Drug Information

Drug (ID: DG00394) and It's Reported Resistant Information

• Name: Dapt (Gsi IX)
• Synonyms: Dapt; 208255-80-5; DAPT (GSI-IX); GSI-IX; gamma-Secretase Inhibitor IX; CHEBI:86193; tert-butyl (2S)-2-[[(2S)-2-[[2-(3,5-difluorophenyl)acetyl]amino]propanoyl]amino]-2-phenylacetate; LY-374973; CHEMBL255682; MFCD04974585; (S)-tert-butyl 2-((S)-2-(2-(3,5-difluorophenyl)acetamido)propanamido)-2-phenylacetate; Glycine, N-[2-(3,5-difluorophenyl)acetyl]-L-alanyl-2-phenyl-, 1,1-dimethylethyl ester, (2S)-; tert-butyl (S)-2-((S)-2-(2-(3,5-difluorophenyl)acetamido)propanamido)-2-phenylacetate; N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine tert-butyl ester; DAPT (peptide); GSIIX; GSI IX; N-(2FPhAc)Ala-phenyl-Gly t-butyl ester; DAPT,GSI-IX; DAPT - GSI-IX; MLS006010075; QCR-29; SCHEMBL1360313; TB2634-GMP; GTPL11363; DTXSID00415519; EX-A324; C23H26F2N2O4; HMS3413L17; HMS3677L17; HMS3884P09; AOB33372; ZINC1549363; BDBM50478375; N-(N-(3,5-difluorophenacetyl)alanyl)phenylglycine tert-butyl ester; s2215; AKOS024457209; N-[N-(3,5-Difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester; CCG-264944; CS-0264; MRF-0000012; NCGC00167803-03; (3,5-Difluorophenylacetyl)-Ala-Phg-OtBu; AC-23163; AS-19399; HY-13027; SMR004701228; AB0033805; D4257; SW219339-1; X7572; AB01566837_01; J-013656; J-524356; Q27158972; (3,5-Difluorophenylacetyl)-L-alanyl-L-2-phenylglycine tert-Butyl Ester; (2S)-N-[(3,5-Difluorophenyl)acetyl]-L-alanyl-2-phenyl]glycine 1,1-dimethylethyl ester; (2S)-N-[(3,5-Difluorophenyl)acetyl]-L-alanyl-2-phenylglycine 1,1-dimethylethyl ester; N-[2-(3,5-Difluorophenyl)acetyl]-L-alanyl-L-(2-phenyl)glycine tert-butyl ester; N-{N-[2-(3,5-Difluorophenyl)acetyl]-(S)-alanyl}- (S)-phenylglycine tert-butyl ester; tert-butyl (2S)-({N-[(3,5-difluorophenyl)acetyl]-L-alanyl}amino)(phenyl)acetate; (S)-{(S)-2-[2-(3,5-Difluoro-phenyl)-acetylamino]-propionylamino}-phenyl-acetic acid tert-butyl ester; t-butyl (2s)-2-[[(2s)-2-[[2-(3,5-difluorophenyl)acetyl]amino]propanoyl]amino]-2-phenylacetate; tert-butyl (2R)-[((2S)-2-{[(3,5-difluorophenyl)acetyl]aMino}propanoyl)aMino](phenyl)ethanoate
• Drug Resistance Disease(s):
  Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (1 diseases)
  Mature T-cell lymphoma [ICD-11: 2A90]; [1]
• Formula: C23H26F2N2O4
• IsoSMILES: C[C@@H](C(=O)N[C@@H](C1=CC=CC=C1)C(=O)OC(C)(C)C)NC(=O)CC2=CC(=CC(=C2)F)F
• InChI: 1S/C23H26F2N2O4/c1-14(26-19(28)12-15-10-17(24)13-18(25)11-15)21(29)27-20(16-8-6-5-7-9-16)22(30)31-23(2,3)4/h5-11,13-14,20H,12H2,1-4H3,(H,26,28)(H,27,29)/t14-,20-/m0/s1
• InChIKey: DWJXYEABWRJFSP-XOBRGWDASA-N
• PubChem CID: 5311272

Type(s) of Resistant Mechanism of This Drug

  EADR: Epigenetic Alteration of DNA, RNA or Protein

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-02: Benign/in-situ/malignant neoplasm

Mature T-cell lymphoma [ICD-11: 2A90]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-mir-223 [1]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Acute T-cell lymphocytic leukemia [ICD-11: 2A90.5]
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• Cell Pathway Regulation: Notch/NF-kB signaling pathway; Regulation; hsa04330
• In Vitro Model: Jurkat cells; Pleural effusion; Homo sapiens (Human); CVCL_0065
• In Vitro Model: DND41 cells; Pleural effusion; Homo sapiens (Human); CVCL_2022
• In Vitro Model: Jurkat IkkGamma -/- cells; Pleural effusion; Homo sapiens (Human); CVCL_0065
• In Vitro Model: Molt3 cells; Pleural effusion; Homo sapiens (Human); CVCL_0624
• In Vitro Model: TALL-1 cells; Pleural effusion; Homo sapiens (Human); CVCL_1736
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: Trypan blue staining; MTT assay; Promega assay
• Mechanism Description: Specific inhibition of miR-223 restores GSI sensitivity in GSI-resistant Molt3 cells carrying wt FBXW7. Therefore, upregulation of FBXW7 through the specific inhibition of miR-223 could offer an attractive targeted therapy for GSI-resistant T-ALLs harboring wt FBXW7 and overexpressing miR-223.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: F-box/WD repeat-containing protein 7 (FBXW7) [1]

• Molecule Alteration: Expression; Down-regulation
• Resistant Disease: Acute T-cell lymphocytic leukemia [ICD-11: 2A90.5]
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• Cell Pathway Regulation: Notch/NF-kB signaling pathway; Regulation; hsa04330
• In Vitro Model: Jurkat cells; Pleural effusion; Homo sapiens (Human); CVCL_0065
• In Vitro Model: DND41 cells; Pleural effusion; Homo sapiens (Human); CVCL_2022
• In Vitro Model: Jurkat IkkGamma -/- cells; Pleural effusion; Homo sapiens (Human); CVCL_0065
• In Vitro Model: Molt3 cells; Pleural effusion; Homo sapiens (Human); CVCL_0624
• In Vitro Model: TALL-1 cells; Pleural effusion; Homo sapiens (Human); CVCL_1736
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Trypan blue staining; MTT assay; Promega assay
• Mechanism Description: Specific inhibition of miR-223 restores GSI sensitivity in GSI-resistant Molt3 cells carrying wt FBXW7. Therefore, upregulation of FBXW7 through the specific inhibition of miR-223 could offer an attractive targeted therapy for GSI-resistant T-ALLs harboring wt FBXW7 and overexpressing miR-223.

References

• Ref 1: Notch and NF-kB signaling pathways regulate miR-223/FBXW7 axis in T-cell acute lymphoblastic leukemia. Leukemia. 2014 Dec;28(12):2324-35. doi: 10.1038/leu.2014.133. Epub 2014 Apr 14.