WO2023005841A1 - Composés polypeptidiques contenant des ponts lactame - Google Patents

Composés polypeptidiques contenant des ponts lactame Download PDF

Info

Publication number
WO2023005841A1
WO2023005841A1 PCT/CN2022/107395 CN2022107395W WO2023005841A1 WO 2023005841 A1 WO2023005841 A1 WO 2023005841A1 CN 2022107395 W CN2022107395 W CN 2022107395W WO 2023005841 A1 WO2023005841 A1 WO 2023005841A1
Authority
WO
WIPO (PCT)
Prior art keywords
add
dmf
resin
liquid flows
flows out
Prior art date
Application number
PCT/CN2022/107395
Other languages
English (en)
Chinese (zh)
Inventor
潘志祥
贺海鹰
江志赶
陈曙辉
Original Assignee
南京明德新药研发有限公司
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 南京明德新药研发有限公司 filed Critical 南京明德新药研发有限公司
Publication of WO2023005841A1 publication Critical patent/WO2023005841A1/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/22—Hormones
    • A61K38/26—Glucagons
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/575—Hormones
    • C07K14/605—Glucagons

Definitions

  • the invention relates to a series of polypeptide compounds containing lactam bridges and their application in the preparation of medicines for treating related diseases.
  • CVD cardiovascular disease
  • Glucagon-like peptide-1 (GLP-1) protects islet ⁇ cells in islets, stimulates islet ⁇ cells to release insulin in a glucose-dependent manner, and effectively controls postprandial blood sugar. Because of its unique mechanism of action, the risk of hypoglycemia is greatly reduced. Although GLP-1R agonists have demonstrated excellent hypoglycemic effects in clinical practice, there are still many type 2 diabetics who have not achieved their hypoglycemic and weight loss goals.
  • GLP-1R glucose-dependent insulinotropic polypeptide receptor
  • GCGR glucagon receptor
  • Glucose-dependent insulinotropic polypeptide receptor is a polypeptide secreted by neuroendocrine K cells of the small intestine. Its physiological effects are mediated by GIPR, mainly non-glucose-dependent stimulation of insulin secretion, enhancement of glucagon secretion, and enhancement of lipid metabolism. Although the beneficial effects of GIPR agonists appear to be attenuated in hyperglycemic symptoms in patients with type 2 diabetes, studies have shown that the diminished insulinotropic effect of GIP can be fully restored after a period of normalization of plasma glucose levels. Therefore, introducing GIPR agonist activity into GLP-1R agonists may obtain better hypoglycemic effect.
  • Glucagon is secreted by the pancreas and combines with GCGR to produce a hormone with physiological functions. Glucagon promotes the rise of blood sugar by increasing gluconeogenesis and glycogenolysis. In addition, GCG can also reduce fatty acid synthesis in liver adipose tissue and promote fat decomposition. The introduction of GCGR agonistic activity into GLP-1R agonists can be more beneficial to patients' weight control. In summary, the development of GLP-1R/GIPR/GCGR triple agonists has great medical prospects for the treatment of diabetes, obesity and related diseases.
  • the invention provides a polypeptide (SEQ ID NO: 1):
  • a lactam bridge is formed between the amino acid side chains at positions i and i+4 or between the amino acid side chains at positions j and j+3, wherein i is 16, 20 or 24, and j is 17;
  • K 0 represents lysine, and the amino group on the lysine side chain is linked to -X 0 ;
  • n are each independently 1, 2 or 3;
  • p 8, 9 or 10.
  • the invention provides a polypeptide (SEQ ID NO: 1):
  • a lactam bridge is formed between the amino acid side chains at positions i and i+4 or between the amino acid side chains at positions j and j+3, wherein i is 16, 20 or 24, and j is 17;
  • K 0 represents lysine, and the amino group on the lysine side chain is linked to -X 0 ;
  • n are each independently 1, 2 or 3;
  • p 8, 9 or 10.
  • the C-terminus of the amino acid at position 39 is amidated, and other variables are as defined in the present invention.
  • m and n are each independently 2, and other variables are as defined in the present invention.
  • the above-X is selected from
  • polypeptide is selected from:
  • a lactam bridge is formed between the amino acid side chains at positions i and i+4 or between the amino acid side chains at positions j and j+3, wherein i is 16, 20 or 24, and j is 17;
  • Aib and K0 are as defined herein.
  • the present invention also provides a polypeptide represented by the following formula,
  • the present invention also provides the above-mentioned pharmaceutical composition, which comprises, as an active ingredient, a therapeutically effective amount of the above-mentioned polypeptide compound or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.
  • the application of the above-mentioned polypeptide compound or its pharmaceutically acceptable salt or the above-mentioned composition in the preparation of a medicament for treating type 2 diabetes.
  • the polypeptide of the present invention has strong agonistic activity to GIP/GLP-1/GCG; among them, there is a large difference in the agonistic activity of different compounds for GCG, which will be of guiding significance for the study of the balance of the three target activities; the compound of the present invention has Excellent pharmacokinetic properties and in vivo efficacy.
