DOCSLIB.ORG

(12) United States Patent (10) Patent No.: US 9,687,493 B2 Weglicki Et Al

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
(12) United States Patent (10) Patent No.: US 9,687,493 B2 Weglicki Et Al US009687493B2 (12) United States Patent (10) Patent No.: US 9,687,493 B2 Weglicki et al. (45) Date of Patent: *Jun. 27, 2017 (54) USE OF NK-1 RECEPTOR ANTAGONISTS ionized Mg, Mg metabolism and electrolytes in serum of human FOR TREATING HYPOMAGNESEMLA, volunteers.” Journal of the American College of Nutrition, 1994; NEUROGENIC INFLAMMATION, AND 13(5): 447-454. CARDAC DYSFUNCTIONASSOCATED Barbagallo et al., “Magnesium homeostasis and aging.” Magnesium WITH EGFR-BLOCKING DRUGS Research, 2009; 22(4): 235-246. Cao et al., “Methionine Sulfoxide reductase B1 (MSrB1) recovers TRPM6 channel activity during oxidative stress.” Journal of Bio (71) Applicant: THE GEORGE WASHINGTON logical Chemistry, Aug. 20, 2010; 285(34):26081-7. UNIVERSITY, Washington, DC (US) Chen et al., “Mechanisms of cardiac dysfunction associated with tyrosine kinase inhibitor cancer therapeutics.” Circulation, 2008; (72) Inventors: William B. Weglicki, Potomac, MD 117: 84-95. (US); Iu Tong Mak, Gaithersburg, MD Dehlin et al., “Substance P acting via the neurokinin-1 receptor regulates adverse myocardial remodeling in a rat model of hyper (US) tension.” International Journal of Cardiology, 2013 12; 168(5):4643-51. (73) Assignee: THE GEORGE WASHINGTON Dimke et al., “Effects of the EGFR Inhibitor Erlotinib on Magne UNIVERSITY, Washington, DC (US) sium Handling.” Journal of the American Society of Nephrology, Aug. 2010; 21 (8): 1309-16. doi:10.1681/ASN. 2009111153. Epub (*) Notice: Subject to any disclaimer, the term of this Jul. 1, 2010. patent is extended or adjusted under 35 Doherty et al., “Multi-parameter in vitro toxicity testing of crizotinib, Sunitinib, erlotinib, and nilotinib in human U.S.C. 154(b) by 0 days. cardiomyocytes.” Toxicology and Applied Pharmacology, Oct. 1, This patent is Subject to a terminal dis 2013; 272(1):245-55. doi:10.1016/j.taap.2013.04.027. Epub May claimer. 21, 2013. Fletcher et al., “EGFR inhibition induces proinflammatory cytokines via NOX4 in HNSCC.” Molecular Cancer Research, Dec. (21) Appl. No.: 15/278,192 2013; 11(12): 1574-84. doi: 10.1158/1541-7786.MCR-13-0187. Epub Sep. 18, 2013. (22) Filed: Sep. 28, 2016 Garrett et al., “Cetuximab in the treatment of patients with colorectal cancer.” Expert Opinion on Biological Therapy, 2011; 11: (65) Prior Publication Data 937-949. Gill et al., “NADPH oxidases in the kidney.” Antioxidants and US 2017/OO14420 A1 Jan. 19, 2017 Redox Signaling, 2006; 8:1597-1607; 23. Groenestege et al., “Impaired basolateral sorting of pro-EGF causes isolated recessive renal hypomagnesemia.” Journal of Clinical Related U.S. Application Data Investigation, 2007: 117: 2260-2267. Hahn et al., “Cancer therapy-induced cardiotoxicity: basic mecha (63) Continuation of application No. 14/735,396, filed on nisms and potential cardioprotective therapies.” Journal of the Jun. 10, 2015, now Pat. No. 9,474,761. American Heart Association, Apr. 22, 2014:3(2):e()00665. doi:10. 1161 JAHA113.00.0665. Hasinoff, B.B., “The cardiotoxicity and myocyte damage caused by (60) Provisional application No. 62/010, 198, filed on Jun. Small molecule anticancer tyrosine kinase inhibitors is correlated 10, 2014. with lack of target specificity.” Toxicology and Applied Pharma cology, 2010:244(2): 190-195. (51) Int. Cl. Ho et al., “Human monocytes and macrophages express Substance A 6LX 3/5.377 (2006.01) P and neurokinin-1 receptor.” Journal of Immunology, 1997; 159:5654-5660. A6 IK3I/00 (2006.01) Imai et al., “Comparing antibody and Small-molecule therapies for A6 IK 