47 results about "Therapeutic index" patented technology

The invention discloses application of ursolic acid in resisting fish ichthyophthiriasis. The ursolic acid has a remarkable killing effect on ichthyophthirius multifilis in an in-vitro stage, and the 4-hour half effective insecticidal concentration (4h-EC50) of the ursolic acid on a grazing body is 0.3774 mg / L; and the 22-hour half effective insecticidal concentration (22h-EC 50) on the capsule is 4.931 mg / L. An acute toxicity test shows that the 96-hour median lethal concentration (96h-LC50) of ursolic acid to goldfish is 9.358 mg / L, the therapeutic index (TI = 96h-LC50 / 4h-EC50) is up to 24.8, and the safety of ursolic acid is remarkably superior to that of a traditional medicine. Ursolic acid used in the invention is a plant-derived active component, has the characteristics of high environmental compatibility and low biological accumulation, meets the development requirements of green fishery, and has an industrialization basis for being developed into eco-friendly aquatic products.

The present invention relates to an antibody or an antigen-binding fragment thereof binding to CLDN18.2, an antibody-drug conjugate comprising same, and a use of the antibody and the antibody-drug conjugate. An anti-CLDN18.2 monoclonal antibody according to the present invention comprises a fully human antibody sequence, thereby having low in vivo immunogenicity, and exhibits excellent antigen affinity and binding ability specific to a low expression to a high expression level of the CLDN18.2 protein. Thus, the antibody is expected to exhibit high specificity and safety as an antibody-based therapeutic agent such as in the form of a monoclonal antibody and / or an antigen-binding fragment (scFv), an antibody-drug conjugate (ADC), an immune cell engager, a chimeric antigen receptor (CAR), a multispecific antibody, and the like. In addition, the antibody according to the present invention may undergo cellular internalization, enables an anti-CLDN18.2 antibody-drug conjugate comprising said antibodies to be conveniently prepared, and has excellent yield and quality and thus is expected to be highly likely to be developed as a drug. A drug conjugate comprising the anti-CLDN18.2 antibody according to the present invention has excellent in vivo anticancer efficacy and has an expanded therapeutic index (TI) and thus is expected to be usefully employable for the treatment and / or prevention of cancer diseases expressing CLDN18.2 and related diseases.

The invention discloses an aryl oxadiazole compound with a chemical structural formula as shown in the specification or pharmaceutically acceptable salt thereof. In-vitro experiment results show that the compound has a remarkable inhibition effect on DENV, the therapeutic index (TI) of the compound is far higher than that of a clinical reference substance ribavirin, the TI value of a preferred compound such as I-29 exceeds 1131.86, and the TI value of the preferred compound is far higher than that of the clinical reference substance ribavirin. The characteristics of high efficiency and low toxicity are highlighted. In addition, the preparation method is simple in process, high in yield, mild in reaction condition and suitable for large-scale production and clinical popularization.

The invention discloses an anti-cancer oligopeptide designed based on threonine and analogues thereof and application of the anti-cancer oligopeptide, the anti-cancer oligopeptide is obtained by taking KLLKKLLKKLLKKKLLKW as a structural basis, replacing amino acids at different sites with hydroxyl-containing threonine or analogues thereof, and then amidating a C terminal; the structural general formula of the compound is as follows: KXmLKKLLKKLLKW-NH2, wherein X = T, pT, F, Y or pY, and p represents phosphorylation; and m is 2, 3, 6, 7, 10, 11 or 13. The anti-cancer oligopeptide has the advantages of high efficiency, low toxicity, short sequence and the like. In-vitro anti-tumor activity and toxicity experiment results show that the compound has a relatively strong killing effect on various tumor cells, and is low in hemolytic toxicity and high in therapeutic index. Serum stability experiments further show that the protein has relatively high enzymolysis stability. A scanning electron microscope experiment shows that the anti-cancer oligopeptide can quickly kill tumor cells through an effective membrane rupture mechanism. Therefore, the compound has a good application prospect in the aspects of research on novel high-efficiency low-toxicity polypeptide anti-cancer drugs, resistance to multidrug resistance and preparation of anti-cancer drugs.