  • pharmaceutically acceptable refers to those compounds, materials, compositions and/or dosage forms, which are suitable for use in contact with human and animal tissues within the scope of sound medical judgment , without undue toxicity, irritation, allergic reaction or other problems or complications, commensurate with a reasonable benefit/risk ratio.
  • pharmaceutically acceptable salt refers to a salt of a compound of the present invention, which is prepared from a compound having a specific substituent found in the present invention and a relatively non-toxic acid or base.
  • base addition salts can be obtained by contacting such compounds with a sufficient amount of base, either neat solution or in a suitable inert solvent.
  • acid addition salts can be obtained by contacting such compounds with a sufficient amount of the acid, either neat solution or in a suitable inert solvent.
  • Certain specific compounds of the present invention contain basic and acidic functional groups and can thus be converted into either base or acid addition salts.
  • the pharmaceutically acceptable salts of the present invention can be synthesized from the parent compound containing acid groups or bases by conventional chemical methods.
  • such salts are prepared by reacting the free acid or base form of these compounds with a stoichiometric amount of the appropriate base or acid in water or an organic solvent or a mixture of both.
  • amino acid refers to naturally occurring and synthetic amino acids, as well as amino acid analogs and amino acid mimetics that function similarly to naturally occurring amino acids.
  • Naturally occurring amino acids are those encoded by the genetic code, as well as those amino acids that are later modified, eg, hydroxyproline, gamma-carboxyglutamic acid, and O-phosphoserine.
  • Amino acid analogs are compounds that have the same basic chemical structure (such as the alpha carbon bound to a hydrogen, carboxyl group, amino group, and R group) as a naturally occurring amino acid, such as homoserine, norleucine, formazine Thionine sulfoxide, methionine methylsulfonium.
  • Such analogs can have modified R groups (eg, norleucine) or modified peptide backbones, but retain the same basic chemical structure as a naturally occurring amino acid.
  • Amino acid mimetics are chemical compounds whose structure differs from the general chemical structure of amino acids, but which function similarly to naturally occurring amino acids.
  • a or Ala described herein represents alanine, and the structure is R or Arg means arginine, the structure is N or Asn means asparagine, the structure is D or Asp means aspartic acid, the structure is C or Cys means cysteine, the structure is Q or Gln means glutamine, the structure is E or Glu means glutamic acid, the structure is G or Gly means glycine, the structure is H or His means histidine, the structure is I or Ile means isoleucine, the structure is L or Leu means leucine, the structure is ⁇ -MeL or ⁇ -MeLeu means ⁇ -methylleucine, the structure is K or Lys means lysine, the structure is M or Met means methionine, the structure is F or Phe means phenylalanine, the structure is P or Pro means proline, the structure is S or Ser represents serine, the structure is T or Thr means threonine, the structure is W or Trp means tryptophan, the
  • treating includes inhibiting, slowing, stopping or reversing the progression or severity of an existing symptom or condition.
  • the compounds of the invention may exist in particular geometric or stereoisomeric forms.
  • the present invention contemplates all such compounds, including cis and trans isomers, (-)- and (+)-enantiomers, (R)- and (S)-enantiomers, diastereomers isomers, (D)-isomers, (L)-isomers, and their racemic and other mixtures, such as enantiomerically or diastereomerically enriched mixtures, all of which are subject to the present within the scope of the invention.
  • Additional asymmetric carbon atoms may be present in substituents such as alkyl groups. All such isomers, as well as mixtures thereof, are included within the scope of the present invention.
  • enantiomer or “optical isomer” refer to stereoisomers that are mirror images of each other.
  • cis-trans isomers or “geometric isomers” arise from the inability to rotate freely due to the double bond or the single bond of the carbon atoms forming the ring.
  • diastereoisomer refers to stereoisomers whose molecules have two or more chiral centers and which are not mirror images of the molecules.
  • keys with wedge-shaped solid lines and dotted wedge keys Indicates the absolute configuration of a stereocenter, with a straight solid-line bond and straight dashed keys Indicates the relative configuration of the stereocenter, with a wavy line Indicates wedge-shaped solid-line bond or dotted wedge key or with tilde Indicates a straight solid line key or straight dotted key
  • the terms “enriched in an isomer”, “enriched in an isomer”, “enriched in an enantiomer” or “enantiomerically enriched” refer to one of the isomers or enantiomers
  • the content of the enantiomer is less than 100%, and the content of the isomer or enantiomer is greater than or equal to 60%, or greater than or equal to 70%, or greater than or equal to 80%, or greater than or equal to 90%, or greater than or equal to 95%, or Greater than or equal to 96%, or greater than or equal to 97%, or greater than or equal to 98%, or greater than or equal to 99%, or greater than or equal to 99.5%, or greater than or equal to 99.6%, or greater than or equal to 99.7%, or greater than or equal to 99.8%, or greater than or equal to 99.9%.