3/4035 (2006.01) cancer.” Nature Reviews. Cancer. Sep. 2006;6(9):714-27. Review. A6 IK3I/444 (2006.01) International Cosmetic Ingredient Dictionary and Handbook, eds. A6 IK 3/4985 (2006.01) Wenninger and McEwen, pp. 1656-1661, 1626, 1654-1655, 1673 A6 IK 3/495 (2006.01) 1686 and 1693-1697 (The Cosmetic, Toiletry, and Fragrance Assoc. (52) U.S. Cl. Washington, D.C., 7th Edition, 1997). CPC .......... A6 IK3I/5377 (2013.01); A61 K3I/00 Janjigian et al., “Phase I/II trial of cetuximab and erlotinib in (2013.01); A61K 31/4035 (2013.01); A61 K patients with lung adenocarcinoma and acquired resistance to 3 1/444 (2013.01); A61K 31/495 (2013.01); erlotinib.” Clinical Cancer Research, Apr. 15, 2011;17(8): 2521-7. A61K 31/4985 (2013.01) Epub Jan. 19, 2011. (58) Field of Classification Search (Continued) None Primary Examiner — Brian J Davis See application file for complete search history. (74) Attorney, Agent, or Firm — Cooley LLP (56) References Cited (57) ABSTRACT The present disclosure provides methods for alleviating or U.S. PATENT DOCUMENTS preventing the negative physiological side effects associated with the administration of EGFR blocking therapeutics. The 9,474,761 B2 * 10/2016 Weglicki ............ A61K 31,5377 disclosure provides, inter alia, methods for treating or pre venting: hypomagnesemia, cardiac dysfunction, and skin OTHER PUBLICATIONS lesions, which are induced by EGFR blocking drugs, by Altura et al., “Comparative effects of a Mg-enriched diet and administering an NK-1 receptor antagonist. different orally administered magnesium oxide preparations on 18 Claims, 10 Drawing Sheets US 9,687,493 B2 Page 2 (56) References Cited Saif M.W., “Management of hypomagnesemia in cancer patients receiving chemotherapy.” Journal of Supportive Oncology, May Jun. 2008;6(5):243-8. OTHER PUBLICATIONS Sawyers C. “Targeted cancer therapy.” Nature, 432:294-297, 2004. Schettino et al. “Erlotinib: an EGF receptor tyrosine kinase inhibitor Kramer et al., “Dietary Mg-intake influence circulating pro-inflam in non-Small-cell lung cancer treatment.” Expert Review of Respi matory neuropeptide levels and loss of myocardial tolerance to ratory Medicine, Apr. 2008:2(2):167-78. doi:10.1586/17476348.2. postischemic stress.” Experimental Biology and Medicine, 2003; 2,167. 228:665-673. Kramer et al., “Neurogenic inflammation and cardiac dysfunction Tejpar et al., “Magnesium wasting associated with epidermal due to hypomagnesemia.” American Journal of the Medical Sci growth-factor receptor-targeting antibodies in colorectal cancer: a ences, 2009; 338(1):22-27. prospective study.” The Lancet. Oncology, 2007, 8:387-394. Ledeganck et al., “The TRPM6/EGF pathway is downregulated in Thebault S et al., “EGF increases TRPM6 activity and surface a rat model of cisplatin nephrotoxicity.” PLoS One, expression.” Journal of the American Society of Nephrology, Jan. 2013;8(2):e57016. doi: 10.1371/journal.pone.0057016. Epub Feb. 2009:20(1):78-85. Epub Dec. 10, 2008. 15, 2013. Van Angelen et al., “Cisplatin-induced injury of the renal distal Lockhart et al., “The epidermal growth factor receptor as a target for convoluted tubule is associated with hypomagnesaemia in mice.” colorectal cancer therapy.” Seminars in Oncology, 2005; 32: 52-60. Mak et al., “Loss of neutral Endopeptidase activity contributes to Nephrology Dialysis Transplant, 2013; 28:879-89. neutrophil activation and cardiac dysfunction during chronic Vickers et al., “Association of hypomagnesemia with inferior Sur hypomagnesemia: Protection by Substance P receptor blockade.” vival in a phase III, randomized study of cetuximab plus best Experimental and Clinical Cardiology, 2011;16(4): 121-124. supportive care versus best supportive care