Drug Information

Drug (ID: DG01595) and It's Reported Resistant Information

• Name: Uprosertib
• Synonyms: Uprosertib; 1047634-65-0; GSK2141795; UNII-ZXM835LQ5E; GSK795; GSK2141795C; GSK-2141795; ZXM835LQ5E; Uprosertib (GSK2141795); N-((S)-1-Amino-3-(3,4-difluorophenyl)propan-2-yl)-5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)furan-2-carboxamide; N-[(2S)-1-amino-3-(3,4-difluorophenyl)propan-2-yl]-5-chloro-4-(4-chloro-2-methylpyrazol-3-yl)furan-2-carboxamide; Uprosertib [USAN:INN]; Uprosertib (USAN/INN); Akt inhibitor gsk2141795; SCHEMBL168584; Uprosertib, GSK2141795; Akt inhibitor gsk-2141795; GTPL7902; CHEMBL3137336; BCP28204; EX-A1593; BDBM50170284; GSK-2141795C; MFCD28144686; NSC778368; NSC800960; s7492; ZINC43197676; AKOS027323909; CCG-268992; DB11969; NSC-778368; NSC-800960; NCGC00390653-01; AC-30940; HY-15965; D10674; F20800; Q27089099; GSK-2141795; GSK2141795; GSK 2141795; GSK795; GSK-795; GSK 795.; 2-Furancarboxamide, N-((1S)-2-amino-1-((3,4-difluorophenyl)methyl)ethyl)-5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-; N-((1S)-1-(Aminomethyl)-2-(3,4-difluorophenyl)ethyl)-5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)furan-2-carboxamide; N-{(1S)-2-amino-1-[(3,4-difluorophenyl)methyl]ethyl}-5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-2-furancarboxamide
• Indication:
  In total 2 Indication(s)
  Solid tumour/cancer [ICD-11: 2A00-2F9Z]; Phase 2; [1]
  Solid tumour/cancer [ICD-11: 2A00-2F9Z]; Phase 2; [1]
• Target: Fibroblast growth factor receptor (FGFR); NOUNIPROTAC; [2]
• Target: Fibroblast growth factor receptor 1 (FGFR1); FGFR1_HUMAN; [2]
• Formula: 6
• IsoSMILES: CN1C(=C(C=N1)Cl)C2=C(OC(=C2)C(=O)N[C@@H](CC3=CC(=C(C=C3)F)F)CN)Cl
• InChI: InChI=1S/C18H16Cl2F2N4O2/c1-26-16(12(19)8-24-26)11-6-15(28-17(11)20)18(27)25-10(7-23)4-9-2-3-13(21)14(22)5-9/h2-3,5-6,8,10H,4,7,23H2,1H3,(H,25,27)/t10-/m0/s1
• InChIKey: AXTAPYRUEKNRBA-JTQLQIEISA-N
• PubChem CID: 51042438
• TTD Drug ID: D0NU0U
• DrugBank ID: DB11969

Type(s) of Resistant Mechanism of This Drug

  ADTT: Aberration of the Drug's Therapeutic Target

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Their Corresponding Diseases

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

Solid tumour/cancer [ICD-11: 2A00-2F9Z]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: RAC-alpha serine/threonine-protein kinase (AKT1) [2]

• Molecule Alteration: Missense mutation; p.E17K (c.49G>A)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SkOV3 cells; Ovary; Homo sapiens (Human); CVCL_0532
• In Vitro Model: BT474 cells; Breast; Homo sapiens (Human); CVCL_0179
• In Vivo Model: Female nu/nu CD-1 mouse xenograft model; Mus musculus
• Mechanism Description: The missense mutation p.E17K (c.49G>A) in gene AKT1 cause the sensitivity of Uprosertib by aberration of the drug's therapeutic target

Melanoma [ICD-11: 2C30]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: RAC-alpha serine/threonine-protein kinase (AKT1) [1]

• Molecule Alteration: Missense mutation; p.E17K (c.49G>A)
• Sensitive Disease: Melanoma [ICD-11: 2C30.0]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: 19 drug na?ve cell lines and four sub-lines; N.A.; .; N.A.
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: ATP-based luminescent assay; Flow cytometry assay

References

• Ref 1: Effects of AKT inhibitor therapy in response and resistance to BRAF inhibition in melanomaMol Cancer. 2014 Apr 16;13:83. doi: 10.1186/1476-4598-13-83.
• Ref 2: Discovery of novel AKT inhibitors with enhanced anti-tumor effects in combination with the MEK inhibitorPLoS One. 2014 Jun 30;9(6):e100880. doi: 10.1371/journal.pone.0100880. eCollection 2014.