镇痛麻醉药药学院.docx

1、镇痛麻醉药 药学院新药研发动态追踪2016年镇痛麻醉药Biogen公司发现新型ENPP2抑制剂 Biogen公司的研究人员发现新型外核苷酸焦磷酸酶/磷酸二酯酶2（ENPP2；自毒素）抑制剂，据报道可用于治疗多发性硬化症、风湿性关节炎和疼痛。一化合物(Ex 1-14 pg 108; EN 906154)可抑制自毒素的活性，其IC50100 nM。该化合物在大鼠血浆中的IC50 27000和53 nM) (EC50 = 2233和2365 nM)。（专利号：WO 2015185467；WO 2015185584）WO 2015185467WO 2015185584抗肿瘤药物百时美施贵宝公司发现新型

2、IDO抑制剂 百时美施贵宝公司的研究人员发现新型吲哚胺2,3-过氧化酶 (IDO)抑制剂，据报道可用于治疗癌症、感染、免疫疾病和炎症疾病。一化合物(Cpd pgh 0254 pg 68; EN 906251)可抑制IDO酶的活性(IC50 1 mcM)。（专利号：WO 2015188085）北京药理和毒理学研究所发现新型mTOR抑制剂 北京药理和毒理学研究所的研究人员发现新型哺乳动物雷帕霉素靶蛋白(mTOR; FRAP1)抑制剂，据报道可用于治疗癌症。一化合物(Ex 2 pg 22, claim 6; pg 39: En 905687)可抑制A549人肺癌细胞株的肿瘤细胞生长作用，其IC50值

3、为19.31 mcM。该化合物还可抑制A549细胞株内的mTORC1复合物。该化合物可通过降低多药耐药的MES-SA (人子宫肉瘤)和MRC5 (人胚肺成纤维细胞)癌细胞的增殖表现出抗肿瘤活性，其IC50 1811.9。该化合物比雷帕霉素表现出高的溶解性，其溶解度为0.028 mg/ml。（专利号：WO 2015184983）2015年12月全球在研药物动态研发企业药名结构式研发进展治疗作用适应症作用机制Chugai PharmaceuticalMycophenolate mofetil上市治疗骨髓增生异常综合征、肺病、肾病、硬皮病、移植排斥、特应性皮炎、重症肌无力、系统红斑狼疮、自身免疫性疾

4、病免疫抑制剂抗感染药皮肤病药物移植排斥羟基羧酸受体2 (HCAR2; NIACR1; GPR109A) 激动剂；肌苷 5-单磷酸脱氢酶 (IMPDH) 抑制剂；信号传导调节剂Hisamitsu PharmaceuticalKetoprofen上市镇痛药疼痛ToriiHouse dust mite allergy vaccine疫苗上市抗过敏药抗哮喘药过敏性鼻炎Millennium PharmaceuticalsIxazomib citrate上市抗肿瘤药多发性骨髓瘤蛋白酶体抑制剂KyorinMontelukast sodium上市呼吸系统药物过敏性鼻炎白细胞三烯CysLT1 (LTD4) 拮抗

5、剂；白细胞三烯拮抗剂；信号传导调节剂TaihoTrabectedin上市抗肿瘤药软组织肉瘤DNA损害剂；IL-6生成抑制剂；肿瘤相关巨噬细胞靶标药物；信号传导调节剂；凋亡诱导剂Daiichi SankyoDPT-IPV疫苗上市抗感染药破伤风、白喉杆菌感染Chugai PharmaceuticalAlectinib hydrochloride上市抗肿瘤药非小细胞肺癌(NSCLC)ALK抑制剂；ALK酪氨酸激酶受体 (L1196M 突变体) 抑制剂；信号传导调节剂PfizerVenlafaxine hydrochloride上市神经系统药物抑郁去甲肾上腺素再吸收抑制剂 ；5-HT再吸收抑制剂；信号

6、传导调节剂BayerRivaroxaban上市抗凝药治疗非特异性心血管疾病血栓栓塞凝结因子Xa抑制剂；血液凝结通路抑制剂LillyNecitumumabSequence:Heavy chain: QVQLQESGPGLVKPSQTLSLTCTVSGGSISSGDYYWSWIRQPPGKGLEWIGYIYYSGSTDYNPSLKSRVTMSVDTSKNQFSLKVNSVTAADTAVYYCARVSIFGVGTFDYWGQGTLVTVSSASTKGPSVLPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTY

