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1. (WO2010079998) USE OF HOG, RAS, AND CAMP SIGNAL PATHWAY GENES FOR FUNGAL INFECTION TREATMENT
Latest bibliographic data on file with the International Bureau

Pub. No.: WO/2010/079998 International Application No.: PCT/KR2010/000137
Publication Date: 15.07.2010 International Filing Date: 08.01.2010
IPC:
A61K 38/02 (2006.01)
A HUMAN NECESSITIES
61
MEDICAL OR VETERINARY SCIENCE; HYGIENE
K
PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
38
Medicinal preparations containing peptides
02
Peptides of undefined number of amino acids; Derivatives thereof
Applicants:
연세대학교 산학협력단 INDUSTRY-ACADEMIC COOPERATION FOUNDATION , YONSEI UNIVERSITY [KR/KR]; 서울특별시 서대문구 신촌동 134 연세대학교 Yonsei University 134, Sinchon-dong, Seodaemun-gu Seoul 120-749, KR (AllExceptUS)
반용선 BAHN, Yong Sun [KR/KR]; KR (UsOnly)
고영준 KO, Young Joon [KR/KR]; KR (UsOnly)
맹신애 MAENG, Shin Ae [KR/KR]; KR (UsOnly)
정광우 JUNG, Kwang Woo [KR/KR]; KR (UsOnly)
김규범 KIM, Gyu Bum [KR/KR]; KR (UsOnly)
Inventors:
반용선 BAHN, Yong Sun; KR
고영준 KO, Young Joon; KR
맹신애 MAENG, Shin Ae; KR
정광우 JUNG, Kwang Woo; KR
김규범 KIM, Gyu Bum; KR
Agent:
특허법인다나 DANA PATENT LAW FIRM; 서울특별시 강남구 역삼동 648-1 BYC 빌딩 5층 5th Floor, BYC Bldg. 648-1, Yeoksam-dong, Gangnam-gu Seoul 135-080, KR
Priority Data:
10-2009-000194709.01.2009KR
10-2009-012720618.12.2009KR
Title (EN) USE OF HOG, RAS, AND CAMP SIGNAL PATHWAY GENES FOR FUNGAL INFECTION TREATMENT
(FR) UTILISATION DES GÈNES DES VOIES DE SIGNALISATION HOG, RAS ET CAMP À DES FINS DE TRAITEMENT D'UNE INFECTION FONGIQUE
(KO) 진균 감염의 치료를 위한 HOG, RAS 및 CAMP 신호전달경로 유전자의 용도
Abstract:
(EN) The present invention provides a use of HOG, RAS, and CAMP signal pathway genes for a fungal infection treatment. Inventors of the present invention have studied the roles of SSK1, TCO2, SSK2, PBS2, HOG1, ENA1, and NHA1 genes in HOG pathway regulation of Cryptococcus neoformans, and found that the volume of biosynthesis of ergosterol increases when these genes are inhibited. As a great quantity of ergosterols are distributed on the cell membranes of fungi when these genes are inhibited, site of drug action of ergosterol-binding antifungal drugs increases, which significantly increases effects of ergosterol-binding antifungal drugs. Further, inventors of the present invention have studied the roles of RAS1, RAS2, CDC24, GPA1, CAC1, ACA1, PKA1, HSP12, and HSP122 genes in RAS and CAMP pathway regulation of Cryptococcus neoformans, and found that the susceptibility to polyene-based drugs or azole-based drugs increases when these genes are inhibited. Therefore, antifungal medical compositions containing inhibitors of the above-enumerated genes or proteins coded by the genes can be valuably used as superior complex antifungal agents that reduce the dosage of conventional antifungal agents and improve effects.
(FR) La présente invention concerne l'utilisation des gènes des voies de signalisation HOG, RAS et cAMP en vue du traitement d'une infection fongique. Les inventeurs de la présente invention ont étudié le rôle des gènes SSK1, TCO2, SSK2, PBS2, HOG1, ENA1 et NHA1 dans la régulation de la voie HOG de Cryptococcus neoformans et ils ont découvert que la biosynthèse de l'ergostérol augmente en volume lorsque ces gènes sont inhibés. Comme une grande quantité d'ergostérols se répand sur les membranes cellulaires des champignons lorsque ces gènes sont inhibés, le site de l'action médicamenteuse des médicaments antifongiques liant l'ergostérol s'élargit, ce qui accroît, de façon significative, les effets des médicaments antifongiques liant l'ergostérol. En outre, les inventeurs de la présente invention ont étudié le rôle des gènes RAS1, RAS2, CDC24, GPA1, CAC1, ACA1, PKA1, HSP12 et HSP122 dans la régulation des voies RAS et cAMP de Cyrptococcus neoformans et ils ont découvert que la sensibilité aux médicaments à base de polyène ou d'azole augmente quand ces gènes sont inhibés. En conséquence, des compositions médicales antifongiques contenant des inhibiteurs des gènes énumérés ci-dessus ou des protéines codées par lesdits gènes peuvent être avantageusement utilisées en tant qu'agents antifongiques complexes de qualité supérieure, en dose moindre et avec un effet amélioré par rapport aux agents antifongiques traditionnels.
(KO) 본 발명은 진균 감염의 치료를 위한 HOG, Ras 및 cAMP 신호전달경로 유전자의 용도를 제공한다. 본 발명에서는 크립토코쿠스 네오포만스의 HOG 경로 조절에 있어서 SSK1, TCO2, SSK2, PBS2, HOG1, ENA1 NHA1 유전자들이 수행하는 역할에 대해 조사하여, 이들 유전자들이 억제되면 에르고스테롤의 생합성량이 증진됨을 새로이 밝혀냈다. 상기 유전자들을 억제하면 진균의 세포막 상에 에르고스테롤이 다량 분포하게 되므로, 에르고스테롤-결합성 항진균제의 작용점이 많아서 에르고스테롤-결합성 항진균제의 효능을 현저히 상승시킬 수 있게 된다. 또한 본 발명에서는 크립토코쿠스 네오포만스의 Ras 및 cAMP 경로의 조절에 있어서 RAS1, RAS2, CDC24, GPA1, CAC1, ACA1, PKA1, HSP12 HSP122 유전자들이 수행하는 역할에 대해 조사하여, 이들 유전자들이 억제되면 폴리엔계 약물이나 아졸계 약물에 대한 감수성이 증진됨을 새로이 밝혀냈다. 따라서 상기 유전자 또는 이들에 의해 코딩되는 단백질에 대한 저해제를 포함하는 항진균용 의약 조성물은 기존 항진균제의 사용 용량을 절감시키면서 효능을 상승시킬 수 있는 우수한 복합 항균치료제로서 사용할 수 있다.
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Designated States: AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW
African Regional Intellectual Property Organization (ARIPO) (BW, GH, GM, KE, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, ZW)
Eurasian Patent Organization (AM, AZ, BY, KG, KZ, MD, RU, TJ, TM)
European Patent Office (AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, SE, SI, SK, SM, TR)
African Intellectual Property Organization (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, ML, MR, NE, SN, TD, TG)
Publication Language: Korean (KO)
Filing Language: Korean (KO)
Also published as:
US20120093817