  • the terms “isomer excess” or “enantiomeric excess” refer to the difference between the relative percentages of two isomers or two enantiomers. For example, if the content of one isomer or enantiomer is 90% and the other isomer or enantiomer is 10%, then the isomer or enantiomeric excess (ee value) is 80% .
  • Optically active (R)- and (S)-isomers as well as D and L-isomers can be prepared by chiral synthesis or chiral reagents or other conventional techniques. If one enantiomer of a compound of the invention is desired, it can be prepared by asymmetric synthesis or derivatization with chiral auxiliary agents, wherein the resulting diastereomeric mixture is separated and the auxiliary group is cleaved to provide pure desired enantiomer.
  • a diastereoisomeric salt is formed with an appropriate optically active acid or base, and then a diastereomeric salt is formed by a conventional method known in the art. Diastereomeric resolution is performed and the pure enantiomers are recovered. Furthermore, the separation of enantiomers and diastereomers is usually accomplished by the use of chromatography using chiral stationary phases, optionally in combination with chemical derivatization methods (e.g. amines to amino groups formate).
  • the compounds of the present invention may contain unnatural proportions of atomic isotopes at one or more of the atoms that constitute the compounds.
  • compounds may be labeled with radioactive isotopes such as tritium ( 3 H), iodine-125 ( 125 I) or C-14 ( 14 C).
  • radioactive isotopes such as tritium ( 3 H), iodine-125 ( 125 I) or C-14 ( 14 C).
  • heavy hydrogen can be used to replace hydrogen to form deuterated drugs.
  • the bond formed by deuterium and carbon is stronger than the bond formed by ordinary hydrogen and carbon.
  • deuterated drugs can reduce toxic side effects and increase drug stability. , enhance the efficacy, prolong the biological half-life of drugs and other advantages. All changes in isotopic composition of the compounds of the invention, whether radioactive or not, are included within the scope of the invention.
  • linking group listed does not indicate its linking direction
  • its linking direction is arbitrary, for example,
  • the connecting group L in the middle is -MW-, at this time -MW- can connect ring A and ring B in the same direction as the reading order from left to right to form It can also be formed by connecting loop A and loop B in the opposite direction to the reading order from left to right
  • any one or more sites of the group can be linked to other groups through chemical bonds.
  • connection method of the chemical bond is not positioned, and there is an H atom at the connectable site, when the chemical bond is connected, the number of H atoms at the site will decrease correspondingly with the number of chemical bonds connected to become the corresponding valence group.
  • the chemical bonds that the site is connected with other groups can use straight solid line bonds Straight dotted key or tilde express.
  • the straight solid-line bond in -OCH 3 indicates that it is connected to other groups through the oxygen atom in the group;
  • the straight dotted line bond in indicates that the two ends of the nitrogen atom in the group are connected to other groups;
  • the wavy lines in indicate that the 1 and 2 carbon atoms in the phenyl group are connected to other groups.
  • the structure of the compounds of the present invention can be confirmed by conventional methods known to those skilled in the art. If the present invention involves the absolute configuration of the compound, the absolute configuration can be confirmed by conventional technical means in the art. For example, in single crystal X-ray diffraction (SXRD), the cultured single crystal is collected with a Bruker D8 venture diffractometer to collect diffraction intensity data, the light source is CuK ⁇ radiation, and the scanning method is: After scanning and collecting relevant data, the absolute configuration can be confirmed by further analyzing the crystal structure by direct method (Shelxs97).
  • SXRD single crystal X-ray diffraction
  • the compounds of the present invention can be prepared by a variety of synthetic methods well known to those skilled in the art, including the specific embodiments listed below, the embodiments formed by combining them with other chemical synthesis methods, and the methods well known to those skilled in the art Equivalent alternatives, preferred embodiments include but are not limited to the examples of the present invention.
  • the solvent used in the present invention is commercially available.
  • the polypeptide WX002 was obtained.
  • the molecular weight of the polypeptide was confirmed by ESI-MS, the calculated value was 4902.6, and the detected value was 4902.3.
  • the polypeptide WX003 was obtained.
  • the molecular weight of the polypeptide was confirmed by ESI-MS, the calculated value was 4915.7, and the detected value was 4915.8.
  • the polypeptide WX004 was obtained.
  • the molecular weight of the polypeptide was confirmed by ESI-MS, the calculated value was 4910.6, and the detected value was 4910.4.
  • the polypeptide WX005 was obtained.
