Drug Repurposing Patent Applications July–September 2018

Walus M , Kida E , Golabek AA : Functional consequences and rescue potential of pathogenic missense mutations in tripeptidyl peptidase I. Hum Mutat, 2010; 31:710–721.

Steinfeld R , Steinke HB , Isbrandt D , Kohlschütter A , Gärtner J : Mutations in classical late infantile neuronal ceroid lipofuscinosis disrupt transport of tripeptidyl-peptidase I to lysosomes. Hum Mol Genet, 2004; 13:2483–2491.

Datta SR , Ranger AM , Lin MZ , Sturgill JF , Ma YC , Cowan CW , et al.: Survival factor-mediated BAD phosphorylation raises the mitochondrial threshold for apoptosis. Dev Cell, 2002; 3:631–643.

Ghosh A , Corbett GT , Gonzalez FJ , Pahan K : Gemfibrozil and fenofibrate, Food and Drug Administration-approved lipid-lowering drugs, up-regulate tripeptidyl-peptidase 1 in brain cells via peroxisome proliferator-activated receptor α: implications for late infantile Batten disease therapy. J Biol Chem, 2012; 287:38922–38935.

Corbett GT , Roy A , Pahan K : Gemfibrozil, a lipid-lowering drug, upregulates IL-1 receptor antagonist in mouse cortical neurons: implications for neuronal self-defense. J Immunol, 2012; 189:1002–1013.

Conway AM , Rosen RJ : Arteriovenous malformations: syndrome identification and vascular management. Curr Treat Options Cardiovasc Med, 2018; 20:67.

Couto JA , Huang AY , Konczyk DJ , Goss JA , Fishman SJ , Mulliken JB , et al.: Somatic MAP2K1 mutations are associated with extracranial arteriovenous malformation. Am J Hum Genet, 2017; 100:546–554.

Lu J , Anvari R , Wang J , Huang J , Pei S , Xiang Y , et al.: Propranolol as a potentially novel treatment of arteriovenous malformations. JAAD Case Rep, 2018; 4:355–358.

Chen W , Mook RA Jr ., Premont RT , Wang J : Niclosamide: beyond an antihelminthic drug. Cell Signal, 2018; 41:89–96.

Chen B , Wei W , Ma L , Yang B , Gill RM , Chua MS , et al.: Computational discovery of niclosamide ethanolamine, a repurposed drug candidate that reduces growth of hepatocellular carcinoma cells in vitro and in mice by inhibiting cell division cycle 37 signaling. Gastroenterology, 2017; 152:2022–2036.

Noss EH , Pai RK , Sellati TJ , Radolf JD , Belisle J , Golenbock DT , et al.: Toll-like receptor 2-dependent inhibition of macrophage class II MHC expression and antigen processing by 19-kDa lipoprotein of Mycobacterium tuberculosis . J Immunol, 2001; 167:910–948.

Portal-Celhay C , Tufariello JM , Srivastava S , Zahra A , Klevorn T , Grace PS , et al.: Mycobacterium tuberculosis EsxH inhibits ESCRT-dependent CD4+ T-cell activation. Nat Microbiol, 2016; 2:16232.

Leroux LP , Dasanayake D , Rommereim LM , Fox BA , Bzik DJ , Jardim A , et al.: Secreted Toxoplasma gondii molecules interfere with expression of MHC-II in interferon gamma-activated macrophages. Int J Parasitol, 2015; 45:319–332.

Morgan K , Conklin D , Pawson AJ , Sellar R , Ott TR , Millar RP : A transcriptionally active human type II gonadotropin-releasing hormone receptor gene homolog overlaps two genes in the antisense orientation on chromosome 1q.12. Endocrinology, 2003; 144:423–436.

Gómez-Román A , Ortega-Sánchez JA , Rotllant D , Gagliano H , Belda X , Delgado-Morales R , et al.: The neuroendocrine response to stress under the effect of drugs: negative synergy between amphetamine and stressors. Psychoneuroendocrinology, 2016; 63:94–101.