7、ICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKLight chain: EIVMTQSPATLSLSPGERATLSCRASQSVSSYLAWYQ

8、QKPGQAPRLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCHQYGSTPLTFGGGTKAEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECCDR 1 heavy chain: SGDYYWSCDR 2 heavy chain: YIYYSGSTDYNPSLKSCDR 3 heavy chain: VSIFGVGTFDYVH: QVQLQESGPGLVKPSQTLSLTCTVSGGS

9、ISSGDYYWSWIRQPPGKGLEWIGYIYYSGSTDYNPSLKSRVTMSVDTSKNQFSLKVNSVTAADTAVYYCARVSIFGVGTFDYWGQGTLVTVSSCDR 1 light chain: RASQSVSSYLACDR 2 light chain: DASNRATCDR 3 light chain: HQYGSTPLTVL: EIVMTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCHQYGSTPLTFGGGTKAEIK上市抗肿瘤药非小细胞肺癌

10、抗EGFR；信号传导调节剂LillyOlanzapine上市神经系统药物精神病多巴胺 D2 拮抗剂；细胞色素P450 CYP1A2抑制剂；5-HT2A 拮抗剂；信号传导调节剂BaxaltaBAX-855Sequence：ATRRYYLGAVELSWDYMQSDLGELPVDARFPPRVPKSFPFNTSVVYKKTLFVEFTDHLFNIAKPRPPWMGLLGPTIQAEVYDTVVITLKNMASHPVSLHAVGVSYWKASEGAEYDDQTSQREKEDDKVFPGGSHTYVWQVLKENGPMASDPLCLTYSYLSHVDLVKDLNSGLIGALLVCREGSLAKEKTQ

11、TLHKFILLFAVFDEGKSWHSETKNSLMQDRDAASARAWPKMHTVNGYVNRSLPGLIGCHRKSVYWHVIGMGTTPEVHSIFLEGHTFLVRNHRQASLEISPITFLTAQTLLMDLGQFLLFCHISSHQHDGMEAYVKVDSCPEEPQLRMKNNEEAEDYDDDLTDSEMDVVRF DDDNSPSFIQIRSVAKKHPKTWVHYIAAEEEDWDYAPLVLAPDDRSYKSQYLNNGPQRIGRKYKKVRFMAYTDETFKTREAIQHESGILGPLLYGEVGDTLLIIFKNQASRPYNIYPHGITDVRPLYSR

12、RLPKGVKHLKDFPILPGEIFKYKWTVTVEDGPTKSDPRCLTRYYSSFVNMERDLASGLIGPLLICYKESVDQRGNQIMSDKRNVILFSVFDENRSWYLTENIQRFLPNPAGVQLEDPEFQASNIMHSINGYVFDSLQLSVCLHEVAYWYILSIGAQTDFLSVFFSGYTFKHKMVYEDTLTLFPFSGETVFMSMENPGLWILGCHNSDFRNRGMTALLKVSSCDKNTGDYYE DSYEDISAYLLSKNNAIEPRSFSQNSRHPSTRQKQFNATTIPENDIEKTDPWFAHRTPMPKIQNVSSS

13、DLLMLLRQSPTPHGLSLSDLQEAKYETFSDDPSPGAIDSNNSLSEMTHFRPQLHHSGDMVFTPESGLQLRLNEKLGTTAATELKKLDFKVSSTSNNLISTIPSDNLAAGTDNTSSLGPPSMPVHYDSQLDTTLFGKKSSPLTESGGPLSLSEENNDSKLLESGLMNSQESSWGKNVSSTESGRLFKGKRAHGPALLTKDNALFKVSISLLKTNKTSNNSATNRKTHIDGPSLLIENSPSVWQNILESDTEFKKVTPLIHDRMLMDKNATALRLNHMSNKTTSSKNMEMVQQK KEGPIPP