alone: NCIC CTG/ Mak et al., “EGFR-TKI, erlotinib, causes hypomagnesemia, oxida AGITG CO. 17.” Annals of Oncology, Apr. 2013; 24(4):953-60. tive stress, and cardiac dysfunction: attenuation by NK-1 receptor Weglicki WB, et al., “Neutral endopeptidase inhibition enhances blockade.” Journal of Cardiovascular Pharmacology, Jan. 2015; Substance P mediated inflammation due to hypomagnesemia.” Mag 65(1):54-61. nesium Research, 2009; 22:1-7. Mak et al., “Suppression of neutrophil and endothelial activation by Weglicki et al., “Pathobiology of magnesium deficiency: A Substance P receptor blockade in the Mg-deficient rat.” Magnesium cytokine/neurogenic inflammation hypothesis.” American Journal Research, 2003; 16(2):91-97. of Physiology, 1992; 263: R734-R737. Mak, et al., “Mg Supplementation Attenuates Ritonavir-induced Weglicki et al., “The EGFR tyrosine kinase inhibitor tyrphostin Hyperlipidemia, Oxidative Stress and Cardiac Dysfunction in AG-1478 causes hypomagnesemia and cardiac dysfunction.” Cana Rats.” American Journal of Physiology: Regulatory, Integrative and dian Journal of Physiology of Pharmacology, 2012; 90(8): 1145-9. Comparative Physiology, 2013: 305: R1102-R1111. Weglicki et al., “The role of Magnesium Deficiency in Cardiovas Mak, et al., “AZT-Induced cardiovascular toxicity—attenuation by cular and Intestinal Inflammation.” Magnesium Research, 2012; Mg-Supplementation.” Cardiovascular Toxicology, 2009; 9(2):78 23(4): S199-206. 85. Weglicki et al., “Role of free radicals and substance P in magnesium McCutcheon's Detergents and Emulsifiers, North American Edi deficiency.” Cardiovascular Research, 1996:31:677-682. tion, pp. 317-324 (1986). Yang B et al., “Tyrosine kinase inhibitor (TKI)-induced cardiotoxic Metro, et al., “Epidermal growth factor receptor (EGFR) targeted ity: approaches to narrow the gaps between preclinical safety therapies in non-small cell lung cancer (NSCLC).” Rev Recent Clin evaluation and clinical outcome.” Journal of Applied Toxicology, Trials. Jan. 2006;1(1): 1-13. Dec. 2012; 32(12):945-51. doi: 10.1002/jat.2813. Epub Sep. 10, Nistala et al., “Redox control of renal function and hypertension.” 2012. Review. Antioxidants and Redox Signaling, Dec. 2008; 10(12):2047-89. doi: Vincenzi et al., "Aprepitant for Erlotinib-Induced Pruritus.” New 10.1089, arS2008.2034. England Journal of Medicine,
Load more

Recommended publications
  • A Randomized, Double-Blind, Placebo-Controlled Study
    medRxiv preprint doi: https://doi.org/10.1101/2020.04.06.20055715; this version posted April 11, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . 1 Mo%on Sifnos: A randomized, double-blind, placebo-controlled study demonstra%ng the effec%veness of tradipitant in the treatment of mo%on sickness Vasilios M. Polymeropoulos*1, Mark É. Czeisler1#a, Mary M. Gibson1¶, Aus%n A. Anderson1¶, Jane Miglo1#b, Jingyuan Wang1, Changfu Xiao1, Christos M. Polymeropoulos1, Gunther Birznieks1, Mihael H. Polymeropoulos1 1 Vanda Pharmaceu%cals, Washington, District of Columbia, United States of America #a The Ins%tute for Breathing and Sleeping, Aus%n Health, Heidelberg, Victoria, Australia #b College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois, United States of America *Corresponding author Email: [email protected] (VMP) ¶These authors contributed equally to this work. NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice. medRxiv preprint doi: https://doi.org/10.1101/2020.04.06.20055715; this version posted April 11, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . 2 Abstract Background Novel therapies are needed for the treatment of mo%on sickness given the inadequate relief, and bothersome and dangerous adverse effects of currently approved therapies.