  • the molecular weight of the polypeptide was confirmed by ESI-MS, the calculated value was 4968.7, and the detected value was 4968.6.
  • the polypeptide WX006 was obtained.
  • the molecular weight of the polypeptide was confirmed by ESI-MS, the calculated value was 4901.5, and the detected value was 4901.4.
  • the polypeptide WX007 was obtained.
  • the molecular weight of the polypeptide was confirmed by ESI-MS, the calculated value was 4857.5, and the detected value was 4858.2.
  • the polypeptide WX008 was obtained.
  • the molecular weight of the polypeptide was confirmed by ESI-MS, the calculated value was 4901.5, and the detected value was 4902.0.
  • Example 1 In vitro GLP-1R/GIPR/GCGR agonistic activity test
  • the cell line was constructed by Shanghai WuXi PharmaTech. See Table 1 below for details.
  • HSA Human Serum Albumin
  • IBMX 3-Isobutyl-1-methylxanthine
  • the compound to be tested is diluted 4 times at 10 points, the initial concentration is 30 ⁇ M, and Bravo completes the dilution
  • the compound of the present invention has strong agonistic activity on GLP-1R/GIPR/GCGR. Among them, there are large differences in the agonistic activity of different compounds for GCG, which will be of guiding significance for the study of the balance of the activities of the three targets.
  • the compounds of the present invention have excellent effects on improving glucose tolerance.
  • the temperature in the breeding room is maintained at 20-24° C., and the humidity is maintained at 30-70%.
  • the temperature and humidity in the feeding room were monitored in real time by a thermo-hygrometer, and the temperature and humidity were recorded twice a day (once in the morning and once in the afternoon).
  • the daylighting in the animal breeding room is controlled by an electronic timing lighting system, and the lights are turned on for 12 hours and turned off for 12 hours every day (turn on at 7:00 in the morning and turn off at 19:00 in the afternoon).
  • the animals were kept in single cages, and toys were provided for each cage.
  • the animals had free access to food (feed for growth/breeding of rats and mice) and drinking water.
  • Each group of animals was subcutaneously injected with the vehicle and the compound to be tested (10 nmol/kg), the administration time: 9:30 in the morning, the administration frequency was once every three days, and the administration cycle was 22 days.
  • the compounds of the present invention exhibit excellent weight loss efficacy in DIO mice.
  • mice After the db/db mice arrive at the facility, they are kept in an animal breeding room with strictly controlled environmental conditions.
  • the temperature in the breeding room is maintained at 20-24° C., and the humidity is maintained at 30-70%.
  • the temperature and humidity in the feeding room were monitored in real time by a thermo-hygrometer, and the temperature and humidity were recorded twice a day (once in the morning and once in the afternoon).
  • the daylighting in the animal breeding room is controlled by an electronic timing lighting system, and the lights are turned on for 12 hours and turned off for 12 hours every day (turn on at 7:00 in the morning and turn off at 19:00 in the afternoon).
  • the animals were kept in single cages, and toys were provided for each cage. During the experiment, the animals had free access to food (feed for growth/breeding of rats and mice) and drinking water.
  • the vehicle and the compound to be tested (15 nmol/kg) were subcutaneously injected into each group of animals respectively, the administration time: 9:30-11:00 in the morning, the administration frequency was once a day, and the administration was continued for 4 weeks.
  • the compound of the present invention exhibits excellent hypoglycemic efficacy in db/db mice.
  • the pharmacokinetic characteristics of the compounds in rodents after subcutaneous injection were tested according to the standard protocol.
  • the candidate compounds were made into clear solutions and given to mice for subcutaneous injection (SC, 10 nmol/kg).
  • Whole blood was collected, plasma was prepared, drug concentration was analyzed by LC-MS/MS method, and pharmacokinetic parameters were calculated by Phoenix WinNonlin software.
  • the compounds of the present invention have excellent pharmacokinetic properties in mice.
  • the pharmacokinetic characteristics of the compounds in rodents after subcutaneous injection were tested according to the standard protocol.
  • the candidate compounds were made into a clear solution and given to rats for a single subcutaneous injection (SC, 10nmol/kg).
  • Whole blood was collected, plasma was prepared, drug concentration was analyzed by LC-MS/MS method, and pharmacokinetic parameters were calculated by Phoenix WinNonlin software.
  • the compounds of the present invention have excellent pharmacokinetic properties in rats.
  • the mammalian pharmacokinetic characteristics of the compound after subcutaneous injection were tested according to the standard protocol.
  • the candidate compound was formulated into a clear solution and given to cynomolgus monkeys for single subcutaneous injection (SC, 4nmol/kg).
  • Whole blood was collected, plasma was prepared, drug concentration was analyzed by LC-MS/MS method, and pharmacokinetic parameters were calculated by Phoenix WinNonlin software.
  • the compound of the present invention has excellent monkey pharmacokinetic properties.