14、DAQNPDMSFFKMLFLPESARWIQRTHGKNSLNSGQGPSPKQLVSLGPEKSVEGQNFLSEKNKVVVGKGEFTKDVGLKEMVFPSSRNLFLTNLDNLHENNTHNQEKKIQEEIEKKETLIQENVVLPQIHTVTGTKNFMKNLFLLSTRQNVEGSYDGAYAPVLQDFRSLNDSTNRTKKHTAHFSKKGEEENLEGLGNQTKQIVEKYACTTRISPNTSQQNFVTQRSKRALKQFRLPLEETELEKRIIVDDTSTQWSKNMKHLTPSTLTQIDYNEKEKGAITQSPLSDCLTRSHSIPQANRSP

15、LPIAKVSSFPSIRPIYLTRVLFQDNSSHLPAASYRKKDSGVQESSHFLQGAKKNNLSLAILTLEMTGDQREVGSLGTSATNSVTYKKVENTVLPKPDLPKTSGKVELLPKVHIYQKDLFPTETSNGSPGHLDLVEGSLLQGTEGAIKWNEANRPGKVPFLRVATESSAKTPSKLLDPLAWDNHYGTQIPKEEWKSQEKSPEKTAFKKKDTILSLNACESNHAIAAINEGQNKPEIEVTWAKQGRTERLCSQNPPVLKRHQREITRTTLQSDQEEIDYDDTISVEMKKEDFDIYDEDENQS

16、PRSFQKKTRHYFIAAVERLWDYGMSSSPHVLRNRAQSGSVPQFKKVVFQEFTDGSFTQPLYRGELNEHLGLLGPYIRAEVEDNIMVTFRNQASRPYSFYSSLISYEEDQRQGA EPRKNFVKPNETKTYFWKVQHHMAPTKDEFDCKAWAYFSDVDLEKDVHSGLIGPLLVCHTNTLNPAHGRQVTVQEFALFFTIFDETKSWYFTENMERNCRAPCNIQMEDPTFKENYRFHAINGYIMDTLPGLVMAQDQRIRWYLLSMGSNENIHSIHFSGHVFTVRKKEEYKMALYNLYPGVFETV

17、EMLPSKAGIWRVECLIGEHLHAGMSTLFLVYSNKCQTPLGMASGHIRDFQITASGQYGQWAPKLARLHYSGSINAWSTKEPFSWIKVDLLAPMIIHGIKTQGARQKFSSLYISQFIIMYSLDGKKWQTYRGNSTGTLMVFFGNVDSSGIKHNIFNPPIIARYIRLHPTHYSIRS TLRMELMGCDLNSCSMPLGMESKAISDAQITASSYFTNMFATWSPSKARLHLQGRSNAWRPQVNNPKEWLQVDFQKTMKVTGVTTQGVKSLLTSMYVKEFLISSSQDGHQWTLFFQNGKVKVFQG

18、NQDSFTPVVNSLDPPLLTRYLRIHPQSWVHQIALRMEVLGCEAQDLY上市治疗血友病 A凝血因子VIII 缺乏症(血友病 A)Otsuka PharmaceuticalUCB JapanLevetiracetam上市神经系统药物部分发作性癫痫突触小泡蛋白 2A (SV2A)配体；N型钙通道(Ca(v) 2.2)阻断剂；Novo NordiskInsulin degludec/insulin aspart复方上市治疗1、2型糖尿病1、2型糖尿病ShionogiLusutrombopag上市抗血小板减少血小板减少症血小板生成素受体 (TpoR)激动剂；信号传导调节剂Boeh

19、ringer IngelheimOlodaterol/tiotropium bromide复方上市呼吸系统药物慢性阻塞性肺疾病2-肾上腺素受体激动剂；毒覃碱M3受体拮抗剂；信号传导调节剂SanofiRifapentine上市抗真菌药治疗结核病结核病DNA指导RNA 聚合酶抑制剂Janssen BiotechUstekinumab人单克隆抗体上市治疗骨骼肌肉关节疾病、肺间质疾病、炎性肠病、多发性硬化症、特应性皮炎、风湿性关节炎、银屑病关节炎、系统红斑狼疮、肝硬化眼科药物皮肤病药物抗牛皮癣药斑块型银屑病抗IL-23;抗IL-12;信号传导调节剂Bio Products LaboratoryFact

