Details of the Drug

General Information of Drug (ID: DMCHA27)

• Drug Name: Almonertinib
• Synonyms: HS-10296; Ameile; 1899921-05-1; Egfr T790M inhibitor HS-10296; N-(5-((4-(1-Cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide; UNII-T4RS462G19; SCHEMBL17683063; GTPL11136; T4RS462G19; EX-A3721; HS 10296 [WHO-DD]; s8817; HS10296; example 26 [WO2016054987A1]; HY-112823; CS-0066162; 2-Propenamide, N-(5-((4-(1-cyclopropyl-1H-indol-3-yl)-2-pyrimidinyl)amino)-2-((2-(dimethylamino)ethyl)methylamino)-4-methoxyphenyl)-; C1(CC1)N1C=C(C2=CC=CC=C12)C1=NC(=NC=C1)NC=1C(=CC(=C(C=1)NC(C=C)=O)N(C)CCN(C)C)OC; N-[5-[[4-(1-cyclopropylindol-3-yl)pyrimidin-2-yl]amino]-2-[2-(dimethylamino)ethyl-methylamino]-4-methoxyphenyl]prop-2-enamide

Indication

Disease Entry	ICD 11	Status	REF
Non-small-cell lung cancer	2C25.Y	Phase 3	[1]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 2:
  Molecular Weight (mw); 525.6
  Topological Polar Surface Area (xlogp); 4.2
  Rotatable Bond Count (rotbonds); 11
  Hydrogen Bond Donor Count (hbonddonor); 2
  Hydrogen Bond Acceptor Count (hbondacc); 7
• Chemical Identifiers:
  Formula: C30H35N7O2
  IUPAC Name: N-[5-[[4-(1-cyclopropylindol-3-yl)pyrimidin-2-yl]amino]-2-[2-(dimethylamino)ethyl-methylamino]-4-methoxyphenyl]prop-2-enamide
  Canonical SMILES: CN(C)CCN(C)C1=CC(=C(C=C1NC(=O)C=C)NC2=NC=CC(=N2)C3=CN(C4=CC=CC=C43)C5CC5)OC
  InChI: InChI=1S/C30H35N7O2/c1-6-29(38)32-24-17-25(28(39-5)18-27(24)36(4)16-15-35(2)3)34-30-31-14-13-23(33-30)22-19-37(20-11-12-20)26-10-8-7-9-21(22)26/h6-10,13-14,17-20H,1,11-12,15-16H2,2-5H3,(H,32,38)(H,31,33,34)
  InChIKey: DOEOECWDNSEFDN-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 121280087
  CAS Number: 1899921-05-1
  DrugBank ID: DB16640
  TTD ID: DDH8L6

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Epidermal growth factor receptor (EGFR)	TTGKNB4	EGFR_HUMAN	Inhibitor	[2]

Molecular Expression Atlas of This Drug

• The Studied Disease: Non-small-cell lung cancer
• ICD Disease Classification: 2C25.Y

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Epidermal growth factor receptor (EGFR)	DTT	EGFR	5.84E-05	0.32	0.55

References

• [1] ClinicalTrials.gov (NCT04870190) Almonertinib Versus Osimertinib in the Patients With EGFR Mutations in Advanced NSCLC With Brain Metastases (ATTACK). U.S. National Institutes of Health.
• [2] Safety, Efficacy, and Pharmacokinetics of Almonertinib (HS-10296) in Pretreated Patients With EGFR-Mutated Advanced NSCLC: A Multicenter, Open-label, Phase 1 Trial. J Thorac Oncol. 2020 Dec;15(12):1907-1918.
• [3] Nasopharyngeal carcinoma: Current treatment options and future directions. J Nasopharyng Carcinoma, 2014, 1(16): e16.
• [4] Triple negative breast cancer--current status and prospective targeted treatment based on HER1 (EGFR), TOP2A and C-MYC gene assessment. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2009 Mar;153(1):13-7.
• [5] Gefitinib ('Iressa', ZD1839) and new epidermal growth factor receptor inhibitors. Br J Cancer. 2004 Feb 9;90(3):566-72.
• [6] Quantitative prediction of fold resistance for inhibitors of EGFR. Biochemistry. 2009 Sep 8;48(35):8435-48.
• [7] A comparison of physicochemical property profiles of marketed oral drugs and orally bioavailable anti-cancer protein kinase inhibitors in clinical development. Curr Top Med Chem. 2007;7(14):1408-22.
• [8] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1797).
• [9] Boehringer Ingelheim. Product Development Pipeline. June 2 2009.
• [10] Synthesis and Src kinase inhibitory activity of a series of 4-[(2,4-dichloro-5-methoxyphenyl)amino]-7-furyl-3-quinolinecarbonitriles. J Med Chem. 2006 Dec 28;49(26):7868-76.
• [11] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).