IP Library › Granted Patent US 10,787,490
Granted Patent B2
US 10,787,490 · App. 15/745,371 · Granted Sep 29, 2020

Peptide inhibitors of interleukin-23 receptor and their use to treat inflammatory diseases

Inventors: Ashok Bhandari (Pleasanton, CA); Gregory Bourne (Jindalee, AU); Xiaoli Cheng (Mountain View, CA); Brian Troy Frederick (Ben Lomand, CA); Jie Zhang (Salisbury, AU); Dinesh V. Patel (Fremont, CA); David Liu (Palo Alto, CA)
Assignee: Protaganist Therapeutics, Inc.
C07K14/4703A61P1/04A61K38/00
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Quick Facts
Patent No.
US 10,787,490
App. No.
15/745,371
Granted
Sep 29, 2020
Kind
B2
Abstract

Peptide inhibitors of the interleukin-23 receptor, and related compositions and methods of using these peptide inhibitors to treat or prevent a variety of diseases and disorders, including inflammatory bowel diseases, are described.

Claims (368)

1. A peptide inhibitor of an interleukin-23 receptor, or a pharmaceutically acceptable salt thereof, wherein the peptide inhibitor is:

(SEQ ID NO: 1115)

[Palm]-[isoGlu]-[PEG4]-[Pen]-NTWQ-[Pen]-[Phe[4-(2-

aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH 2 ;

(SEQ ID NO: 1116)

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-

[Aib]-[Lys(PEG4-isoGlu-Palm)]-NN-NH 2 ;

(SEQ ID NO: 1117)

Ac-[Pen]-QTWQ-[Pen]-Phe(4-CONH 2 )-[2-Nal]-[a-

MeLys(Ac)]-[Lys(Ac)]-NN-NH 2 ;

(SEQ ID NO: 1118)

[Octanyl]-[IsoGlu]-[PEG4]-[Pen]-NTWQ-[Pen]-[Phe[4-

(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH 2 ;

(SEQ ID NO: 1119)

[Octanyl]-[PEG4]-[Pen]-NTWQ-[Pen]-[Phe[4-(2-

aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH 2 ;

(SEQ ID NO: 1120)

[Palm]-[PEG4]-[Pen]-NTWQ-[Pen]-[Phe[4-(2-

aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH 2 ;

(SEQ ID NO: 1121)

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-(2-

Nal]-[Aib]-[Lys(PEG4-Octanyl)]-NN-NH 2 ;

(SEQ ID NO: 1122)

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-(2-

Nal]-[Aib]-[Lys(PEG4-Palm)]-NN-NH 2 ;

(SEQ ID NO: 1123)

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)-(PEG4-Palm)]-(2-Nal]-[Aib]-

[Lys(Ac)]NN-NH 2 ;

(SEQ ID NO: 1124)

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)-(PEG4-

Lauryl)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH 2 ;

(SEQ ID NO: 1125)

Ac-[Pen]-QTWQ-[Pen]-Phe(4-CONH 2 )-[2-Nal]-[a-

MeLys(PEG4-Palm)-[Lys(Ac)]-NN-NH 2 ;

(SEQ ID NO: 1126)

Ac-[Pen]-QTWQ-[Pen]-Phe(4-CONH 2 )-[2-Nal]-[a-

MeLys(PEG4-Lauryl)]-[Lys(Ac)]-NN-NH 2 ;

(SEQ ID NO: 1127)

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)-(PEG4-

IsoGlu-Palm)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH 2 ;

(SEQ ID NO: 1128)

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)-(PEG4-

IsoGLu-Lauryl)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH 2 ;

(SEQ ID NO: 1129)

Ac-[Pen]-QTWQ-[Pen]-Phe(4-CONH 2 )-[2-Nal]-[a-

MeLys(PEG4-IsoGlu-Palm)]-[Lys(Ac)]-NN-NH 2 ;