Ritov G , Richter-Levin G : Pre-trauma Methylphenidate in rats reduces PTSD-like reactions one month later. Transl Psychiatry, 2017; 7:e1000.

Fortier MÈ , Sengupta SM , Grizenko N , Choudhry Z , Thakur G , Joober R : Genetic evidence for the association of the hypothalamic-pituitary-adrenal (HPA) axis with ADHD and methylphenidate treatment response. Neuromolecular Med, 2013; 15:122–132.

Kriz J : Inflammation in ischemic brain injury: timing is important. Crit Rev Neurobiol, 2006; 18:145–157.

Yang Z , Zhong L , Zhong S , Xian R , Yuan B : Hypoxia induces microglia autophagy and neural inflammation injury in focal cerebral ischemia model. Exp Mol Pathol, 2015; 98:219–224.

Chen YJ , Nguyen HM , Maezawa I , Grössinger EM , Garing AL , Köhler R , et al.: The potassium channel KCa3.1 constitutes a pharmacological target for neuroinflammation associated with ischemia/reperfusion stroke. J Cereb Blood Flow Metab, 2016; 36:2146–2161.

Ataga KI , Reid M , Ballas SK , Yasin Z , Bigelow C , James LS , et al.: Improvements in haemolysis and indicators of erythrocyte survival do not correlate with acute vaso-occlusive crises in patients with sickle cell disease: a phase III randomized, placebo-controlled, double-blind study of the Gardos channel blocker senicapoc (ICA-17043). Br J Haematol, 2011; 153:92–104.

Staal RGW , Khayrullina T , Zhang H , Davis S , Fallon SM , Cajina M , et al.: Inhibition of the potassium channel KCa3.1 by senicapoc reverses tactile allodynia in rats with peripheral nerve injury. Eur J Pharmacol, 2017; 795:1–7.

Staal RGW , Weinstein JR , Nattini M , Cajina M , Chandresana G , Möller T : Senicapoc: repurposing a drug to target microglia KCa3.1 in stroke. Neurochem Res, 2017; 42:2639–2645.

Christensen AV , Svendsen O , Krogsgaard-Larsen P : Pharmacodynamic effects and possible therapeutic uses of THIP, a specific GABA-agonist. Pharm Weekbl Sci, 1982; 4:145–153.

Wafford KA , Ebert B : Gaboxadol—a new awakening in sleep. Curr Opin Pharmacol, 2006; 6:30–36.

Richardson BD , Ling LL , Uteshev VV , Caspary DM : Extrasynaptic GABA(A) receptors and tonic inhibition in rat auditory thalamus. PLoS One, 2011; 6:e16508.

Sametsky EA , Turner JG , Larsen D , Ling L , Caspary DM : Enhanced GABAA-Mediated tonic inhibition in auditory thalamus of rats with behavioral evidence of tinnitus. J Neurosci, 2015; 35:9369–93680.

Green DP , Ruparel S , Roman L , Henry MA , Hargreaves KM : Role of endogenous TRPV1 agonists in a postburn pain model of partial-thickness injury. Pain, 2013; 154:2512–2520.

Green D , Ruparel S , Gao X , Ruparel N , Patil M , Akopian A , et al.: Central activation of TRPV1 and TRPA1 by novel endogenous agonists contributes to mechanical allodynia and thermal hyperalgesia after burn injury. Mol Pain, 2016; 12. pii: 1744806916661725. DOI:10.1177/1744806916661725.

Sánchez-Moreno A , Guevara-Hernández E , Contreras-Cervera R , Rangel-Yescas G , Ladrón-de-Guevara E , Rosenbaum T , et al.: Irreversible temperature gating in trpv1 sheds light on channel activation. Elife, 2018; 7. pii: e36372. DOI:10.7554/eLife.36372.

Melnick C , Kaviany M : Thermal actuation in TRPV1: role of embedded lipids and intracellular domains. J Theor Biol, 2018; 444:38–49.

