Drug Information

Drug (ID: DG00628) and It's Reported Resistant Information

• Name: INK128
• Synonyms: 1224844-38-5; Sapanisertib; INK-128; MLN0128; INK 128; INK128; TAK-228; INK 128 (MLN0128); Sapanisertib (MLN0128); MLN-0128; 5-(4-amino-1-isopropyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)benzo[d]oxazol-2-amine; UNII-JGH0DF1U03; 3-(2-Amino-5-benzoxazolyl)-1-(1-methylethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine; JGH0DF1U03; 5-(4-amino-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-3-yl)-1,3-benzoxazol-2-amine; 5-(4-Amino-1-isopropyl-1H-pyrazolo[3,4-d]-pyrimidin-3-yl)benzo[d]oxazol-2-amine; C15H15N7O; 5-(4-azanyl-1-propan-2-yl-pyrazolo[3,4-d]pyrimidin-3-yl)-1,3-benzoxazol-2-amine; Sapanisertib; INK128; Sapanisertib (USAN/INN); Sapanisertib [USAN:INN]; MLS006011012; GTPL7933; SCHEMBL7902875; CHEMBL3545097; CHEBI:91450; EX-A951; INK-128/INK128; SYN1157; BDBM315477; HMS3656H12; HMS3672C21; INK-128;Sapanisertib;MLN0128; AOB87177; INK-0128; 2477AH; MFCD22124893; NSC764658; NSC768435; NSC780880; s2811; ZINC73069271; AKOS025149512; US10172858, Table 1.1; BCP9000789; CCG-265002; CS-0557; DB11836; NSC-764658; NSC-768435; NSC-780880; SB16566; US10172858, Table 1.22; NCGC00346654-01; NCGC00346654-10; AC-26848; AS-16294; BS170924; HY-13328; SMR004702810; BCP0726000086; A8551; FT-0700125; SW220210-1; D11183; INK-128,CAS:1224844-38-5; J-004811; Q27078072; 1H-Pyrazolo[3,4-d]pyrimidin-4-amine, 3-(2-amino-5-benzoxazolyl)-1-(1-methylethyl)-; 2-Benzoxazolamine, 5-(4-amino-1-(1-methylethyl)-1H-pyrazolo(3,4-d)pyrimidin-3-yl)-; 3-(2-Amino-1,3-benzoxazol-5-yl)-1-isopropyl-1H-pyrazolo(3,4-d)pyrimidin-4-amine; 5-(4-amino-1-isopropyl-pyrazolo[3,4-d]pyrimidin-3-yl)-1,3-benzoxazol-2-amine; FE5; INK-128; ; ; MLN-0128; ; ; 5-(4-Amino-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-3-yl)-1,3-benzoxazol-2-amine
• Indication:
  In total 3 Indication(s)
  Breast cancer [ICD-11: 2C60]; Investigative; [1]
  Multiple myeloma [ICD-11: 2A83]; Investigative; [1]
  Multiple myeloma [ICD-11: 2A83]; Investigative; [1]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
  Breast cancer [ICD-11: 2C60]; [1]
• Target: Serine/threonine-protein kinase mTOR (mTOR); MTOR_HUMAN; [1]
• Formula: C15H15N7O
• IsoSMILES: CC(C)N1C2=NC=NC(=C2C(=N1)C3=CC4=C(C=C3)OC(=N4)N)N
• InChI: 1S/C15H15N7O/c1-7(2)22-14-11(13(16)18-6-19-14)12(21-22)8-3-4-10-9(5-8)20-15(17)23-10/h3-7H,1-2H3,(H2,17,20)(H2,16,18,19)
• InChIKey: GYLDXIAOMVERTK-UHFFFAOYSA-N
• PubChem CID: 45375953
• ChEBI ID: CHEBI:91450
• TTD Drug ID: D03DPZ
• DrugBank ID: DB11836

Type(s) of Resistant Mechanism of This Drug

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Their Corresponding Diseases

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

Breast cancer [ICD-11: 2C60]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Ubiquitin protein ligase E3 component n-recognin 5 (UBR5) [1]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Breast cancer [ICD-11: 2C60.3]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: MCF-7 cells; Breast; Homo sapiens (Human); CVCL_0031
• In Vitro Model: MDA-MB-436 cells; Breast; Homo sapiens (Human); CVCL_0623
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: High nuclear EDD expression in a cohort of 151 women with serous ovarian carcinoma was associated with an increased risk of disease recurrence following first-line chemotherapy, and siRNA-knockdown of EDD gene expression partially restored cisplatin sensitivity in cisplatin-resistant ovarian cancer cells in vitro. Loss of EDD induced cell-cycle arrest at G1 through upregulation of tumour suppressor p53 and p21 proteins in osteosarcoma cells in vitro.

References

• Ref 1: Prolactin-inducible EDD E3 ubiquitin ligase promotes TORC1 signalling, anti-apoptotic protein expression, and drug resistance in breast cancer cells .Am J Cancer Res. 2019 Jul 1;9(7):1484-1503. eCollection 2019.