(SEQ ID NO: 1130)

Ac-[Pen]-QTWQ-[Pen]-Phe(4-CONH 2 )-[2-Nal]-a-Me-

K(PEG4-IsoGlu-Lauryl)]-[Lys(Ac)]-NN-NH 2 ;

(SEQ ID NO: 1131)

Ac-[Pen]-QTWQ-[Pen]-Phe(4-CONH 2 )-[2-Nal]-[a-

MeLys(IVA)]-[Lys(Ac)]-NN-NH 2 ;

(SEQ ID NO: 1132)

Ac-[Pen]-QTWQ-[Pen]-Phe(4-CONH 2 )-[2-Nal]-[a-

MeLys(Biotin)]-[Lys(Ac)]-NN-NH 2 ;

(SEQ ID NO: 1133)

Ac-[Pen]-QTWQ-[Pen]-Phe(4-CONH 2 )-[2-Nal]-[a-

MeLys(Octanyl)]-[Lys(Ac)]-NN-NH 2 ;

(SEQ ID NO: 1134)

Ac-[Pen]-[Lys(IVA)]-TWQ-[Pen]-[Phe[4-(2-

aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH 2 ;

(SEQ ID NO: 1135)

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-

Nal]-[Aib]-[Lys(Ac)]-[Lys(IVA)]-N-NH 2 ;

(SEQ ID NO: 1136)

Ac-[Pen]-[Lys(Biotin)]-TWQ-[Pen]-[Phe[4-(2-

aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH 2 ;

(SEQ ID NO: 1137)

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-

Nal]-[Aib]-[Lys(Ac)]-[Lys(Biotin)]-N-NH 2 ;

(SEQ ID NO: 1138)

Ac-[Pen]-[Lys(Octanyl)]-TWQ-[Pen]-[Phe[4-(2-

aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH 2 ;

(SEQ ID NO: 1139)

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-

Nal]-[Aib]-[Lys(Ac)]-[Lys(octanyl)]-N-NH 2 ;

(SEQ ID NO: 1140)

Ac-[Pen]-[Lys(Palm)]-TWQ-[Pen]-[Phe[4-(2-

aminoethoxy)]-[2-Nal]--[Aib]-[Lys(Ac)]-NN-NH 2 ;

(SEQ ID NO: 1141)

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-

Nal]-[Aib]-[Lys(Ac)]-Lys(Palm)]-N-NH 2 ;

(SEQ ID NO: 1142)

Ac-[Pen]-[Lys(PEG8)]-TWQ-[Pen]-[Phe[4-(2-

aminoethoxy)]-[2-Nal]--[Aib]-[Lys(Ac)]-NN-NH 2 ;

(SEQ ID NO: 1143)

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-

Nal]-[Aib]-[Lys(Ac)]-[Lys(PEG8)]-N-NH 2 ;

(SEQ ID NO: 1144)

Ac-[Pen]-K(Peg11-Palm)TWQ-[Pen]-[Phe[4-(2-

aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH 2 ;

(SEQ ID NO: 1145)

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-

Nal]-[Aib]-[Lys(Ac)]-[Lys(Peg11-palm)]-N-NH 2 ;

(SEQ ID NO: 1146)

Ac-[Pen]-[Cit]-TW-[Cit]-[Pen]-[Phe[4-(2-

aminoethoxy)]-[2-Nal]--[Aib]-[Lys(Ac)]-NN-NH 2 ;

(SEQ ID NO: 1147)

Ac-[Pen]-[Lys(Ac)]-TW-[Cit]-[Pen]-[Phe[4-(2-

aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH 2 ;

(SEQ ID NO: 1148)

Ac-[Pen]-NT-[Phe(3,4-OCH 3 ) 2 ]-Q-[Pen]-[Phe[4-(2-

aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH 2 ;

(SEQ ID NO: 1149)