Abstract

L'invention concerne une série de composés polypeptidiques contenant des ponts lactame et leur utilisation dans la préparation d'un médicament pour le traitement de maladies associées.
PCT/CN2022/107395 2021-07-30 2022-07-22 Composés polypeptidiques contenant des ponts lactame WO2023005841A1 (fr)

Applications Claiming Priority (8)

Application Number Priority Date Filing Date Title
CN202110873054 2021-07-30
CN202110873054.9 2021-07-30
CN202111087337.7 2021-09-16
CN202111087337 2021-09-16
CN202210138834.3 2022-02-15
CN202210138834 2022-02-15
CN202210828556.4 2022-07-13
CN202210828556 2022-07-13

Publications (1)

Publication Number Publication Date
WO2023005841A1 true WO2023005841A1 (fr) 2023-02-02

Family

ID=85086282

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2022/107395 WO2023005841A1 (fr) 2021-07-30 2022-07-22 Composés polypeptidiques contenant des ponts lactame

Country Status (2)

Country Link
TW (1) TW202313667A (fr)
WO (1) WO2023005841A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2023193727A1 (fr) * 2022-04-07 2023-10-12 广东众生睿创生物科技有限公司 Utilisation pharmaceutique de polypeptide dans la préparation de médicaments pour le traitement et/ou la prévention du diabète et de l'obésité et de maladies associées

