Shur, Vladimir Roumak. The NS1A binding protein in alveolar epithelial cells as centerpiece of Influenza virus A lung injury mechanism mediated via AhR/Arnt signaling pathway. Lecture at ERS International Congress 2017, Sept 2017.
Tsyrlov I.B. Keynote Lecture on "Xenobiotical Virology: Basic Definition & Clinical Implications". CSDD-2016, Jul 2016.
Ilya B. Tsyrlov. Survey of Russian Publications on Xenobiotics. ISSX Newsletter. 01/1989; Volume 8, Number 3, pp. 5-8, Jan 1989.
Ilya B. Tsyrlov HALOBIPHENYLS - NEW CLASS OF XENOBIOTICS-INDUCERS OF MULTIPLE MOLECULAR FORMS OF CYTOCHROME P-450. Biological Reviews.106 (4):85-101, Jan 1988
I. B. Tsyrlov, V. V. Lyakhovich. Biological aspects of genetic regulation of monooxygenase induction by polycyclic hydrocarbons. Biological Reviews, 88(2):181-97, Feb 1979.
I. B. Tsyrlov, V. V. Lyakhovich. Role of microsomal phospholipids in the organization and regulation of the activity of monooxygenases. Biological Reviews, 84(1):13-21, Feb 1977.Journal publications (not completed yet):
PDF list of journal publications; not completed yet
Patent
Ilya Tsyrlov and K. Gerasimov: Mode of Production of Long-Acting Drugs Capable of Induction of Mono-Oxygenase System in Human Liver. Ref. No: 145759 3 (Claim # 4105655), Year: 05/1988