    [Show full text]
  • Neurokinin Receptor NK Receptor
    Neurokinin Receptor NK receptor There are three main classes of neurokinin receptors: NK1R (the substance P preferring receptor), NK2R, and NK3R. These tachykinin receptors belong to the class I (rhodopsin-like) G-protein coupled receptor (GPCR) family. The various tachykinins have different binding affinities to the neurokinin receptors: NK1R, NK2R, and NK3R. These neurokinin receptors are in the superfamily of transmembrane G-protein coupled receptors (GPCR) and contain seven transmembrane loops. Neurokinin-1 receptor interacts with the Gαq-protein and induces activation of phospholipase C followed by production of inositol triphosphate (IP3) leading to elevation of intracellular calcium as a second messenger. Further, cyclic AMP (cAMP) is stimulated by NK1R coupled to the Gαs-protein. The neurokinin receptors are expressed on many cell types and tissues. www.MedChemExpress.com 1 Neurokinin Receptor Antagonists, Agonists, Inhibitors, Modulators & Activators Aprepitant Befetupitant (MK-0869; MK-869; L-754030) Cat. No.: HY-10052 (Ro67-5930) Cat. No.: HY-19670 Aprepitant (MK-0869) is a selective and Befetupitant is a high-affinity, nonpeptide, high-affinity neurokinin 1 receptor antagonist competitive tachykinin 1 receptor (NK1R) with a Kd of 86 pM. antagonist. Purity: 99.67% Purity: >98% Clinical Data: Launched Clinical Data: No Development Reported Size: 10 mM × 1 mL, 5 mg, 10 mg, 50 mg, 100 mg, 200 mg Size: 1 mg, 5 mg Biotin-Substance P Casopitant mesylate Cat. No.: HY-P2546 (GW679769B) Cat. No.: HY-14405A Biotin-Substance P is the biotin tagged Substance Casopitant mesylate (GW679769B) is a potent, P. Substance P (Neurokinin P) is a neuropeptide, selective, brain permeable and orally active acting as a neurotransmitter and as a neurokinin 1 (NK1) receptor antagonist.
    [Show full text]
  • Stembook 2018.Pdf
    The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances FORMER DOCUMENT NUMBER: WHO/PHARM S/NOM 15 WHO/EMP/RHT/TSN/2018.1 © World Health Organization 2018 Some rights reserved. This work is available under the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 IGO licence (CC BY-NC-SA 3.0 IGO; https://creativecommons.org/licenses/by-nc-sa/3.0/igo). Under the terms of this licence, you may copy, redistribute and adapt the work for non-commercial purposes, provided the work is appropriately cited, as indicated below. In any use of this work, there should be no suggestion that WHO endorses any specific organization, products or services. The use of the WHO logo is not permitted. If you adapt the work, then you must license your work under the same or equivalent Creative Commons licence. If you create a translation of this work, you should add the following disclaimer along with the suggested citation: “This translation was not created by the World Health Organization (WHO). WHO is not responsible for the content or accuracy of this translation. The original English edition shall be the binding and authentic edition”. Any mediation relating to disputes arising under the licence shall be conducted in accordance with the mediation rules of the World Intellectual Property Organization. Suggested citation. The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances. Geneva: World Health Organization; 2018 (WHO/EMP/RHT/TSN/2018.1). Licence: CC BY-NC-SA 3.0 IGO. Cataloguing-in-Publication (CIP) data.