Ac-[Pen]-NT-[Phe(2,4-CH 3 ) 2 ]-Q-[Pen]-[Phe[4-(2-

aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH 2 ;

(SEQ ID NO: 1150)

Ac-[Pen]-NT-[Phe(3-CH 3 )]-Q-[Pen]-[Phe[4-(2-

aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH 2 ;

(SEQ ID NO: 1151)

Ac-[Pen]-NT-[Phe(4-CH 3 )]-Q-[Pen]-[Phe[4-(2-amino-

ethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH 2 ;

(SEQ ID NO: 1152)

Ac[(D)Arg]-[Pen]-NTWQ-[Pen]-[Phe[4-(2-amino-

ethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-N-[bAla]-NH 2 ;

(SEQ ID NO: 1153)

Ac-[(D)Tyr]-[Pen]-NTWQ-[Pen]-[Phe[4-(2-

aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-N-[bAla]-NH 2 ;

(SEQ ID NO: 1154)

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-

Nal]-[Aib]-[Lys(Ac)]-QN-NH 2 ;

(SEQ ID NO: 1155)

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-

Nal]-[Aib]-[Lys(Ac)]-[Lys(Ac)]-N-NH 2 ;

(SEQ ID NO: 1156)

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-

Nal]-[Aib]-[Lys(Ac)]-N-[Lys(Ac)]-NH 2 ;

(SEQ ID NO: 1157)

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-QQ-NH 2 ;

(SEQ ID NO: 1158)

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-

Nal]-[Aib]-[Lys(Ac)]-Q-[bAla]-NH 2 ;

(SEQ ID NO: 1159)

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-N-[Cit]-NH 2 ;

(SEQ ID NO: 1160)

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-

Nal]-[Aib]-(Lys(Ac)]-[Cit]-NNH 2 ;

(SEQ ID NO: 1161)

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-

Nal]-[Aib]-(Lys(Ac)]-[Cit]-Q-NH 2 ;

(SEQ ID NO: 1162)

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-

Nal]-[Aib]-(Lys(Ac)]-[Cit]-[Lys(Ac)]-NH 2 ;

(SEQ ID NO: 1163)

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-

Nal]-[Aib]-[Lys(Ac)]-[Lys(Ac)]-[Cit]-NH 2 ;

(SEQ ID NO: 1164)

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-

Nal]-[Aib]-QN-[bAla]-NH 2 ;

(SEQ ID NO: 1165)

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-

Nal]-[Aib]-E-[Cit]-Q-NH 2 ;

(SEQ ID NO: 1166)

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-

Nal]-[Aib]-CitNCitNH 2 ;

(SEQ ID NO: 1167)

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-

Nal]-[Aib]-[Cit]-Q-[Cit]-NH 2 ;

(SEQ ID NO: 1168)

Ac-[Pen]-[Cit]-TWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-

[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH 2 ;

(SEQ ID NO: 1169)

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-

Nal]-[Aib]-[Lys(Ac)]-NN-NH 2 ;

(SEQ ID NO: 1170)

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-

Nal]-[Aib]-QNN-NH 2 ;

(SEQ ID NO: 1171)

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-

Nal]-[Aib]-ENQ-NH 2 ;

(SEQ ID NO: 1172)

Ac-[Pen]-GPWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-

Nal]-[Aib]-[Lys(Ac)]-NN-NH 2 ;

(SEQ ID NO: 1173)

Ac-[Pen]-PGWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-

Nal]-[Aib]-[Lys(Ac)]-NN-NH 2 ;

(SEQ ID NO: 1174)

Ac-[Pen]-NTWN-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-

Nal]-[Aib]-[Lys(Ac)]-NN-NH 2 ;

(SEQ ID NO: 1175)

Ac-[Pen]-NSWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-

Nal]-[Aib]-[Lys(Ac)]-NN-NH 2 ;

(SEQ ID NO: 1176)