20、or XX因子上市血液系统药物 凝血因子X 缺乏症研发企业药名结构式研发进展治疗作用适应症作用机制ToriiJapanese cedar tree pollen allergy vaccine疫苗注册前治疗过敏性鼻炎过敏性鼻炎SK ChemicalsNBP607-QIV(Quadrivalent)疫苗注册抗感染药流感A,BNovartisSecukinumabSequence:variable domain of light chain: EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISR

21、LEPEDFAVYYCQQYGSSPCTFGQGTRLEIKRvariable domain of heavy chain: EVQLVESGGGLVQPGGSLRLSCAASGFTFSNYWMNWVRQAPGKGLEWVAAINQDGSEKYYVGSVKGRFTISRDNAKNSLYLQMNSLRVEDTAVYYCVRDYYDILTDYYIHYWYFDLWGRGTLVTVSS注册治疗1型糖尿病、骨骼肌肉关节疾病、炎性肠病、多发性硬化症、强直性脊柱炎、骨关节炎、风湿性关节炎、银屑病关节炎毛发生长刺激剂 眼科药物抗银屑病药物脓疱性银屑病抗IL-17；信号传导调节剂KowaSanwaAnaglip

22、tin注册治疗2型糖尿病2型糖尿病二肽基肽酶IV (CD26; DPP-IV; DP-IV)抑制剂；信号传导调节剂PfizerBristol-Myers SquibbApixaban 注册治疗中风、心绞痛抗凝剂深静脉血栓形成、肺动脉栓塞凝血因子 Xa 抑制剂；血液凝结通路抑制剂CSL KKAlbutrepenonacog alfa凝血因子IX融合蛋白多肽, from 41 AA注册前治疗血友病B凝血因子IX 缺乏症(血友病B)CelgeneLenalidomide注册抗肿瘤药物多发性骨髓瘤TNF-生成抑制剂；小脑(CRBN)抑制剂；信号传导调节剂；血管生成抑制剂MSD KKPembrolizu

23、mabSequenceHeavy chain sequence: QVQLVQSGVEVKKPGASVKVSCKASGYTFTNYYMYWVRQAPGQGLEWMGGINPSNGGTNFNEKFKNRVTLTTDSSTTTAYMELKSLQFDDTAVYYCARRDYRFDMGFDYWGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVS

24、QEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTK NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKLight chain sequence:EIVLTQSPATLSLSPGERATLSCRASKGVSTSGYSYLHWYQQKPGQAPRLLIYLASYLESGVPARFSGSGSGTDFTLTISSLEPEDFAVYYCQHSRDL

25、PLTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECLight chain CDR1: RASKGVSTSGYSYLHLight chain CDR2: LASYLESLight chain CDR3: QHSRDLPLTHeavy chain CDR1: NYYMYHeavy chain CDR2: GINPSNGGTNFNEKFKNHeavy chain CDR3: RDYRFDMGFDY注册前抗肿瘤药物

26、恶性黑色素瘤抗PD-1；免疫检验点抑制剂Mitsubishi Tanabe PharmaInfliximabSequenceVariable heavy chain: EVKLEESGGGLVQPGGSMKLSCVSGFIFSNHWMNWVRQSPEKGLEWVaEIRSKSINSATHYAESVKGRFTISRDDSKSAVYLQMTDLRTE DTGVYYCSRNYYGSTYDYWGQGTTLTVSVariable light chain:DILLTQSPAILSVSPGERVSFSCRASQFVGSSIHWYQQRTNGSPRLLIKYASESMSGIPSRFSGSGSGTDFTLSINTVESEDIADYYCQQSHSWPFTFGSGTNLEVK注册治疗间质性肺病、炎性肠病、黄斑性疾病、糖尿病视网膜病、强直性脊柱炎、炎症、其它免疫性疾病、风湿性关节炎、银屑病关节炎、癌症相关疾病神经系统药物抗抑郁药抗银屑病皮肤病药物川崎病抗TNF-；信号传导调节剂Mitsubishi Tanabe PharmaEdaravone注册治疗出血性中风、缺血性中风、肌萎缩侧索硬化症、脑血管疾病、缺血肌萎缩侧索硬化症5-核苷酸酶 (CD73)