The application discloses a high-safety tumor treatment preparation based on a prodrug-enzyme-neutralizing antibody three-system, and a preparation method and application thereof. The preparation comprises three core components: (a) a prodrug, which is coupled by an anti-tumor drug (such as doxorubicin) and cephalosporin; (b) an activating enzyme, such as beta-lactamase, which is specifically expressed in the tumor by phage, catalyzes the hydrolysis of the prodrug, and releases the active drug; and (c) a neutralizing antibody, such as an anti-doxorubicin monoclonal antibody, which can specifically bind and neutralize the active drug overflowing into the blood circulation. The application first integrates the precise killing strategy of "prodrug-local activation" and the safety strategy of "neutralizing antibody-systematic protection" into a complete treatment closed loop, utilizes the "differential neutralization" characteristics of the anti-doxorubicin antibody, effectively protects normal tissues from toxic damage under the premise of not affecting the local efficacy of the tumor, and significantly improves the therapeutic index of the chemotherapy drug, reduces the side effects such as cardiotoxicity and bone marrow suppression, and provides a new paradigm with high efficiency and safety for tumor treatment.

V1a RECEPTOR PARTIAL AGONISTS AND METHODS OF USE SOLUTION: The present invention provides novel partial V1a agonists for partial activation of V1a receptors. The partial V1a agonists have therapeutic indices of at least 20 (e.g., at least 30, at least 40, at least 50, at least 60, at least 70, at least 80, at least 90, at least 100). Also provided is a method of treating liver fibrosis, hepatocirrhosis, portal hypertension, peritoneal fluid, esophageal varices, fundic varices, hemorrhage, arterial hypotension, and / or hepatorenal syndrome, comprising administering to a subject in need thereof a therapeutically effective dose of a composition comprising one or more of the disclosed partial V1a agonists, optionally in combination with a V2 antagonist.SELECTED DRAWING: None

The problem to be solved by the present invention is to provide cationic lipids for oligonucleotide delivery which can provide a high drug: lipid ratio, which protect the nucleic acid from degradation and clearance in serum, which are suitable for systemic delivery, which can result in intracellular delivery of the nucleic acid, and which are well tolerated, provide an adequate therapeutic index, and treatment of patients with an effective dose of the nucleic acid is not associated with significant toxicity and / or risk to the patient.SOLUTION: The present invention relates to cationic lipids having one or more biodegradable groups located in the lipid portion (e.g., hydrophobic chain) of the cationic lipid. These cationic lipids can be incorporated into lipid particles for the delivery of active agents such as nucleic acids. The present invention also relates to a lipid particle comprising a neutral lipid, a lipid capable of reducing aggregation, a cationic lipid of the invention and optionally a sterol. The lipid particles may further comprise a therapeutic agent, such as a nucleic acid.SELECTED DRAWING: None

Antibodies against the CD3 complex are being tested in bispecific and trispecific antibody formats that further recognize a tumor-associated antigen. Such antibodies are commonly associated with on-target toxicities, however. It is discovered herein that the toxicities can be reduced or avoided if the bispecific and trispecific antibody adopts a suitable structure and uses an anti-CD3 unit having a suitably balanced T cell activation activity level. Provided are such bispecific and trispecific antibody structures. Also provided is a broad spectrum of anti-CD3 antibodies having different levels of T cell activation activities that can be readily used in different scenarios.

The invention discloses an aryl bishydrazide compound with a structural formula shown in the following formula: in-vitro experiment results show that the compound has remarkable inhibitory activity on dengue virus (DENV), the therapeutic index (TI) of the compound is remarkably higher than that of a clinical positive control drug ribavirin, and in addition, the compound can be used for preparing an aryl bishydrazide compound with the structural formula shown in the specification. The preparation method disclosed by the invention is simple and efficient in process, good in yield and mild in reaction condition, has good large-scale production potential, and provides a feasible synthesis basis for further clinical transformation and application.

The present invention concerns antibody-conjugate having general structure (2):wherein AB is an antibody capable of targeting Trop-2-expressing tumours and D is selected from the group consisting of taxanes, anthracyclines, camptothecins, epothilones, mytomycins, combretastatins, vinca alkaloids, maytansinoids, enediynes such as calicheamicins, duocarmycins, tubulysins, amatoxins, bleomycins, dolastatins and auristatins, pyrrolobenzodiazepine dimers, indolinobenzodiazepine dimers, radioisotopes, therapeutic proteins and peptides (or fragments thereof), kinase inhibitors, MEK inhibitors, KSP inhibitors, and analogues or prodrugs thereof. These antibody-conjugates exhibit an improved therapeutic index. The invention further concerns a process for preparing the antibody-conjugate according to the invention, a method for targeting Trop-2-expressing cells, medical uses of the antibody-conjugates according to the invention.

