Drug Information

Drug (ID: DG01540) and It's Reported Resistant Information

• Name: Ipatasertib
• Synonyms: Ipatasertib; GDC-0068; 1001264-89-6; Ipatasertib (GDC-0068); UNII-524Y3IB4HQ; RG7440; GDC0068; GDC 0068; RG-7440; GDC-0068 (RG7440); 524Y3IB4HQ; CHEMBL2177390; (S)-2-(4-chlorophenyl)-1-(4-((5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazin-1-yl)-3-(isopropylamino)propan-1-one; RG 7440; (2S)-2-(4-Chlorophenyl)-1-[4-[(5R,7R)-6,7-dihydro-7-hydroxy-5-methyl-5H-cyclopentapyrimidin-4-yl]-1-piperazinyl]-3-[(1-methylethyl)amino]-1-propanone; (2S)-2-(4-chlorophenyl)-1-[4-[(5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl]piperazin-1-yl]-3-(propan-2-ylamino)propan-1-one; C24H32ClN5O2; (2s)-2-(4-Chlorophenyl)-1-{4-[(5r,7r)-7-Hydroxy-5-Methyl-6,7-Dihydro-5h-Cyclopenta[d]pyrimidin-4-Yl]piperazin-1-Yl}-3-(Propan-2-Ylamino)propan-1-One; 1-Propanone, 2-(4-chlorophenyl)-1-(4-((5R,7R)-6,7-dihydro-7-hydroxy-5-methyl-5H-cyclopentapyrimidin-4-yl)-1-piperazinyl)-3-((1-methylethyl)amino)-, (2S)-; Ipatasertib [USAN:INN]; MFCD22124514; 1-Propanone, 2-(4-chlorophenyl)-1-[4-[(5R,7R)-6,7-dihydro-7-hydroxy-5-methyl-5H-cyclopentapyrimidin-4-yl]-1-piperazinyl]-3-[(1-methylethyl)amino]-, (2S)-; GDC0068 di-HCl; Ipatasertib (USAN/INN); GDC-0068 di-HCl; Ipatasertib; GDC-0068; RG-7440 di-HCl; SCHEMBL191659; GTPL7887; CHEBI:95089; AOB87386; EX-A2077; BDBM50398379; NSC767898; NSC781451; NSC800986; NSC832484; s2808; ZINC68250459; AKOS025396463; BCP9000712; CCG-269312; CS-0975; DB11743; NSC-767898; NSC-781451; NSC-800986; NSC-832484; NCGC00346714-01; (2S)-2-(4-Chlorophenyl)-1-(4-((5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta(d)pyrimidin-4-yl)piperazin-1-yl(-3-((propan-2-yl)amino)propan-1-one; 2-(4-chlorophenyl)-1-(4-(7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta(d)pyrimidin-4-yl)piperazin-1-yl)-3-(isopropylamino)propan-1-one; AC-28420; AS-17027; HY-15186; QC-10488; BCP0726000195; X6541; J3.478.537F; D10641; Q27078088; (2S)-2-(4-chlorophenyl)-1-[4-[(5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[e]pyrimidin-4-yl]piperazin-1-yl]-3-(propan-2-ylamino)propan-1-one; 0RF
• Indication:
  In total 2 Indication(s)
  Basal cell carcinoma [ICD-11: 2C32]; Phase 3; [1]
  Primitive neuroectodermal tumour medulloblastoma [ICD-11: 2A00]; Phase 3; [1]
• Target: Smoothened homolog (SMO); SMO_HUMAN; [1]
• Formula: 6
• IsoSMILES: C[C@@H]1C[C@H](C2=C1C(=NC=N2)N3CCN(CC3)C(=O)[C@H](CNC(C)C)C4=CC=C(C=C4)Cl)O
• InChI: InChI=1S/C24H32ClN5O2/c1-15(2)26-13-19(17-4-6-18(25)7-5-17)24(32)30-10-8-29(9-11-30)23-21-16(3)12-20(31)22(21)27-14-28-23/h4-7,14-16,19-20,26,31H,8-13H2,1-3H3/t16-,19-,20-/m1/s1
• InChIKey: GRZXWCHAXNAUHY-NSISKUIASA-N
• PubChem CID: 24788740
• ChEBI ID: CHEBI:95089
• TTD Drug ID: D03EDQ
• DrugBank ID: DB11743

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 Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

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

• Sensitive Disease: HER2 negative breast cancer [ICD-11: 2C60.11]
• Molecule Alteration: Missense mutation; p.E17K (c.49G>A)
• Wild Type Structure: Method: X-ray diffraction; Resolution: 1.65 Å; PDB: 1UNP
• Mutant Type Structure: Method: X-ray diffraction; Resolution: 1.94 Å; PDB: 2UZR

RMSD: 0.26; TM score: 0.99569; Amino acid change: E17K

• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: AKT signaling pathway; Inhibition; hsa04151
• In Vivo Model: SCID beige mouse PDX model; Mus musculus
• Experiment for Drug Resistance: CellTitre-Glo assay; Wallac multilabel reader assay
• Mechanism Description: Ipatasertib (GDC-0068) is a novel selective ATP-competitive small-molecule inhibitor of AKT that preferentially targets active phosphorylated AKT (pAKT) and is potent in cell lines with evidence of AKT activation.

References

• Ref 1: A First-in-Human Phase I Study of the ATP-Competitive AKT Inhibitor Ipatasertib Demonstrates Robust and Safe Targeting of AKT in Patients with Solid TumorsCancer Discov. 2017 Jan;7(1):102-113. doi: 10.1158/2159-8290.CD-16-0512. Epub 2016 Nov 21.