Ac-[Pen]-N-[Aib]-WQ-[Pen]-[Phe[4-(2-aminoethoxy)]-

[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH 2 ;

(SEQ ID NO: 1177)

Ac-[Pen]-NTW-[Aib]-[Pen]-[Phe[4-(2-aminoethoxy)]-

[2-Nal]-[Aib]-[Lys(Ac)]N-[Aib]-NH 2 ;

(SEQ ID NO: 1178)

Ac-[Pen]-QTW-[Lys(Ac)]-[Pen]-[Phe[4-(2-

aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH 2 ;

(SEQ ID NO: 1179)

Ac-[Pen]-[Lys(Ac)]-TWQ-[Pen]-(Phe[4-(2-

aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]NNNH 2 ;

(SEQ ID NO: 1180)

Ac-[Pen]-QVWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-

Nal]-[Aib]-[Lys(Ac)]-NN-NH 2 ;

(SEQ ID NO: 1181)

Ac-[Pen]-NT-[2-Nal]-Q-[Pen]-[Phe[4-(2-

aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH 2 ;

(SEQ ID NO: 1182)

Ac-[Pen]-NT-[1-Nal]-Q-[Pen]-[Phe[4-(2-

aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH 2 ;

(SEQ ID NO: 1183)

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-

Nal]-[a-MeLeu]-[Lys(Ac)]-NN-NH 2 ;

(SEQ ID NO: 1184)

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-

Nal]-[a-MeLys]-[Lys(Ac)]-NN-NH 2 ;

(SEQ ID NO: 1185)

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-

Nal]-(4-amino-4-carboxy-tetrahydropyran]-

[Lys(Ac)]-NN-NH 2 ;

(SEQ ID NO: 1186)

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-

Nal]-[a-MeLeu]-[Lys(Ac)]-N-[bAla]-NH 2 ;

(SEQ ID NO: 1187)

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-

Nal]-[a-MeLys]-[Lys(Ac)]-N-[bAla]-NH 2 ;

(SEQ ID NO: 1188)

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-

Nal]-(4-amino-4-carboxy-tetrahydropyran]-

[Lys(Ac)]-N-[bAla]-NH 2 ;

(SEQ ID NO: 1189)

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-

Nal]-[Aib]-[Lys(Ac)]-LN-NH 2 ;

(SEQ ID NO: 1190)

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-

Nal]-[Aib]-[Lys(Ac)]-GN-NH 2 ;

(SEQ ID NO: 1191)

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-

Nal]-[Aib]-[Lys(Ac)]-SN-NH 2 ;

(SEQ ID NO: 1192)

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-

Nal]-[Aib]-[Lys(Ac)]-[Aib]-N-NH 2 ;

(SEQ ID NO: 1193)

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-

Nal]-[Aib]-[Lys(Ac)]-FN-NH 2 ;

(SEQ ID NO: 1194)

Ac-[Pen]-NTW-[Cit]-[Pen]-[Phe[4-(2-aminoethoxy)]-

(2-Nal]-[Aib]-[Lys(Ac)]-NN-NH 2 ;

(SEQ ID NO: 1195)

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-

Nal]-[Aib]-(Lys(Ac)]-[Tic]-[bAla]-NH 2 ;

(SEQ ID NO: 1196)

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-

Nal]-[Aib]-]Lys(Ac)]-[nLeu]-[bAla]-NH 2 ;

(SEQ ID NO: 1197)

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-

Nal]-[Aib]-[Lys(Ac)]-G-[bAla]-NH 2 ;

(SEQ ID NO: 1198)

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-

Nal]-[Aib]-[Lys(Ac)]-R-[bAla]-NH 2 ;

(SEQ ID NO: 1199)

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-

Nal]-[Aib]-[Lys(Ac)]-W-[bAla]-NH 2 ;

(SEQ ID NO: 1200)

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-

Nal]-[Aib]-[Lys(Ac)]-S-[bAla]-NH 2 ;