The application discloses a cannabidiol derivative and application thereof, and belongs to the technical field of medicinal chemistry. The structural general formula of the cannabidiol derivative is shown as formula (I): (I) R1 is selected from one of hydrogen, chlorine, bromine, a hydroxyl group, a cyano group, an acetoxy group, an acryloyloxy group, a benzoyl group, an acetamide group, an acrylamide group, a propiolamide group, an ethyl thiourea group, a 3-chloro-2,2-dimethylpropionyl group, a 2-ethylsulfonamide acetyl group, a 2-ethylsulfonamide-N-(2-amino-2-oxoethyl) acetyl group, a methylsulfonyl group, an ethylsulfonyl group, a vinylsulfonyl group, an alkyne propylsulfonyl group, a phenylsulfonyl group and a styrylsulfonyl group; and R2 is selected from one of C2-C5 alkyl groups. The cannabidiol derivative disclosed by the application has significantly improved anti-neuroinflammatory activity, significantly reduced cytotoxicity, and a generally improved treatment index of more than 10 times, or even more than 260 times, compared with cannabidiol.

The present disclosure provides novel V1a partial agonists for partially activating a V1a receptor. The partial V1a agonist has a therapeutic index of at least 20 (e.g., at least 30, at least 40, at least 50, at least 60, at least 70, at least 80, at least 90, at least 100). Also provided are method of treating liver fibrosis, cirrhosis, portal hypertension, ascites, esophageal varices, fundal varices, bleeding, arterial hypotension, and / or hepatorenal syndrome, including administering to a subject in need thereof a therapeutically effective dose of a composition including the V1a partial agonist(s) of the present disclosure, optionally in combination with a V2 antagonist.

The invention belongs to the technical field of biological medicines, and discloses a fusion polypeptide of tachyplesin antibacterial peptide and carrier protein and a preparation method of the fusion polypeptide. The fusion polypeptide is formed by sequentially connecting an N-terminal tachyplesin antibacterial peptide, an intermediate microenvironment response type connection module and a C-terminal carrier protein, wherein the connection module is a GFLGVR sequence with both acid sensitivity and MMP-9 cleavability or a chemical equivalent structure of the GFLGVR sequence. Through a bionically designed double-response connection module, the fusion polypeptide is highly stable under physiological conditions, active components are efficiently released in an infected microenvironment, and the therapeutic index is remarkably improved; the in-vivo half-life period of the tachyplesin antibacterial peptide is prolonged from the minute level to the hour level by utilizing the natural long-cycle characteristic of the carrier protein, so that the defect of rapid removal of the tachyplesin antibacterial peptide is overcome; lesion targeted activation is realized by depending on infection microenvironment specific signals, and whole body exposure and potential toxicity are reduced; the preparation process is mature and controllable, is suitable for large-scale production, and lays a foundation for clinical transformation.

The application discloses application of BMS-833923 and derivatives thereof and a medicine, and belongs to the technical field of antibiotics. The BMS-833923 and the derivatives thereof can be used as colistin adjuvants to jointly inhibit or eliminate gram-negative bacteria, and can also independently inhibit or eliminate gram-positive bacteria. The gram-negative bacteria can include at least one of Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, pan-drug-resistant strains BAA-1800, BAA-1794 and BAA-1792, and the gram-positive bacteria can include at least one of Staphylococcus aureus and Bacillus subtilis. By taking the BMS-833923 and the derivatives thereof as adjuvants of colistin, the therapeutic index of the colistin can be effectively expanded, and lower, non-toxic doses of the colistin can be used in clinical treatment of effective treatment of drug-resistant bacterial infections.

A PEGylated ICD inducer-IDO inhibitor nanoconjugate and a preparation method and use thereof. The nanoconjugate has a structural formula as follows:where R is H orwith a weight-average molecular weight of 1000-5000. For the PEGylated ICD inducer-IDO inhibitor nanoconjugate provided in an aqueous medium, the PEGylated drug conjugate can self-assemble into a drug-based nanoconjugate, which can not only reduce non-specific accumulation in MPS-related organs, but also improve the passive targeting capability to solid tumors through the enhanced permeability and retention effect, thereby increasing the therapeutic index.

The invention belongs to the technical field of biological medicines, discloses a ganoderma lucidum oligopeptide for inhibiting tumor cell growth and a preparation method and application thereof, and aims to overcome the technical defects of unknown active ingredients, low yield, poor purity and high toxicity of the existing ganoderma lucidum oligopeptide. The sequence of the ganoderma lucidum oligopeptide is Trp-Gly-Ala-Pro-Arg, the molecular weight is 623.7 Da, the isoelectric point is 8.92, and the ganoderma lucidum oligopeptide plays a tumor inhibition role by reducing a PI3K / Akt / mTOR signal channel in a targeted manner. The preparation method comprises the following steps: carrying out superfine grinding on a lucid ganoderma raw material, carrying out composite enzymatic hydrolysis by using papain, alkaline protease and flavourzyme (5: 3: 2), and carrying out ultrafiltration, gel chromatography and RP-HPLC (Reverse Phase-High Performance Liquid Chromatography) purification, so that the yield is 1.16-1.20%, and the purity is greater than or equal to 98%. The ICs of the peptide to six tumor cells such as lung cancer A549 are 0.8-1.4 [mu] mol / L, and the ICs of the peptide to normal cells are ICgt; the therapeutic index is greater than or equal to 15.4; the cells PPappgt of Caco-2 are subjected to cell culture; 1 * 10 cm / s, the plasma protein binding rate is 65%-68%, LDgt; the density is 500 mg / kg. The compound can be prepared into dosage forms such as injections and the like, and the tumor inhibition rate reaches 85% when the compound is combined with cis-platinum, and CI is equal to 0.65. The process is stable, and the product is high in activity, safe, suitable for tumor treatment and adjuvant therapy and good in industrialization prospect.

This invention provides a liver-targeting glycoligand molecule modified with dual-antenna GalNAc and its drug delivery system. This liver-targeting glycoligand molecule and its drug delivery system, through ASGPR recognition, can maximize the concentration of therapeutic drugs in liver tumor parenchymal cells, thereby improving the targeting of drug distribution, increasing the therapeutic index, reducing systemic toxicity, and improving patient survival time and quality of life. The liver-targeting glycoligand molecule of this invention is synthesized using an enzymatic synthesis method, which involves fewer synthesis steps, mild enzymatic reaction conditions, high regioselectivity, high reaction efficiency, is environmentally friendly, and has low production costs, making it highly promising for industrialization.

The invention discloses a mirror symmetry antibacterial oligopeptide rich in tryptophan and arginine and application of the mirror symmetry antibacterial oligopeptide. The antibacterial oligopeptide is obtained in the mode that tryptophan W and arginine R form a mirror symmetry peptide structure, then hydrophobic amino acid is modified at the two ends of the peptide sequence, and amidation is conducted on the C tail end; the structural general formula of the fluorescent probe is XRnWmRWmRnX-NH2, and the fluorescent probe is marked as RXm, or XWnRmWRmWnX-NH2, which is marked as WXm; or X (WR) 3WX-NH2, which is marked as RX; or X (RW) 3RX-NH2, which is marked as WX; wherein n = 0, 1 or 2, m = 1, 2 or 3, and n + m = 3. An in-vitro antibacterial activity experiment and a hemolysis experiment show that the antibacterial oligopeptide has relatively strong antibacterial activity on gram-positive bacteria and gram-negative bacteria, and meanwhile, the antibacterial oligopeptide has low hemolysis toxicity. The optimal antibacterial oligopeptide WF is obtained by calculating the therapeutic index, the corresponding full D-type amino acid sequence wf is synthesized, and the wf has high-efficiency antibacterial activity and low toxicity and also has high enzymolysis stability. Therefore, the antibacterial oligopeptide provided by the invention has a good application prospect in preparation of clinical antibacterial drugs.

The present disclosure provides a modified bispecific molecule that targets (a) a tumor-specific mutant peptide or mutation-associated neoantigen (MANA) presented by human leukocyte antigens (HLA) on the surface of target cancer cells; and (b) a surface protein (e.g., CD3) expressed on effector immune cells (e.g., T cells), as well as a method of using the molecule in cell therapy to diagnose, prevent, and / or treat human diseases including cancer. The bispecific molecule is modified to additionally include domain orientation modifications, linker modifications, and functional moieties including, e.g., Fc fragments, serum albumin, and / or polyethylene glycol (PEG) groups, which can improve efficacy, therapeutic index, half-life, and ease of manufacture while maintaining functionality and specificity in the treatment of diseases such as cancer.