    [Show full text]
  • Chronic Itch Clinical Cases & Management
    Chronic Itch Clinical Cases & Management Gil Yosipovitch MD FAAD Professor & Director Miami Itch Center DISCLOSURE Disclosures WITH INDUSTRY • Advisory Boards: Trevi, Pfizer, Sanofi, Menlo, Galderma, Sienna • Consultant: Opko LEO, J&J, Menlo, Novartis • PI; Tioga, Roche, Pfizer, Allergen • Funded:, GSK, LEO Foundation, Pfizer, Sun Pharma Outline • Understanding itch of different types • Pathophysiology of itch in PN and its treatment • Atopic itch and its new management • Itch without rash and its management • Neuropathic itch Stander et al. IFSI consensus group. Acta Dermatol 2007 Yosipovitch & Bernhard NEJM 2013 Important Questions to Ask an Itchy Patient • Duration: years/weeks/days • Severity • Localization; generalised/ localized/ • Periodicity; paroxysmal, continuous, occurring in short bouts, nocturnal • Affect on sleep • History of itch in other personal contacts • Factors that exacerbate itch; heat, water, dryness • Factors that alleviate itch (drugs or cooling agents) • Drugs (opiates, aspirin, penicillin, antimalarials) • History of atopy • Travel history PN in African Americans and AD • Population coding • Molecular specificity of receptor activation TSLP IL-33 ST2 TSLPR Il-31 IL-31R Mrgprs H H1, H4 NPPB GRP NPRA Yosipovitch and Bernhard, NEJM. 2013 Apr 25; 368 (17):1625. GRPR Prurigo Nodularis Itch Neurogenic Activation of inflammation, retrograde attraction of signaling inflammatory pathways cells ‘Axiotomy’ of epidermal Scratching peripheral nerve endings Various Forms of Prurigo The first three may develop subsequently Zeidler et al. Acta Derm Venereol. 2018 Treatment for PN . m- and kappa opioid receptor of Step antagonists sleep . Immunosuppressants the . Thalidomide injection 4 . NK-1 inhibitors treat treatment : . Topical KAL , Capsaicin Step 3 . Antidepressants intralesional , necessary if concomitant ); emollients , . Gabapentinoids lesions Step 2 psychsomatic single , disease (in .
    [Show full text]
  • Neurokinin-1 Antagonist Orvepitant for EGFRI- Induced
    Open access Original research BMJ Open: first published as 10.1136/bmjopen-2019-030114 on 6 February 2020. Downloaded from Neurokinin-1 antagonist orvepitant for EGFRI- induced pruritus in patients with cancer: a randomised, placebo- controlled phase II trial Bruno Vincenzi ,1 Mike Trower ,2 Ajay Duggal ,3 Pamela Guglielmini ,4 Peter Harris ,2 David Jackson ,5 Mario E Lacouture ,6 Emiliangelo Ratti ,2 Giuseppe Tonini ,1 Andrew Wood ,7 Sonja Ständer 8 To cite: Vincenzi B, Trower M, ABSTRACT Strengths and limitations of this study Duggal A, et al. Neurokinin-1 Objective To evaluate the efficacy of orvepitant (10 or antagonist orvepitant for 30 mg given once daily, orally for 4 weeks), a neurokinin-1 EGFRI- induced pruritus ► The RELIEVE 1 study was the first randomised, in patients with cancer: a receptor antagonist, compared with placebo in reducing double- blind, placebo- controlled study of a neuroki- randomised, placebo- controlled the intensity of epidermal growth factor receptor inhibitor nin-1 antagonist for epidermal growth factor recep- phase II trial. BMJ Open (EGFRI)- induced intense pruritus. tor inhibitor- induced pruritus. 2020;10:e030114. doi:10.1136/ Design Randomised, double- blind, placebo- controlled ► Patients reported scores for the primary endpoint of bmjopen-2019-030114 clinical trial. reduction of itch intensity on a daily basis using an ► Prepublication history for Setting 15 hospitals in Italy and five hospitals in the UK. interactive voice response system. this paper is available online. Participants 44 patients aged ≥18 years receiving an ► Effects on sleep and quality of life were also To view these files, please visit EGFRI for a histologically confirmed malignant solid tumour measured.