Kheniser KG , Polanco Santos CM , Kashyap SR : The effects of diabetes therapy on bone: a clinical perspective. J Diabetes Complications, 2018; 32:713–719.

Gamble JM , Donnan JR , Chibrikov E , Twells LK , Midodzi WK , Majumdar SR : The risk of fragility fractures in new users of dipeptidyl peptidase-4 inhibitors compared to sulfonylureas and other anti-diabetic drugs: a cohort study. Diabetes Res Clin Pract, 2018; 136:159–167.

Yang J , Huang C , Wu S , Xu Y , Cai T , Chai S , et al.: The effects of dipeptidyl peptidase-4 inhibitors on bone fracture among patients with type 2 diabetes mellitus: a network meta-analysis of randomized controlled trials. PLoS One, 2017; 12:e0187537.

Chung SD , Chen CH , Hung SH , Lin HC , Wang LH : A population-based study on the association between statin use and sudden sensorineural hearing loss. Otolaryngol Head Neck Surg, 2015; 152:319–325.

Olzowy B , Canis M , Hempel JM , Mazurek B , Suckfüll M : Effect of atorvastatin on progression of sensorineural hearing loss and tinnitus in the elderly: results of a prospective, randomized, double-blind clinical trial. Otol Neurotol, 2007; 28:455–458.

Hameed MK , Sheikh ZA , Ahmed A , Najam A : Atorvastatin in the management of tinnitus with hyperlipidemias. J Coll Physicians Surg Pak, 2014; 24:927–930.

Jahani L , Mehrparvar AH , Esmailidehaj M , Rezvani ME , Moghbelolhossein B , Razmjooei Z : The effect of atorvastatin on preventing noise-induced hearing loss: an experimental study. Int J Occup Environ Med, 2016; 7:15–21.

Park JS , Kim SW , Park K , Choung YH , Jou I , Park SM : Pravastatin attenuates noise-induced cochlear injury in mice. Neuroscience, 2012; 208:123–132.

Brand Y , Setz C , Levano S , Listyo A , Chavez E , Pak K , et al.: Simvastatin protects auditory hair cells from gentamicin-induced toxicity and activates Akt signaling in vitro. BMC Neurosci, 2011; 12:114.

Navada SC , Silverman LR : The safety and efficacy of rigosertib in the treatment of myelodysplastic syndromes. Expert Rev Anticancer Ther, 2016; 16:805–810.

Maehama T , Fukasawa M , Date T , Wakita T , Hanada K : A class II phosphoinositide 3-kinase plays an indispensable role in hepatitis C virus replication. Biochem Biophys Res Commun, 2013; 440:150–156.

Delang L , Harak C , Benkheil M , Khan H , Leyssen P , Andrews M , et al.: PI4KIII inhibitor enviroxime impedes the replication of the hepatitis C virus by inhibiting PI3 kinases. J Antimicrob Chemother 2018 [Epub ahead of print]; DOI: 10.1093/jac/dky327.

Shwetha S , Kumar A , Mullick R , Vasudevan D , Mukherjee N , Das S : HuR displaces polypyrimidine tract binding protein to facilitate la binding to the 3′ untranslated region and enhances hepatitis C virus replication. J Virol, 2015; 89:11356–11371.

Spångberg K , Wiklund L , Schwartz S : HuR, a protein implicated in oncogene and growth factor mRNA decay, binds to the 3′ ends of hepatitis C virus RNA of both polarities. Virology, 2000; 274:378–390.

Schult P , Roth H , Adams RL , Mas C , Imbert L , Orlik C , et al.: microRNA-122 amplifies hepatitis C virus translation by shaping the structure of the internal ribosomal entry site. Nat Commun, 2018; 9:2613.

Mukherjee K , Ghoshal B , Ghosh S , Chakrabarty Y , Shwetha S , Das S , et al.: Reversible HuR-microRNA binding controls extracellular export of miR-122 and augments stress response. EMBO Rep, 2016; 17:1184–1203.