The application provides a kind of double amidino-containing compound and the application of pharmaceutically acceptable salt in antifungal, belong to medical technical field.The double amidino-containing compound of the application has the structure shown in formula I R1 and R2 independently selected from hydrogen, substituted or unsubstituted C 1‑12 Alkyl or C 3‑12 Cycloalkyl, or R1 and R2 and N form substituted or unsubstituted 3-6 membered ring, R3 is independently selected from hydrogen, substituted or unsubstituted alkyl; or R2 and R3 are connected to form substituted or unsubstituted 5-7 membered ring with amidino, R1 is independently selected from hydrogen, substituted or unsubstituted alkyl; R is independently selected from hydrogen, halogen, haloalkyl or alkoxy; X and Y are independently selected from C or N; Q is independently selected from oxygen, amine group, alkylamine group, alkyne group, alkoxy or Q group is not present, i.e. two aromatic rings are directly connected.The double amidino-containing compound of the application has good Candida albicans activity and therapeutic index, and can be used for clinical treatment of Candida albicans, to solve the problem of fungal drug resistance.

The application discloses a method for modifying pH sensitivity of an antibody based on yeast display. A degenerate codon VAM (coding H, E, D, K, N, Q) is used to construct a yeast display library for at least two region combinations in LCDR1, HCDR1 and HCDR3, and 1-2 mutations are introduced into each CDR region, taking the antibody to be modified as a template. The library is transformed into Saccharomyces cerevisiae EBY100 to induce expression, and fast dissociation clones are enriched through four rounds of flow sorting (including pH 7.4 binding, pH 6.0 non-binding and'saturated binding-acid dissociation-neutral re-binding' screening). The obtained antibody has a KD ratio at pH 5.8 to pH 7.4 of up to 674.46, an expression amount of up to 263.3 mg / L, excellent physicochemical properties, and can enhance the curative effect of antibody conjugated drugs and improve the therapeutic index.

The application provides a derivative of plinabulin with the structure of formula (I), which is used for anti-tumor, preventing chemotherapy-induced neutropenia and preventing chemotherapy-induced myelosuppression. In the field of cancer treatment, the two derivatives provided by the application have lower toxic side effects under the similar therapeutic effect of plinabulin, have stronger therapeutic effect and higher therapeutic index under the similar toxic side effects, have similar ability of preventing neutropenia and lower toxic side effects compared with plinabulin, have better therapeutic effect than the combination of the commercialized white blood cell increasing drug Neulasta and plinabulin, and can significantly increase the number of various blood cells when combined with a chemotherapy drug. The derivatives provided by the application have wide application prospects in anti-tumor treatment, prevention of neutropenia and prevention of myelosuppression.

This invention discloses a breiaconitine A derivative having analgesic activity, a method for preparing the same, and its use, relating to the field of medicinal chemistry. A breiaconitine A derivative is a compound represented by formula (I), its isomer, its deuterated compound, its solvate, its prodrug, its metabolite, its crystalline form, or its pharmaceutically acceptable salt. The breiaconitine A derivatives provided in this invention have advantages such as high analgesic activity, good anti-inflammatory activity, low toxicity, high therapeutic index, and high water solubility, and can be applied to the preparation of low-toxicity, highly effective, and independent anti-inflammatory analgesics. [Formula 1] TIFF2026511621000134.tif45170 Formula I

The invention discloses a praziquantel derivative PT-28 as well as a preparation method and application thereof. According to the praziquantel derivative PT-28, a thymol precursor and amino-praziquantel react to generate the derivative. The praziquantel derivative PT-28 can be used as a drug for resisting third-generation insect diseases, and compared with the national standard anti-parasitic drug praziquantel, the safety index-therapeutic index (TI value) of the drug is improved by 8.89 times. The compound has the characteristics of being safe to fishes, low in toxicity and good in killing effect on third-generation insects, and has wide application prospects in development of novel insect-resistant fishery drugs.

The invention relates to the technical field of magnetic field therapeutic machines, in particular to a gyromagnetic therapeutic machine control method based on multi-sensor fusion, and the method comprises the steps: collecting multi-source information, and carrying out the data fusion, so as to construct a multi-dimensional evaluation model which comprises a result prediction sub-model, a tolerance evaluation sub-model and a risk monitoring sub-model; carrying out dynamic weighted fusion to obtain a comprehensive control evaluation value; when it is judged that the reason for abnormity in the control process of the therapeutic machine is a multi-dimensional evaluation model based on the multiple comprehensive therapeutic indexes, a differential updating strategy is adopted to update the corresponding sub-model; and determining a corresponding control process decision based on comparison of the comprehensive control evaluation value and a comprehensive evaluation threshold value, controlling the therapeutic machine to enhance the magnetic field intensity based on the index difference value when the enhanced control mode is adopted, and controlling the therapeutic machine to weaken the magnetic field intensity based on the index deviation value when the safety control mode is adopted. The control precision, the accuracy and the use reliability of the therapeutic machine can be improved.