    [Show full text]
  • WO 2018/005695 Al O
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date W O 2018/005695 A l 0 4 January 2018 (04.01.2018) W ! P O PCT (51) International Patent Classification: (72) Inventors: BASTA, Steven; 590 Berkeley Avenue, Menlo A61K 31/4035 (2006.01) A61P 17/04 (2006.01) Park, CA 94025 (US). JOING, Mark; 936 Clara Drive, Pa A61K 45/06 (2006.01) lo Alto, CA 94303 (US). ZHANG, Xiaoming; 1089 Rem- sen Court, Sunnyvale, CA 94087 (US). KWON, Paul; 3349 (21) International Application Number: Deer Hollow Dr, Danville, CA 94506 (US). PCT/US20 17/039829 (74) Agent: SILVERMAN, Lisa, N.; Morrison & Foerster LLP, (22) International Filing Date: 755 Page Mill Road, Palo Alto, CA 94304-1018 (US). 28 June 2017 (28.06.2017) (81) Designated States (unless otherwise indicated, for every (25) Filing Language: English kind of national protection available): AE, AG, AL, AM, (26) Publication Language: English AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, (30) Priority Data: DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, 62/356,280 29 June 2016 (29.06.2016) US HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, 62/356,291 29 June 2016 (29.06.2016) US KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, 62/356,301 29 June 2016 (29.06.2016) us MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, 62/356,294 29 June 2016 (29.06.2016) us OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, 62/356,286 29 June 2016 (29.06.2016) us SC, SD, SE, SG, SK, SL, SM, ST, SV, SY,TH, TJ, TM, TN, 62/356,271 29 June 2016 (29.06.2016) us TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW.
    [Show full text]
  • 2020.04.06.20055715V1.Full.Pdf
    medRxiv preprint doi: https://doi.org/10.1101/2020.04.06.20055715; this version posted April 11, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . 1 Mo%on Sifnos: A randomized, double-blind, placebo-controlled study demonstra%ng the effec%veness of tradipitant in the treatment of mo%on sickness Vasilios M. Polymeropoulos*1, Mark É. Czeisler1#a, Mary M. Gibson1¶, Aus%n A. Anderson1¶, Jane Miglo1#b, Jingyuan Wang1, Changfu Xiao1, Christos M. Polymeropoulos1, Gunther Birznieks1, Mihael H. Polymeropoulos1 1 Vanda Pharmaceu%cals, Washington, District of Columbia, United States of America #a The Ins%tute for Breathing and Sleeping, Aus%n Health, Heidelberg, Victoria, Australia #b College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois, United States of America *Corresponding author Email: [email protected] (VMP) ¶These authors contributed equally to this work. NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice. medRxiv preprint doi: https://doi.org/10.1101/2020.04.06.20055715; this version posted April 11, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . 2 Abstract Background Novel therapies are needed for the treatment of mo%on sickness given the inadequate relief, and bothersome and dangerous adverse effects of currently approved therapies.
    [Show full text]
  • Farmacoterapia Atual Das Náuseas E Vômitos Induzidos Por
    Research, Society and Development, v. 10, n. 9, e58910918435, 2021 (CC BY 4.0) | ISSN 2525-3409 | DOI: http://dx.doi.org/10.33448/rsd-v10i9.18435 Farmacoterapia atual das náuseas e vômitos induzidos por antineoplásicos Current pharmacotherapy of antineoplastic-induced nausea and vomiting Farmacoterapia actual de náuseas y vómitos inducidos por antineoplásticos Recebido: 19/07/2021 | Revisado: 23/07/2021 | Aceito: 27/07/2021 | Publicado: 02/08/2021 Aline Kely Felício de Sousa Santos ORCID: https://orcid.org/0000-0002-2720-3129 Residência Multiprofissional em Saúde da Criança, Brasil E-mail: [email protected] Anaís Bezerra de Gusmão ORCID: https://orcid.org/0000-0001-7170-9410 Universidade de Pernambuco, Brasil E-mail: [email protected] Lucas Nóbrega de Oliveira ORCID: https://orcid.org/0000-0003-2656-6910 Residência Multiprofissional em Saúde da Criança, Brasil E-mail: [email protected] Richard Morrinson Couras de Carvalho ORCID: https://orcid.org/0000-0002-2564-3657 Residência Multiprofissional em Saúde da Criança, Brasil E-mail: [email protected] Cibério Landim Macedo ORCID: https://orcid.org/0000-0002-0824-4056 Residência Multiprofissional em Saúde da Criança, Brasil E-mail: [email protected] Resumo As náuseas e vômitos induzidos por quimioterapia (NVIQ) são reações adversas à medicamentos comuns com o uso de antineoplásicos. Embora existam avanços na terapêutica profilática, o manejo de medicamentos antieméticos na prática clínica ainda tem sido um desafio a ser enfrentado. O objetivo do presente estudo foi buscar na literatura científica as principais terapias farmacológicas utilizadas nesta condição. Uma revisão sistemática foi realizada, no qual buscou-se artigos científicos indexados no PubMed, ScienseDirect e Web of Science, utilizando os seguintes descritores: chemotherapy; nausea; vomiting; drug therapy; serotonin 5-HT3 receptor antagonists, neurokinin-1 receptor antagonista.