(SEQ ID NO: 1201)

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-

Nal]-[Aib]-[Lys(Ac)]-L-[bAla]-NH 2 ;

(SEQ ID NO: 1202)

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-

Nal]-[Aib]-[Lys(Ac)]-[AIB]-[bAla]-NH 2 ;

(SEQ ID NO: 1203)

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-

Nal]-[Aib]-[Lys(Ac)]-(N-MeAla[-[bAla]-NH 2 ;

(SEQ ID NO: 1204)

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-

Nal]-[Aib]-[Lys(Ac)]-[2-Nap]-[bAla]-NH 2 ;

(SEQ ID NO: 1205)

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-

Nal]-[Aib]-[Lys(Ac)]-F-[bAla]-NH 2 ;

or

(SEQ ID NO: 1206)

Ac-[(D)Arg]-[Pen]-NTWQ-[Pen]-[Phe[4-(2-

aminoethoxy)]-[2-Nal]-[4-amino-4-

carboxy-tetrahydropyran]-[Lys(Ac)]-NN-NH 2 .

wherein the peptide inhibitor is cyclized via a disulfide bond between Pen and Pen; and

wherein 2-Nal is L-2-napthylalanine, α-MeLys is alpha-methyl-L-Lysine, α-MeLeu is alpha-methyl-L-Leucine, and Aib is 2-aminoisobutyric acid.

2. The peptide inhibitor or pharmaceutically acceptable salt thereof according to claim 1 , wherein the peptide inhibitor is:

(SEQ ID NO: 1178)

Ac-[Pen]-QTW-[Lys(Ac)]-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH 2 ;

(SEQ ID NO: 1183)

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[α-MeLeu]-[Lys(Ac)]-NN-NH 2 ;

(SEQ ID NO: 1186)

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[α-MeLeu]-[Lys(Ac)]-N-[βAla+-NH 2 ;

(SEQ ID NO: 1187)

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[α-MeLys]-[Lys(Ac)]-N-[βAla]-NH 2 ;

(SEQ ID NO: 1188)

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-

[Lys(Ac)]-N-[βAla]-NH 2 ;

(SEQ ID NO: 1191)

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-SN-NH 2 ;

(SEQ ID NO: 1193)

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-FN-NH 2 ;

(SEQ ID NO: 1194)

Ac-[Pen]-NTW-[Cit]-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH 2 ;

(SEQ ID NO: 1197)

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-G-[βAla]-NH 2 ;

(SEQ ID NO: 1198)

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-R-[βAla]-NH 2 ;

(SEQ ID NO: 1200)

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-S-[βAla]-NH 2 ;

(SEQ ID NO: 1204)

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-[2-Nap]-[βAla]-NH 2 ;

or

(SEQ ID NO: 1205)

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-F-[βAla]-NH 2 .

3. The peptide inhibitor or pharmaceutically acceptable salt thereof according to claim 1 , wherein the peptide inhibitor is:

(SEQ ID NO: 1178)

Ac-[Pen]-QTW-[Lys(Ac)]-[Pen]-[Phe[4-(2-

aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH 2 .

4. The peptide inhibitor or pharmaceutically acceptable salt thereof according to claim 1 , wherein the peptide inhibitor is:

(SEQ ID NO: 1183)

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-

Nal]-[α-MeLeu]-[Lys(Ac)]-NN-NH 2 .

5. The peptide inhibitor or pharmaceutically acceptable salt thereof according to claim 1 , wherein the peptide inhibitor is:

(SEQ ID NO: 1186)

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-

[2-Nal]-[α-MeLeu]-[Lys(Ac)]-N-[βAla]-NH 2 .

6. The peptide inhibitor or pharmaceutically acceptable salt thereof according to claim 1 , wherein the peptide inhibitor is:

(SEQ ID NO: 1194)

Ac-[Pen]-NTW-[Cit]-[Pen]-[Phe[4-(2-aminoethoxy)]-

[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH 2 .