Disclosed herein are therapeutic constructs including a delivery particle, at least one anti-cancer agent (e.g., a mitotic kinase inhibitor), and at least one immune checkpoint inhibitor. Also disclosed are therapeutic constructs including a mitotic kinase inhibitor, an immune checkpoint inhibitor, and a chemical linker. These therapeutic constructs cause cancer death by both therapeutic and immune effects and promote targeted delivery of more therapeutics to the surviving cancer cells in a positive feed-back loop. They enhance therapeutic index of free drugs and can be used intratumorally or systemically. This strategy can treat broad cancer types and is particular useful for cancer without obvious receptors for cancer-targeted delivery of otherwise toxic therapeutics.

The present invention relates to: an antibody-drug conjugate (ADC) in which a linker drug is site-specifically conjugated to an antibody through an engineered cysteine at a specific position of the antibody; and a pharmaceutical composition for preventing or treating proliferative diseases, comprising same. The site-specifically conjugated ADC according to the present invention exhibited improved physicochemical, pharmacological, and / or pharmacokinetic properties. The ADC of the present invention has binding properties similar to those of wild-type antibodies, excellent in vivo efficacy, increased therapeutic index, and / or improved stability, and thus can exhibit therapeutic effects on various diseases including cancer superior to those of conventional antibodies or ADCs.

This invention relates to the field of rat coronary heart disease complicated with depression treatment and intervention technology, and discloses a rat coronary heart disease complicated with depression treatment and intervention system, including a multidimensional acquisition module and an intelligent intervention module. The system acquires experimental data, metabolomics data, and efficacy data of intervention programs from all rats through the multidimensional acquisition module, and classifies them into datasets. The intelligent intervention module calculates a disease index based on the multidimensional data, accurately quantifies the severity of symptoms, and achieves dual correlation verification between metabolic mechanisms and pathological phenotypes. The multidimensional correlation has high accuracy. The intelligent intervention module evaluates the treatment effect of each rat after receiving different intervention programs, generates a treatment index, and assesses the population coverage of each intervention program's effect, generating an effectiveness index. It determines the symptom level and efficacy level of each rat, outputs corresponding evaluation results and intervention suggestions, and optimizes the intervention program through population data feedback. The intelligent intervention treatment effect is excellent.

The novel compound 3-(1-(2,3-dichloro-4-methoxyphenyl)ethyl)-1-methyl-1-(1,3,3-trimethylpiperidin-4-yl)urea monohydrochloride has high permeability, is able to cross the blood-brain barrier and shows consistent ghrelin agonist activity at the level of the central nervous system; the compound is effective in the treatment and / or prevention of medical conditions mediated by ghrelin receptors in the central nervous system. In particular, in experimental tests, the compound shows high efficacy in the treatment of neurotoxic injuries and has an effective neuroprotective action combination pattern at both central and peripheral levels. The compound is also useful in the treatment of diseases requiring a reduction in heart rate. The compound has pharmacological activity at low to moderate doses, thus showing a good therapeutic index.

This disclosure relates to novel GSPT1 degraders and the use of novel GSPT1 degraders. More specifically, this disclosure relates to a compound represented by formula I, or its stereoisomer, hydrate, solvate, or pharmaceutically acceptable salt, a pharmaceutical composition containing the same for treating disorders of uncontrolled cell proliferation, and a method for treating disorders of uncontrolled cell proliferation by administering the same to a mammal. The compounds relating to this disclosure exhibit high selectivity and sustained degrading activity for GSPT1, excellent pH stability, and low cytotoxicity to normal cells, and therefore have excellent anticancer efficacy and a high therapeutic index. In addition, the compounds relating to this disclosure may exhibit excellent anticancer activity against cancers exhibiting a neuroendocrine phenotype, such as small cell lung cancer (SCLC), neuroendocrine pulmonary cancer (NEC), and neuroendocrine prostate cancer (NEPC).