    [Show full text]
  • Neurokinin Receptor NK Receptor
    Neurokinin Receptor NK receptor There are three main classes of neurokinin receptors: NK1R (the substance P preferring receptor), NK2R, and NK3R. These tachykinin receptors belong to the class I (rhodopsin-like) G-protein coupled receptor (GPCR) family. The various tachykinins have different binding affinities to the neurokinin receptors: NK1R, NK2R, and NK3R. These neurokinin receptors are in the superfamily of transmembrane G-protein coupled receptors (GPCR) and contain seven transmembrane loops. Neurokinin-1 receptor interacts with the Gαq-protein and induces activation of phospholipase C followed by production of inositol triphosphate (IP3) leading to elevation of intracellular calcium as a second messenger. Further, cyclic AMP (cAMP) is stimulated by NK1R coupled to the Gαs-protein. The neurokinin receptors are expressed on many cell types and tissues. www.MedChemExpress.com 1 Neurokinin Receptor Inhibitors & Modulators Aprepitant Befetupitant (MK-0869; MK-869; L-754030) Cat. No.: HY-10052 (Ro67-5930) Cat. No.: HY-19670 Bioactivity: Aprepitant (MK-0869) is a selective and high-affinity Bioactivity: Befetupitant is a high-affinity, nonpeptide, competitive neurokinin 1 receptor antagonist with a Kd of 86 pM. tachykinin 1 receptor ( NK1R) antagonist. Purity: 99.93% Purity: >98% Clinical Data: Launched Clinical Data: No Development Reported Size: 10mM x 1mL in DMSO, Size: 1 mg, 5 mg, 10 mg, 20 mg 5 mg, 10 mg, 50 mg, 100 mg, 200 mg, 500 mg Fezolinetant Fosaprepitant (ESN-364) Cat. No.: HY-19632 (L-758298) Cat. No.: HY-14407 Bioactivity: Fezolinetant is an antagonist of the neurokinin 3 receptor Bioactivity: Fosaprepitant (L-758298) is a neurokinin-1 receptor antagonist (NK3R), used for the treatment of menopausal hot flushes.
    [Show full text]
  • The Implications of Pruritogens in the Pathogenesis of Atopic Dermatitis
    International Journal of Molecular Sciences Review The Implications of Pruritogens in the Pathogenesis of Atopic Dermatitis Lai-San Wong 1 , Yu-Ta Yen 2 and Chih-Hung Lee 1,* 1 Department of Dermatology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan; [email protected] 2 Department of Dermatology, Fooying University Hospital, Pingtung 928, Taiwan; [email protected] * Correspondence: [email protected]; Tel.: +886-7-7317123 (ext. 2299) Abstract: Atopic dermatitis (AD) is a prototypic inflammatory disease that presents with intense itching. The pathophysiology of AD is multifactorial, involving environmental factors, genetic susceptibility, skin barrier function, and immune responses. A recent understanding of pruritus transmission provides more information about the role of pruritogens in the pathogenesis of AD. There is evidence that pruritogens are not only responsible for eliciting pruritus, but also interact with immune cells and act as inflammatory mediators, which exacerbate the severity of AD. In this review, we discuss the interaction between pruritogens and inflammatory molecules and summarize the targeted therapies for AD. Keywords: itch; atopic dermatitis; pruritogens 1. Introduction Citation: Wong, L.-S.; Yen, Y.-T.; Lee, Pruritus is defined as a desire to scratch, which is a defense mechanism to eliminate C.-H. The Implications of Pruritogens possible noxious stimuli; however, it may damage the skin barrier. Atopic dermatitis in the Pathogenesis of Atopic (AD) is a chronic inflammatory disease characterized by pruritus, and is recognized as a Dermatitis. Int. J. Mol. Sci. 2021, 22, prototype of chronic pruritic dermatosis [1]. 7227. https://doi.org/10.3390/ The pathophysiology of AD is complex, involving several mechanisms.