7. The peptide inhibitor or pharmaceutically acceptable salt thereof according to claim 1 , wherein the peptide inhibitor is:

(SEQ ID NO: 1200)

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-

[2-Nal]--[Aib]-[Lys(Ac)]-S-[βAla]-NH 2 .

8. The peptide inhibitor or pharmaceutically acceptable salt thereof according to claim 1 , wherein the peptide inhibitor is:

(SEQ ID NO: 1204)

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-

Nal]-[Aib]-[Lys(Ac)]-[2-Nap]-[βAla]-NH 2 .

9. The peptide inhibitor or pharmaceutically acceptable salt thereof according to claim 1 , wherein the peptide inhibitor is:

(SEQ ID NO: 1205)

Ac-[Pen]-NTWQ-[Pen]-[Phe]4-(2-aminoethoxy)]-[2-

Nal]-[Aib]-[Lys(Ac)]-F-[βAla]-NH 2 .

10. A method for treating an Inflammatory Bowel Disease (IBD) in a subject, comprising administering to the subject an effective amount of the peptide inhibitor or pharmaceutically acceptable salt thereof of claim 1 .

11. The method of claim 10 , wherein the IBD is ulcerative colitis or Crohn's disease.

12. The method of claim 10 , wherein the peptide inhibitor is:

(SEQ ID NO: 1178)

Ac-[Pen]-QTW-[Lys(Ac)]-[Pen]-[Phe[4-(2-

aminoethoxy)]-[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH 2 .

13. The method of claim 10 , wherein the peptide inhibitor is:

(SEQ ID NO: 1183)

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-

Nal]-[α-MeLeu]-[Lys(Ac)]-NN-NH2.

14. The method of claim 10 , wherein the peptide inhibitor is:

(SEQ ID NO: 1186)

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-

Nal]-[α-MeLeu]-[Lys(Ac)]-N-[βAla]-NH 2 .

15. The method of claim 10 , wherein the peptide inhibitor is:

(SEQ ID NO: 1194)

Ac-[Pen]-NTW-[Cit]-[Pen]-[Phe[4-(2-aminoethoxy)]-

[2-Nal]-[Aib]-[Lys(Ac)]-NN-NH 2 .

16. The method of claim 10 , wherein the peptide inhibitor is:

(SEQ ID NO: 1200)

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-

Nal]-[Aib]-[Lys(Ac)]-S-[βAla]-NH 2 .

17. The method of claim 10 , wherein the peptide inhibitor is:

(SEQ ID NO: 1204)

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2-

Nal]-[Aib]-[Lys(Ac)]-[2-Nap]-[βAla]-NH 2 .

18. The method of claim 10 , wherein the peptide inhibitor is:

(SEQ ID NO: 1205)

Ac-[Pen]-NTWQ-[Pen]-[Phe[4-(2-aminoethoxy)]-[2- 

Nal]-[Aib]-[Lys(Ac)]-F-[βAla]-NH 2 .

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 20, 2019
From: BHANDARI, ASHOK; BOURNE, GREGORY THOMAS; CHENG, XIAOLI; FREDERICK, BRIAN TROY; ZHANG, JIE; PATEL, DINESH V.; LIU, DAVID
To: PROTAGONIST THERAPEUTICS, INC.
Reel/Frame 048383/0433 →
Continuity (5)
Continuation In Part 14800627 · Jul 15, 2015
Continuation In Part PCTUS2015040658 · Jul 15, 2015
Provisional Application 62264820 · Dec 8, 2015
Provisional Application 62281123 · Jan 20, 2016
Related Publication 20190300590A1 · Oct 3, 2019
Cited By (6)
US 12,358,951 US 12,478,617 US 12,552,836 US 12,655,185 US 12,673,974 US 12,729,236