Target Information
| Target General Information | Top | |||||
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| Target ID |
T75716
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| Target Name |
Delta-like protein 3 (DLL3)
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| Synonyms |
pudgy; pu; delta like canonical Notch ligand 3; SCDO1; Drosophila Delta homolog 3; Delta3
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| Gene Name |
DLL3
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Lung cancer [ICD-11: 2C25] | |||||
| Function |
May be required to divert neurons along a specific differentiation pathway. Plays a role in the formation of somite boundaries during segmentation of the paraxial mesoderm. Inhibits primary neurogenesis.
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| UniProt ID | ||||||
| Sequence |
MVSPRMSGLLSQTVILALIFLPQTRPAGVFELQIHSFGPGPGPGAPRSPCSARLPCRLFF
RVCLKPGLSEEAAESPCALGAALSARGPVYTEQPGAPAPDLPLPDGLLQVPFRDAWPGTF SFIIETWREELGDQIGGPAWSLLARVAGRRRLAAGGPWARDIQRAGAWELRFSYRARCEP PAVGTACTRLCRPRSAPSRCGPGLRPCAPLEDECEAPLVCRAGCSPEHGFCEQPGECRCL EGWTGPLCTVPVSTSSCLSPRGPSSATTGCLVPGPGPCDGNPCANGGSCSETPRSFECTC PRGFYGLRCEVSGVTCADGPCFNGGLCVGGADPDSAYICHCPPGFQGSNCEKRVDRCSLQ PCRNGGLCLDLGHALRCRCRAGFAGPRCEHDLDDCAGRACANGGTCVEGGGAHRCSCALG FGGRDCRERADPCAARPCAHGGRCYAHFSGLVCACAPGYMGARCEFPVHPDGASALPAAP PGLRPGDPQRYLLPPALGLLVAAGVAGAALLLVHVRRRGHSQDAGSRLLAGTPEPSVHAL PDALNNLRTQEGSGDGPSSSVDWNRPEDVDPQGIYVISAPSIYAREVATPLFPPLHTGRA GQRQHLLFPYPSSILSVK Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| Drugs and Modes of Action | Top | |||||
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| Clinical Trial Drug(s) | [+] 6 Clinical Trial Drugs | + | ||||
| 1 | Rova-T | Drug Info | Phase 3 | Small-cell lung cancer | [1], [2], [3] | |
| 2 | Tarlatamab | Drug Info | Phase 2 | Small-cell lung cancer | [4] | |
| 3 | HPN328 | Drug Info | Phase 1/2 | Small-cell lung cancer | [5] | |
| 4 | AMG 119 | Drug Info | Phase 1 | Small-cell lung cancer | [6] | |
| 5 | AMG 757 | Drug Info | Phase 1 | Small-cell lung cancer | [2] | |
| 6 | RG6524 | Drug Info | Phase 1 | Aggressive cancer | [7] | |
| Mode of Action | [+] 1 Modes of Action | + | ||||
| Inhibitor | [+] 3 Inhibitor drugs | + | ||||
| 1 | Rova-T | Drug Info | [1] | |||
| 2 | AMG 119 | Drug Info | [10] | |||
| 3 | AMG 757 | Drug Info | [10] | |||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Pathway Affiliation
of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes
(Pharmacol Rev, 58: 259-279, 2006).
Human Similarity Proteins
Human Pathway Affiliation
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| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
|---|---|---|---|
| Notch signaling pathway | hsa04330 | Affiliated Target |
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| Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
| Th1 and Th2 cell differentiation | hsa04658 | Affiliated Target |
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| Class: Organismal Systems => Immune system | Pathway Hierarchy | ||
| Target Affiliated Biological Pathways | Top | |||||
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| KEGG Pathway | [+] 5 KEGG Pathways | + | ||||
| 1 | Endocrine resistance | |||||
| 2 | Notch signaling pathway | |||||
| 3 | Th1 and Th2 cell differentiation | |||||
| 4 | Pathways in cancer | |||||
| 5 | Breast cancer | |||||
| References | Top | |||||
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| REF 1 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 2 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 3 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 4 | ClinicalTrials.gov (NCT05060016) A Phase 2 Study Evaluating the Efficacy, Safety, Tolerability, and Pharmacokinetics of Tarlatamab in Subjects With Relapsed/Refractory Small Cell Lung Cancer After Two or More Prior Lines of Treatment (DeLLphi-301). U.S.National Institutes of Health. | |||||
| REF 5 | ClinicalTrials.gov (NCT04471727) Study in Patients With Advanced Cancers Associated With Expression of DLL3 Who Have Failed Standard Available Therapy. U.S. National Institutes of Health. | |||||
| REF 6 | ClinicalTrials.gov (NCT03392064) A Phase 1 Study Evaluating the Safety, Tolerability and Efficacy of AMG 119 in Subjects With RR SCLC | |||||
| REF 7 | Clinical pipeline report, company report or official report of Roche | |||||
| REF 8 | Tarlatamab, a First-in-Class DLL3-Targeted Bispecific T-Cell Engager, in Recurrent Small-Cell Lung Cancer: An Open-Label, Phase I Study. J Clin Oncol. 2023 Jun 1;41(16):2893-2903. | |||||
| REF 9 | Clinical pipeline report, company report or official report of Harpoon Therapeutics. | |||||
| REF 10 | Clinical pipeline report, company report or official report of Amgen. | |||||
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