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014096145A1 (fr) * 2012-12-21 2014-06-26 Sanofi Dérivés de l'exendine 4 utilisés comme agonistes de glp1/gip ou de glp1/gip/glucagon
CN108699125A (zh) * 2015-12-31 2018-10-23 韩美药品株式会社 激活胰高血糖素、glp-1和gip受体的三重激活剂
WO2020143625A1 (fr) * 2019-01-07 2020-07-16 鸿绪生物医药科技（北京）有限公司 Nouveau polypeptide et son application thérapeutique

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014096145A1 (fr) * 2012-12-21 2014-06-26 Sanofi Dérivés de l'exendine 4 utilisés comme agonistes de glp1/gip ou de glp1/gip/glucagon
CN104870009A (zh) * 2012-12-21 2015-08-26 赛诺菲 官能化的毒蜥外泌肽-4衍生物
CN104902919A (zh) * 2012-12-21 2015-09-09 赛诺菲 Glp1/gip双重激动剂或glp1/gip/胰高血糖素三重激动剂
CN108699125A (zh) * 2015-12-31 2018-10-23 韩美药品株式会社 激活胰高血糖素、glp-1和gip受体的三重激活剂
CN109071624A (zh) * 2015-12-31 2018-12-21 韩美药品株式会社 激活胰高血糖素、glp-1和gip受体的三重激活剂的持久缀合物
WO2020143625A1 (fr) * 2019-01-07 2020-07-16 鸿绪生物医药科技（北京）有限公司 Nouveau polypeptide et son application thérapeutique

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
CUI, J. ET AL.: "Rational design of a GLP-1/GIP/Gcg receptor triagonist to correct hyperglycemia, obesity and diabetic nephropathy in rodent animals", LIFE SCIENCES, vol. 260, 22 August 2020 (2020-08-22), XP086316320, DOI: 10.1016/j.lfs.2020.118339 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2023193727A1 (fr) * 2022-04-07 2023-10-12 广东众生睿创生物科技有限公司 Utilisation pharmaceutique de polypeptide dans la préparation de médicaments pour le traitement et/ou la prévention du diabète et de l'obésité et de maladies associées

Also Published As

Publication number Publication date
TW202313667A (zh) 2023-04-01

Similar Documents

Publication Publication Date Title
US20100009904A1 (en) Modified Exedins and Uses Thereof
US20030104981A1 (en) Human insulin analogues
CN110590934B (zh) 一种glp-1化合物
MXPA04006679A (es) Analogos extendidos de peptido-1 de tipo glucagon.
NO328077B1 (no) Anvendelse av en eksendin eller eksendinagonist for fremstilling av en farmasoytisk formulering.
US20220347270A1 (en) Exenatide analog
WO2020120463A1 (fr) Conjugués d'insuline
TW202144393A (zh) Ｇｌｐ－１和ｇｉｐ受體雙重激動劑化合物及其應用
WO2022117056A1 (fr) Composés polypeptidiques modifiés par lactame
WO2023005841A1 (fr) Composés polypeptidiques contenant des ponts lactame
EP3321279B1 (fr) Modificateur de l'exénatide et utilisation de ce dernier
TWI827077B (zh) 多肽的製備及其應用
TWI828434B (zh) 釘合肽及其應用
WO2022262825A1 (fr) Composé polypeptidique contenant un pont lactame
WO2023088140A1 (fr) Peptide agrafé et son utilisation
WO2023016346A1 (fr) Composé polypeptidique contenant un pont lactame
WO2023088143A1 (fr) Polypeptides contenant des agrafes et leur application
WO2023193727A1 (fr) Utilisation pharmaceutique de polypeptide dans la préparation de médicaments pour le traitement et/ou la prévention du diabète et de l'obésité et de maladies associées
WO2023020485A1 (fr) Conjugué polypeptide-médicament ayant une nouvelle structure et son application
RU2809189C2 (ru) Конъюгаты инсулина
KR20240042656A (ko) 신규구조를 갖는 폴리펩타이드 접합체 약물 및 그 응용
WO2022253051A1 (fr) Médicament conjugué à un polypeptide et son utilisation
CN117586373A (zh) 一种长效双激动剂化合物

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 22848446

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE