Drug Information

Drug (ID: DG01642) and It's Reported Resistant Information

• Name: M2698
• Synonyms: M2698 free base; M2698; 1379545-95-5; MSC2363318A; UNII-0DXG50I4WD; 0DXG50I4WD; 1379545-95-5 (free base); M-2698; (S)-4-((2-(Azetidin-1-yl)-1-(4-chloro-3-(trifluoromethyl)phenyl)ethyl)amino)quinazoline-8-carboxamide; SCHEMBL15262358; BCP19488; EX-A1187; MSC-2363318A; NSC795142; DB15431; NSC-795142; HY-100501; CS-0019628; M2698(MSC-2363318A); M-2698;M 2698; MSC-2363318A; MSC 2363318A; MSC2363318A; 4-[[(1S)-2-(azetidin-1-yl)-1-[4-chloro-3-(trifluoromethyl)phenyl]ethyl]amino]quinazoline-8-carboxamide; 8-Quinazolinecarboxamide, 4-(((1S)-2-(1-azetidinyl)-1-(4-chloro-3-(trifluoromethyl)phenyl)ethyl)amino)-
• Indication:
  In total 2 Indication(s)
  Acute myelogenous leukaemia [ICD-11: 2A60]; Phase 1; [1]
  Acute myeloid leukaemia [ICD-11: 2A60]; Phase 1; [1]
• Target: Isocitrate dehydrogenase (IDH); IDHC_HUMAN IDHP_HUMAN IDH3A_HUMAN IDH3B_HUMAN IDH3G_HUMAN; [1]
• Formula: 6
• IsoSMILES: C1CN(C1)C[C@H](C2=CC(=C(C=C2)Cl)C(F)(F)F)NC3=NC=NC4=C3C=CC=C4C(=O)N
• InChI: InChI=1S/C21H19ClF3N5O/c22-16-6-5-12(9-15(16)21(23,24)25)17(10-30-7-2-8-30)29-20-14-4-1-3-13(19(26)31)18(14)27-11-28-20/h1,3-6,9,11,17H,2,7-8,10H2,(H2,26,31)(H,27,28,29)/t17-/m1/s1
• InChIKey: HXAUJHZZPCBFPN-QGZVFWFLSA-N
• PubChem CID: 89808643
• TTD Drug ID: D0K7FT

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: PI3-kinase alpha (PIK3CA) [1]

• Molecule Alteration: Missense mutation; p.H1047R (c.3140A>G)
• Sensitive Disease: Breast adenocarcinoma [ICD-11: 2C60.1]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: PI3K signaling pathway; Inhibition; hsa04151
• In Vitro Model: U251 cells; Brain; Homo sapiens (Human); CVCL_0021
• In Vitro Model: MDA-MB-453 cells; Breast; Homo sapiens (Human); CVCL_0418
• In Vitro Model: MDA-MB-468 cells; Breast; Homo sapiens (Human); CVCL_0419
• In Vitro Model: JIMT-1 cells; Breast; Homo sapiens (Human); CVCL_2077
• In Vitro Model: HCC1419 cells; Breast; Homo sapiens (Human); CVCL_1251
• In Vivo Model: Nude mouse PDX model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: SRB staining assay
• Mechanism Description: M2698 blocked p70S6K to provide potent PAM pathway inhibition while simultaneously targeting Akt to overcome the compensatory feedback loop.

References

• Ref 1: M2698 is a potent dual-inhibitor of p70S6K and Akt that affects tumor growth in mouse models of cancer and crosses the blood-brain barrierAm J Cancer Res. 2016 Mar 15;6(4):806-18. eCollection 2016.