    [Show full text]
  • Pruritus: from the Bench to the Bedside
    BioMed Research International Pruritus: From the Bench to the Bedside Lead Guest Editor: Adam Reich Guest Editors: Laurent Misery and Kenji Takamori Pruritus: From the Bench to the Bedside BioMed Research International Pruritus: From the Bench to the Bedside Lead Guest Editor: Adam Reich Guest Editors: Laurent Misery and Kenji Takamori Copyright © 2018 Hindawi. All rights reserved. This is a special issue published in “BioMed Research International.” All articles are open access articles distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Contents Pruritus: From the Bench to the Bedside Adam Reich ,LaurentMisery ,andKenjiTakamori Editorial (2 pages), Article ID 5742753, Volume 2018 (2018) Pruritus: Progress toward Pathogenesis and Treatment Jing Song , Dehai Xian, Lingyu Yang , Xia Xiong, Rui Lai, and Jianqiao Zhong Review Article (12 pages), Article ID 9625936, Volume 2018 (2018) Do Tonic Itch and Pain Stimuli Draw Attention towards Their Location? Antoinette I. M. van Laarhoven, Stefaan van Damme, A. (Sjan) P. M. Lavrijsen, Dimitri M. van Ryckeghem, Geert Crombez, and Andrea W. M. Evers Clinical Study (11 pages), Article ID 2031627, Volume 2017 (2018) 12-Item Pruritus Severity Scale: Development and Validation of New Itch Severity Questionnaire Adam Reich, Agnieszka Bożek, Katarzyna Janiszewska, and Jacek C. Szepietowski Research Article (7 pages), Article ID 3896423, Volume 2017 (2018) Prevalence and Relevance of Pruritus in Pregnancy Justyna Szczęch, Artur Wiatrowski, Lidia Hirnle, and Adam Reich Research Article (6 pages), Article ID 4238139, Volume 2017 (2018) Aprepitant for the Treatment of Chronic Refractory Pruritus Alice He, Jihad M.
    [Show full text]
  • Endocrinology Compound Library (96-Well)
    • Bioactive Molecules • Building Blocks • Intermediates www.ChemScene.com Endocrinology Compound Library (96-well) Product Details: Catalog Number: CS-L047 Formulation: A collection of 717 endocrinology compounds supplied as pre-dissolved Solutions or Solid Container: 96- or 384-well Plate with Peelable Foil Seal; 96-well Format Sample Storage Tube With Screw Cap and Optional 2D Barcode Storage: -80°C Shipping: Blue ice Packaging: Inert gas Plate layout: CS-L047-1 1 2 3 4 5 6 7 8 9 10 11 12 AT2 receptor MCHR1 NVP- a Empty Vonoprazan agonist C21 SCH 546738 Org41841 KW-8232 antagonist 2 GSK583 BAW2881 Treprostinil TCS-OX2-29 Empty Landiolol Piperoxan b Empty Plerixafor Aprepitant Maropitant MSDC 0160 SecinH3 (hydrochlorid HT-2157 Kynurenic (hydrochlorid PCO371 Empty e) acid e) Adenosine 5′- ZK756326 c Empty Zibotentan diphosphorib (dihydrochlori C2 Ceramide JNJ- Asenapine BI 689648 Silodosin CCR2 RS 17053 Empty ose (sodium) de) 39758979 antagonist 3 hydrochloride IT1t Tedatioxetine d Empty L-765314 Thyroxine Nicotinamide Vanilpyruvic VUF10460 Darbufelone (dihydrochlori GSK1059865 (9Z,11E)- (hydrobromid Empty sulfate N-oxide acid (mesylate) de) Prodlure e) ZD PD 123319 e Empty Linsitinib Prostaglandin Navarixin BMS-754807 SSTR5 7155(hydroch NVP- AG1024 (ditrifluoroace BMS-536924 Empty E2 antagonist 1 loride) ADW742 tate) JP1302 f Empty TC-G-1008 E7046 Amibegron dihydrochlorid SCH28080 Proglumide SB297006 GW-870086 S 38093 MK-2894 Empty hydrochloride e (sodium) GSK1904529 Nomegestrol JNJ- g Empty AH 6809 Eprotirome A RU 58841 acetate PF-00446687
    [Show full text]